Publications by authors named "J Scott Roth"

4,260 Publications

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Robotic Surgery and Anatomic Segmentectomy: An Analysis of Trends, Patient Selection, and Outcomes.

Ann Thorac Surg 2021 Apr 7. Epub 2021 Apr 7.

Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas, USA 77030. Electronic address:

Background: It is unclear whetherrobotic segmentectomies are advantageous. We describe our experience with the robot, comparing patient populations and outcomes with videoscopic thoracic surgery (VATS) and open resection.

Methods: Patients who received anatomic segmentectomy from 2004-2019 were reviewed. Resection methods were categorized as robotic, VATS, or open. Segmentectomies were categorized as simple or complex. Baseline characteristics and perioperative outcomes were analyzed from 2015-2019 due to implementation of ERAS protocol.

Results: Since 2004, there has been an increase in segmentectomies, including robotic and complex segmentectomies. There were 222 segmentectomies from 2015-2019, of which 77(35%) were robotic, 40(18%) VATS, and 105(47%) open. Complex segmentectomies were higher in the robotic group compared to VATS and open (45% vs. 15% vs. 22%; p<0.001), operative time for robotic resections were also longer compared to VATS and open (205 vs. 147 vs. 147 minutes; p<0.001), but had lower blood loss (50 vs. 75 vs. 100 ml; p<0.001), shorter chest tube days (2 vs. 2 vs. 3 days; p=0.004) and length of stay (3 vs. 3 vs. 4 days; p<0.001). Perioperative mortality was low in all groups. No robotic segmentectomy converted to open compared to 7.5% for VATS (p=0.038). Prolonged air leak was lower for robotic compared to open (4% vs. 13%; p=0.038).

Conclusions: Robotic segmentectomy has increased in our institution, with concurrent rise in atypical segmentectomies. Despite performing more complex procedures, there were no conversions, and low perioperative morbidity and mortality. Our results suggest that the robotic platform can facilitate performance of complex anatomic segmentectomies.
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http://dx.doi.org/10.1016/j.athoracsur.2021.03.068DOI Listing
April 2021

Observation of a New Excited D_{s}^{+} Meson in B^{0}→D^{-}D^{+}K^{+}π^{-} Decays.

Authors:
R Aaij C Abellán Beteta T Ackernley B Adeva M Adinolfi H Afsharnia C A Aidala S Aiola Z Ajaltouni S Akar J Albrecht F Alessio M Alexander A Alfonso Albero Z Aliouche G Alkhazov P Alvarez Cartelle S Amato Y Amhis L An L Anderlini A Andreianov M Andreotti F Archilli A Artamonov M Artuso K Arzymatov E Aslanides M Atzeni B Audurier S Bachmann M Bachmayer J J Back S Baker P Baladron Rodriguez V Balagura W Baldini J Baptista Leite R J Barlow S Barsuk W Barter M Bartolini F Baryshnikov J M Basels G Bassi B Batsukh A Battig A Bay M Becker F Bedeschi I Bediaga A Beiter V Belavin S Belin V Bellee K Belous I Belov I Belyaev G Bencivenni E Ben-Haim A Berezhnoy R Bernet D Berninghoff H C Bernstein C Bertella E Bertholet A Bertolin C Betancourt F Betti M O Bettler Ia Bezshyiko S Bhasin J Bhom L Bian M S Bieker S Bifani P Billoir M Birch F C R Bishop A Bizzeti M Bjørn M P Blago T Blake F Blanc S Blusk D Bobulska J A Boelhauve O Boente Garcia T Boettcher A Boldyrev A Bondar N Bondar S Borghi M Borisyak M Borsato J T Borsuk S A Bouchiba T J V Bowcock A Boyer C Bozzi M J Bradley S Braun A Brea Rodriguez M Brodski J Brodzicka A Brossa Gonzalo D Brundu A Buonaura C Burr A Bursche A Butkevich J S Butter J Buytaert W Byczynski S Cadeddu H Cai R Calabrese L Calefice L Calero Diaz S Cali R Calladine M Calvi M Calvo Gomez P Camargo Magalhaes A Camboni P Campana D H Campora Perez A F Campoverde Quezada S Capelli L Capriotti A Carbone G Carboni R Cardinale A Cardini I Carli P Carniti L Carus K Carvalho Akiba A Casais Vidal G Casse M Cattaneo G Cavallero S Celani J Cerasoli A J Chadwick M G Chapman M Charles Ph Charpentier G Chatzikonstantinidis C A Chavez Barajas M Chefdeville C Chen S Chen A Chernov S-G Chitic V Chobanova S Cholak M Chrzaszcz A Chubykin V Chulikov P Ciambrone M F Cicala X Cid Vidal G Ciezarek P E L Clarke M Clemencic H V Cliff J Closier J L Cobbledick V Coco J A B Coelho J Cogan E Cogneras L Cojocariu P Collins T Colombo L Congedo A Contu N Cooke G Coombs G Corti C M Costa Sobral B Couturier D C Craik J Crkovská M Cruz Torres R Currie C L Da Silva E Dall'Occo J Dalseno C D'Ambrosio A Danilina P d'Argent A Davis O De Aguiar Francisco K De Bruyn S De Capua M De Cian J M De Miranda L De Paula M De Serio D De Simone P De Simone J A de Vries C T Dean W Dean D Decamp L Del Buono B Delaney H-P Dembinski A Dendek V Denysenko D Derkach O Deschamps F Desse F Dettori B Dey P Di Nezza S Didenko L Dieste Maronas H Dijkstra V Dobishuk A M Donohoe F Dordei A C Dos Reis L Douglas A Dovbnya A G Downes K Dreimanis M W Dudek L Dufour V Duk P Durante J M Durham D Dutta M Dziewiecki A Dziurda A Dzyuba S Easo U Egede V Egorychev S Eidelman S Eisenhardt S Ek-In L Eklund S Ely A Ene E Epple S Escher J Eschle S Esen T Evans A Falabella J Fan Y Fan B Fang N Farley S Farry D Fazzini P Fedin M Féo P Fernandez Declara A Fernandez Prieto J M Fernandez-Tenllado Arribas F Ferrari L Ferreira Lopes F Ferreira Rodrigues S Ferreres Sole M Ferrillo M Ferro-Luzzi S Filippov R A Fini M Fiorini M Firlej K M Fischer C Fitzpatrick T Fiutowski F Fleuret M Fontana F Fontanelli R Forty V Franco Lima M Franco Sevilla M Frank E Franzoso G Frau C Frei D A Friday J Fu Q Fuehring W Funk E Gabriel T Gaintseva A Gallas Torreira D Galli S Gambetta Y Gan M Gandelman P Gandini Y Gao M Garau L M Garcia Martin P Garcia Moreno J García Pardiñas B Garcia Plana F A Garcia Rosales L Garrido C Gaspar R E Geertsema D Gerick L L Gerken E Gersabeck M Gersabeck T Gershon D Gerstel Ph Ghez V Gibson M Giovannetti A Gioventù P Gironella Gironell L Giubega C Giugliano K Gizdov E L Gkougkousis V V Gligorov C Göbel E Golobardes D Golubkov A Golutvin A Gomes S Gomez Fernandez F Goncalves Abrantes M Goncerz G Gong P Gorbounov I V Gorelov C Gotti E Govorkova J P Grabowski R Graciani Diaz T Grammatico L A Granado Cardoso E Graugés E Graverini G Graziani A Grecu L M Greeven P Griffith L Grillo S Gromov B R Gruberg Cazon C Gu M Guarise P A Günther E Gushchin A Guth Y Guz T Gys T Hadavizadeh G Haefeli C Haen J Haimberger T Halewood-Leagas P M Hamilton Q Han X Han T H Hancock S Hansmann-Menzemer N Harnew T Harrison C Hasse M Hatch J He M Hecker K Heijhoff K Heinicke A M Hennequin K Hennessy L Henry J Heuel A Hicheur D Hill M Hilton S E Hollitt J Hu J Hu W Hu W Huang X Huang W Hulsbergen R J Hunter M Hushchyn D Hutchcroft D Hynds P Ibis M Idzik D Ilin P Ilten A Inglessi A Ishteev K Ivshin R Jacobsson S Jakobsen E Jans B K Jashal A Jawahery V Jevtic M Jezabek F Jiang M John D Johnson C R Jones T P Jones B Jost N Jurik S Kandybei Y Kang M Karacson M Karpov N Kazeev F Keizer M Kenzie T Ketel B Khanji A Kharisova S Kholodenko K E Kim T Kirn V S Kirsebom O Kitouni S Klaver K Klimaszewski S Koliiev A Kondybayeva A Konoplyannikov P Kopciewicz R Kopecna P Koppenburg M Korolev I Kostiuk O Kot S Kotriakhova P Kravchenko L Kravchuk R D Krawczyk M Kreps F Kress S Kretzschmar P Krokovny W Krupa W Krzemien W Kucewicz M Kucharczyk V Kudryavtsev H S Kuindersma G J Kunde T Kvaratskheliya D Lacarrere G Lafferty A Lai A Lampis D Lancierini J J Lane R Lane G Lanfranchi C Langenbruch J Langer O Lantwin T Latham F Lazzari R Le Gac S H Lee R Lefèvre A Leflat S Legotin O Leroy T Lesiak B Leverington H Li L Li P Li X Li Y Li Y Li Z Li X Liang T Lin R Lindner V Lisovskyi R Litvinov G Liu H Liu S Liu X Liu A Loi J Lomba Castro I Longstaff J H Lopes G Loustau G H Lovell Y Lu D Lucchesi S Luchuk M Lucio Martinez V Lukashenko Y Luo A Lupato E Luppi O Lupton A Lusiani X Lyu L Ma S Maccolini F Machefert F Maciuc V Macko P Mackowiak S Maddrell-Mander O Madejczyk L R Madhan Mohan O Maev A Maevskiy D Maisuzenko M W Majewski S Malde B Malecki A Malinin T Maltsev H Malygina G Manca G Mancinelli R Manera Escalero D Manuzzi D Marangotto J Maratas J F Marchand U Marconi S Mariani C Marin Benito M Marinangeli P Marino J Marks P J Marshall G Martellotti L Martinazzoli M Martinelli D Martinez Santos F Martinez Vidal A Massafferri M Materok R Matev A Mathad Z Mathe V Matiunin C Matteuzzi K R Mattioli A Mauri E Maurice J Mauricio M Mazurek M McCann L Mcconnell T H Mcgrath A McNab R McNulty J V Mead B Meadows C Meaux G Meier N Meinert D Melnychuk S Meloni M Merk A Merli L Meyer Garcia M Mikhasenko D A Milanes E Millard M Milovanovic M-N Minard L Minzoni S E Mitchell B Mitreska D S Mitzel A Mödden R A Mohammed R D Moise T Mombächer I A Monroy S Monteil M Morandin G Morello M J Morello J Moron A B Morris A G Morris R Mountain H Mu F Muheim M Mukherjee M Mulder D Müller K Müller C H Murphy D Murray P Muzzetto P Naik T Nakada R Nandakumar T Nanut I Nasteva M Needham I Neri N Neri S Neubert N Neufeld R Newcombe T D Nguyen C Nguyen-Mau E M Niel S Nieswand N Nikitin N S Nolte C Nunez A Oblakowska-Mucha V Obraztsov D P O'Hanlon R Oldeman M E Olivares C J G Onderwater A Ossowska J M Otalora Goicochea T Ovsiannikova P Owen A Oyanguren B Pagare P R Pais T Pajero A Palano M Palutan Y Pan G Panshin A Papanestis M Pappagallo L L Pappalardo C Pappenheimer W Parker C Parkes C J Parkinson B Passalacqua G Passaleva A Pastore M Patel C Patrignani C J Pawley A Pearce A Pellegrino M Pepe Altarelli S Perazzini D Pereima P Perret K Petridis A Petrolini A Petrov S Petrucci M Petruzzo T T H Pham A Philippov L Pica M Piccini B Pietrzyk G Pietrzyk M Pili D Pinci F Pisani A Piucci Resmi P K V Placinta J Plews M Plo Casasus F Polci M Poli Lener M Poliakova A Poluektov N Polukhina I Polyakov E Polycarpo G J Pomery S Ponce D Popov S Popov S Poslavskii K Prasanth L Promberger C Prouve V Pugatch H Pullen G Punzi W Qian J Qin R Quagliani B Quintana N V Raab R I Rabadan Trejo B Rachwal J H Rademacker M Rama M Ramos Pernas M S Rangel F Ratnikov G Raven M Reboud F Redi F Reiss C Remon Alepuz Z Ren V Renaudin R Ribatti S Ricciardi D S Richards K Rinnert P Robbe A Robert G Robertson A B Rodrigues E Rodrigues J A Rodriguez Lopez A Rollings P Roloff V Romanovskiy M Romero Lamas A Romero Vidal J D Roth M Rotondo M S Rudolph T Ruf J Ruiz Vidal A Ryzhikov J Ryzka J J Saborido Silva N Sagidova N Sahoo B Saitta D Sanchez Gonzalo C Sanchez Gras R Santacesaria C Santamarina Rios M Santimaria E Santovetti D Saranin G Sarpis M Sarpis A Sarti C Satriano A Satta M Saur D Savrina H Sazak L G Scantlebury Smead S Schael M Schellenberg M Schiller H Schindler M Schmelling T Schmelzer B Schmidt O Schneider A Schopper M Schubiger S Schulte M H Schune R Schwemmer B Sciascia A Sciubba S Sellam A Semennikov M Senghi Soares A Sergi N Serra L Sestini A Seuthe P Seyfert D M Shangase M Shapkin I Shchemerov L Shchutska T Shears L Shekhtman Z Shen V Shevchenko E B Shields E Shmanin J D Shupperd B G Siddi R Silva Coutinho G Simi S Simone I Skiba N Skidmore T Skwarnicki M W Slater J C Smallwood J G Smeaton A Smetkina E Smith M Smith A Snoch M Soares L Soares Lavra M D Sokoloff F J P Soler A Solovev I Solovyev F L Souza De Almeida B Souza De Paula B Spaan E Spadaro Norella P Spradlin F Stagni M Stahl S Stahl P Stefko O Steinkamp S Stemmle O Stenyakin H Stevens S Stone M E Stramaglia M Straticiuc D Strekalina S Strokov F Suljik J Sun L Sun Y Sun P Svihra P N Swallow K Swientek A Szabelski T Szumlak M Szymanski S Taneja F Teubert E Thomas K A Thomson M J Tilley V Tisserand S T'Jampens M Tobin S Tolk L Tomassetti D Torres Machado D Y Tou M Traill M T Tran E Trifonova C Trippl G Tuci A Tully N Tuning A Ukleja D J Unverzagt A Usachov A Ustyuzhanin U Uwer A Vagner V Vagnoni A Valassi G Valenti N Valls Canudas M van Beuzekom M Van Dijk H Van Hecke E van Herwijnen C B Van Hulse M van Veghel R Vazquez Gomez P Vazquez Regueiro C Vázquez Sierra S Vecchi J J Velthuis M Veltri A Venkateswaran M Veronesi M Vesterinen D Vieira M Vieites Diaz H Viemann X Vilasis-Cardona E Vilella Figueras P Vincent G Vitali A Vollhardt D Vom Bruch A Vorobyev V Vorobyev N Voropaev R Waldi J Walsh C Wang J Wang J Wang J Wang J Wang M Wang R Wang Y Wang Z Wang H M Wark N K Watson S G Weber D Websdale C Weisser B D C Westhenry D J White M Whitehead D Wiedner G Wilkinson M Wilkinson I Williams M Williams M R J Williams F F Wilson W Wislicki M Witek L Witola G Wormser S A Wotton H Wu K Wyllie Z Xiang D Xiao Y Xie A Xu J Xu L Xu M Xu Q Xu Z Xu Z Xu D Yang Y Yang Z Yang Z Yang Y Yao L E Yeomans H Yin J Yu X Yuan O Yushchenko E Zaffaroni K A Zarebski M Zavertyaev M Zdybal O Zenaiev M Zeng D Zhang L Zhang S Zhang Y Zhang Y Zhang A Zhelezov Y Zheng X Zhou Y Zhou X Zhu V Zhukov J B Zonneveld S Zucchelli D Zuliani G Zunica

Phys Rev Lett 2021 Mar;126(12):122002

Department of Physics and Astronomy, University of Manchester, Manchester, United Kingdom.

Using pp collision data corresponding to an integrated luminosity of 5.4  fb^{-1} collected with the LHCb detector at a center-of-mass energy of 13 TeV, the B^{0}→D^{-}D^{+}K^{+}π^{-} decay is studied. A new excited D_{s}^{+} meson is observed decaying into the D^{+}K^{+}π^{-} final state with large statistical significance. The pole mass and width, and the spin parity of the new state are measured with an amplitude analysis to be m_{R}=2591±6±7  MeV, Γ_{R}=89±16±12  MeV, and J^{P}=0^{-}, where the first uncertainty is statistical and the second systematic. Fit fractions for all components in the amplitude analysis are also reported. The new resonance, denoted as D_{s0}(2590)^{+}, is a strong candidate to be the D_{s}(2^{1}S_{0})^{+} state, the radial excitation of the pseudoscalar ground-state D_{s}^{+} meson.
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http://dx.doi.org/10.1103/PhysRevLett.126.122002DOI Listing
March 2021

Resolution of vascular inflammation in patients with new-onset giant cell arteritis: data from the RIGA study.

Rheumatology (Oxford) 2021 Apr 8. Epub 2021 Apr 8.

Rheumatology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.

Objectives: Efficacy evaluation of giant cell arteritis (GCA) treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT.

Methods: Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with methotrexate (MTX) or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients.

Results: We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX, and 19 with TOC. PETVAS decreased from 18.9-8.0 units at follow-up in the overall population (p< 0.001). PETVAS changes were numerically higher in patients receiving MTX (-12.3 units) or TOC (-11.7 units) compared with PRED (-8.7). Mean cumulative prednisolone dosages were 5637, 4418, and 2984 mg in patients treated with PRED, MTX, and TOC (p= 0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95%CI 1.01-45.29; p= 0.049) and 16.25 (95%CI 2.60-101.73; p= 0.003) for MTX and TOC users compared with PRED users.

Conclusion: Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX, and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy.
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http://dx.doi.org/10.1093/rheumatology/keab332DOI Listing
April 2021

Voices: Insulin and beyond.

Cell Metab 2021 Apr;33(4):692-699

Marking insulin's centennial, we share stories of researchers and clinicians whose seminal work has advanced our understanding of insulin, islet biology, insulin resistance, and diabetes. The past century of pursuing the "hormone of hormones" and advancing diabetes therapies is replete with stories of collaboration, perseverance, and triumph.
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http://dx.doi.org/10.1016/j.cmet.2021.03.017DOI Listing
April 2021

MRI-based diagnosis and treatment of pediatric brain tumors: is tissue sample always needed?

Childs Nerv Syst 2021 Apr 5. Epub 2021 Apr 5.

Departments of Neurosurgery and Pediatric Neurosurgery, Tel-Aviv Medical Center and Dana Children's Hospital, Tel Aviv University, 6 Weizmann Street, Tel Aviv, Israel.

Traditional management of newly diagnosed pediatric brain tumors (PBTs) consists of cranial imaging, typically magnetic resonance imaging (MRI), and is frequently followed by tissue diagnosis, through either surgical biopsy or tumor resection. Therapy regimes are typically dependent on histological diagnosis. To date, many treatment regimens are based on molecular biology. The scope of this article is to discuss the role of diagnosis and further treatment of PBTs based solely on MRI features, in light of the latest treatment protocols. Typical MRI findings and indications for surgical biopsy of these lesions are described.
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http://dx.doi.org/10.1007/s00381-021-05148-1DOI Listing
April 2021

Can Good Intraoperative Judgement Be Taught?: Pediatric Neurosurgeons' Pedagogical Approaches to Training Residents on Intraoperative Decision-Making.

J Surg Educ 2021 Apr 2. Epub 2021 Apr 2.

Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel.

Objective: To explore how pediatric neurosurgeons train residents in developing intraoperative decision-making judgement.

Design: This study used the Grounded Theory Method in its study design. In-depth interviews were conducted with pediatric neurosurgeons about their approaches to training residents in intraoperative decision making. Data was analyzed line-by-line with codes and categories emerging from participants narratives.

Setting & Participants: Twenty-six pediatric neurosurgeons from 12 countries were interviewed using video-conferencing technology.

Results: Pediatric Neurosurgeons used a variety of training approaches that included pre-surgery discussions, didactic communication during surgery, post-surgery debriefing, allowing residents to model and observe their own intraoperative behaviors, using case studies to teach, and ongoing mentorship. In addition, they encouraged residents to ask for help when needed and emphasized the importance of empathy as a surgeon. Challenges to training residents included the notion that decision-making could only be learned through personal experience, the trainee's personality, and an over-reliance on algorithms and standardized medicine.

Conclusions: Training neurosurgical residents about intraoperative decision-making appears to be ad-hoc and dependent on both the institution and the availability and willingness of senior surgeons to make this a part of their pedagogy. Surgical departments could use these findings to reflect on their own teaching practices and explore whether they wish to teach these skills more explicitly, and in what ways these skills can be best taught to residents.
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http://dx.doi.org/10.1016/j.jsurg.2021.03.006DOI Listing
April 2021

Patient Knowledge and Expectations About Return of Genomic Results in a Biomarker-Driven Master Protocol Trial (SWOG S1400GEN).

JCO Oncol Pract 2021 Apr 2:OP2000770. Epub 2021 Apr 2.

Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose: Biomarker-driven master protocols represent a new paradigm in oncology clinical trials, but their complex designs and wide-ranging genomic results returned can be difficult to communicate to participants. The objective of this pilot study was to evaluate patient knowledge and expectations related to return of genomic results in the Lung Cancer Master Protocol (Lung-MAP).

Methods: Eligible participants with previously treated advanced non-small-cell lung cancer were recruited from patients enrolled in Lung-MAP. Participants completed a 38-item telephone survey ≤ 30 days from Lung-MAP consent. The survey assessed understanding about the benefits and risks of Lung-MAP participation and knowledge of the potential uses of somatic testing results returned. Descriptive statistics and odds ratios for associations between demographic factors and correct responses to survey items were assessed.

Results: From August 1, 2017, to June 30, 2019, we recruited 207 participants with a median age of 67, 57.3% male, and 94.2% White. Most participants "strongly/somewhat agreed" with statements that they "received enough information to understand" Lung-MAP benefits (82.6%) and risks (69.5%). In items asking about potential uses of Lung-MAP genomic results, 87.0% correctly indicated that the results help to select cancer treatment, but < 20% correctly indicated that the results are not used to confirm cancer diagnosis, would not reveal risk of developing diseases besides cancer, and would not indicate if family members had increased cancer risk. There were no associations between sociodemographic factors and proportions providing correct responses.

Conclusion: In a large National Clinical Trials Network biomarker-driven master protocol, most participants demonstrated incorrect knowledge and expectations about the uses of genomic results provided in the study despite most indicating that they had enough information to understand benefits and risks.
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http://dx.doi.org/10.1200/OP.20.00770DOI Listing
April 2021

Antipsychotics in routine treatment are minor contributors to QT prolongation compared to genetics and age.

J Psychopharmacol 2021 Mar 28:2698811211003477. Epub 2021 Mar 28.

Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany.

Background: Drug-induced prolongation of cardiac repolarization limits the treatment with many psychotropic drugs. Recently, the contribution of polygenic variation to the individual duration of the QT interval was identified.

Aims: To explore the interaction between antipsychotic drugs and the individual polygenic influence on the QT interval.

Methods: Retrospective analysis of clinical and genotype data of 804 psychiatric inpatients diagnosed with a psychotic disorder. The individual polygenic influence on the QT interval was calculated according to the method of Arking et al.

Results: Linear regression modelling showed a significant association of the individual polygenic QT interval score (ß = 0.176, < 0.001) and age (ß = 0.139, < 0.001) with the QTc interval corrected according to Fridericia's formula. Sex showed a nominal trend towards significance (ß = 0.064, = 0.064). No association was observed for the number of QT prolonging drugs according to AZCERT taken. Subsample analysis ( = 588) showed a significant association of potassium serum concentrations with the QTc interval (ß = -0.104, = 0.010). Haloperidol serum concentrations were associated with the QTc interval only in single medication analysis ( = 26, ß = 0.101, = 0.004), but not in multivariate regression analysis. No association was observed for aripiprazole, clozapine, quetiapine and perazine, while olanzapine and the sum of risperidone and its metabolite showed a negative association.

Conclusions: Individual genetic factors and age are main determinants of the QT interval. Antipsychotic drug serum concentrations within the therapeutic range contribute to QTc prolongation on an individual level.
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http://dx.doi.org/10.1177/02698811211003477DOI Listing
March 2021

In focus in HCB.

Histochem Cell Biol 2021 Mar 28;155(3):319-322. Epub 2021 Mar 28.

University of Zurich, CH-8091, Zurich, Switzerland.

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http://dx.doi.org/10.1007/s00418-021-01976-zDOI Listing
March 2021

Observation of Multiplicity Dependent Prompt χ_{c1}(3872) and ψ(2S) Production in pp Collisions.

Authors:
R Aaij C Abellán Beteta T Ackernley B Adeva M Adinolfi H Afsharnia C A Aidala S Aiola Z Ajaltouni S Akar J Albrecht F Alessio M Alexander A Alfonso Albero Z Aliouche G Alkhazov P Alvarez Cartelle S Amato Y Amhis L An L Anderlini A Andreianov M Andreotti F Archilli A Artamonov M Artuso K Arzymatov E Aslanides M Atzeni B Audurier S Bachmann M Bachmayer J J Back S Baker P Baladron Rodriguez V Balagura W Baldini J Baptista Leite R J Barlow S Barsuk W Barter M Bartolini F Baryshnikov J M Basels G Bassi B Batsukh A Battig A Bay M Becker F Bedeschi I Bediaga A Beiter V Belavin S Belin V Bellee K Belous I Belov I Belyaev G Bencivenni E Ben-Haim A Berezhnoy R Bernet D Berninghoff H C Bernstein C Bertella E Bertholet A Bertolin C Betancourt F Betti M O Bettler Ia Bezshyiko S Bhasin J Bhom L Bian M S Bieker S Bifani P Billoir M Birch F C R Bishop A Bizzeti M Bjørn M P Blago T Blake F Blanc S Blusk D Bobulska J A Boelhauve O Boente Garcia T Boettcher A Boldyrev A Bondar N Bondar S Borghi M Borisyak M Borsato J T Borsuk S A Bouchiba T J V Bowcock A Boyer C Bozzi M J Bradley S Braun A Brea Rodriguez M Brodski J Brodzicka A Brossa Gonzalo D Brundu A Buonaura C Burr A Bursche A Butkevich J S Butter J Buytaert W Byczynski S Cadeddu H Cai R Calabrese L Calefice L Calero Diaz S Cali R Calladine M Calvi M Calvo Gomez P Camargo Magalhaes A Camboni P Campana D H Campora Perez A F Campoverde Quezada S Capelli L Capriotti A Carbone G Carboni R Cardinale A Cardini I Carli P Carniti K Carvalho Akiba A Casais Vidal G Casse M Cattaneo G Cavallero S Celani J Cerasoli A J Chadwick M G Chapman M Charles Ph Charpentier G Chatzikonstantinidis C A Chavez Barajas M Chefdeville C Chen S Chen A Chernov S-G Chitic V Chobanova S Cholak M Chrzaszcz A Chubykin V Chulikov P Ciambrone M F Cicala X Cid Vidal G Ciezarek P E L Clarke M Clemencic H V Cliff J Closier J L Cobbledick V Coco J A B Coelho J Cogan E Cogneras L Cojocariu P Collins T Colombo L Congedo A Contu N Cooke G Coombs G Corti C M Costa Sobral B Couturier D C Craik J Crkovská M Cruz Torres R Currie C L Da Silva E Dall'Occo J Dalseno C D'Ambrosio A Danilina P d'Argent A Davis O De Aguiar Francisco K De Bruyn S De Capua M De Cian J M De Miranda L De Paula M De Serio D De Simone P De Simone J A de Vries C T Dean W Dean D Decamp L Del Buono B Delaney H-P Dembinski A Dendek V Denysenko D Derkach O Deschamps F Desse F Dettori B Dey P Di Nezza S Didenko L Dieste Maronas H Dijkstra V Dobishuk A M Donohoe F Dordei A C Dos Reis L Douglas A Dovbnya A G Downes K Dreimanis M W Dudek L Dufour V Duk P Durante J M Durham D Dutta M Dziewiecki A Dziurda A Dzyuba S Easo U Egede V Egorychev S Eidelman S Eisenhardt S Ek-In L Eklund S Ely A Ene E Epple S Escher J Eschle S Esen T Evans A Falabella J Fan Y Fan B Fang N Farley S Farry D Fazzini P Fedin M Féo P Fernandez Declara A Fernandez Prieto F Ferrari L Ferreira Lopes F Ferreira Rodrigues S Ferreres Sole M Ferrillo M Ferro-Luzzi S Filippov R A Fini M Fiorini M Firlej K M Fischer C Fitzpatrick T Fiutowski F Fleuret M Fontana F Fontanelli R Forty V Franco Lima M Franco Sevilla M Frank E Franzoso G Frau C Frei D A Friday J Fu Q Fuehring W Funk E Gabriel T Gaintseva A Gallas Torreira D Galli S Gambetta Y Gan M Gandelman P Gandini Y Gao M Garau L M Garcia Martin P Garcia Moreno J García Pardiñas B Garcia Plana F A Garcia Rosales L Garrido D Gascon C Gaspar R E Geertsema D Gerick L L Gerken E Gersabeck M Gersabeck T Gershon D Gerstel Ph Ghez V Gibson M Giovannetti A Gioventù P Gironella Gironell L Giubega C Giugliano K Gizdov E L Gkougkousis V V Gligorov C Göbel E Golobardes D Golubkov A Golutvin A Gomes S Gomez Fernandez M Goncerz G Gong P Gorbounov I V Gorelov C Gotti E Govorkova J P Grabowski R Graciani Diaz T Grammatico L A Granado Cardoso E Graugés E Graverini G Graziani A Grecu L M Greeven P Griffith L Grillo S Gromov L Gruber B R Gruberg Cazon C Gu M Guarise P A Günther E Gushchin A Guth Y Guz T Gys T Hadavizadeh G Haefeli C Haen J Haimberger S C Haines T Halewood-Leagas P M Hamilton Q Han X Han T H Hancock S Hansmann-Menzemer N Harnew T Harrison C Hasse M Hatch J He M Hecker K Heijhoff K Heinicke A M Hennequin K Hennessy L Henry J Heuel A Hicheur D Hill M Hilton S E Hollitt P H Hopchev J Hu J Hu W Hu W Huang X Huang W Hulsbergen R J Hunter M Hushchyn D Hutchcroft D Hynds P Ibis M Idzik D Ilin P Ilten A Inglessi A Ishteev K Ivshin R Jacobsson S Jakobsen E Jans B K Jashal A Jawahery V Jevtic M Jezabek F Jiang M John D Johnson C R Jones T P Jones B Jost N Jurik S Kandybei Y Kang M Karacson J M Kariuki N Kazeev M Kecke F Keizer M Kenzie T Ketel B Khanji A Kharisova S Kholodenko K E Kim T Kirn V S Kirsebom O Kitouni S Klaver K Klimaszewski S Koliiev A Kondybayeva A Konoplyannikov P Kopciewicz R Kopecna P Koppenburg M Korolev I Kostiuk O Kot S Kotriakhova P Kravchenko L Kravchuk R D Krawczyk M Kreps F Kress S Kretzschmar P Krokovny W Krupa W Krzemien W Kucewicz M Kucharczyk V Kudryavtsev H S Kuindersma G J Kunde T Kvaratskheliya D Lacarrere G Lafferty A Lai A Lampis D Lancierini J J Lane R Lane G Lanfranchi C Langenbruch J Langer O Lantwin T Latham F Lazzari R Le Gac S H Lee R Lefèvre A Leflat S Legotin O Leroy T Lesiak B Leverington H Li L Li P Li X Li Y Li Y Li Z Li X Liang T Lin R Lindner V Lisovskyi R Litvinov G Liu H Liu S Liu X Liu A Loi J Lomba Castro I Longstaff J H Lopes G Loustau G H Lovell Y Lu D Lucchesi S Luchuk M Lucio Martinez V Lukashenko Y Luo A Lupato E Luppi O Lupton A Lusiani X Lyu L Ma S Maccolini F Machefert F Maciuc V Macko P Mackowiak S Maddrell-Mander O Madejczyk L R Madhan Mohan O Maev A Maevskiy D Maisuzenko M W Majewski S Malde B Malecki A Malinin T Maltsev H Malygina G Manca G Mancinelli R Manera Escalero D Manuzzi D Marangotto J Maratas J F Marchand U Marconi S Mariani C Marin Benito M Marinangeli P Marino J Marks P J Marshall G Martellotti L Martinazzoli M Martinelli D Martinez Santos F Martinez Vidal A Massafferri M Materok R Matev A Mathad Z Mathe V Matiunin C Matteuzzi K R Mattioli A Mauri E Maurice J Mauricio M Mazurek M McCann L Mcconnell T H Mcgrath A McNab R McNulty J V Mead B Meadows C Meaux G Meier N Meinert D Melnychuk S Meloni M Merk A Merli L Meyer Garcia M Mikhasenko D A Milanes E Millard M-N Minard L Minzoni S E Mitchell B Mitreska D S Mitzel A Mödden R A Mohammed R D Moise T Mombächer I A Monroy S Monteil M Morandin G Morello M J Morello J Moron A B Morris A G Morris R Mountain H Mu F Muheim M Mukherjee M Mulder D Müller K Müller C H Murphy D Murray P Muzzetto P Naik T Nakada R Nandakumar T Nanut I Nasteva M Needham I Neri N Neri S Neubert N Neufeld R Newcombe T D Nguyen C Nguyen-Mau E M Niel S Nieswand N Nikitin N S Nolte C Nunez A Oblakowska-Mucha V Obraztsov D P O'Hanlon R Oldeman C J G Onderwater A Ossowska J M Otalora Goicochea T Ovsiannikova P Owen A Oyanguren B Pagare P R Pais T Pajero A Palano M Palutan Y Pan G Panshin A Papanestis M Pappagallo L L Pappalardo C Pappenheimer W Parker C Parkes C J Parkinson B Passalacqua G Passaleva A Pastore M Patel C Patrignani C J Pawley A Pearce A Pellegrino M Pepe Altarelli S Perazzini D Pereima P Perret K Petridis A Petrolini A Petrov S Petrucci M Petruzzo A Philippov L Pica M Piccini B Pietrzyk G Pietrzyk M Pili D Pinci J Pinzino F Pisani A Piucci Resmi P K V Placinta S Playfer J Plews M Plo Casasus F Polci M Poli Lener M Poliakova A Poluektov N Polukhina I Polyakov E Polycarpo G J Pomery S Ponce A Popov D Popov S Popov S Poslavskii K Prasanth L Promberger C Prouve V Pugatch A Puig Navarro H Pullen G Punzi W Qian J Qin R Quagliani B Quintana N V Raab R I Rabadan Trejo B Rachwal J H Rademacker M Rama M Ramos Pernas M S Rangel F Ratnikov G Raven M Reboud F Redi F Reiss C Remon Alepuz Z Ren V Renaudin R Ribatti S Ricciardi D S Richards K Rinnert P Robbe A Robert G Robertson A B Rodrigues E Rodrigues J A Rodriguez Lopez A Rollings P Roloff V Romanovskiy M Romero Lamas A Romero Vidal J D Roth M Rotondo M S Rudolph T Ruf J Ruiz Vidal A Ryzhikov J Ryzka J J Saborido Silva N Sagidova N Sahoo B Saitta D Sanchez Gonzalo C Sanchez Gras C Sanchez Mayordomo R Santacesaria C Santamarina Rios M Santimaria E Santovetti D Saranin G Sarpis M Sarpis A Sarti C Satriano A Satta M Saur D Savrina H Sazak L G Scantlebury Smead S Schael M Schellenberg M Schiller H Schindler M Schmelling T Schmelzer B Schmidt O Schneider A Schopper M Schubiger S Schulte M H Schune R Schwemmer B Sciascia A Sciubba S Sellam A Semennikov M Senghi Soares A Sergi N Serra J Serrano L Sestini A Seuthe P Seyfert D M Shangase M Shapkin I Shchemerov L Shchutska T Shears L Shekhtman V Shevchenko E B Shields E Shmanin J D Shupperd B G Siddi R Silva Coutinho G Simi S Simone I Skiba N Skidmore T Skwarnicki M W Slater J C Smallwood J G Smeaton A Smetkina E Smith M Smith A Snoch M Soares L Soares Lavra M D Sokoloff F J P Soler A Solovev I Solovyev F L Souza De Almeida B Souza De Paula B Spaan E Spadaro Norella P Spradlin F Stagni M Stahl S Stahl P Stefko O Steinkamp S Stemmle O Stenyakin H Stevens S Stone M E Stramaglia M Straticiuc D Strekalina S Strokov F Suljik J Sun L Sun Y Sun P Svihra P N Swallow K Swientek A Szabelski T Szumlak M Szymanski S Taneja Z Tang T Tekampe F Teubert E Thomas K A Thomson M J Tilley V Tisserand S T'Jampens M Tobin S Tolk L Tomassetti D Torres Machado D Y Tou M Traill M T Tran E Trifonova C Trippl A Tsaregorodtsev G Tuci A Tully N Tuning A Ukleja D J Unverzagt A Usachov A Ustyuzhanin U Uwer A Vagner V Vagnoni A Valassi G Valenti N Valls Canudas M van Beuzekom H Van Hecke E van Herwijnen C B Van Hulse M van Veghel R Vazquez Gomez P Vazquez Regueiro C Vázquez Sierra S Vecchi J J Velthuis M Veltri A Venkateswaran M Veronesi M Vesterinen D Vieira M Vieites Diaz H Viemann X Vilasis-Cardona E Vilella Figueras P Vincent G Vitali A Vollhardt D Vom Bruch A Vorobyev V Vorobyev N Voropaev R Waldi J Walsh C Wang J Wang J Wang J Wang J Wang M Wang R Wang Y Wang Z Wang D R Ward H M Wark N K Watson S G Weber D Websdale C Weisser B D C Westhenry D J White M Whitehead D Wiedner G Wilkinson M Wilkinson I Williams M Williams M R J Williams F F Wilson W Wislicki M Witek L Witola G Wormser S A Wotton H Wu K Wyllie Z Xiang D Xiao Y Xie H Xing A Xu J Xu L Xu M Xu Q Xu Z Xu Z Xu D Yang Y Yang Z Yang Z Yang Y Yao L E Yeomans H Yin J Yu X Yuan O Yushchenko K A Zarebski M Zavertyaev M Zdybal O Zenaiev M Zeng D Zhang L Zhang S Zhang Y Zhang A Zhelezov Y Zheng X Zhou Y Zhou X Zhu V Zhukov J B Zonneveld S Zucchelli D Zuliani G Zunica

Phys Rev Lett 2021 Mar;126(9):092001

Department of Physics and Astronomy, University of Manchester, Manchester, United Kingdom.

The production of χ_{c1}(3872) and ψ(2S) hadrons is studied as a function of charged particle multiplicity in pp collisions at a center-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 2  fb^{-1}. For both states, the fraction that is produced promptly at the collision vertex is found to decrease as charged particle multiplicity increases. The ratio of χ_{c1}(3872) to ψ(2S) cross sections for promptly produced particles is also found to decrease with multiplicity, while no significant dependence on multiplicity is observed for the equivalent ratio of particles produced away from the collision vertex in b-hadron decays. This behavior is consistent with a calculation that models the χ_{c1}(3872) structure as a compact tetraquark. Comparisons with model calculations and implications for the binding energy of the χ_{c1}(3872) state are discussed.
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March 2021

Measurement of CP Violation in the Decay B^{+}→K^{+}π^{0}.

Authors:
R Aaij C Abellán Beteta T Ackernley B Adeva M Adinolfi H Afsharnia C A Aidala S Aiola Z Ajaltouni S Akar J Albrecht F Alessio M Alexander A Alfonso Albero Z Aliouche G Alkhazov P Alvarez Cartelle S Amato Y Amhis L An L Anderlini A Andreianov M Andreotti J E Andrews F Archilli A Artamonov M Artuso K Arzymatov E Aslanides M Atzeni B Audurier S Bachmann M Bachmayer J J Back S Baker P Baladron Rodriguez V Balagura W Baldini J Baptista Leite R J Barlow S Barsuk W Barter M Bartolini F Baryshnikov J M Basels G Bassi B Batsukh A Battig A Bay M Becker F Bedeschi I Bediaga A Beiter V Belavin S Belin V Bellee K Belous I Belov I Belyaev G Bencivenni E Ben-Haim A Berezhnoy R Bernet D Berninghoff H C Bernstein C Bertella E Bertholet A Bertolin C Betancourt F Betti Ia Bezshyiko S Bhasin J Bhom L Bian M S Bieker S Bifani P Billoir M Birch F C R Bishop A Bizzeti M Bjørn M P Blago T Blake F Blanc S Blusk D Bobulska J A Boelhauve O Boente Garcia T Boettcher A Boldyrev A Bondar N Bondar S Borghi M Borisyak M Borsato J T Borsuk S A Bouchiba T J V Bowcock A Boyer C Bozzi M J Bradley S Braun A Brea Rodriguez M Brodski J Brodzicka A Brossa Gonzalo D Brundu A Buonaura C Burr A Bursche A Butkevich J S Butter J Buytaert W Byczynski S Cadeddu H Cai R Calabrese L Calefice L Calero Diaz S Cali R Calladine M Calvi M Calvo Gomez P Camargo Magalhaes A Camboni P Campana A F Campoverde Quezada S Capelli L Capriotti A Carbone G Carboni R Cardinale A Cardini I Carli P Carniti L Carus K Carvalho Akiba A Casais Vidal G Casse M Cattaneo G Cavallero S Celani J Cerasoli A J Chadwick M G Chapman M Charles Ph Charpentier G Chatzikonstantinidis C A Chavez Barajas M Chefdeville C Chen S Chen A Chernov S-G Chitic V Chobanova S Cholak M Chrzaszcz A Chubykin V Chulikov P Ciambrone M F Cicala X Cid Vidal G Ciezarek P E L Clarke M Clemencic H V Cliff J Closier J L Cobbledick V Coco J A B Coelho J Cogan E Cogneras L Cojocariu P Collins T Colombo L Congedo A Contu N Cooke G Coombs G Corti C M Costa Sobral B Couturier D C Craik J Crkovská M Cruz Torres R Currie C L Da Silva E Dall'Occo J Dalseno C D'Ambrosio A Danilina P d'Argent A Davis O De Aguiar Francisco K De Bruyn S De Capua M De Cian J M De Miranda L De Paula M De Serio D De Simone P De Simone J A de Vries C T Dean W Dean D Decamp L Del Buono B Delaney H-P Dembinski A Dendek V Denysenko D Derkach O Deschamps F Desse F Dettori B Dey P Di Nezza S Didenko L Dieste Maronas H Dijkstra V Dobishuk A M Donohoe F Dordei A C Dos Reis L Douglas A Dovbnya A G Downes K Dreimanis M W Dudek L Dufour V Duk P Durante J M Durham D Dutta M Dziewiecki A Dziurda A Dzyuba S Easo U Egede V Egorychev S Eidelman S Eisenhardt S Ek-In L Eklund S Ely A Ene E Epple S Escher J Eschle S Esen T Evans A Falabella J Fan Y Fan B Fang N Farley S Farry D Fazzini P Fedin M Féo P Fernandez Declara A Fernandez Prieto J M Fernandez-Tenllado Arribas F Ferrari L Ferreira Lopes F Ferreira Rodrigues S Ferreres Sole M Ferrillo M Ferro-Luzzi S Filippov R A Fini M Fiorini M Firlej K M Fischer C Fitzpatrick T Fiutowski F Fleuret M Fontana F Fontanelli R Forty V Franco Lima M Franco Sevilla M Frank E Franzoso G Frau C Frei D A Friday J Fu Q Fuehring W Funk E Gabriel T Gaintseva A Gallas Torreira D Galli S Gambetta Y Gan M Gandelman P Gandini Y Gao M Garau L M Garcia Martin P Garcia Moreno J García Pardiñas B Garcia Plana F A Garcia Rosales L Garrido C Gaspar R E Geertsema D Gerick L L Gerken E Gersabeck M Gersabeck T Gershon D Gerstel Ph Ghez V Gibson M Giovannetti A Gioventù P Gironella Gironell L Giubega C Giugliano K Gizdov E L Gkougkousis V V Gligorov C Göbel E Golobardes D Golubkov A Golutvin A Gomes S Gomez Fernandez F Goncalves Abrantes M Goncerz G Gong P Gorbounov I V Gorelov C Gotti E Govorkova J P Grabowski R Graciani Diaz T Grammatico L A Granado Cardoso E Graugés E Graverini G Graziani A Grecu L M Greeven P Griffith L Grillo S Gromov B R Gruberg Cazon C Gu M Guarise P A Günther E Gushchin A Guth Y Guz T Gys T Hadavizadeh G Haefeli C Haen J Haimberger T Halewood-Leagas P M Hamilton Q Han X Han T H Hancock S Hansmann-Menzemer N Harnew T Harrison C Hasse M Hatch J He M Hecker K Heijhoff K Heinicke A M Hennequin K Hennessy L Henry J Heuel A Hicheur D Hill M Hilton S E Hollitt J Hu J Hu W Hu W Huang X Huang W Hulsbergen R J Hunter M Hushchyn D Hutchcroft D Hynds P Ibis M Idzik D Ilin P Ilten A Inglessi A Ishteev K Ivshin R Jacobsson S Jakobsen E Jans B K Jashal A Jawahery V Jevtic M Jezabek F Jiang M John D Johnson C R Jones T P Jones B Jost N Jurik S Kandybei Y Kang M Karacson M Karpov N Kazeev F Keizer M Kenzie T Ketel B Khanji A Kharisova S Kholodenko K E Kim T Kirn V S Kirsebom O Kitouni S Klaver K Klimaszewski S Koliiev A Kondybayeva A Konoplyannikov P Kopciewicz R Kopecna P Koppenburg M Korolev I Kostiuk O Kot S Kotriakhova P Kravchenko L Kravchuk R D Krawczyk M Kreps F Kress S Kretzschmar P Krokovny W Krupa W Krzemien W Kucewicz M Kucharczyk V Kudryavtsev H S Kuindersma G J Kunde T Kvaratskheliya D Lacarrere G Lafferty A Lai A Lampis D Lancierini J J Lane R Lane G Lanfranchi C Langenbruch J Langer O Lantwin T Latham F Lazzari R Le Gac S H Lee R Lefèvre A Leflat S Legotin O Leroy T Lesiak B Leverington H Li L Li P Li Y Li Y Li Z Li X Liang T Lin R Lindner V Lisovskyi R Litvinov G Liu H Liu S Liu X Liu A Loi J Lomba Castro I Longstaff J H Lopes G Loustau G H Lovell Y Lu D Lucchesi S Luchuk M Lucio Martinez V Lukashenko Y Luo A Lupato E Luppi O Lupton A Lusiani X Lyu L Ma R Ma S Maccolini F Machefert F Maciuc V Macko P Mackowiak S Maddrell-Mander O Madejczyk L R Madhan Mohan O Maev A Maevskiy D Maisuzenko M W Majewski J J Malczewski S Malde B Malecki A Malinin T Maltsev H Malygina G Manca G Mancinelli R Manera Escalero D Manuzzi D Marangotto J Maratas J F Marchand U Marconi S Mariani C Marin Benito M Marinangeli P Marino J Marks P J Marshall G Martellotti L Martinazzoli M Martinelli D Martinez Santos F Martinez Vidal A Massafferri M Materok R Matev A Mathad Z Mathe V Matiunin C Matteuzzi K R Mattioli A Mauri E Maurice J Mauricio M Mazurek M McCann L Mcconnell T H Mcgrath A McNab R McNulty J V Mead B Meadows C Meaux G Meier N Meinert D Melnychuk S Meloni M Merk A Merli L Meyer Garcia M Mikhasenko D A Milanes E Millard M Milovanovic M-N Minard L Minzoni S E Mitchell B Mitreska D S Mitzel A Mödden R A Mohammed R D Moise T Mombächer I A Monroy S Monteil M Morandin G Morello M J Morello J Moron A B Morris A G Morris R Mountain H Mu F Muheim M Mukherjee M Mulder D Müller K Müller C H Murphy D Murray P Muzzetto P Naik T Nakada R Nandakumar T Nanut I Nasteva M Needham I Neri N Neri S Neubert N Neufeld R Newcombe T D Nguyen C Nguyen-Mau E M Niel S Nieswand N Nikitin N S Nolte C Nunez A Oblakowska-Mucha V Obraztsov D P O'Hanlon R Oldeman M E Olivares C J G Onderwater A Ossowska J M Otalora Goicochea T Ovsiannikova P Owen A Oyanguren B Pagare P R Pais T Pajero A Palano M Palutan Y Pan G Panshin A Papanestis M Pappagallo L L Pappalardo C Pappenheimer W Parker C Parkes C J Parkinson B Passalacqua G Passaleva A Pastore M Patel C Patrignani C J Pawley A Pearce A Pellegrino M Pepe Altarelli S Perazzini D Pereima P Perret K Petridis A Petrolini A Petrov S Petrucci M Petruzzo T T H Pham A Philippov L Pica M Piccini B Pietrzyk G Pietrzyk M Pili D Pinci F Pisani A Piucci Resmi P K V Placinta J Plews M Plo Casasus F Polci M Poli Lener M Poliakova A Poluektov N Polukhina I Polyakov E Polycarpo G J Pomery S Ponce D Popov S Popov S Poslavskii K Prasanth L Promberger C Prouve V Pugatch H Pullen G Punzi W Qian J Qin R Quagliani B Quintana N V Raab R I Rabadan Trejo B Rachwal J H Rademacker M Rama M Ramos Pernas M S Rangel F Ratnikov G Raven M Reboud F Redi F Reiss C Remon Alepuz Z Ren V Renaudin R Ribatti S Ricciardi K Rinnert P Robbe A Robert G Robertson A B Rodrigues E Rodrigues J A Rodriguez Lopez A Rollings P Roloff V Romanovskiy M Romero Lamas A Romero Vidal J D Roth M Rotondo M S Rudolph T Ruf J Ruiz Vidal A Ryzhikov J Ryzka J J Saborido Silva N Sagidova N Sahoo B Saitta D Sanchez Gonzalo C Sanchez Gras R Santacesaria C Santamarina Rios M Santimaria E Santovetti D Saranin G Sarpis M Sarpis A Sarti C Satriano A Satta M Saur D Savrina H Sazak L G Scantlebury Smead S Schael M Schellenberg M Schiller H Schindler M Schmelling B Schmidt O Schneider A Schopper M Schubiger S Schulte M H Schune R Schwemmer B Sciascia A Sciubba S Sellam A Semennikov M Senghi Soares A Sergi N Serra L Sestini A Seuthe P Seyfert D M Shangase M Shapkin I Shchemerov L Shchutska T Shears L Shekhtman Z Shen V Shevchenko E B Shields E Shmanin J D Shupperd B G Siddi R Silva Coutinho G Simi S Simone I Skiba N Skidmore T Skwarnicki M W Slater J C Smallwood J G Smeaton A Smetkina E Smith M Smith A Snoch M Soares L Soares Lavra M D Sokoloff F J P Soler A Solovev I Solovyev F L Souza De Almeida B Souza De Paula B Spaan E Spadaro Norella P Spradlin F Stagni M Stahl S Stahl P Stefko O Steinkamp S Stemmle O Stenyakin H Stevens S Stone M E Stramaglia M Straticiuc D Strekalina S Strokov F Suljik J Sun L Sun Y Sun P Svihra P N Swallow K Swientek A Szabelski T Szumlak M Szymanski S Taneja F Teubert E Thomas K A Thomson M J Tilley V Tisserand S T'Jampens M Tobin S Tolk L Tomassetti D Torres Machado D Y Tou M Traill M T Tran E Trifonova C Trippl G Tuci A Tully N Tuning A Ukleja D J Unverzagt E Ursov A Usachov A Ustyuzhanin U Uwer A Vagner V Vagnoni A Valassi G Valenti N Valls Canudas M van Beuzekom M Van Dijk E van Herwijnen C B Van Hulse M van Veghel R Vazquez Gomez P Vazquez Regueiro C Vázquez Sierra S Vecchi J J Velthuis M Veltri A Venkateswaran M Veronesi M Vesterinen D Vieira M Vieites Diaz H Viemann X Vilasis-Cardona E Vilella Figueras P Vincent G Vitali A Vollhardt D Vom Bruch A Vorobyev V Vorobyev N Voropaev R Waldi J Walsh C Wang J Wang J Wang J Wang J Wang M Wang R Wang Y Wang Z Wang H M Wark N K Watson S G Weber D Websdale C Weisser B D C Westhenry D J White M Whitehead D Wiedner G Wilkinson M Wilkinson I Williams M Williams M R J Williams F F Wilson W Wislicki M Witek L Witola G Wormser S A Wotton H Wu K Wyllie Z Xiang D Xiao Y Xie A Xu J Xu L Xu M Xu Q Xu Z Xu Z Xu D Yang S Yang Y Yang Z Yang Z Yang Y Yao L E Yeomans H Yin J Yu X Yuan O Yushchenko E Zaffaroni K A Zarebski M Zavertyaev M Zdybal O Zenaiev M Zeng D Zhang L Zhang S Zhang Y Zhang Y Zhang A Zhelezov Y Zheng X Zhou Y Zhou X Zhu V Zhukov J B Zonneveld S Zucchelli D Zuliani G Zunica

Phys Rev Lett 2021 Mar;126(9):091802

Department of Physics and Astronomy, University of Manchester, Manchester, United Kingdom.

A measurement of CP violation in the decay B^{+}→K^{+}π^{0} is reported using data corresponding to an integrated luminosity of 5.4  fb^{-1} collected with the LHCb experiment at a center-of-mass energy of sqrt[s]=13  TeV. The CP asymmetry is measured to be 0.025±0.015±0.006±0.003, where the uncertainties are statistical, systematic, and due to an external input. This is the most precise measurement of this quantity. It confirms and significantly enhances the observed anomalous difference between the direct CP asymmetries of the B^{0}→K^{+}π^{-} and B^{+}→K^{+}π^{0} decays, known as the Kπ puzzle.
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http://dx.doi.org/10.1103/PhysRevLett.126.091802DOI Listing
March 2021

A Budget Impact Analysis of Gene Therapy for Sickle Cell Disease: The Medicaid Perspective.

JAMA Pediatr 2021 Mar 22. Epub 2021 Mar 22.

University of Washington School of Pharmacy, Fred Hutchinson Institute for Cancer Outcomes Research, Seattle.

Importance: Hundreds of gene therapies are undergoing clinical testing and are likely to be priced more than $1 million per course of treatment. The association that high prices will have with insurance coverage of gene therapy remains unclear. Gene therapy for sickle cell disease has shown early success and would be one of the first gene therapies available for a relatively large population.

Objectives: To estimate the budget impact and affordability of a gene therapy for severe sickle cell disease from the perspective of US Medicaid programs with the highest prevalence of sickle cell disease while exploring the impact of an annuity payment model.

Design, Setting, And Participants: A budget impact analysis was performed from January 1 to May 31, 2020, for a sickle cell disease gene therapy from the perspective of 10 state Medicaid plans with a 5-year time horizon, using state-level disease prevalence data from 2012. Disease prevalence, Medicaid enrollment, and expenditures were derived from the available literature. The eligible population was based on modified clinical trial inclusion criteria including individuals aged 13 to 45 years with severe disease.

Exposures: The gene therapy was assumed to be administered to 7% of the eligible population annually and was curative (no subsequent disease-related expenditures). The gene therapy price was $1.85 million in the base case, and baseline disease-related expenditures were $42 200 per year.

Main Outcomes And Measures: The main outcomes were total budget impact and budget impact per member per month in years 1 through 5. One-way sensitivity analysis was used to evaluate uncertainty of market diffusion, size of eligible population, price of therapy, and cost of routine care.

Results: An estimated 5464 Medicaid enrollees would be eligible for the gene therapy nationally, with 2315 individuals in the 10 Medicaid programs of interest (16 per 100 000 enrollees). The model projected a mean 1-year budget impact of $29.96 million per state Medicaid program in the sample ($1.91 per member per month). A 5-year annuity payment reduced the short-term budget impact.

Conclusions And Relevance: This study suggests that a gene therapy for severe sickle cell disease is likely to produce a considerable budget impact for many Medicaid plans while potentially offering substantial benefit to patients. Payers may need to take steps to ensure affordability and access. Gene therapy for sickle cell disease is likely to provide an early demonstration of the unique financial challenges associated with this emerging drug class.
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http://dx.doi.org/10.1001/jamapediatrics.2020.7140DOI Listing
March 2021

Diagnostic biomarkers from proteomic characterization of cerebrospinal fluid in patients with brain malignancies.

J Neurochem 2021 Mar 18. Epub 2021 Mar 18.

Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Recent technological advances in molecular diagnostics through liquid biopsies hold the promise to repetitively monitor tumor evolution and treatment response of brain malignancies without the need of invasive surgical tissue accrual. Here, we implemented a mass spectrometry-based protein analysis pipeline which identified hundreds of proteins in 251 cerebrospinal fluid (CSF) samples from patients with four types of brain malignancies (glioblastoma, lymphoma, brain metastasis, and leptomeningeal disease [LMD]) and from healthy individuals with a focus on glioblastoma in a retrospective and confirmatory prospective observational study. CSF proteome deregulation via disruption of the blood brain barrier appeared to be largely conserved across brain tumor entities. CSF analysis of glioblastoma patients identified two proteomic clusters that correlated with tumor size and patient survival. By integrating CSF data with proteomic analyses of matching glioblastoma tumor tissue and primary glioblastoma cells, we identified potential CSF biomarkers for glioblastoma, in particular chitinase-3-like protein 1 (CHI3L1) and glial fibrillary acidic protein (GFAP). Key findings were validated in a prospective cohort consisting of 35 glioma patients. Finally, in LMD patients who frequently undergo repeated CSF work-up, we explored our proteomic pipeline as a mean to profile consecutive CSF samples. Therefore, proteomic analysis of CSF in brain malignancies has the potential to reveal biomarkers for diagnosis and therapy monitoring.
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http://dx.doi.org/10.1111/jnc.15350DOI Listing
March 2021

The Role of 3D Reconstruction of the Skull in Patients with Suspected Shunt Malfunction.

Pediatr Neurosurg 2021 17;56(2):110-115. Epub 2021 Mar 17.

Departments of Neurosurgery and Pediatric Neurosurgery, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel.

Background: Mechanical shunt malfunction may lead to significant morbidity and mortality. Shunt series assessments help evaluate shunt integrity; however, they are of limited value in the area of the skull due to skull curvature, thickness, and air sinuses. We describe the role of 3D bone reconstruction CT (3DCT) in demonstrating the shunt integrity over the skull, comparing this technique to skull X-rays (SXR).

Methods: Data were collected retrospectively for shunted patients with concurrent SXR and 3DCT and for patients presenting with shunt failures at the region of the skull, including clinical course and radiological findings. We compared the SXR and 3DCT findings. The 3DCT was reconstructed from standard diagnostic CT protocols performed during evaluation of suspected shunt malfunction and not thin-slice CT protocols.

Results: Forty-eight patients with 57 shunts underwent SXR and 3DCT. Interobserver agreement was high for most variables. Both SXR and 3DCT had a high sensitivity, specificity, and accuracy identifying tubing disconnections (between 0.83 and 1). Full valve type and setting were significantly more accurate based on SXR versus 3DCT (>90 vs. <20%), and valve integrity was significantly more readily verified on 3DCT versus SXR (100 vs. 52%).

Conclusions: 3DCT and SXR complement each other in diagnosing mechanical shunt malfunctions over the skull. The main limitation of 3DCT is identification of valve type and settings, which are clearer on SXR, while the main limitation of SXR is a less ability to evaluate valve integrity. 3DCT also enables an intuitive 3D understanding of the shunt tubing over the skull.
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http://dx.doi.org/10.1159/000514065DOI Listing
March 2021

Opioid-Induced Respiratory Depression: Is Hydromorphone Safer Than Morphine?

Authors:
Jonathan V Roth

Anesth Analg 2021 04;132(4):e60

Albert Einstein Medical Center, Department of Anesthesiology, Philadelphia, Pennsylvania,

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http://dx.doi.org/10.1213/ANE.0000000000005413DOI Listing
April 2021

How do Pediatric Neurosurgeons Make Intraoperative Decisions?

World Neurosurg 2021 Mar 12. Epub 2021 Mar 12.

Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel.

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http://dx.doi.org/10.1016/j.wneu.2021.03.019DOI Listing
March 2021

Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis.

Front Immunol 2021 26;12:553911. Epub 2021 Feb 26.

Department of Clinical Microbiology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.

Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial and pro-inflammatory protein complex used as a biomarker for diagnosis of numerous inflammatory disorders. Here we describe the role of S100A8/A9 in inflammatory collateral tissue damage (ICTD). Using a mouse model of disseminated intra-abdominal candidiasis (IAC) in wild-type and S100A8/A9-deficient mice in the presence or absence of S100A9 inhibitor paquinimod, the role of S100A8/A9 during ICTD and fungal clearance were investigated. S100A8/A9-deficient mice developed less ICTD than wild-type mice. Restoration of S100A8/A9 in knockout mice by injection of recombinant protein resulted in increased ICTD and fungal clearance comparable to wild-type levels. Treatment with paquinimod abolished ICTD and S100A9-deficient mice showed increased survival compared to wild-type littermates. The data indicates that S100A8/A9 controls ICTD levels and antimicrobial activity during IAC and that targeting of S100A8/A9 could serve as promising adjunct therapy against this challenging disease.
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http://dx.doi.org/10.3389/fimmu.2021.553911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953150PMC
February 2021

First Observation of the Decay B_{s}^{0}→K^{-}μ^{+}ν_{μ} and a Measurement of |V_{ub}|/|V_{cb}|.

Authors:
R Aaij C Abellán Beteta T Ackernley B Adeva M Adinolfi H Afsharnia C A Aidala S Aiola Z Ajaltouni S Akar J Albrecht F Alessio M Alexander A Alfonso Albero Z Aliouche G Alkhazov P Alvarez Cartelle S Amato Y Amhis L An L Anderlini A Andreianov M Andreotti F Archilli A Artamonov M Artuso K Arzymatov E Aslanides M Atzeni B Audurier S Bachmann M Bachmayer J J Back S Baker P Baladron Rodriguez V Balagura W Baldini J Baptista Leite R J Barlow S Barsuk W Barter M Bartolini F Baryshnikov J M Basels G Bassi B Batsukh A Battig A Bay M Becker F Bedeschi I Bediaga A Beiter V Belavin S Belin V Bellee K Belous I Belov I Belyaev G Bencivenni E Ben-Haim A Berezhnoy R Bernet D Berninghoff H C Bernstein C Bertella E Bertholet A Bertolin C Betancourt F Betti M O Bettler Ia Bezshyiko S Bhasin J Bhom L Bian M S Bieker S Bifani P Billoir M Birch F C R Bishop A Bizzeti M Bjørn M P Blago T Blake F Blanc S Blusk D Bobulska J A Boelhauve O Boente Garcia T Boettcher A Boldyrev A Bondar N Bondar S Borghi M Borisyak M Borsato J T Borsuk S A Bouchiba T J V Bowcock A Boyer C Bozzi M J Bradley S Braun A Brea Rodriguez M Brodski J Brodzicka A Brossa Gonzalo D Brundu A Buonaura C Burr A Bursche A Butkevich J S Butter J Buytaert W Byczynski S Cadeddu H Cai R Calabrese L Calefice L Calero Diaz S Cali R Calladine M Calvi M Calvo Gomez P Camargo Magalhaes A Camboni P Campana D H Campora Perez A F Campoverde Quezada S Capelli L Capriotti A Carbone G Carboni R Cardinale A Cardini I Carli P Carniti L Carus K Carvalho Akiba A Casais Vidal G Casse M Cattaneo G Cavallero S Celani J Cerasoli A J Chadwick M G Chapman M Charles Ph Charpentier G Chatzikonstantinidis C A Chavez Barajas M Chefdeville C Chen S Chen A Chernov S-G Chitic V Chobanova S Cholak M Chrzaszcz A Chubykin V Chulikov P Ciambrone M F Cicala X Cid Vidal G Ciezarek P E L Clarke M Clemencic H V Cliff J Closier J L Cobbledick V Coco J A B Coelho J Cogan E Cogneras L Cojocariu P Collins T Colombo L Congedo A Contu N Cooke G Coombs G Corti C M Costa Sobral B Couturier D C Craik J Crkovská M Cruz Torres R Currie C L Da Silva E Dall'Occo J Dalseno C D'Ambrosio A Danilina P d'Argent A Davis O De Aguiar Francisco K De Bruyn S De Capua M De Cian J M De Miranda L De Paula M De Serio D De Simone P De Simone J A de Vries C T Dean W Dean D Decamp L Del Buono B Delaney H-P Dembinski A Dendek V Denysenko D Derkach O Deschamps F Desse F Dettori B Dey P Di Nezza S Didenko L Dieste Maronas H Dijkstra V Dobishuk A M Donohoe F Dordei A C Dos Reis L Douglas A Dovbnya A G Downes K Dreimanis M W Dudek L Dufour V Duk P Durante J M Durham D Dutta M Dziewiecki A Dziurda A Dzyuba S Easo U Egede V Egorychev S Eidelman S Eisenhardt S Ek-In L Eklund S Ely A Ene E Epple S Escher J Eschle S Esen T Evans A Falabella J Fan Y Fan B Fang N Farley S Farry D Fazzini P Fedin M Féo P Fernandez Declara A Fernandez Prieto J M Fernandez-Tenllado Arribas F Ferrari L Ferreira Lopes F Ferreira Rodrigues S Ferreres Sole M Ferrillo M Ferro-Luzzi S Filippov R A Fini M Fiorini M Firlej K M Fischer C Fitzpatrick T Fiutowski F Fleuret M Fontana F Fontanelli R Forty V Franco Lima M Franco Sevilla M Frank E Franzoso G Frau C Frei D A Friday J Fu Q Fuehring W Funk E Gabriel T Gaintseva A Gallas Torreira D Galli S Gambetta Y Gan M Gandelman P Gandini Y Gao M Garau L M Garcia Martin P Garcia Moreno J García Pardiñas B Garcia Plana F A Garcia Rosales L Garrido C Gaspar R E Geertsema D Gerick L L Gerken E Gersabeck M Gersabeck T Gershon D Gerstel Ph Ghez V Gibson M Giovannetti A Gioventù P Gironella Gironell L Giubega C Giugliano K Gizdov E L Gkougkousis V V Gligorov C Göbel E Golobardes D Golubkov A Golutvin A Gomes S Gomez Fernandez F Goncalves Abrantes M Goncerz G Gong P Gorbounov I V Gorelov C Gotti E Govorkova J P Grabowski R Graciani Diaz T Grammatico L A Granado Cardoso E Graugés E Graverini G Graziani A Grecu L M Greeven P Griffith L Grillo S Gromov B R Gruberg Cazon C Gu M Guarise P A Günther E Gushchin A Guth Y Guz T Gys T Hadavizadeh G Haefeli C Haen J Haimberger T Halewood-Leagas P M Hamilton Q Han X Han T H Hancock S Hansmann-Menzemer N Harnew T Harrison C Hasse M Hatch J He M Hecker K Heijhoff K Heinicke A M Hennequin K Hennessy L Henry J Heuel A Hicheur D Hill M Hilton S E Hollitt J Hu J Hu W Hu W Huang X Huang W Hulsbergen R J Hunter M Hushchyn D Hutchcroft D Hynds P Ibis M Idzik D Ilin P Ilten A Inglessi A Ishteev K Ivshin R Jacobsson S Jakobsen E Jans B K Jashal A Jawahery V Jevtic M Jezabek F Jiang M John D Johnson C R Jones T P Jones B Jost N Jurik S Kandybei Y Kang M Karacson M Karpov N Kazeev F Keizer M Kenzie T Ketel B Khanji A Kharisova S Kholodenko K E Kim T Kirn V S Kirsebom O Kitouni S Klaver K Klimaszewski S Koliiev A Kondybayeva A Konoplyannikov P Kopciewicz R Kopecna P Koppenburg M Korolev I Kostiuk O Kot S Kotriakhova P Kravchenko L Kravchuk R D Krawczyk M Kreps F Kress S Kretzschmar P Krokovny W Krupa W Krzemien W Kucewicz M Kucharczyk V Kudryavtsev H S Kuindersma G J Kunde T Kvaratskheliya D Lacarrere G Lafferty A Lai A Lampis D Lancierini J J Lane R Lane G Lanfranchi C Langenbruch J Langer O Lantwin T Latham F Lazzari R Le Gac S H Lee R Lefèvre A Leflat S Legotin O Leroy T Lesiak B Leverington H Li L Li P Li Y Li Y Li Z Li X Liang T Lin R Lindner V Lisovskyi R Litvinov G Liu H Liu S Liu X Liu A Loi J Lomba Castro I Longstaff J H Lopes G Loustau G H Lovell Y Lu D Lucchesi S Luchuk M Lucio Martinez V Lukashenko Y Luo A Lupato E Luppi O Lupton A Lusiani X Lyu L Ma S Maccolini F Machefert F Maciuc V Macko P Mackowiak S Maddrell-Mander O Madejczyk L R Madhan Mohan O Maev A Maevskiy D Maisuzenko M W Majewski J J Malczewski S Malde B Malecki A Malinin T Maltsev H Malygina G Manca G Mancinelli R Manera Escalero D Manuzzi D Marangotto J Maratas J F Marchand U Marconi S Mariani C Marin Benito M Marinangeli P Marino J Marks P J Marshall G Martellotti L Martinazzoli M Martinelli D Martinez Santos F Martinez Vidal A Massafferri M Materok R Matev A Mathad Z Mathe V Matiunin C Matteuzzi K R Mattioli A Mauri E Maurice J Mauricio M Mazurek M McCann L Mcconnell T H Mcgrath A McNab R McNulty J V Mead B Meadows C Meaux G Meier N Meinert D Melnychuk S Meloni M Merk A Merli L Meyer Garcia M Mikhasenko D A Milanes E Millard M Milovanovic M-N Minard L Minzoni S E Mitchell B Mitreska D S Mitzel A Mödden R A Mohammed R D Moise T Mombächer I A Monroy S Monteil M Morandin G Morello M J Morello J Moron A B Morris A G Morris R Mountain H Mu F Muheim M Mukherjee M Mulder D Müller K Müller C H Murphy D Murray P Muzzetto P Naik T Nakada R Nandakumar T Nanut I Nasteva M Needham I Neri N Neri S Neubert N Neufeld R Newcombe T D Nguyen C Nguyen-Mau E M Niel S Nieswand N Nikitin N S Nolte C Nunez A Oblakowska-Mucha V Obraztsov D P O'Hanlon R Oldeman M E Olivares C J G Onderwater A Ossowska J M Otalora Goicochea T Ovsiannikova P Owen A Oyanguren B Pagare P R Pais T Pajero A Palano M Palutan Y Pan G Panshin A Papanestis M Pappagallo L L Pappalardo C Pappenheimer W Parker C Parkes C J Parkinson B Passalacqua G Passaleva A Pastore M Patel C Patrignani C J Pawley A Pearce A Pellegrino M Pepe Altarelli S Perazzini D Pereima P Perret K Petridis A Petrolini A Petrov S Petrucci M Petruzzo T T H Pham A Philippov L Pica M Piccini B Pietrzyk G Pietrzyk M Pili D Pinci F Pisani A Piucci Resmi P K V Placinta J Plews M Plo Casasus F Polci M Poli Lener M Poliakova A Poluektov N Polukhina I Polyakov E Polycarpo G J Pomery S Ponce D Popov S Popov S Poslavskii K Prasanth L Promberger C Prouve V Pugatch H Pullen G Punzi W Qian J Qin R Quagliani B Quintana N V Raab R I Rabadan Trejo B Rachwal J H Rademacker M Rama M Ramos Pernas M S Rangel F Ratnikov G Raven M Reboud F Redi F Reiss C Remon Alepuz Z Ren V Renaudin R Ribatti S Ricciardi K Rinnert P Robbe A Robert G Robertson A B Rodrigues E Rodrigues J A Rodriguez Lopez A Rollings P Roloff V Romanovskiy M Romero Lamas A Romero Vidal J D Roth M Rotondo M S Rudolph T Ruf J Ruiz Vidal A Ryzhikov J Ryzka J J Saborido Silva N Sagidova N Sahoo B Saitta D Sanchez Gonzalo C Sanchez Gras R Santacesaria C Santamarina Rios M Santimaria E Santovetti D Saranin G Sarpis M Sarpis A Sarti C Satriano A Satta M Saur D Savrina H Sazak L G Scantlebury Smead S Schael M Schellenberg M Schiller H Schindler M Schmelling T Schmelzer B Schmidt O Schneider A Schopper M Schubiger S Schulte M H Schune R Schwemmer B Sciascia A Sciubba S Sellam A Semennikov M Senghi Soares A Sergi N Serra L Sestini A Seuthe P Seyfert D M Shangase M Shapkin I Shchemerov L Shchutska T Shears L Shekhtman Z Shen V Shevchenko E B Shields E Shmanin J D Shupperd B G Siddi R Silva Coutinho G Simi S Simone I Skiba N Skidmore T Skwarnicki M W Slater J C Smallwood J G Smeaton A Smetkina E Smith I T Smith M Smith A Snoch M Soares L Soares Lavra M D Sokoloff F J P Soler A Solovev I Solovyev F L Souza De Almeida B Souza De Paula B Spaan E Spadaro Norella P Spradlin F Stagni M Stahl S Stahl P Stefko O Steinkamp S Stemmle O Stenyakin H Stevens S Stone M E Stramaglia M Straticiuc D Strekalina S Strokov F Suljik J Sun L Sun Y Sun P Svihra P N Swallow K Swientek A Szabelski T Szumlak M Szymanski S Taneja F Teubert E Thomas K A Thomson M J Tilley V Tisserand S T'Jampens M Tobin S Tolk L Tomassetti D Torres Machado D Y Tou M Traill M T Tran E Trifonova C Trippl G Tuci A Tully N Tuning A Ukleja D J Unverzagt E Ursov A Usachov A Ustyuzhanin U Uwer A Vagner V Vagnoni A Valassi G Valenti N Valls Canudas M van Beuzekom M Van Dijk E van Herwijnen C B Van Hulse M van Veghel R Vazquez Gomez P Vazquez Regueiro C Vázquez Sierra S Vecchi J J Velthuis M Veltri A Venkateswaran M Veronesi M Vesterinen D Vieira M Vieites Diaz H Viemann X Vilasis-Cardona E Vilella Figueras P Vincent G Vitali A Vollhardt D Vom Bruch A Vorobyev V Vorobyev N Voropaev R Waldi J Walsh C Wang J Wang J Wang J Wang J Wang M Wang R Wang Y Wang Z Wang H M Wark N K Watson S G Weber D Websdale C Weisser B D C Westhenry D J White M Whitehead D Wiedner G Wilkinson M Wilkinson I Williams M Williams M R J Williams F F Wilson W Wislicki M Witek L Witola G Wormser S A Wotton H Wu K Wyllie Z Xiang D Xiao Y Xie A Xu J Xu L Xu M Xu Q Xu Z Xu Z Xu D Yang Y Yang Z Yang Z Yang Y Yao L E Yeomans H Yin J Yu X Yuan O Yushchenko E Zaffaroni K A Zarebski M Zavertyaev M Zdybal O Zenaiev M Zeng D Zhang L Zhang S Zhang Y Zhang Y Zhang A Zhelezov Y Zheng X Zhou Y Zhou X Zhu V Zhukov J B Zonneveld S Zucchelli D Zuliani G Zunica

Phys Rev Lett 2021 Feb;126(8):081804

Department of Physics and Astronomy, University of Manchester, Manchester, United Kingdom.

The first observation of the suppressed semileptonic B_{s}^{0}→K^{-}μ^{+}ν_{μ} decay is reported. Using a data sample recorded in pp collisions in 2012 with the LHCb detector, corresponding to an integrated luminosity of 2  fb^{-1}, the branching fraction B(B_{s}^{0}→K^{-}μ^{+}ν_{μ}) is measured to be [1.06±0.05(stat)±0.08(syst)]×10^{-4}, where the first uncertainty is statistical and the second one represents the combined systematic uncertainties. The decay B_{s}^{0}→D_{s}^{-}μ^{+}ν_{μ}, where D_{s}^{-} is reconstructed in the final state K^{+}K^{-}π^{-}, is used as a normalization channel to minimize the experimental systematic uncertainty. Theoretical calculations on the form factors of the B_{s}^{0}→K^{-} and B_{s}^{0}→D_{s}^{-} transitions are employed to determine the ratio of the Cabibbo-Kobayashi-Maskawa matrix elements |V_{ub}|/|V_{cb}| at low and high B_{s}^{0}→K^{-} momentum transfer.
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http://dx.doi.org/10.1103/PhysRevLett.126.081804DOI Listing
February 2021

Troubleshooting problems with antegrade continent enema flushes: The Indiana university algorithm.

J Pediatr Urol 2021 Feb 22. Epub 2021 Feb 22.

Department of Urology, Section of Pediatric Urology, Riley Hospital for Children at IU Health, 702 Barnhill Drive, Suite 4230, Indianapolis, IN, 46202, USA.

Introduction: Antegrade continence enemas have transformed treatment and improved the quality of life in children with neuropathic bowel, refractory constipation and fecal incontinence. However, it can often be difficult to manage problems that arise with ACE flushes.

Objective: We report the use of an online tool designed for nurses to help troubleshoot calls for problems associated with antegrade continence enema (ACE) flushes as well as update our algorithm for managing refractory constipation/fecal incontinence in a large single institution experience.

Study Design: We developed an online tool based on our management protocol for managing refractory constipation/fecal incontinence (Summary Figure). Patient frequency and bother was assessed prior to the intervention and at one month after the intervention using 5- and 4-point Likert scales respectively. Patient demographics, MACE/Chait information, type of difficulty, volume of flush, and use of additives were recorded. Nurses were also interviewed prior to using the tool and 14 months after its development with regards to taking these phone calls and the helpfulness of the tool.

Results: Over 14 months, the nurses received 22 patients calls via the nursing triage line regarding ACE flush problems and prospectively collected data. Half reported multiple episodes of fecal incontinence. Other complaints included no response to flush (8, 36.4%), occasional episodes of liquid fecal incontinence (2, 9.1%) and time of flush exceeding 60 min (1, 4.5%). While patients did not report decreased frequency of problems as a result of nurse troubleshooting using the ACE algorithm (2.5 vs. 2, p = 0.55), patients did report a significant improvement in their bother scores (4 vs. 2, p = 0.02). All but one patient reported that the recommendation was "some" or "a lot" helpful on follow up interview. The nurses all indicated that the tool helped "some" or "a lot."

Discussion: The antegrade continence enema is valuable in managing neurogenic bowel, refractory constipation, and fecal incontinence, however, some patients experience problems with flushes that can often be difficult to manage.

Conclusion: Patients reported less bother with their bowel issues after using our algorithm for managing refractory constipation/fecal incontinence and nurses reported that the tool was helpful.
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http://dx.doi.org/10.1016/j.jpurol.2021.02.019DOI Listing
February 2021

Sonic Hedgehog modulates the inflammatory response and improves functional recovery after spinal cord injury in a thoracic contusion-compression model.

Eur Spine J 2021 Mar 11. Epub 2021 Mar 11.

Department of Neurosurgery, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany.

Purpose: The Sonic Hedgehog (Shh) pathway has been associated with a protective role after injury to the central nervous system (CNS). We, therefore, investigated the effects of intrathecal Shh-administration in the subacute phase after thoracic spinal cord injury (SCI) on secondary injury processes in rats.

Methods: Twenty-one Wistar rats were subjected to thoracic clip-contusion/compression SCI at T9. Animals were randomized into three treatment groups (Shh, Vehicle, Sham). Seven days after SCI, osmotic pumps were implanted for seven-day continuous intrathecal administration of Shh. Basso, Beattie and Bresnahan (BBB) score, Gridwalk test and bodyweight were weekly assessed. Animals were sacrificed six weeks after SCI and immunohistological analyses were conducted. The results were compared between groups and statistical analysis was performed (p < 0.05 was considered significant).

Results: The intrathecal administration of Shh led to significantly increased polarization of macrophages toward the anti-inflammatory M2-phenotype, significantly decreased T-lymphocytic invasion and significantly reduced resident microglia six weeks after the injury. Reactive astrogliosis was also significantly reduced while changes in size of the posttraumatic cyst as well as the overall macrophagic infiltration, although reduced, remained insignificant. Finally, with the administration of Shh, gain of bodyweight (216.6 ± 3.65 g vs. 230.4 ± 5.477 g; p = 0.0111) and BBB score (8.2 ± 0.2 vs. 5.9 ± 0.7 points; p = 0.0365) were significantly improved compared to untreated animals six weeks after SCI as well.

Conclusion: Intrathecal Shh-administration showed neuroprotective effects with attenuated neuroinflammation, reduced astrogliosis and improved functional recovery six weeks after severe contusion/compression SCI.
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http://dx.doi.org/10.1007/s00586-021-06796-2DOI Listing
March 2021

Current trends in pediatric moyamoya: a survey of international practitioners.

Childs Nerv Syst 2021 Mar 10. Epub 2021 Mar 10.

Pediatric Neurosurgery Department, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.

Objective: Moyamoya angiopathy (MM) is a chronic, progressive steno-occlusive arteriopathy of the distal internal carotid artery and its proximal branches. MM is recognized as a shared end-pathway common to a broad range of inciting pathologies, suggesting that tailored management is important. Pediatric MM differs from MM in adults. Currently, there are many uncertainties and controversies regarding the diagnosis and management of children with MM. Hence, we conducted an international survey to identify the contemporary management trends followed worldwide.

Methods: A survey relating to lifestyle modifications, medical management, diagnosis, surgical management, and follow-up for pediatric MM was circulated across web-based platforms, through various international pediatric neurological and neurosurgical societies. Data collected included geographic region of practice, experience, responses to questions, and comments.

Results: One hundred twenty-seven responses were evaluated (104 neurosurgeons and 23 neurologists, from 32 countries, across 6 continents). We found wide variations in the recommendations for management and lifestyle modification, with significant differences between regions of practice. Eighty percent recommend restrictions on physical activity, particularly for symptomatic and non-operated patients. Eighty-four percent prescribe aspirin. Sixty-five percent perform indirect revascularization. Seventy-eight percent recommend performing a staged surgery for bilateral MM. Only 26% perform acetazolamide challenge SPECT to evaluate brain perfusion. Only 15% of responders were from highly experienced centers.

Conclusion: This survey reflects the contemporary trends in management of pediatric MM, while highlighting the heterogeneity in the management approach of these patients. There is a need for multicenter, international studies to evaluate the safety, efficacy, and long-term outcome of various aspects of treatment of these patients.
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http://dx.doi.org/10.1007/s00381-021-05074-2DOI Listing
March 2021

Years of potential life lost in pre-diabetes and diabetes mellitus: data from a 40-year follow-up of the Israel study on Glucose intolerance, Obesity and Hypertension.

BMJ Open Diabetes Res Care 2021 Mar;9(1)

Unit for Cardiovascular Epidemiology, Gertner Institute for Epidemiology and Health Policy Research, Tel HaShomer, Israel

Introduction: We examined years of potential life lost (YPLL) associated with pre-diabetes as compared with either normoglycemia or diabetes, using data of the Israel cohort of Glucose intolerance, Obesity and Hypertension 40-year follow-up.

Research Design And Methods: Men and women (N=2844, mean age 52.0±8.2 years) who underwent oral glucose tolerance test and anthropometric measurements, during 1976-1982, were followed for mortality until May 2019. Multiple imputation procedures for missing mortality dates and multivariable regression mixed models were applied.

Results: At baseline, 35.8%, 48.8% and 15.4% individuals were found with normoglycemia, pre-diabetes, and diabetes, respectively. The average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 4.3 years (95% CI 3.3 to 5.2; p<0.001). YPLL were 1 year higher in women with pre-diabetes than in men with pre-diabetes. These differences persisted mainly in individuals younger than 60 years, and those with body mass index (BMI) <25 kg/m, at baseline. Adjusting for age, sex, country of origin, smoking status, BMI, and blood pressure, the average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 2.0 years (95% CI 1.2 to 2.8; p<0.001). Significant reductions of 5.9 years (95% CI 4.8 to 7.0) on average were observed for diabetes as compared with pre-diabetes and 7.9 years (95% CI 6.7 to 9.1) as compared with individuals with normoglycemia.

Conclusions: This study reveals that life expectancy of middle-aged individuals with pre-diabetes is shorter than of normoglycemic ones. These findings are especially relevant in view of the rising worldwide prevalence of pre-diabetes within younger age groups and underscore the crucial importance of interventions by either lifestyle modification or drug therapy capable of delaying progression from pre-diabetes to diabetes to reduce the YPLL in this high-risk group.
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http://dx.doi.org/10.1136/bmjdrc-2020-001981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949441PMC
March 2021

Characterization of physical literacy in children with chronic medical conditions compared to healthy controls: a cross-sectional study.

Appl Physiol Nutr Metab 2021 Mar 9. Epub 2021 Mar 9.

Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada.

To determine the physical literacy, defined as the capability for a physically active lifestyle, of children with medical conditions compared with healthy peers, this multicenter cross-sectional study recruited children with medical conditions from cardiology, neurology (including concussion), rheumatology, mental health, respirology, oncology, hematology, and rehabilitation (including cerebral palsy) clinics. Participants aged 8-12 years (N=130; mean age: 10.0±1.44 years; 44% female) were randomly matched to three healthy peers from a normative database, based on age, sex, and month of testing. Total physical literacy was assessed by the Canadian Assessment of Physical Literacy, a validated assessment of physical literacy measuring physical competence, daily behavior, knowledge/understanding, and motivation/confidence. Total physical literacy mean scores(/100) did not differ (t(498)=-0.67; p=0.44) between participants (61.0±14.2) and matched healthy peers (62.0±10.7). Children with medical conditions had lower mean physical competence scores (/30; -6.5 [-7.44, -5.51]; p<0.001) but higher mean motivation/confidence scores (/30; 2.6 [1.67, 3.63]; p<0.001). Mean daily behavior and knowledge/understanding scores did not differ from matches (/30; 1.8 [0.26, 3.33]; p=0.02; /10; -0.04 [-0.38, 0.30]; p=0.81; respectively). Children with medical conditions are motivated to be physically active but demonstrate impaired movement skills and fitness, suggesting the need for targeted interventions to improve their physical competence. Novelty bullets: • Physical literacy in children with diverse chronic medical conditions is similar to healthy peers • Children with medical conditions have lower physical competence than healthy peers, but higher motivation and confidence • Physical competence (motor skill, fitness) interventions, rather than motivation or education, are needed for these youth.
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http://dx.doi.org/10.1139/apnm-2020-0957DOI Listing
March 2021

Interleukin 17 Promotes Expression of Alarmins S100A8 and S100A9 During the Inflammatory Response of Keratinocytes.

Front Immunol 2020 12;11:599947. Epub 2021 Feb 12.

Institute of Immunology, University of Muenster, Muenster, Germany.

Psoriasis is one of the most common immune-mediated inflammatory skin diseases. Expression and secretion of two pro-inflammatory molecules of the S100-alarmin family, S100A8 and S100A9, in keratinocytes is a hallmark of psoriasis, which is also characterized by an altered differentiation of keratinocytes. Dimers of S100A8/S100A9 (calprotectin) bind to Toll-like receptor 4 and induce an inflammatory response in target cells. Targeted deletion of S100A9 reduced the inflammatory phenotype of psoriasis-like inflammation in mice. A role of S100-alarmins in differentiation and activation of keratinocytes was suggested but has been never shown in primary keratinocytes. We now confirm that induction of S100-alarmins in an imiquimod-induced murine model of psoriasis-like skin inflammation was associated with an increased expression of interleukin (IL)-1α, IL-6, IL-17A, or TNFα. This association was confirmed in transcriptome data obtained from controls, lesional and non-lesional skin of psoriasis patients, and a down-regulation of S100-alarmin expression after IL-17 directed therapy. However, analyzing primary S100A9 keratinocytes we found that expression of S100A8/S100A9 has no significant role for the maturation and inflammatory response pattern of keratinocytes. Moreover, keratinocytes are no target cells for the pro-inflammatory effects of S100A8/S100A9. However, different cytokines, especially IL-17A and F, highly abundant in psoriasis, strongly induced expression of S100-alarmins preferentially during early maturation stages of keratinocytes. Our data indicate that expression of S100A8 and S100A9 does not primarily influence maturation or activation of keratinocytes but rather represents the inflammatory response of these cells during psoriasis.
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http://dx.doi.org/10.3389/fimmu.2020.599947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906991PMC
February 2021

Evaluation of the QUANTUM BLUE sCAL rapid test as a point of care tool to identify patients with peritonsillar abscess.

Sci Rep 2021 Feb 24;11(1):4497. Epub 2021 Feb 24.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Münster, 48149, Münster, Germany.

S100A8/A9 (Calprotectin) serves as a biomarker for various inflammatory diseases, such as for peritonsillar abscess (PTA). Recently, the PTA score was developed for reliable PTA identification. It uses a combination of characteristic clinical symptoms and elevated calprotectin levels in serum and saliva to determine this score. Although well-established point-of-care tests (POCT) to determine serum or faecal calprotectin levels exist, a reliable and rapid tool to analyse salivary calprotectin has not yet been described. In this study, we analysed the potential of the QUANTUM BLUE sCAL Test (QBT, BÜHLMANN Laboratories AG, Switzerland) to determine S100A8/A9 levels during outpatient management. These QBT measurements are combined with other clinical factors to determine the PTA score. Significantly higher calprotectin levels were determined by QBT in patients with PTA compared to healthy controls. The receiver operating characteristic (ROC) curves for the QBT revealed cut-off values of 2940 ng/ml (sensitivity = 0.88, specificity = 0.78) in serum and 5310 ng/ml (sensitivity = 0.80, specificity = 0.50) in saliva. By adding the QBT results to determine PTA values, a ROC analysis provided a statistical cut-off score of 2.5 points to identify the existence of a PTA with a sensitivity of 100% and a specificity of 89.3%. The QUANTUM BLUE sCAL Test (QBT) is an appropriate POCT to determine serum and salivary calprotectin levels. Thus, PTA scores can be determined within a short time frame by applying the QBT during outpatient management.
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http://dx.doi.org/10.1038/s41598-021-84027-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904841PMC
February 2021

3D Bioprinting using UNIversal Orthogonal Network (UNION) Bioinks.

Adv Funct Mater 2021 Feb 20;31(7). Epub 2020 Nov 20.

Department of Materials Science & Engineering, Stanford University, Stanford, CA 94305, USA.

Three-dimensional (3D) bioprinting is a promising technology to produce tissue-like structures, but a lack of diversity in bioinks is a major limitation. Ideally each cell type would be printed in its own customizable bioink. To fulfill this need for a universally applicable bioink strategy, we developed a versatile, bioorthogonal bioink crosslinking mechanism that is cell compatible and works with a range of polymers. We term this family of materials UNIversal, Orthogonal Network (UNION) bioinks. As demonstration of UNION bioink versatility, gelatin, hyaluronic acid (HA), recombinant elastin-like protein (ELP), and polyethylene glycol (PEG) were each used as backbone polymers to create inks with storage moduli spanning 200 to 10,000 Pa. Because UNION bioinks are crosslinked by a common chemistry, multiple materials can be printed together to form a unified, cohesive structure. This approach is compatible with any support bath that enables diffusion of UNION crosslinkers. Both matrix-adherent human corneal mesenchymal stromal cells and non-matrix-adherent human induced pluripotent stem cell-derived neural progenitor spheroids were printed with UNION bioinks. The cells retained high viability and expressed characteristic phenotypic markers after printing. Thus, UNION bioinks are a versatile strategy to expand the toolkit of customizable materials available for 3D bioprinting.
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http://dx.doi.org/10.1002/adfm.202007983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888563PMC
February 2021

Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial.

Nat Med 2021 03 18;27(3):504-514. Epub 2021 Feb 18.

Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC.
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http://dx.doi.org/10.1038/s41591-020-01224-2DOI Listing
March 2021

Microrheology reveals simultaneous cell-mediated matrix stiffening and fluidization that underlie breast cancer invasion.

Sci Adv 2021 Feb 17;7(8). Epub 2021 Feb 17.

Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.

Living tissues embody a unique class of hybrid materials in which active and thermal forces are inextricably linked. Mechanical characterization of tissues demands descriptors that respect this hybrid nature. In this work, we develop a microrheology-based force spectrum analysis (FSA) technique to dissect the active and passive fluctuations of the extracellular matrix (ECM) in three-dimensional (3D) cell culture models. In two different stromal models and a 3D breast cancer spheroid model, our FSA reveals emergent hybrid dynamics that involve both high-frequency stress stiffening and low-frequency fluidization of the ECM. We show that this is a general consequence of nonlinear coupling between active forces and the frequency-dependent viscoelasticity of stress-stiffening networks. In 3D breast cancer spheroids, this dual active stiffening and fluidization is tightly connected with invasion. Our results suggest a mechanism whereby breast cancer cells reconcile the seemingly contradictory requirements for both tension and malleability in the ECM during invasion.
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http://dx.doi.org/10.1126/sciadv.abe1969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888921PMC
February 2021