Publications by authors named "Grace Lee"

626 Publications

Do Not Stop Anti-TNF Medications in Children With IBD When They Are Working.

Inflamm Bowel Dis 2021 Apr 9. Epub 2021 Apr 9.

Division of Pediatric Gastroenterology, C.S. Mott Children's Hospital, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.

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http://dx.doi.org/10.1093/ibd/izab047DOI Listing
April 2021

Naloxone-induced analgesia mediated by central kappa opioid system in chronic inflammatory pain.

Brain Res 2021 Mar 23;1762:147445. Epub 2021 Mar 23.

Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea; Dental Research Institute and Department of Neurobiology & Physiology, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address:

Opioids, which are widely used for the treatment of chronic pain, have an analgesic effect by mainly activating mu-opioid receptor (MOR). Paradoxically, a high dose of naloxone, non-selective opioid receptor antagonist, is also known to induce analgesia, but the underlying mechanism remains unclear. Since kappa-opioid receptor (KOR) and dynorphin (KOR ligand) have been implicated in the naloxone-induced analgesia, we aimed to elucidate its mechanism by focusing on the kappa-opioid system in the brain under inflammatory pain condition. Systemic administration of naloxone (10 mg/kg, i.p.) decreased spontaneous pain behaviors only in complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model but not in the formalin-induced acute pain model. Immunohistochemistry analysis in the CFA model revealed both a significant decrease in MOR expression and an increase in prodynorphin density in the central nucleus of theamygdala (CeA) and nucleus accumbens (NAc) but not in other brain areas. Systemic administration of KOR antagonist (norbinaltorphimine, nor-BNI 10 mg/kg) also decreased spontaneous pain behaviors in the CFA model. Furthermore, microinjection of both naloxone and nor-BNI into NAc and CeA significantly reduced spontaneous chronic pain behavior. Taken together, our results suggest that naloxone-induced analgesia may be mediated by blocking facilitated kappa-opioid systems in the NAc and CeA.
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http://dx.doi.org/10.1016/j.brainres.2021.147445DOI Listing
March 2021

Pruritus assessment tools for 6 to 7-year-old children: KidsItchyQoL and ItchyQuant.

Pediatr Dermatol 2021 Mar 19. Epub 2021 Mar 19.

Department of Dermatology, Duke School of Medicine, Durham, NC, USA.

Background/objectives: Measures of pruritus severity and quality of life (QoL) are necessary for the development of therapeutics for children with chronic pruritus. In children, questionnaires need to be developed for specific age groups given the differences in cognitive levels. In this study, we aimed to develop tools to assess QoL and pruritus severity in children 6 to 7-years-old with chronic pruritus.

Methods: Based on open interviews with children, we developed a cartoon-annotated QoL instrument, KidsItchyQoL, and validated an existing pruritus severity instrument, ItchyQuant, that measures pruritus impact and severity for the preceding week. Both instruments were administered to 100 children aged 6-7 years with chronic pruritus. The data were analyzed for reliability, reproducibility, construct validity, and responsiveness.

Results: We found the 14-item KidsItchyQoL to be reliable (Cronbach's α = 0.846) and reproducible (intraclass correlation coefficient (ICC) = 0.66) as was the ItchyQuant (ICC = 0.47). With respect to construct validity, examination of eigenvalues of the inter-item polychoric correlation matrix suggested three dominant factors. A subsequent confirmatory factor analysis suggested that a 3-dimensional simple structure model with correlated factors provided a reasonable data representation. The responsiveness of KidsItchyQoL and ItchyQuant (P = .005, GLM procedure) were demonstrated with scores changing as expected with the self-reported change of itch severity.

Conclusions: These results demonstrate promise for a new set of reliable research tools to assess QoL and pruritus severity in children 6 to 7 years of age.
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http://dx.doi.org/10.1111/pde.14563DOI Listing
March 2021

Evaluation of YouTube videos as a patient education source for novel surgical techniques in thyroid surgery.

Gland Surg 2021 Feb;10(2):697-705

Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA.

Background: Patients and physicians are increasingly utilizing online video sharing sites such as YouTube for obtaining and disseminating health-related information in multimedia format; however, due to its free, open-access platform, YouTube videos fall short in providing validated, up-to-date medical information, and may even convey unintended messages to patients who are seeking additional information on surgeries. We evaluated the relevance, reliability, and quality of YouTube videos on novel surgical techniques in thyroid surgery.

Methods: The top 50 indexed YouTube videos for the queries, "robotic thyroid surgery" and "transoral thyroid surgery", were assessed by two independent reviewers for video quality and reliability for patient understanding. Videos were scored using Global Quality Score (GQS), a scale for video quality, and DISCERN Scoring, a questionnaire for reliability and quality measures of information presented.

Results: The mean ± standard deviation (SD) duration of the videos (n=50) was 8.1±3.7 minutes. Total views were 261,440 and the mean ± SD time since upload was 3.6±2.6 years. The median and interquartile range of video power index (VPI) was 1.9 (0.5-3.7), GQS was 3.0 (2.0-4.0), and DISCERN score was 2.8 (2.3-3.2). Most videos were uploaded by physicians (75.8%) and the highest number of videos (63.6%) uploaded were from the United States (US). Videos with higher quality and reliability scores were uploaded by academic professionals, and included videos of physicians who described procedural information, perioperative instructions, and possible postoperative complications (P<0.05). Adequate medical information on the procedure and discussion of complications in YouTube videos were independent predictors of advanced educational quality and reliability.

Conclusions: Clinical information on new surgical techniques such as transoral and robotic thyroid surgeries in YouTube videos scored low on quality and reliability as a source of patient education. Physicians should provide supplemental educational material online and offline to aid patient understanding of novel procedures.
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http://dx.doi.org/10.21037/gs-20-734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944056PMC
February 2021

Can Online Academic Integrity Instruction Affect University Students' Perceptions of and Engagement in Academic Dishonesty? Results From a Natural Experiment in New Zealand.

Front Psychol 2021 17;12:569133. Epub 2021 Feb 17.

The University of Auckland, Auckland, New Zealand.

The problem of academic dishonesty is as old as it is widespread - dating back millennia and perpetrated by the majority of students. Attempts to promote academic integrity, by comparison, are relatively new and rare - stretching back only a few hundred years and implemented by a small fraction of schools and universities. However, the past decade has seen an increase in efforts among universities to promote academic integrity among students, particularly through the use of online courses or tutorials. Previous research has found this type of instruction to be effective in increasing students' knowledge of academic integrity and reducing their engagement in academic dishonesty. The present study contributes to this literature with a natural experiment on the effects of the Academic Integrity Course (AIC) at The University of Auckland, which became mandatory for all students in 2015. In 2012, a convenience sample of students ( = 780) had been asked to complete a survey on their perceptions of the University's academic integrity polices and their engagement in several forms of academic dishonesty over the past year. In 2017, the same procedures and survey were used to collect data from second sample of students ( = 608). After establishing measurement invariance across the two samples on all latent factors, analysis of variance revealed mixed support for the studies hypotheses. Unexpectedly, students who completed the AIC (i.e., the 2017 sample) reported: (1) significantly lower (not higher) levels of understanding, support, and effectiveness with respect to the University's academic integrity policies; (2) statistically equivalent (not higher) levels of peer disapproval of academic misconduct, and; (3) significantly higher (not lower) levels of peer engagement in academic misconduct. However, results related to participants' personal engagement in academic misconduct offered partial support for hypotheses - those who completed the AIC reported significantly lower rates of engagement on three of the eight behaviors included in the study. The implications and limitations of these findings are discussed as well as possible future directions for research.
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http://dx.doi.org/10.3389/fpsyg.2021.569133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928306PMC
February 2021

Predominance of Non-carbapenemase Producing Carbapenem-Resistant Enterobacterales in South Texas.

Front Microbiol 2020 10;11:623574. Epub 2021 Feb 10.

The University of Texas at Austin, College of Pharmacy, Austin, TX, United States.

Background: Carbapenem-resistant Enterobacterales (CRE) pose a significant global public health threat. Resistance among CRE is particularly complex, owing to numerous possible resistance mechanisms and broad definitions. We aimed to characterize the clinical and molecular profiles of CRE in the South Texas region.

Materials And Methods: We compared the clinical, genotypic, and phenotypic profiles of carbapenemase producing Enterobacterales (CPE) with those of non-carbapenemase producers (NCPE) isolated from South Texas, United States between 2011 and 2019. Molecular characteristics and resistance mechanisms were analyzed using whole-genome sequences.

Results: The majority (59%) of the CRE isolates were NCPE while 41% of isolates harbored carbapenemases, predmonantly -type. The most common CPE was while majority of and were NCPE Among , the clonal group 307 has emerged as a predmoninant group and was associated with as many CRE infections as the previous common clonal group 258. Patients with NCPE compared to CPE infections were associated with higher antimicrobial exposure prior to culture collection (days of therapy, 795 vs. 242; < 0.001) and emergency department visits within past 90 days (22% vs. 4%; = 0.011). The all cause 30-day mortality was 21%.

Conclusions: This study highlights the diversity of resistance mechanisms underlying CRE in South Texas, with 59% not harboring a carbapenemase. Individuals with NCPE infections were more likely to have had prior antimicrobial therapy and emergency department visits compared to those with CPE. Identification and distinction of these mechanisms by rapid identification of species and carbapenemase would allow for optimal treatment and infection control efforts.
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http://dx.doi.org/10.3389/fmicb.2020.623574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902696PMC
February 2021

Prophylactic external beam radiation therapy for keloid prevention in thyroid surgery patients.

Gland Surg 2021 Jan;10(1):65-72

Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA.

Background: Poor cosmesis, secondary to keloid or hypertrophic scar, following thyroid surgery may cause considerable patient distress and be a significant challenge to treat. In this case series we examined the efficacy of prophylactic external beam radiation therapy (EBRT) for prevention of keloid formation in keloid-prone patients undergoing thyroid surgery. While much has been published about documenting the efficacy in reducing keloid formation following keloid excision, very little literature exists documenting prophylactic use related to surgeries with the goal of prevent keloid formation.

Methods: We retrospectively evaluated a series of ten patients, who underwent a prophylactic EBRT for keloid prevention after thyroid surgery between January 2013 and February 2019. Patient demographics, primary diagnosis, surgical procedure, EBRT dosage, and post-operative visit records were reviewed.

Results: All ten patients who received EBRT for keloid prophylaxis following a thyroid surgery were female. Half of the patients were African Americans, 40% Caucasians, and 10% Hispanic. The mean age was 46.40±15.63 years with BMI of 31.5±5.5 kg/m. Radiation was initiated within 6 hours of the surgery with an average radiation dose per session of 5.7±1.7 Gy. The total average EBRT dose delivered was 17.4±4.2 Gy. Mean follow-up period was 13 months post-thyroidectomy, with the longest follow-up at 23 months. One patient, who underwent a lateral neck dissection in addition to thyroid surgery, developed hypertrophic scar in less than 10% of her incision length. Nine other patients (90%) showed no post-surgical keloid nor hypertrophic scar formation and patients were satisfied with postsurgical cosmesis.

Conclusions: We examined the efficacy of prophylactic EBRT in keloid-prone patients undergoing thyroid surgery. Prophylactic EBRT following thyroid surgery is effective in achieving a satisfactory cosmetic outcome in patients at high risk for keloid formation.
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http://dx.doi.org/10.21037/gs-20-511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882325PMC
January 2021

Can HIT testing lose its radioactivity?

Authors:
Grace M Lee

Blood 2021 Feb;137(8):1008-1010

Duke University.

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http://dx.doi.org/10.1182/blood.2020008908DOI Listing
February 2021

Regulation of neonatal IgA production by the maternal microbiota.

Proc Natl Acad Sci U S A 2021 Mar;118(9)

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061;

Infants are prone to enteric infections due to an underdeveloped immune system. The maternal microbiota, through shaping the neonatal microbiota, helps establish a strong immune system in infants. We and others have observed the phenomenon of enhanced early neonatal immunoglobulin A (IgA) production in preweaning immunocompetent mice nursed by immunodeficient dams. Here, we show that this enhancement of IgA in neonates results from maternally derived microbiota. In addition, we have found that the neonatal IgA production can be induced by , which is enriched in the milk of immunodeficient dams. Moreover, we show that while the production of neonatal IgA is dependent on neonatal T cells, the immunodeficient maternal microbiota-mediated enhancement of neonatal IgA has a T cell-independent component. Indeed, this enhancement may be dependent on type 3 innate lymphoid cells in the neonatal small intestinal lamina propria. Interestingly, maternal microbiota-induced neonatal IgA does not cross-react with common enteric pathogens. Future investigations will determine the functional consequences of having this extra IgA.
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http://dx.doi.org/10.1073/pnas.2015691118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936341PMC
March 2021

Intra-Arterial Adjunctive Medications for Acute Ischemic Stroke During Mechanical Thrombectomy: A Meta-Analysis.

Stroke 2021 Apr 22;52(4):1192-1202. Epub 2021 Feb 22.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore (V.H.E.C., G.K.H.L., A.S.T.L., Y.-K.T., C.G., V.K.S., B.Y.Q.T., L.L.L.Y.).

Background And Purpose: In patients with acute ischemic stroke with large vessel occlusion, the role of intra-arterial adjunctive medications (IAMs), such as urokinase, tPA (tissue-type plasminogen activator), or glycoprotein IIb/IIIa inhibitors, during mechanical thrombectomy (MT) has not been clearly established. We aim to evaluate the efficacy and safety of concomitant or rescue IAM for acute ischemic stroke with large vessel occlusion patients undergoing MT.

Methods: We searched Medline, Embase, and Cochrane Stroke Group Trials Register databases from inception until March 13, 2020. We analyzed all studies with patients diagnosed with acute ischemic stroke with large vessel occlusion in the anterior or posterior circulation that provided data for the two treatment arms, (1) MT+IAM and (2) MT only, and also reported on at least one of the following efficacy outcomes, recanalization and 90-day modified Rankin Scale, or safety outcomes, symptomatic intracranial hemorrhage and 90-day mortality. Data were collated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results: Sixteen nonrandomized observational studies with a total of 4581 patients were analyzed. MT only was performed in 3233 (70.6%) patients, while 1348 (29.4%) patients were treated with both MT and IAM. As compared with patients treated with MT alone, patients treated with combination therapy (MT+IAM) had a higher likelihood of achieving good functional outcome (risk ratio, 1.13 [95% CI, 1.03-1.24]) and a lower risk of 90-day mortality (risk ratio, 0.82 [95% CI, 0.72-0.94]). There was no significant difference in successful recanalization (risk ratio, 1.02 [95% CI, 0.99-1.06]) and symptomatic intracranial hemorrhage between the two groups (risk ratio, 1.13 [95% CI, 0.87-1.46]).

Conclusions: In acute ischemic stroke with large vessel occlusion, the use of IAM together with MT may achieve better functional outcomes and lower mortality rates. Randomized controlled trials are warranted to establish the safety and efficacy of IAM as adjunctive treatment to MT.
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http://dx.doi.org/10.1161/STROKEAHA.120.031738DOI Listing
April 2021

Evolution of IgA nephropathy in Singapore over four decades and a comparison of two cohorts from the first and fourth decade.

Clin Nephrol 2021 Feb 19. Epub 2021 Feb 19.

Objective: In this study, we trace the changes in the clinical and histological pattern of IgA nephritis (IgAN) in Singapore as it has evolved over 4 decades and compare the clinical, demographic, histological, and renal outcome of patients with IgAN from the 1 decade and the 4 decade.

Materials And Methods: This is a retrospective study of all histologically proven IgAN diagnosed between 1976 and 2018. Clinical, laboratory, and histological characteristics between the 1 and the 4 decade, including treatment which could influence the disease progression and renal outcome of these two groups, were compared. We used the Oxford classification to compare the renal biopsy changes for these 2 decades as we were able to retrieve 125 renal biopsy tissues for the 1 cohort of IgAN studied in the 1970s for the comparative study.

Results: The commonest clinical presentation throughout the first 3 decades was asymptomatic hematuria and proteinuria (63, 52, and 49%, respectively). In the 4 decade, nephrotic syndrome (31%) was the commonest followed by asymptomatic hematuria and proteinuria (30%), hypertension (21%), and chronic renal failure (11%). The data showed that treatment can modify the Oxford MEST - Crescent scores. Renin-angiotensin system (RAS) blockers modified the S scores, immunosuppressants modified the T and C scores, and combination therapy with RAS blockers and immunosuppressants modified the E, S, and T scores.

Conclusion: The Oxford MEST classification offers a robust and expressive classification for early and late disease progression with respect to the development of end-stage renal disease (ESRD). E and S seem to be indices of continuing disease activity with progressive glomerulosclerosis, probably still amenable to therapy, but T was a predictive indicator for those destined for ESRD and no longer amenable to therapy.
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http://dx.doi.org/10.5414/CN110317DOI Listing
February 2021

A functional genomics screen identifying blood cell development genes in Drosophila by undergraduates participating in a course-based research experience.

Authors:
Cory J Evans John M Olson Bama Charan Mondal Pratyush Kandimalla Ariano Abbasi Mai M Abdusamad Osvaldo Acosta Julia A Ainsworth Haris M Akram Ralph B Albert Elitzander Alegria-Leal Kai Y Alexander Angelica C Ayala Nataliya S Balashova Rebecca M Barber Harmanjit Bassi Sean P Bennion Miriam Beyder Kush V Bhatt Chinmay Bhoot Aaron W Bradshaw Tierney G Brannigan Boyu Cao Yancey Y Cashell Timothy Chai Alex W Chan Carissa Chan Inho Chang Jonathan Chang Michael T Chang Patrick W Chang Stephen Chang Neel Chari Alexander J Chassiakos Iris E Chen Vivian K Chen Zheying Chen Marsha R Cheng Mimi Chiang Vivian Chiu Sharon Choi Jun Ho Chung Liset Contreras Edgar Corona Courtney J Cruz Renae L Cruz Jefferson M Dang Suhas P Dasari Justin R O De La Fuente Oscar M A Del Rio Emily R Dennis Petros S Dertsakyan Ipsita Dey Rachel S Distler Zhiqiao Dong Leah C Dorman Mark A Douglass Allysen B Ehresman Ivy H Fu Andrea Fua Sean M Full Arash Ghaffari-Rafi Asmar Abdul Ghani Bosco Giap Sonia Gill Zafar S Gill Nicholas J Gills Sindhuja Godavarthi Talin Golnazarian Raghav Goyal Ricardo Gray Alexander M Grunfeld Kelly M Gu Natalia C Gutierrez An N Ha Iman Hamid Ashley Hanson Celesti Hao Chongbin He Mengshi He Joshua P Hedtke Ysrael K Hernandez Hnin Hlaing Faith A Hobby Karen Hoi Ashley C Hope Sahra M Hosseinian Alice Hsu Jennifer Hsueh Eileen Hu Spencer S Hu Stephanie Huang Wilson Huang Melanie Huynh Carmen Javier Na Eun Jeon Sunjong Ji Jasmin Johal Amala John Lauren Johnson Saurin Kadakia Namrata Kakade Sarah Kamel Ravinder Kaur Jagteshwar S Khatra Jeffrey A Kho Caleb Kim Emily Jin-Kyung Kim Hee Jong Kim Hyun Wook Kim Jin Hee Kim Seong Ah Kim Woo Kyeom Kim Brian Kit Cindy La Jonathan Lai Vivian Lam Nguyen Khoi Le Chi Ju Lee Dana Lee Dong Yeon Lee James Lee Jason Lee Jessica Lee Ju-Yeon Lee Sharon Lee Terrence C Lee Victoria Lee Amber J Li Jialing Li Alexandra M Libro Irvin C Lien Mia Lim Jeffrey M Lin Connie Y Liu Steven C Liu Irene Louie Shijia W Lu William Y Luo Tiffany Luu Josef T Madrigal Yishan Mai Darron I Miya Mina Mohammadi Sayonika Mohanta Tebogo Mokwena Tonatiuh Montoya Dallas L Mould Mark R Murata Janani Muthaiya Seethim Naicker Mallory R Neebe Amy Ngo Duy Q Ngo Jamie A Ngo Anh T Nguyen Huy C X Nguyen Rina H Nguyen Thao T T Nguyen Vincent T Nguyen Kevin Nishida Seo-Kyung Oh Kristen M Omi Mary C Onglatco Guadalupe Ortega Almazan Jahzeel Paguntalan Maharshi Panchal Stephanie Pang Harin B Parikh Purvi D Patel Trisha H Patel Julia E Petersen Steven Pham Tien M Phan-Everson Megha Pokhriyal Davis W Popovich Adam T Quaal Karl Querubin Anabel Resendiz Nadezhda Riabkova Fred Rong Sarah Salarkia Nateli Sama Elaine Sang David A Sanville Emily R Schoen Zhouyang Shen Ken Siangchin Gabrielle Sibal Garuem Sin Jasmine Sjarif Christopher J Smith Annisa N Soeboer Cristian Sosa Derek Spitters Bryan Stender Chloe C Su Jenny Summapund Beatrice J Sun Christine Sutanto Jaime S Tan Nguon L Tan Parich Tangmatitam Cindy K Trac Conny Tran Daniel Tran Duy Tran Vina Tran Patrick A Truong Brandon L Tsai Pei-Hua Tsai C Kimberly Tsui Jackson K Uriu Sanan Venkatesh Maique Vo Nhat-Thi Vo Phuong Vo Timothy C Voros Yuan Wan Eric Wang Jeffrey Wang Michael K Wang Yuxuan Wang Siman Wei Matthew N Wilson Daniel Wong Elliott Wu Hanning Xing Jason P Xu Sahar Yaftaly Kimberly Yan Evan Yang Rebecca Yang Tony Yao Patricia Yeo Vivian Yip Puja Yogi Gloria Chin Young Maggie M Yung Alexander Zai Christine Zhang Xiao X Zhang Zijun Zhao Raymond Zhou Ziqi Zhou Mona Abutouk Brian Aguirre Chon Ao Alexis Baranoff Angad Beniwal Zijie Cai Ryan Chan Kenneth Chang Chien Umar Chaudhary Patrick Chin Praptee Chowdhury Jamlah Dalie Eric Y Du Alec Estrada Erwin Feng Monica Ghaly Rose Graf Eduardo Hernandez Kevin Herrera Vivien W Ho Kaitlyn Honeychurch Yurianna Hou Jo M Huang Momoko Ishii Nicholas James Gah-Eun Jang Daphne Jin Jesse Juarez Ayse Elif Kesaf Sat Kartar Khalsa Hannah Kim Jenna Kovsky Chak Lon Kuang Shraddha Kumar Gloria Lam Ceejay Lee Grace Lee Li Li Joshua Lin Josephine Liu Janice Ly Austin Ma Hannah Markovic Cristian Medina Jonelle Mungcal Bilguudei Naranbaatar Kayla Patel Lauren Petersen Amanda Phan Malcolm Phung Nadiyah Priasti Nancy Ruano Tanveer Salim Kristen Schnell Paras Shah Jinhua Shen Nathan Stutzman Alisa Sukhina Rayna Tian Andrea Vega-Loza Joyce Wang Jun Wang Rina Watanabe Brandon Wei Lillian Xie Jessica Ye Jeffrey Zhao Jill Zimmerman Colton Bracken Jason Capili Andrew Char Michel Chen Pingdi Huang Sena Ji Emily Kim Kenneth Kim Julie Ko Sean Louise G Laput Sam Law Sang Kuk Lee Olivia Lee David Lim Eric Lin Kyle Marik Josh Mytych Andie O'Laughlin Jensen Pak Claire Park Ruth Ryu Ashwin Shinde Manny Sosa Nick Waite Mane Williams Richard Wong Jocelyn Woo Jonathan Woo Vishaal Yepuri Dorothy Yim Dan Huynh Dinali Wijiewarnasurya Casey Shapiro Marc Levis-Fitzgerald Leslie Jaworski David Lopatto Ira E Clark Tracy Johnson Utpal Banerjee

G3 (Bethesda) 2021 Jan;11(1)

Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.
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http://dx.doi.org/10.1093/g3journal/jkaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022729PMC
January 2021

'Cost-benefit analysis comparing trough, two-level AUC, and Bayesian AUC dosing for vancomycin': authors' reply.

Clin Microbiol Infect 2021 Jan 30. Epub 2021 Jan 30.

Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Fetal & Neonatal Institute, Division of Neonatology, Children's Hospital Los Angeles, Los Angeles, CA, USA; Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cmi.2021.01.015DOI Listing
January 2021

Mispair-bound human MutS-MutL complex triggers DNA incisions and activates mismatch repair.

Cell Res 2021 Jan 28. Epub 2021 Jan 28.

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

DNA mismatch repair (MMR) relies on MutS and MutL ATPases for mismatch recognition and strand-specific nuclease recruitment to remove mispaired bases in daughter strands. However, whether the MutS-MutL complex coordinates MMR by ATP-dependent sliding on DNA or protein-protein interactions between the mismatch and strand discrimination signal is ambiguous. Using functional MMR assays and systems preventing proteins from sliding, we show that sliding of human MutSα is required not for MMR initiation, but for final mismatch removal. MutSα recruits MutLα to form a mismatch-bound complex, which initiates MMR by nicking the daughter strand 5' to the mismatch. Exonuclease 1 (Exo1) is then recruited to the nick and conducts 5' → 3' excision. ATP-dependent MutSα dissociation from the mismatch is necessary for Exo1 to remove the mispaired base when the excision reaches the mismatch. Therefore, our study has resolved a long-standing puzzle, and provided new insights into the mechanism of MMR initiation and mispair removal.
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http://dx.doi.org/10.1038/s41422-021-00468-yDOI Listing
January 2021

Implementation of clinical practice changes in the PICU: a qualitative study using and refining the iPARIHS framework.

Implement Sci 2021 Jan 28;16(1):15. Epub 2021 Jan 28.

George Warren Brown School of Social Work, Washington University in Saint Louis, Saint Louis, MO, USA.

Background: Like in many settings, implementation of evidence-based practices often fall short in pediatric intensive care units (PICU). Very few prior studies have applied implementation science frameworks to understand how best to improve practices in this unique environment. We used the relatively new integrated Promoting Action on Research Implementation in Health Services (iPARIHS) framework to assess practice improvement in the PICU and to explore the utility of the framework itself for that purpose.

Methods: We used the iPARIHS framework to guide development of a semi-structured interview tool to examine barriers, facilitators, and the process of change in the PICU. A framework approach to qualitative analysis, developed around iPARIHS constructs and subconstructs, helped identify patterns and themes in provider interviews. We assessed the utility of iPARIHS to inform PICU practice change.

Results: Fifty multi-professional providers working in 8 U.S. PICUs completed interviews. iPARIHS constructs shaped the development of a process model for change that consisted of phases that include planning, a decision to adopt change, implementation and facilitation, and sustainability; the PICU environment shaped each phase. Large, complex multi-professional teams, and high-stakes work at near-capacity impaired receptivity to change. While the unit leaders made decisions to pursue change, providers' willingness to accept change was based on the evidence for the change, and provider's experiences, beliefs, and capacity to integrate change into a demanding workflow. Limited analytic structures and resources frustrated attempts to monitor changes' impacts. Variable provider engagement, time allocated to work on changes, and limited collaboration impacted facilitation. iPARIHS constructs were useful in exploring implementation; however, we identified inter-relation of subconstructs, unique concepts not captured by the framework, and a need for subconstructs to further describe facilitation.

Conclusions: The PICU environment significantly shaped the implementation. The described process model for implementation may be useful to guide efforts to integrate changes and select implementation strategies. iPARIHS was adequate to identify barriers and facilitators of change; however, further elaboration of subconstructs for facilitation would be helpful to operationalize the framework.

Trial Registration: Not applicable, as no health care intervention was performed.
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http://dx.doi.org/10.1186/s13012-021-01080-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841901PMC
January 2021

Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases.

J Allergy Clin Immunol 2021 Jan 22. Epub 2021 Jan 22.

Veterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, TX 78229; Foundation for Advancing Veterans' Health Research, South Texas Veterans Health Care System, San Antonio, TX 78229; Department of Microbiology, Immunology & Molecular Genetics, UT Health San Antonio, San Antonio, TX 78229; Department of Medicine, UT Health San Antonio, San Antonio, TX 78229; Departments of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX 78229. Electronic address:

Background: Signifying the two-compartments/one-disease paradigm, allergic rhinoconjunctivitis (ARC) and asthma (AA) are prevalent, comorbid conditions triggered by environmental factors (e.g., house dust mites (HDMs)). However, despite the ubiquity of triggers, progression to severe ARC/AA is infrequent, suggesting either resistance or adaptation.

Objective: Determine if ARC/AA severity relates to maladaptive responses to disease triggers.

Methods: Adults with HDM-associated ARC were challenged repetitively with HDMs in an aeroallergen challenge chamber; associated mechanistic traits were identified.

Results: HDM challenges evoked maladaptive (persistently higher ARC symptoms), adaptive (progressive symptom reduction), and resilient (resistance to symptom induction) phenotypes. Symptom severity in the natural environment was an imprecise correlate of the phenotypes. Nasal airway traits, defined by low inflammation-effectual epithelial integrity, moderate inflammation-effectual epithelial integrity, and higher inflammation-ineffectual epithelial integrity, were hallmarks of the resilient, adaptive, and maladaptive evoked phenotypes, respectively. Highlighting a crosstalk mechanism, peripheral blood inflammatory tone calibrated these traits: ineffectual epithelial integrity correlated with CD8+ T-cells, whereas airway inflammation correlated with CD8+ T-cells and eosinophils. Hallmark peripheral blood maladaptive traits were increased NK and CD8+ cells, lower CD4+ MAIT cells, and deficiencies along the TLR-IRF-IFN antiviral pathway. Maladaptive traits tracking HDM-associated ARC also contributed to AA risk and severity models.

Conclusions: Repetitive challenges with HDMs revealed that maladaptation to disease triggers may underpin ARC/AA disease severity. A combinatorial therapeutic approach may involve reversal of loss-of-beneficial-function traits (ineffectual epithelial integrity, TLR-IRF-IFN deficiencies), mitigation of gain-of-adverse-function traits (inflammation), and blocking of a detrimental crosstalk between the peripheral blood and airway compartments.

Clinical Implications: The wide variation in allergic rhinoconjunctivitis disease severity may be underpinned by an imbalance in epithelial integrity and inflammation manifesting as maladaptation to disease triggers such as house dust mites.
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http://dx.doi.org/10.1016/j.jaci.2021.01.008DOI Listing
January 2021

Multidisciplinary management of a previously unreported presentation of severe aplasia cutis congenita.

Pediatr Dermatol 2021 Jan 22. Epub 2021 Jan 22.

Division of Plastic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.

Aplasia cutis congenita (ACC) is characterized by the complete or partial absence of skin at birth, with 85% of cases of ACC involving the scalp vertex. The etiology of ACC is unclear and appears to be multifactorial. We present the case of a 3-month-old boy who presented with a diagnosis of non-scalp ACC affecting approximately 80% of his total body surface area at birth. This case adds to the literature due to the patient's survival beyond the first day of life and his unique and severe distribution of defects, which led to respiratory compromise and required multidisciplinary management.
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http://dx.doi.org/10.1111/pde.14528DOI Listing
January 2021

Strategies for Management of Peritoneal Dialysis Patients in Singapore during COVID-19 Pandemic.

Ann Acad Med Singap 2020 12;49(12):1025-1028

Department of Renal Medicine, Singapore General Hospital, Singapore.

Peritoneal dialysis (PD) is the only well-established home-based dialysis therapy in Singapore. As it is a home-based modality, PD should be considered as a preferred mode of kidney replacement therapy (KRT) for patients with kidney failure during this COVID-19 pandemic as it avoids frequent visits to hospitals and/or satellite dialysis centres. The highly infectious nature of this virus has led to the implementation of the Disease Outbreak Response System Condition orange status in Singapore since early February 2020. This paper summarises the strategies for management of several aspects of PD in Singapore during this COVID-19 pandemic, including PD catheter insertion, PD training, home visit and assisted PD, outpatient PD clinic, inpatient management of PD patients with or without COVID-19 infection, PD as KRT for COVID-19 patients with acute kidney injury, management of common complications in PD (peritonitis and fluid overload), and management of PD inventory.
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December 2020

Effects of traditional Cantonese opera songs on Cantonese-speaking, community-dwelling older adults' cognitive and psychological function, well-being, and health.

Aging Ment Health 2021 Jan 19:1-13. Epub 2021 Jan 19.

CHG Heath Service Limited Hong Kong, Cheung Sha Wan, Kowloon, Hong Kong.

Experiencing multi-sensory cognitive stimulation through the enjoyment of Cantonese opera songs, with their lively rhythms, familiar folk tales, meaningful lyrics and pleasant scenarios, has the potential to increase neuroplasticity and prevent cognitive decline. This prospective pre- and post-test quasi-experimental randomised controlled trial design study aimed to explore the social benefits of older adults' active participation in practising Cantonese opera songs as compared with passive participation (as an audience) and a non-interventional control group on cognitive function psychological function, functional independence, well-being and health. By recruiting a group of older adults who were receiving day activities social service in Hong Kong. Thirty participants were randomly allocated to active participation in Cantonese opera (ACO). They participated in practising Cantonese opera songs. Thirty-four participants were assigned to passive participation in Cantonese opera (PCO). They received passive intervention by listening to and appreciating the opera songs as a social event. Thirty-one participants were used as a control group and received no similar training. (Results) ACO caused a positive change in cognitive function as compared to PCO and to no intervention, which implies that active learning and practise of opera songs benefits global cognitive function. The psychological function of the participants in the PCO group showed an elevated positive affect and a reduced negative affect. A statistically significant difference was noted in the time effect among the physical domains of health status, functional independence and well-being of participants who underwent Cantonese opera intervention.
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http://dx.doi.org/10.1080/13607863.2021.1871880DOI Listing
January 2021

Variable clinical features of patients with Fabry disease and outcome of enzyme replacement therapy.

Mol Genet Metab Rep 2021 Mar 31;26:100700. Epub 2020 Dec 31.

Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, Irvine, CA, USA.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme α-galactosidase A due to mutations in the gene. This leads to an accumulation of globotriaosylceramide (GL-3) in many tissues, which results in progressive damage to the kidneys, heart, and nervous system. We present the molecular and clinical characteristics and long-term outcomes of FD patients from a multidisciplinary clinic at the University of California, Irvine treated with agalsidase beta enzyme replacement therapy (ERT) for 2-20 years. This cohort comprised 24 adults (11 males, 13 females) and two male children (median age 45; range 10-68 years). Of the 26 patients in this cohort, 20 were on ERT (12 males, 8 females). We describe one novel variant not previously reported in the literature in a patient with features of 'classic' FD. The vast majority of patients in this cohort presented with symptoms of 'classic' FD including peripheral neuropathic pain, some form of cardiac involvement, angiokeratomas, corneal verticillata, hypohidrosis, tinnitus, and gastrointestinal symptoms, primarily abdominal pain. The majority of males had clinically evident renal involvement. An annual eGFR reduction of -1.88 mL/min/1.73 m/yr during the course of ERT was seen in this cohort. The most common renal presentation was proteinuria, and one individual required a renal transplant. Other common findings were pulmonary involvement, lymphedema, hearing loss, and significantly, three patients had strokes. Notably, there was a high prevalence of endocrine dysfunction and low bone mineral density, including several with osteoporosis. While enzyme replacement therapy (ERT) cleared plasma GL-3 in this cohort, there was limited improvement in renal function or health-related quality of life based on the patient-reported SF-36 Health Survey. Physical functioning significantly declined over the course of ERT treatment, which may be, in part, due to the late initiation of ERT in several patients. Further delineation of the phenotypic and genotypic spectrum in patients with FD and the long-term outcome of ERT will help improve management and treatment options for this disease.
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http://dx.doi.org/10.1016/j.ymgmr.2020.100700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788237PMC
March 2021

Recurrence of Clostridium Difficile and Cytomegalovirus Infections in Patients with Ulcerative Colitis Who Undergo Ileal Pouch-Anal Anastomosis.

Dig Dis Sci 2021 Jan 12. Epub 2021 Jan 12.

Division of Gastrointestinal and Oncologic Surgery, Northwestern Medicine, Arkes Family Pavilion, 676 North Saint Clair Street, Suite 650, Chicago, IL, 60611, USA.

Background: Patients with ulcerative colitis (UC) are at increased risk for infections such as Clostridium difficile and cytomegalovirus (CMV) colitis due to chronic immunosuppression. These patients often undergo multiple surgeries putting them at risk for recurrence of the infection. However, rates of recurrence in this setting and outcomes are not well understood.

Aim: The aim of this study is to determine rates of recurrence of C difficile and CMV infection in patients undergoing multistage UC surgeries and effects of antibiotic prophylaxis on outcomes.

Methods: All patients with UC who underwent IPAA between 2001 and 2017 (at two tertiary referral centers were identified. History of C. difficile or CMV colitis prior to any surgery and recurrence after IPAA was noted RESULTS: A total of 633 patients with UC who underwent IPAA were identified, of whom 8.1% patients had C. difficile and 2.7% had CMV infections. 9.8% of C. difficile and 5.9% of CMV patients recurred after IPAA. Rates of abdominal sepsis (14.7% vs. 12.7%), 90-day mortality (0% vs. 0.4%), pouchitis (36.8% vs. 45.0%), or return to stoma (7.4% vs. 5.4%) were similar between patients who did or did not have infections. In patients with C. difficile infection prior to first surgery, none of the patients who received prophylaxis had recurrent infection.

Conclusions: Rates of C. difficile and CMV infections remain high in patients undergoing surgery for UC, with substantial minority developing recurrent infection during subsequent surgical procedures. Antibiotic prophylaxis in patients with a history of C difficile may reduce the rate of recurrent infection.
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http://dx.doi.org/10.1007/s10620-020-06772-8DOI Listing
January 2021

Vegetarian diets, circulating miRNA expression and healthspan in subjects living in the Blue Zone.

Precis Clin Med 2020 Dec 23;3(4):245-259. Epub 2020 Oct 23.

Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.

A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan, but the underlying mechanisms for these observations are largely unknown. Particularly, it is not known whether a long-term vegetarian dietary pattern may affect the circulating miRNA expression in such a way as to modulate the healthspan. The Adventist Health Study-2 (AHS-2) cohort includes a large number of older adults who primarily follow vegetarian dietary patterns and reside in Loma Linda, California, one of five "Blue Zones" in the world in which a higher proportion of the population enjoys a longer than average lifespan. We performed miRNA-seq in 96 subjects selected from the AHS-2 cohort with different dietary patterns. We identified several differentially expressed miRNAs between vegetarians and non-vegetarians, which are involved in immune response and cytokine signaling, cell growth and proliferation as well as age-related diseases such as cardiovascular diseases and neurodegenerative diseases. Overall, our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs, which may be related in a beneficial manner to the healthspan. Further investigation is needed to validate these miRNAs as potential biomarkers for diet-modulated longevity in humans.
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http://dx.doi.org/10.1093/pcmedi/pbaa037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757436PMC
December 2020

The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Moderna COVID-19 Vaccine - United States, December 2020.

MMWR Morb Mortal Wkly Rep 2021 Jan 1;69(5152):1653-1656. Epub 2021 Jan 1.

On December 18, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Moderna COVID-19 (mRNA-1273) vaccine (ModernaTX, Inc; Cambridge, Massachusetts), a lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccine encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). This vaccine is the second COVID-19 vaccine authorized under an EUA for the prevention of COVID-19 in the United States (2). Vaccination with the Moderna COVID-19 vaccine consists of 2 doses (100 μg, 0.5 mL each) administered intramuscularly, 1 month (4 weeks) apart. On December 19, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Moderna COVID-19 vaccine in persons aged ≥18 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP employed the Evidence to Recommendation (EtR) Framework, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Use of all COVID-19 vaccines authorized under an EUA, including the Moderna COVID-19 vaccine, should be implemented in conjunction with ACIP's interim recommendations for allocating initial supplies of COVID-19 vaccines (3). The ACIP recommendation for the use of the Moderna COVID-19 vaccine under EUA is interim and will be updated as additional information becomes available.
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http://dx.doi.org/10.15585/mmwr.mm695152e1DOI Listing
January 2021

The Advisory Committee on Immunization Practices' Updated Interim Recommendation for Allocation of COVID-19 Vaccine - United States, December 2020.

MMWR Morb Mortal Wkly Rep 2021 Jan 1;69(5152):1657-1660. Epub 2021 Jan 1.

The first vaccines for prevention of coronavirus disease 2019 (COVID-19) in the United States were authorized for emergency use by the Food and Drug Administration (FDA) (1) and recommended by the Advisory Committee on Immunization Practices (ACIP) in December 2020.* However, demand for COVID-19 vaccines is expected to exceed supply during the first months of the national COVID-19 vaccination program. ACIP advises CDC on population groups and circumstances for vaccine use. On December 1, ACIP recommended that 1) health care personnel and 2) residents of long-term care facilities be offered COVID-19 vaccination first, in Phase 1a of the vaccination program (2). On December 20, 2020, ACIP recommended that in Phase 1b, vaccine should be offered to persons aged ≥75 years and frontline essential workers (non-health care workers), and that in Phase 1c, persons aged 65-74 years, persons aged 16-64 years with high-risk medical conditions, and essential workers not recommended for vaccination in Phase 1b should be offered vaccine.** These recommendations for phased allocation provide guidance for federal, state, and local jurisdictions while vaccine supply is limited. In its deliberations, ACIP considered scientific evidence regarding COVID-19 epidemiology, ethical principles, and vaccination program implementation considerations. ACIP's recommendations for COVID-19 vaccine allocation are interim and might be updated based on changes in conditions of FDA Emergency Use Authorization, FDA authorization for new COVID-19 vaccines, changes in vaccine supply, or changes in COVID-19 epidemiology.
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http://dx.doi.org/10.15585/mmwr.mm695152e2DOI Listing
January 2021

Usability Testing of a Sensor-Controlled Digital Game to Engage Older Adults with Heart Failure in Physical Activity and Weight Monitoring.

Appl Clin Inform 2020 10 30;11(5):873-881. Epub 2020 Dec 30.

School of Nursing, The University of Texas, Austin, Texas, United States.

Background: Poor self-management of heart failure (HF) has contributed to poor health outcomes. Sensor-controlled digital games (SCDGs) integrates data from behavior-tracking sensors to trigger progress, rewards, content, and positive feedback in a digital game to motivate real-time behaviors.

Objectives: To assess the usability of an SCDG prototype over a week of game-playing among 10 older adults with HF in their homes.

Methods: During initial play, participants' SCDG experiences were observed in their homes using a checklist based on the seven-item Serious Game User Evaluator (SeGUE) instrument. After a week of game-playing, participants completed a survey guided by the Intrinsic Motivation Inventory, to provide their perceptions of the SCDG's usability. Qualitative analysis via semistructured interview-derived themes on experiences playing the SCDG, perceptions regarding engaging with the SCDG, and any usability issues encountered.

Results: Ten HF participants (50% women and 50% White) played the SCDG for an average of 6 out of 7 days. Nine found the SCDG to be interesting, satisfying, and easy to play. The average step count over a week was 4,117 steps (range: 967-9,892). Average adherence with weight monitoring was 5.9 days in a week. Qualitative analysis yielded outcomes regarding attitudes toward SCDG, and barriers and facilitators that influenced participants' engagement with the SCDG.

Conclusion: To the best of the authors' knowledge, this usability and feasibility study is the first to report an SCDG designed to improve HF self-management behaviors of older adults in their homes. Future research should consider several issues, such as user profiles, prior game-playing experiences, and network conditions most suitable for connected health interventions for older adults living in the community.
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http://dx.doi.org/10.1055/s-0040-1721399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773503PMC
October 2020

The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine - United States, December 2020.

MMWR Morb Mortal Wkly Rep 2020 Dec 18;69(50):1922-1924. Epub 2020 Dec 18.

On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine (Pfizer, Inc; Philadelphia, Pennsylvania), a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 doses (30 μg, 0.3 mL each) administered intramuscularly, 3 weeks apart. On December 12, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP employed the Evidence to Recommendation (EtR) Framework, using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The recommendation for the Pfizer-BioNTech COVID-19 vaccine should be implemented in conjunction with ACIP's interim recommendation for allocating initial supplies of COVID-19 vaccines (2). The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine under EUA is interim and will be updated as additional information becomes available.
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http://dx.doi.org/10.15585/mmwr.mm6950e2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745957PMC
December 2020

N-Acetyl-L-cysteine Promotes Growth and Expansion of Single Circulating Tumor Cells by Mitigating Cellular Stress Responses.

Mol Cancer Res 2021 Mar 10;19(3):441-450. Epub 2020 Dec 10.

Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California.

Circulating tumor cells (CTC) can be isolated via a minimally invasive blood draw and are considered a "liquid biopsy" of their originating solid tumors. CTCs contain a small subset of metastatic precursors that can form metastases in secondary organs and provide a resource to identify mechanisms underlying metastasis-initiating properties. Despite technological advancements that allow for highly sensitive approaches of detection and isolation, CTCs are very rare and often present as single cells, posing an extreme challenge for expansion after isolation. Here, using previously established patient-derived CTC lines, we performed a small-molecule drug screen to identify compounds that can improve culture efficiency for single CTCs. We found that N-acetyl-L-cysteine (NAC) and other antioxidants can promote expansion of single CTCs, by reducing oxidative and other stress particularly at the initial stage of single-cell expansion. RNA-seq analysis of growing clones and nongrowing clones confirmed the effect by NAC, but also indicates that NAC-induced decrease in oxidative stress is insufficient for promoting proliferation of a subset of cells with predominant senescent features. Despite the challenge in expanding all CTCs, NAC treatment led to establishment of single CTC clones that have similar tumorigenic features. IMPLICATIONS: Through a small molecule screen and validation study, we found that NAC could improve the success of expansion of single CTCs by mitigating the initial stress, with the potential to facilitate the investigation of functional heterogeneity in CTCs.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925378PMC
March 2021