Publications by authors named "M John Chapman"

2,209 Publications

  • Page 1 of 1

"Death Diamond" Tracing on Thromboelastography as a Marker of Poor Survival After Trauma.

Am Surg 2021 Feb 25:3134821998684. Epub 2021 Feb 25.

Departments of Trauma, Surgery, and Critical Care Medicine, 5973Christiana Care Health Services, Wilmington, DE, USA.

Background: Improvements in health care innovations have resulted in an enhanced ability to extend patient viability. As a consequence, resources are being increasingly utilized at an unsustainable level. As we implement novel treatments, identifying futility should be a focus. The "death diamond" (DD) is a unique thrombelastography (TEG) tracing that is indicative of failure of the coagulation system, with a mortality rate exceeding 90%. The purpose of this study was to determine if the DD was a consistent marker of poor survival in a multicenter study population. We hypothesize that the DD, while an infrequent occurrence, predicts poor survival and can be used to stratify patients in whom resuscitation efforts are futile.

Methods: A retrospective multi-institutional study of trauma patients presenting with TEG DDs between 8/2008 and 12/2018 at four American College of Surgeons trauma centers was completed. Demographics, injury mechanisms, TEG results, management, and survival were examined.

Results: A total of 50 trauma patients presented with DD tracings, with a 94% (n = 47) mortality rate. Twenty-six (52%) patients received a repeat TEG with 10 patients re-demonstrating the DD tracing. There was 100% mortality in patients with serial DD tracings. The median use of total blood products was 18 units (interquartile range 6, 34.25) per patient.

Discussion: The DD is highly predictive of trauma-associated mortality. This multicenter study highlights that serial DDs may represent a possible biomarker of futility.
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http://dx.doi.org/10.1177/0003134821998684DOI Listing
February 2021

Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays.

Alzheimers Dement (Amst) 2021 6;13(1):e12131. Epub 2021 Feb 6.

Dementia Research Centre UCL Queen Square Institute of Neurology, University College London London UK.

Introduction: We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).

Methods: In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site 181 (p-tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays and inter-platform Pearson correlations derived. Lumipulse Aβ42 measures were adjusted to incorporate standardization to certified reference materials. Logistic regressions and receiver operating characteristics analysis generated CSF cut-points optimizing concordance with F-florbetapir amyloid PET status (n = 63).

Results: Measurements of CSF Aβ, p-tau181, and their ratios correlated well across platforms (r 0.84 to 0.94, < .0001); those of t-tau and t-tau/Aβ42 correlated moderately (r 0.57 to 0.79, < .0001). The best concordance with amyloid PET (100% sensitivity and 94% specificity) was afforded by cut-points of 0.075 for Lumipulse Aβ42/Aβ40, 0.087 for MSD Aβ42/Aβ40 and 17.3 for Lumipulse Aβ42/p-tau181.

Discussion: The Lumipulse platform provides comparable sensitivity and specificity to established CSF immunoassays in identifying pre-symptomatic AD pathology.
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http://dx.doi.org/10.1002/dad2.12131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867115PMC
February 2021

Cardiac reverse remodeling following mitral valve replacement in men and women.

J Card Surg 2021 Feb 15. Epub 2021 Feb 15.

Second Department of Internal Medicine, University of Toyama, Toyama, Japan.

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http://dx.doi.org/10.1111/jocs.15424DOI Listing
February 2021

Effects of Standard vs Energy-Dense Formulae on Gastric Retention, Energy Delivery, and Glycemia in Critically Ill Patients.

JPEN J Parenter Enteral Nutr 2021 Feb 5. Epub 2021 Feb 5.

Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Background: Energy-dense formulae are often provided to critically ill patients with enteral feed intolerance with the aim of increasing energy delivery, yet the effect on gastric emptying is unknown. The rate of gastric emptying of a standard compared with an energy-dense formula was quantified in critically ill patients.

Methods: Mechanically ventilated adults were randomized to receive radiolabeled intragastric infusions of 200 mL standard (1 kcal/mL) or 100 mL energy-dense (2 kcal/mL) enteral formulae on consecutive days in this noninferiority, blinded, crossover trial. The primary outcome was scintigraphic measurement of gastric retention (percentage at 120 minutes). Other measures included area under the curve (AUC) for gastric retention and intestinal energy delivery (calculated from gastric retention of formulae over time), blood glucose (peak and AUC), and intestinal glucose absorption (using 3-O-methyl-D-gluco-pyranose [3-OMG] concentrations). Comparisons were undertaken using paired mixed-effects models. Data presented are mean ± SE.

Results: Eighteen patients were studied (male/female, 14:4; age, 55.2 ± 5.3 years). Gastric retention at 120 minutes was greater with the energy-dense formula (standard, 17.0 ± 5.9 vs energy-dense, 32.5 ± 7.1; difference, 12.7% [90% confidence interval, 0.8%-30.1%]). Energy delivery (AUC , 13,038 ± 1119 vs 9763 ± 1346 kcal/120 minutes; P = 0.057), glucose control (peak glucose, 10.1 ± 0.3 vs 9.7 ± 0.3 mmol/L, P = 0.362; and glucose AUC 8.7 ± 0.3 vs 8.5 ± 0.3 mmol/L.120 minutes, P = 0.661), and absorption (3-OMG AUC , 38.5 ± 4.0 vs 35.7 ± 4.0 mmol/L.120 minutes; P = .508) were not improved with the energy-dense formula.

Conclusion: In critical illness, administration of an energy-dense formula does not reduce gastric retention, increase energy delivery to the small intestine, or improve glucose absorption or glucose control; instead, there is a signal for delayed gastric emptying.
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http://dx.doi.org/10.1002/jpen.2065DOI Listing
February 2021

Association between left atrial sphericity index and clinical outcomes in patients with systolic heart failure.

Clin Cardiol 2021 Feb 4. Epub 2021 Feb 4.

Second Department of Internal Medicine, University of Toyama, Toyama, Japan.

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http://dx.doi.org/10.1002/clc.23562DOI Listing
February 2021

Gut dysfunction in the ICU: diagnosis and management.

Curr Opin Crit Care 2021 Jan 21. Epub 2021 Jan 21.

Intensive Care Unit, Royal Adelaide Hospital School of Medicine, University of Adelaide, South Australia Intensive Care Unit, Royal Melbourne Hospital Centre for Integrated Critical Care, University of Melbourne, Victoria, Australia.

Purpose Of Review: Progress has been made in our understanding of gut dysfunction in critical illness. This review will outline new findings and give perspectives based on previous knowledge and concurrent advances in nutrition.

Recent Findings: The relationship between gut dysfunction and poor outcomes in critical illness has received considerable interest. It remains uncertain whether gut dysfunction is merely a marker of illness severity or if it is directly responsible for prolonged critical illness and increased mortality. This relationship is difficult to ascertain given there is no agreed method for identification and quantification; biomarkers such as intestinal fatty acid binding protein and citrulline show promise but require further study. Recent studies have investigated strategies to deliver enteral nutrition targets with impacts on gut function, including high calorie or protein formulae, intermittent regimes and novel prokinetics.

Summary: Gut dysfunction is associated with poor outcomes, but it remains uncertain whether strategies to improve gut function will influence survival and recovery.
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http://dx.doi.org/10.1097/MCC.0000000000000813DOI Listing
January 2021

Model-Independent Study of Structure in B^{+}→D^{+}D^{-}K^{+} 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 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 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 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 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 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 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 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 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 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 2020 Dec;125(24):242001

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

The only anticipated resonant contributions to B^{+}→D^{+}D^{-}K^{+} decays are charmonium states in the D^{+}D^{-} channel. A model-independent analysis, using LHCb proton-proton collision data taken at center-of-mass energies of sqrt[s]=7, 8, and 13 TeV, corresponding to a total integrated luminosity of 9  fb^{-1}, is carried out to test this hypothesis. The description of the data assuming that resonances only manifest in decays to the D^{+}D^{-} pair is shown to be incomplete. This constitutes evidence for a new contribution to the decay, potentially one or more new charm-strange resonances in the D^{-}K^{+} channel with masses around 2.9  GeV/c^{2}.
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http://dx.doi.org/10.1103/PhysRevLett.125.242001DOI Listing
December 2020

Enteral nutrition in circulatory shock: friend or foe?

Curr Opin Clin Nutr Metab Care 2021 Mar;24(2):159-164

Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Purpose Of Review: Circulatory shock is associated with reduced splanchnic blood flow and impaired gut epithelial barrier function (EBF). Early enteral nutrition (EN) has been shown in animal models to preserve EBF. There are limited human data informing early EN in circulatory shock and critical care nutrition guidelines provide disparate recommendations regarding the optimal timing and dose. The purpose of this review is to describe the harms and benefits of early EN in circulatory shock by identifying and appraising recent human data.

Recent Findings: The cumulative risk of nonocclusive bowel ischemia and necrosis in patients with circulatory shock is no higher than 0.3% across observational and randomized controlled trial-level data, and whether the risk is increased by EN delivery remains uncertain. Observational data suggest that early EN in circulatory shock is associated with improved clinical outcomes but data from robust randomized controlled trials remain equivocal, so the optimal timing and dose remain unknown.

Summary: Based on the best available data, initiating restrictive dose EN into the stomach after initial resuscitation in patients with circulatory shock does not appear to be harmful. In fact, early EN may preserve EBF and improve clinical outcomes.
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http://dx.doi.org/10.1097/MCO.0000000000000731DOI Listing
March 2021

Constraints on the K_{S}^{0}→μ^{+}μ^{-} Branching Fraction.

Authors:
R Aaij C Abellán Beteta T Ackernley B Adeva M Adinolfi H Afsharnia C A Aidala S Aiola Z Ajaltouni S Akar P Albicocco J Albrecht F Alessio M Alexander A Alfonso Albero G Alkhazov P Alvarez Cartelle A A Alves S Amato Y Amhis L An L Anderlini G Andreassi M Andreotti F Archilli J Arnau Romeu A Artamonov M Artuso K Arzymatov E Aslanides M Atzeni B Audurier S Bachmann J J Back S Baker V Balagura W Baldini A Baranov R J Barlow S Barsuk W Barter M Bartolini F Baryshnikov G Bassi V Batozskaya B Batsukh A Battig A Bay M Becker F Bedeschi I Bediaga A Beiter L J Bel V Belavin S Belin N Beliy V Bellee K Belous I Belyaev G Bencivenni E Ben-Haim S Benson S Beranek 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 M S Bieker S Bifani P Billoir A Bizzeti M Bjørn M P Blago T Blake F Blanc S Blusk D Bobulska V Bocci O Boente Garcia T Boettcher A Boldyrev A Bondar N Bondar S Borghi M Borisyak M Borsato J T Borsuk T J V Bowcock C Bozzi M J Bradley S Braun A Brea Rodriguez M Brodski J Brodzicka A Brossa Gonzalo D Brundu E Buchanan A Büchler-Germann A Buonaura C Burr A Bursche J S Butter J Buytaert W Byczynski S Cadeddu H Cai R Calabrese L Calero Diaz S Cali R Calladine M Calvi M Calvo Gomez A Camboni P Campana D H Campora Perez L Capriotti A Carbone G Carboni R Cardinale A Cardini P Carniti K Carvalho Akiba A Casais Vidal G Casse M Cattaneo G Cavallero S Celani R Cenci J Cerasoli M G Chapman M Charles Ph Charpentier G Chatzikonstantinidis M Chefdeville V Chekalina C Chen S Chen A Chernov S-G Chitic V Chobanova M Chrzaszcz A Chubykin P Ciambrone M F Cicala X Cid Vidal G Ciezarek F Cindolo 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 A Comerma-Montells A Contu N Cooke G Coombs S Coquereau G Corti C M Costa Sobral B Couturier D C Craik J Crkovská A Crocombe 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 P De Simone J A de Vries C T Dean W Dean D Decamp L Del Buono B Delaney H-P Dembinski M Demmer A Dendek V Denysenko D Derkach O Deschamps F Desse F Dettori B Dey A Di Canto P Di Nezza S Didenko H Dijkstra V Dobishuk F Dordei M Dorigo A C Dos Reis L Douglas A Dovbnya K Dreimanis M W Dudek L Dufour G Dujany P Durante J M Durham D Dutta M Dziewiecki A Dziurda A Dzyuba S Easo U Egede V Egorychev S Eidelman S Eisenhardt R Ekelhof S Ek-In L Eklund S Ely A Ene E Epple S Escher S Esen T Evans A Falabella J Fan 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 C Frei D A Friday J Fu Q Fuehring W Funk E Gabriel A Gallas Torreira D Galli S Gallorini S Gambetta Y Gan M Gandelman P Gandini Y Gao L M Garcia Martin J García Pardiñas B Garcia Plana F A Garcia Rosales J Garra Tico L Garrido D Gascon C Gaspar D Gerick E Gersabeck M Gersabeck T Gershon D Gerstel Ph Ghez V Gibson A Gioventù O G Girard P Gironella Gironell L Giubega C Giugliano K Gizdov V V Gligorov C Göbel E Golobardes D Golubkov A Golutvin A Gomes 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 R Greim P Griffith L Grillo L Gruber B R Gruberg Cazon C Gu P A Günther E Gushchin A Guth Yu Guz T Gys T Hadavizadeh G Haefeli C Haen S C Haines P M Hamilton Q Han X Han T H Hancock S Hansmann-Menzemer N Harnew T Harrison R Hart C Hasse M Hatch J He M Hecker K Heijhoff K Heinicke A Heister A M Hennequin K Hennessy L Henry J Heuel A Hicheur D Hill M Hilton P H Hopchev J Hu W Hu W Huang W Hulsbergen T Humair R J Hunter M Hushchyn D Hutchcroft D Hynds P Ibis M Idzik P Ilten A Inglessi A Inyakin K Ivshin R Jacobsson S Jakobsen E Jans B K Jashal A Jawahery V Jevtic F Jiang M John D Johnson C R Jones B Jost N Jurik S Kandybei M Karacson J M Kariuki N Kazeev M Kecke F Keizer M Kelsey M Kenzie T Ketel B Khanji A Kharisova K E Kim T Kirn V S Kirsebom S Klaver K Klimaszewski S Koliiev A Kondybayeva A Konoplyannikov P Kopciewicz R Kopecna P Koppenburg M Korolev I Kostiuk O Kot S Kotriakhova 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 D Lancierini J J Lane G Lanfranchi C Langenbruch O Lantwin T Latham F Lazzari C Lazzeroni R Le Gac R Lefèvre A Leflat O Leroy T Lesiak B Leverington H Li X Li Y Li Z Li X Liang R Lindner V Lisovskyi G Liu X Liu D Loh A Loi J Lomba Castro I Longstaff J H Lopes G Loustau G H Lovell Y Lu D Lucchesi M Lucio Martinez Y Luo A Lupato E Luppi O Lupton A Lusiani X Lyu S Maccolini F Machefert F Maciuc V Macko P Mackowiak S Maddrell-Mander 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 M McCann L Mcconnell A McNab R McNulty J V Mead B Meadows C Meaux G Meier N Meinert D Melnychuk S Meloni M Merk A Merli M Mikhasenko D A Milanes E Millard M-N Minard O Mineev L Minzoni S E Mitchell B Mitreska D S Mitzel A Mödden A Mogini 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 V Müller C H Murphy D Murray P Muzzetto P Naik T Nakada R Nandakumar A Nandi T Nanut I Nasteva M Needham 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 S Ogilvy D P O'Hanlon R Oldeman C J G Onderwater J D Osborn A Ossowska J M Otalora Goicochea T Ovsiannikova P Owen A Oyanguren P R Pais T Pajero A Palano M Palutan G Panshin A Papanestis M Pappagallo L L Pappalardo C Pappenheimer W Parker C Parkes G Passaleva A Pastore M Patel C Patrignani A Pearce A Pellegrino M Pepe Altarelli S Perazzini D Pereima P Perret L Pescatore K Petridis A Petrolini A Petrov S Petrucci M Petruzzo B Pietrzyk G Pietrzyk M Pili D Pinci J Pinzino F Pisani A Piucci 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 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 S Ricciardi S Richards K Rinnert P Robbe A Robert A B Rodrigues E Rodrigues J A Rodriguez Lopez M Roehrken S Roiser A Rollings V Romanovskiy M Romero Lamas A Romero Vidal J D Roth M Rotondo M S Rudolph T Ruf J Ruiz Vidal J Ryzka J J Saborido Silva N Sagidova B Saitta C Sanchez Gras C Sanchez Mayordomo R Santacesaria C Santamarina Rios M Santimaria E Santovetti G Sarpis A Sarti C Satriano A Satta M Saur D Savrina L G Scantlebury Smead S Schael M Schellenberg M Schiller H Schindler M Schmelling T Schmelzer B Schmidt O Schneider A Schopper H F Schreiner M Schubiger S Schulte M H Schune R Schwemmer B Sciascia A Sciubba S Sellam A Semennikov A Sergi N Serra J Serrano L Sestini A Seuthe P Seyfert D M Shangase M Shapkin L Shchutska T Shears L Shekhtman V Shevchenko E Shmanin J D Shupperd B G Siddi R Silva Coutinho L Silva de Oliveira G Simi S Simone I Skiba N Skidmore T Skwarnicki M W Slater 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 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 M Stepanova H Stevens S Stone S Stracka M E Stramaglia M Straticiuc S Strokov J Sun L Sun Y Sun P Svihra K Swientek A Szabelski T Szumlak M Szymanski S Taneja Z Tang T Tekampe G Tellarini F Teubert E Thomas K A Thomson M J Tilley V Tisserand S T'Jampens M Tobin S Tolk L Tomassetti D Tonelli D Torres Machado D Y Tou E Tournefier M Traill M T Tran C Trippl A Trisovic A Tsaregorodtsev G Tuci A Tully N Tuning A Ukleja A Usachov A Ustyuzhanin U Uwer A Vagner V Vagnoni A Valassi G Valenti 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 Vernet M Veronesi M Vesterinen J V Viana Barbosa D Vieira M Vieites Diaz H Viemann X Vilasis-Cardona A Vitkovskiy A Vollhardt D Vom Bruch A Vorobyev V Vorobyev N Voropaev R Waldi J Walsh J Wang J Wang J Wang M Wang Y Wang Z Wang D R Ward H M Wark N K Watson D Websdale A Weiden 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 T 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 L Xu M Xu Q Xu Z Xu Z Xu Z Yang Z Yang Y Yao L E Yeomans H Yin J Yu X Yuan O Yushchenko K A Zarebski M Zavertyaev M Zdybal M Zeng D Zhang L Zhang S Zhang W C Zhang Y Zhang A Zhelezov Y Zheng X Zhou Y Zhou X Zhu V Zhukov J B Zonneveld S Zucchelli

Phys Rev Lett 2020 Dec;125(23):231801

INFN Sezione di Bologna, Bologna, Italy.

A search for the decay K_{S}^{0}→μ^{+}μ^{-} is performed using proton-proton collision data, corresponding to an integrated luminosity of 5.6  fb^{-1} and collected with the LHCb experiment during 2016, 2017, and 2018 at a center-of-mass energy of 13 TeV. The observed signal yield is consistent with zero, yielding an upper limit of B(K_{S}^{0}→μ^{+}μ^{-})<2.2×10^{-10} at 90% C.L.. The limit reduces to B(K_{S}^{0}→μ^{+}μ^{-})<2.1×10^{-10} at 90% C.L. once combined with the result from data taken in 2011 and 2012.
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http://dx.doi.org/10.1103/PhysRevLett.125.231801DOI Listing
December 2020

Functional Amyloids Are the Rule Rather Than the Exception in Cellular Biology.

Microorganisms 2020 Dec 9;8(12). Epub 2020 Dec 9.

Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.

Amyloids are a class of protein aggregates that have been historically characterized by their relationship with human disease. Indeed, amyloids can be the result of misfolded proteins that self-associate to form insoluble, extracellular plaques in diseased tissue. For the first 150 years of their study, the pathogen-first definition of amyloids was sufficient. However, new observations of amyloids foster an appreciation for non-pathological roles for amyloids in cellular systems. There is now evidence from all domains of life that amyloids can be non-pathogenic and functional, and that their formation can be the result of purposeful and controlled cellular processes. So-called functional amyloids fulfill an assortment of biological functions including acting as structural scaffolds, regulatory mechanisms, and storage mechanisms. The conceptual convergence of amyloids serving a functional role has been repeatedly confirmed by discoveries of additional functional amyloids. With dozens already known, and with the vigorous rate of discovery, the biology of amyloids is robustly represented by non-pathogenic amyloids.
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http://dx.doi.org/10.3390/microorganisms8121951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764130PMC
December 2020

Use of a High-Protein Enteral Nutrition Formula to Increase Protein Delivery to Critically Ill Patients: A Randomized, Blinded, Parallel-Group, Feasibility Trial.

JPEN J Parenter Enteral Nutr 2020 Dec 9. Epub 2020 Dec 9.

Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Background: International guidelines recommend critically ill adults receive more protein than most receive. We aimed to establish the feasibility of a trial to evaluate whether feeding protein to international recommendations would improve outcomes, in which 1 group received protein doses representative of international guideline recommendations (high protein) and the other received doses similar to usual practice.

Methods: We conducted a prospective, randomized, blinded, parallel-group, feasibility trial across 6 intensive care units. Critically ill, mechanically ventilated adults expected to receive enteral nutrition (EN) for ≥2 days were randomized to receive EN containing 63 or 100 g/L protein for ≤28 days. Data are mean (SD) or median (interquartile range).

Results: The recruitment rate was 0.35 (0.13) patients per day, with 120 patients randomized and data available for 116 (n = 58 per group). Protein delivery was greater in the high-protein group (1.52 [0.52] vs 0.99 [0.27] grams of protein per kilogram of ideal body weight per day; difference, 0.53 [95% CI, 0.38-0.69] g/kg/d protein), with no difference in energy delivery (difference, -26 [95% CI, -190 to 137] kcal/kg/d). There were no between-group differences in the duration of feeding (8.7 [7.3] vs 8.1 [6.3] days), and blinding of the intervention was confirmed. There were no differences in clinical outcomes, including 90-day mortality (14/55 [26%] vs 15/56 [27%]; risk difference, -1.3% [95% CI, -17.7% to 15.0%]).

Conclusion: Conducting a multicenter blinded trial is feasible to compare protein delivery at international guideline-recommended levels with doses similar to usual care during critical illness.
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http://dx.doi.org/10.1002/jpen.2059DOI Listing
December 2020

In lieu of penectomy: complete resolution of penile melanoma in situ with topical imiquimod and tretinoin.

Int J Dermatol 2020 Dec 5. Epub 2020 Dec 5.

Geisel School of Medicine at Dartmouth, Hanover, NH, USA.

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http://dx.doi.org/10.1111/ijd.15261DOI Listing
December 2020

Observation of Enhanced Double Parton Scattering in Proton-Lead Collisions at sqrt[s_{NN}]=8.16  TeV.

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 A A Alves S Amato Y Amhis L An L Anderlini G Andreassi 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 V Batozskaya 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 V Bocci 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 E Buchanan 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 R Cenci 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 S Coquereau 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 A Di Canto P Di Nezza S Didenko L Dieste Maronas H Dijkstra V Dobishuk A M Donohoe F Dordei M Dorigo 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 Gallorini 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 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 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 R Hart 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 T Humair 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 Kelsey 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 S Ogilvy D P O'Hanlon R Oldeman C J G Onderwater J D Osborn 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 M Roehrken 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 H F Schreiner 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 Z Shen V Shevchenko E B Shields E Shmanin J D Shupperd B G Siddi R Silva Coutinho L Silva de Oliveira 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 Vitkovskiy 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 M Winn 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 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 2020 Nov;125(21):212001

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

A study of prompt charm-hadron pair production in proton-lead collisions at sqrt[s_{NN}]=8.16  TeV is performed using data corresponding to an integrated luminosity of about 30  nb^{-1}, collected with the LHCb experiment. Production cross sections for different pairs of charm hadrons are measured and kinematic correlations between the two charm hadrons are investigated. This is the first measurement of associated production of two charm hadrons in proton-lead collisions. The results confirm the predicted enhancement of double parton scattering production in proton-lead collisions compared to the single parton scattering production.
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http://dx.doi.org/10.1103/PhysRevLett.125.212001DOI Listing
November 2020

Trial Design in Critical Care Nutrition: The Past, Present and Future.

Nutrients 2020 Nov 30;12(12). Epub 2020 Nov 30.

Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.

The specialty of nutrition in critical care is relatively modern, and accordingly, trial design has progressed over recent decades. In the past, small observational and physiological studies evolved to become small single-centre comparative trials, but these had significant limitations by today's standards. Power calculations were often not undertaken, outcomes were not specified a priori, and blinding and randomisation were not always rigorous. These trials have been superseded by larger, more carefully designed and conducted multi-centre trials. Progress in trial conduct has been facilitated by a greater understanding of statistical concepts and methodological design. In addition, larger numbers of potential study participants and increased access to funding support trials able to detect smaller differences in outcomes. This narrative review outlines why critical care nutrition research is unique and includes a historical critique of trial design to provide readers with an understanding of how and why things have changed. This review focuses on study methodology, population group, intervention, and outcomes, with a discussion as to how these factors have evolved, and concludes with an insight into what we believe trial design may look like in the future. This will provide perspective on the translation of the critical care nutrition literature into clinical practice.
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http://dx.doi.org/10.3390/nu12123694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760682PMC
November 2020

What People Really Think About Safety around Horses: The Relationship between Risk Perception, Values and Safety Behaviours.

Animals (Basel) 2020 Nov 26;10(12). Epub 2020 Nov 26.

UniSA Business, University of South Australia, 101 Currie Street, Adelaide, SA 5001, Australia.

The equestrian industry reports high rates of serious injuries, illness and fatalities when compared to other high-risk sports and work environments. To address these ongoing safety concerns, a greater understanding of the relationship between human risk perception, values and safety behaviours is required. This paper presents results from an international survey that explored relationships between a respondents' willingness to take risk during daily activities along with, their perceptions of risk and behaviours during horse-related interactions. Respondents' comments around risk management principles and safety-first inspirations were also analysed. We examined what humans think about hazardous situations or activities and how they managed risk with suitable controls. Analysis identified three important findings. First, safe behaviours around horses were associated with safety training (formal and/or informal). Second, unsafe behaviours around horses were associated with higher levels of equestrian experience as well as income from horse-related work. Finally, findings revealed a general acceptance of danger and imminent injury during horse interactions. This may explain why some respondents de-emphasised or 'talked-down' the importance of safety-first principles. In this paper we predominantly reported quantitative findings of respondents self-reported safety behaviours, general and horse-related risk perceptions despite injury or illness. We discussed the benefits of improved safety-first principles like training, risk assessments, rider-horse match with enriched safety communications to enhance risk-mitigation during human-horse interactions.
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http://dx.doi.org/10.3390/ani10122222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761269PMC
November 2020

Use of the Ovesco remOVE DC cutter to trim a metal biliary stent with excess length in the duodenum allowing biliary access for ERCP.

Endoscopy 2020 Nov 26. Epub 2020 Nov 26.

Department of Gastroenterology, University College London Hospitals, London, UK.

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http://dx.doi.org/10.1055/a-1292-4205DOI Listing
November 2020

Acceleration of Gastric Emptying by Insulin-Induced Hypoglycemia is Dependent on the Degree of Hypoglycemia.

J Clin Endocrinol Metab 2021 Jan;106(2):364-371

Adelaide Medical School, University of Adelaide, Adelaide, Australia.

Context: Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized "non-severe" hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. "Marked" hypoglycemia (~2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of "mild" hypoglycemia (3.0-3.9 mmol/L) is unknown.

Objective: To determine the effects of 2 levels of hypoglycemia, 2.6 mmol/L ("marked") and 3.6 mmol/L ("mild"), on gastric emptying in health.

Design, Setting, And Subjects: Fourteen healthy male participants (mean age: 32.9 ± 8.3 years; body mass index: 24.5 ± 3.4 kg/m2) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100 g beef) by scintigraphy over 120 minutes on 3 separate occasions, while blood glucose was maintained at either ~2.6 mmol/L, ~3.6 mmol/L, or ~6 mmol/L in random order from 15 minutes before until 60 minutes after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days.

Results: Gastric emptying was accelerated during both mild (P = 0.011) and marked (P = 0.001) hypoglycemia when compared to euglycemia, and was more rapid during marked compared with mild hypoglycemia (P = 0.008). Hypoglycemia-induced gastric emptying acceleration during mild (r = 0.57, P = 0.030) and marked (r = 0.76, P = 0.0014) hypoglycemia was related to gastric emptying during euglycemia.

Conclusion: In health, acceleration of gastric emptying by insulin-induced hypoglycemia is dependent on the degree of hypoglycemia and baseline rate of emptying.
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http://dx.doi.org/10.1210/clinem/dgaa854DOI Listing
January 2021

Plasmin thrombelastography rapidly identifies trauma patients at risk for massive transfusion, mortality, and hyperfibrinolysis: A diagnostic tool to resolve an international debate on tranexamic acid?

J Trauma Acute Care Surg 2020 12;89(6):991-998

From the Koch Institute for Integrative Cancer Research (C.D.B., S.D., M.B.Y.), Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge; Division of Acute Care Surgery and Critical Care (C.D.B., M.B.Y.), Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Surgery (H.B.M., N.V., A.S., E.E.M.), University of Colorado Denver, Denver, Colorado; Ernest E. Moore Shock and Trauma Center (J.C., E.E.M.), Denver Health Medical Center; and Department of Radiology (M.P.C.), University of Colorado Denver, Denver, Colorado.

Background: Trauma patients with hyperfibrinolysis and depletion of fibrinolytic inhibitors (DFIs) measured by thrombelastography (TEG) gain clot strength with TXA, but TEG results take nearly an hour. We aimed to develop an assay, plasmin TEG (P-TEG), to more expeditiously stratify risk for massive transfusion (MT), mortality, and hyperfibrinolysis.

Methods: Trauma patients (N = 148) were assessed using TEG assays without exogenous additives (rapid/native), with exogenous plasmin (P-TEG) or tissue plasminogen activator (tPA TEG). The plasmin dose used does not effect healthy-control clot lysis 30 minutes after maximum amplitude (LY30) but causes shortened reaction time (R time) relative to native TEG (P-TEG R time < native TEG R time considered P-TEG negative). If P-TEG R time is greater than or equal to native TEG R time, the patient was considered P-TEG positive. Each assay's ability to predict MT, mortality, and (risk for) hyperfibrinolysis was determined. χ and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Results were reported as median ± interquartile range or n (%).

Results: Plasmin TEG provided results faster than all other assays (4.7 ± 2.5-9.1 minutes), approximately 11-fold faster than rapid-TEG (rTEG) LY30 (54.2 ± 51.1-58.1 minutes; p < 0.001). Plasmin TEG-positive patients had greater than fourfold higher MT rate (30% vs. 7%; p = 0.0015) with an area under the receiver operating characteristic curve of 0.686 (p = 0.028), greater than fourfold higher 24-hour mortality (33.3% vs. 7.8%; p = 0.0177), greater than twofold higher 30-day mortality (35% vs. 16.4%; p = 0.0483), higher rates of DFI (55% vs. 18%; p < 0.001), and a trend toward elevated D-dimer (19.9 vs. 3.3 μg/mL; p = 0.14). Plasmin TEG was associated with hyperfibrinolysis on rTEG LY30 at the 7.6% threshold (p = 0.04) but not the 3% threshold (p = 0.40). Plasmin TEG performed best in relation to DFI, with a positive predictive value of 58% and negative predictive value of 81%. When combined with tPA TEG time to maximum amplitude, P-TEG outperformed rTEG LY30 for predicting MT (area under the receiver operating characteristic curve, 0.811 vs. 0.708).

Conclusion: Within 5 minutes, P-TEG can stratify patients at highest risk for MT, mortality, and risk for hyperfibrinolysis. In composite with tPA TEG time to maximum amplitude, P-TEG outperforms rTEG LY30 for predicting MT and does so four times faster (12.7 vs. 54.1 minutes). The rapid results of P-TEG may be useful for those who practice selective TXA administration to maximize TXA's time-dependent efficacy.

Level Of Evidence: Diagnostic test, level V.
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http://dx.doi.org/10.1097/TA.0000000000002941DOI Listing
December 2020

The Structure of an AAV5-AAVR Complex at 2.5 Å Resolution: Implications for Cellular Entry and Immune Neutralization of AAV Gene Therapy Vectors.

Viruses 2020 11 18;12(11). Epub 2020 Nov 18.

Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.

Adeno-Associated Virus is the leading vector for gene therapy. Although it is the vector for all in vivo gene therapies approved for clinical use by the US Food and Drug Administration, its biology is still not yet fully understood. It has been shown that different serotypes of AAV bind to their cellular receptor, AAVR, in different ways. Previously we have reported a 2.4Å structure of AAV2 bound to AAVR that shows ordered structure for only one of the two AAVR domains with which AAV2 interacts. In this study we present a 2.5Å resolution structure of AAV5 bound to AAVR. AAV5 binds to the first polycystic kidney disease (PKD) domain of AAVR that was not ordered in the AAV2 structure. Interactions of AAV5 with AAVR are analyzed in detail, and the implications for AAV2 binding are explored through molecular modeling. Moreover, we find that binding sites for the antibodies ADK5a, ADK5b, and 3C5 on AAV5 overlap with the binding site of AAVR. These insights provide a structural foundation for development of gene therapy agents to better evade immune neutralization without disrupting cellular entry.
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http://dx.doi.org/10.3390/v12111326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698955PMC
November 2020

Cutaneous leishmaniasis successfully treated with miltefosine.

Cutis 2020 Oct;106(4):206-209

Department of Dermatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.

Leishmaniasis is a neglected tropical disease with notable worldwide burden and increasing prevalence in the United States due to globalization. We describe 2 cases of cutaneous leishmaniasis in New England, United States, both caused by the New World subgenus Viannia, in adults returning from Central America. Both patients underutilized preventive measures against bites from phlebotomine sand flies while abroad. They were successfully treated with oral miltefosine, which was well tolerated. Avoidance of vector transmission is the most important preventive measure. Prompt identification and treatment of cutaneous leishmaniasis caused by species with potential for mucocutaneous spread are key to limiting morbidity and mortality. This responsibility should be shared among medical specialties, including dermatologists. Partnering with the Centers for Disease Control and Prevention (CDC) is critical for timely diagnosis and thus treatment. Miltefosine should be considered a first-line agent for cutaneous leishmaniasis given its efficacy, tolerability, availability, and ease of administration. Ondansetron can be prescribed concurrently.
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http://dx.doi.org/10.12788/cutis.0086DOI Listing
October 2020

Laboratory biomarkers associated with COVID-19 severity and management.

Clin Immunol 2020 12 22;221:108614. Epub 2020 Oct 22.

Neuroimmunology and CSF laboratory, University College London Hospitals NHS Trust National Hospital of Neurology and Neurosurgery, Queen Square, London, UK.

The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome (ARDS), multi-organ failure and death. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokines implicated in COVID-19 for their potential application as biomarkers of disease severity, respiratory failure and need of higher-level care. From analysis of 203 samples, CRP, IL-6, IL-10 and LDH were most strongly correlated with the WHO ordinal scale of illness severity, the fraction of inspired oxygen delivery, radiological evidence of ARDS and level of respiratory support (p ≤ 0.001). IL-6 levels of ≥3.27 pg/ml provide a sensitivity of 0.87 and specificity of 0.64 for a requirement of ventilation, and a CRP of ≥37 mg/l of 0.91 and 0.66. Reliable stratification of high-risk cases has significant implications on patient triage, resource management and potentially the initiation of novel therapies in severe patients.
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http://dx.doi.org/10.1016/j.clim.2020.108614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581344PMC
December 2020

Bos d 11 in baked milk poses a risk for adverse reactions in milk-allergic patients.

Clin Exp Allergy 2021 Jan 15;51(1):132-140. Epub 2020 Nov 15.

Indoor Biotechnologies Inc, Charlottesville, VA, USA.

Background: Patients are commonly challenged with foods containing baked milk, for example muffins, yet little is known about the specific allergen content of muffins used in milk challenges or of the effect that baking has on allergenicity.

Objective: Our objective was to compare the levels of major milk allergens in uncooked and baked muffins using monoclonal immunoassays and IgE antibody binding before and after baking.

Methods: Uncooked and baked muffins were prepared using recipes from Mount Sinai and Imperial College. Allergen levels were compared by ELISA for Bos d 5 (β-lactoglobulin) and Bos d 11 (β-casein). IgE reactivity was assessed using sera from milk-sensitized donors in direct binding and inhibition ELISA.

Results: Bos d 5 was reduced from 680 µg/g in uncooked muffin mix to 0.17 µg/g in baked muffins, representing a >99% decrease after baking. Conversely, Bos d 11 levels in baked muffin remained high and only decreased by 30% from a mean of 4249 µg/g in uncooked muffin mix to 2961 µg/g when baked (~181 mg Bos d 11 per muffin). Baked muffins retained ~70% of the IgE binding to uncooked muffin mix. Baked muffin extract inhibited IgE binding to uncooked muffin mix by up to 80%, demonstrating retention of in vitro IgE reactivity.

Conclusions And Clinical Relevance: High levels of Bos d 11 in baked muffins pose a risk for adverse reactions, especially in patients who have high anti-casein IgE antibodies.
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http://dx.doi.org/10.1111/cea.13774DOI Listing
January 2021

Association of depression and resilience with fertility quality of life among patients presenting to the infertility centre for treatment in Karachi, Pakistan.

BMC Public Health 2020 Oct 23;20(1):1607. Epub 2020 Oct 23.

Department of Psychiatry, Aga Khan University, Karachi, Pakistan.

Background: In Pakistan there is a dire need to explore the quality of life in infertile males and females and its undesirable psychological outcomes. This, study aimed to compare the quality of life (QoL) of males and females visiting an infertility centre for treatment and to assess its association with resilience, depression, and other socio-demographic factors.

Methods: An Analytical Cross-Sectional study was conducted amongst infertile males and females at the Australian Concept Infertility Medical Centre (ACIMC), Karachi, Pakistan. The non-probability (purposive) sampling strategy was used to recruit the participants. The sample size was 668. Data was analysed using STATA version 12. FertiQoL tool, Beck II Depression Inventory Tool and Resilience Scale 14 (RS-14) were used for assessing the quality of life, depression and resilience respectively of infertile patients.

Results: Total 668 infertile patients, 334 males and 334 females participated in the study. The mean age was 35.53 ± 6.72, among males, and 30.87 ± 6.12 among females. The mean resilience scores were significantly higher among males, (77.64 ± 8.56), as compared to females (76.19 ± 8.69) (95% CI; - 2.757, - 0.1347). However, a significantly higher proportion of females were depressed (13.8%) as compared to males (6%). The mean QoL scores for the general health domain, emotional domain, mind and body domain, and relational domain, and the total QoL were significantly higher in males as compared to females (p value< 0.001); however, QoL for the social domain was not significantly different in both the groups. On multivariable linear regression resilience and depression among males had a significant association with QoL, after adjusting for the covariates educational status, monthly income, and number of friends. Similar association was observed among females after adjusting for the covariate monthly income only.

Conclusion: Fertility related QoL of men and women has a significant association with no formal education, number of friends, income, depression and resilience. Therefore, health care professionals in the field of infertility must be adequately trained to respond to the needs of individuals going through these psychological problems.
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http://dx.doi.org/10.1186/s12889-020-09706-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585180PMC
October 2020

Adeno-Associated Virus (AAV-DJ)-Cryo-EM Structure at 1.56 Å Resolution.

Viruses 2020 10 20;12(10). Epub 2020 Oct 20.

Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.

Adeno-associated virus is the leading viral vector for gene therapy. AAV-DJ is a recombinant variant developed for tropism to the liver. The AAV-DJ structure has been determined to 1.56 Å resolution through cryo-electron microscopy (cryo-EM). Only apoferritin is reported in preprints at 1.6 Å or higher resolution, and AAV-DJ nearly matches the highest resolutions ever attained through X-ray diffraction of virus crystals. However, cryo-EM has the advantage that most of the hydrogens are clear, improving the accuracy of atomic refinement, and removing ambiguity in hydrogen bond identification. Outside of secondary structures where hydrogen bonding was predictable a priori, the networks of hydrogen bonds coming from direct observation of hydrogens and acceptor atoms are quite different from those inferred even at 2.8 Å resolution. The implications for understanding viral assembly mean that cryo-EM will likely become the favored approach for high resolution structural virology.
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http://dx.doi.org/10.3390/v12101194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589773PMC
October 2020

Beyond cardiovascular medicine: potential future uses of icosapent ethyl.

Eur Heart J Suppl 2020 Oct 6;22(Suppl J):J54-J64. Epub 2020 Oct 6.

CGH Medical Center, 101 East Miller Road, Sterling, IL 61081, USA.

The REDUCE-IT trial demonstrated that icosapent ethyl, an ethyl ester of eicosapentaenoic acid (EPA), reduced cardiovascular events in an at-risk population by a substantial degree. While the cardiovascular protective properties of this compound are now proven, several other potential uses are being actively explored in clinical studies. These areas of investigation include cancer, inflammatory bowel disease, infections, Alzheimer's disease, dementia, and depression. The next decade promises to deepen our understanding of the beneficial effects that EPA may offer beyond cardiovascular risk reduction.
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http://dx.doi.org/10.1093/eurheartj/suaa119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537800PMC
October 2020

Efficacy and safety of icosapent ethyl in hypertriglyceridaemia: a recap.

Eur Heart J Suppl 2020 Oct 6;22(Suppl J):J21-J33. Epub 2020 Oct 6.

Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, Herlev, Denmark.

Although low-density lipoprotein cholesterol lowering is effective in atherosclerotic cardiovascular disease (ASCVD) prevention, considerable 'lipid-associated' residual risk remains, particularly in patients with mild-to-moderate hypertriglyceridaemia (2-10 mmol/L; 176-880 mg/dL). Triglyceride (TG)-rich lipoproteins carry both TGs and cholesterol (remnant-cholesterol). At TG levels >5 mmol/L (440 mg/dL) vs. <1 mmol/L (88 mg/dL) or remnant-cholesterol >2.3 mmol/L (89 mg/dL) vs. <0.5 mmol/L (19 mg/dL), risk is ∼1.5-fold elevated for aortic stenosis, 2-fold for all-cause mortality, 3-fold for ischaemic stroke, 5-fold for myocardial infarction (MI), and 10-fold for acute pancreatitis. Furthermore, Mendelian randomization studies indicate that elevated TG-rich lipoproteins are causally related to increased risk of ASCVD and even all-cause mortality. While genetic and epidemiological data strongly indicate that TG-rich lipoproteins are causally linked to ASCVD, intervention data are ambiguous. Fibrates, niacin and low-dose omega-3 fatty acids have all been used in outcome trials, but have failed to demonstrate clear benefit in combination with statins. Whether the lack of additional benefit relates to methodological issues or true failure is indeterminate. Importantly, a recent intervention trial evaluating a high dose of eicosapentaenoic-acid showed clear benefit. Thus, REDUCE-IT evaluated the effect of icosapent ethyl (4 g/day) on cardiovascular outcomes in 8179 high-risk patients with moderate TG elevation on statin therapy. Over a median duration of 4.9 years, the relative risk for the primary endpoint (composite of cardiovascular death, non-fatal MI, non-fatal stroke, coronary revascularization, or unstable angina) was reduced by 25% (absolute risk 17.2% vs. 22.0%;  < 0.0001; number needed to treat 21). High-dose icosapent ethyl intervention therefore confers substantial cardiovascular benefit in high-risk patients with moderate hypertriglyceridaemia on statin therapy.
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http://dx.doi.org/10.1093/eurheartj/suaa116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537801PMC
October 2020

Innovative breeding technologies in lettuce for improved post-harvest quality.

Postharvest Biol Technol 2020 Oct;168:111266

Department of Plant Sciences, University of California, Davis, 95616, USA.

Societal awareness of healthy eating is increasing alongside the market for processed bagged salads, which remain as one of the strongest growing food sectors internationally, including most recently from indoor growing systems. Lettuce represents a significant proportion of this ready-to-eat salad market. However, such products typically have a short shelf life, with decay of post-harvest quality occurring through complex biochemical and physiological changes in leaves and resulting in spoilage, food waste and risks to health. We review the functional and quantitative genetic understanding of lettuce post-harvest quality, revealing that few findings have translated into improved cultivar development. We identify (i) phytonutrient status (for enhanced antioxidant and vitamin status, aroma and flavour) (ii) leaf biophysical, cell wall and water relations traits (for longer shelf life) (iii) leaf surface traits (for enhanced food safety and reduced spoilage) and (iv) chlorophyll, other pigments and developmental senescence traits (for appearance and colour), as key targets for future post-harvest breeding. Lettuce is well-placed for rapid future exploitation to address postharvest quality traits with extensive genomic resources including the recent release of the lettuce genome and the development of innovative breeding technologies. Although technologies such as CRISPR/Cas genome editing are paving the way for accelerated crop improvement, other equally important resources available for lettuce include extensive germplasm collections, bi-parental mapping and wide populations with genotyping for genomic selection strategies and extensive multiomic datasets for candidate gene discovery. We discuss current progress towards post-harvest quality breeding for lettuce and how such resources may be utilised for future crop improvement.
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http://dx.doi.org/10.1016/j.postharvbio.2020.111266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397847PMC
October 2020

Duality of roles and the provision of high-quality end-of-life care in the intensive care.

J Crit Care 2020 Sep 25. Epub 2020 Sep 25.

Australian National University, Medical School, Canberra, Australia; University of Canberra, Faculty of Health, Canberra, Australia; Canberra Hospital, Canberra, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.jcrc.2020.09.023DOI Listing
September 2020