tbuckley/cabot-search huggingface dataset:
Whole-genome risk prediction of common diseases in human preimplantation embryos
Authors: Akash Kumar, Kate Im, Milena Banjevic, Pauline C. Ng, Tate Tunstall, Geronimo Garcia, Luisa Galhardo, Jiayi Sun, Oren N. Schaedel, Brynn Levy, Donna Hongo, Dusan Kijacic, Michelle Kiehl, Nam D. Tran, Peter C. Klatsky, Matthew Rabinowitz
Journal: Nature Medicine (2022)

Abstract Preimplantation genetic testing (PGT) of in-vitro-fertilized embryos has been proposed as a method to reduce transmission of common disease; however, more comprehensive embryo genetic assessment, combining the effects of common variants and rare variants, remains unavailable. Here, we used a combination of molecular and statistical techniques to reliably infer inherited genome sequence in 110 embryos and model susceptibility across 12 common conditions. We observed a genotype accuracy of 99.0–99.4% at sites relevant to polygenic risk scoring in cases from day-5 embryo biopsies and 97.2–99.1% in cases from day-3 embryo biopsies. Combining rare variants with polygenic risk score (PRS) magnifies predicted differences across sibling embryos. For example, in a couple with a pathogenic BRCA1 variant, we predicted a 15-fold difference in odds ratio (OR) across siblings when combining versus a 4.5-fold or 3-fold difference with BRCA1 or PRS alone. Our findings may inform the discussion of utility and implementation of genome-based PGT in clinical practice.
Association of Neonatal Hypoglycemia With Academic Performance in Mid-Childhood
Authors: Rajesh Shah, Darren W. T. Dai, Jane M. Alsweiler, Gavin T. L. Brown, J. Geoffrey Chase, Gregory D. Gamble, Deborah L. Harris, Peter Keegan, Samson Nivins, Trecia A. Wouldes, Benjamin Thompson, Jason Turuwhenua, Jane E. Harding, Christopher J. D. McKinlay, Heidi Feldman, William Hay, Robert Hess, Darrell Wilson, Jenny Rogers, Steven Miller, Eleanor Kennedy, Arijit Chakraborty, Jennifer Knopp, Tony Zhou, Jocelyn Ledger, Stephanie Macdonald, Alecia McNeill, Coila Bevan, Nataliia Burakevych, Robyn May, Safayet Hossin, Grace McKnight, Rashedul Hasan, Jessica Wilson
Journal: JAMA (2022)

Neonatal hypoglycemia is associated with increased risk of poor executive and visual-motor function, but implications for later learning are uncertain.To test the hypothesis that neonatal hypoglycemia is associated with educational performance at age 9 to 10 years.Prospective cohort study of moderate to late preterm and term infants born at risk of hypoglycemia. Blood and masked interstitial sensor glucose concentrations were measured for up to 7 days. Infants with hypoglycemic episodes (blood glucose concentration <47 mg/dL [2.6 mmol/L]) were treated to maintain a blood glucose concentration of at least 47 mg/dL. Six hundred fourteen infants were recruited at Waikato Hospital, Hamilton, New Zealand, in 2006-2010; 480 were assessed at age 9 to 10 years in 2016-2020.Hypoglycemia was defined as at least 1 hypoglycemic event, representing the sum of nonconcurrent hypoglycemic and interstitial episodes (sensor glucose concentration <47 mg/dL for ≥10 minutes) more than 20 minutes apart.The primary outcome was low educational achievement, defined as performing below or well below the normative curriculum level in standardized tests of reading comprehension or mathematics. There were 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.Of 587 eligible children (230 [48%] female), 480 (82%) were assessed at a mean age of 9.4 (SD, 0.3) years. Children who were and were not exposed to neonatal hypoglycemia did not significantly differ on rates of low educational achievement (138/304 [47%] vs 82/176 [48%], respectively; adjusted risk difference, -2% [95% CI, -11% to 8%]; adjusted relative risk, 0.95 [95% CI, 0.78-1.15]). Children who were exposed to neonatal hypoglycemia, compared with those not exposed, were significantly less likely to be rated by teachers as being below or well below the curriculum level for reading (68/281 [24%] vs 49/157 [31%], respectively; adjusted risk difference, -9% [95% CI, -17% to -1%]; adjusted relative risk, 0.72 [95% CI, 0.53-0.99; P = .04]). Groups were not significantly different for other secondary end points.Among participants at risk of neonatal hypoglycemia who were screened and treated if needed, exposure to neonatal hypoglycemia compared with no such exposure was not significantly associated with lower educational achievement in mid-childhood.
Improving the generalizability of infant psychological research: The ManyBabies model
Authors: Ingmar Visser, Christina Bergmann, Krista Byers-Heinlein, Rodrigo Dal Ben, Wlodzislaw Duch, Samuel Forbes, Laura Franchin, Michael C. Frank, Alessandra Geraci, J. Kiley Hamlin, Zsuzsa Kaldy, Louisa Kulke, Catherine Laverty, Casey Lew-Williams, Victoria Mateu, Julien Mayor, David Moreau, Iris Nomikou, Tobias Schuwerk, Elizabeth A. Simpson, Leher Singh, Melanie Soderstrom, Jessica Sullivan, Marion I. van den Heuvel, Gert Westermann, Yuki Yamada, Lorijn Zaadnoordijk, Martin Zettersten
Journal: Behavioral and Brain Sciences (2022)

Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.
PREDICTORS OF POSTOPERATIVE ATRIAL FIBRILLATION FOLLOWING CORONARY ARTERY BYPASS GRAFTING AMONG HISPANICS
Authors: Christian D. Avalos, Humberto Mochizuki, Carlos Ceron Castro, Khaled Sherif, Kristina Vatcheva, Jorge Alejandro Bernal, Monica M. Betancourt-Garcia, Cesar H. Gutierrez, R. Armour Forse, Y. Wady Aude
Journal: Journal of the American College of Cardiology (2022)
A pan‐genotype hepatitis C virus viral vector vaccine generates T cells and neutralizing antibodies in mice
Authors: Timothy Donnison, Joey McGregor, Senthil Chinnakannan, Claire Hutchings, Rob J. Center, Pantelis Poumbourios, Paul Klenerman, Heidi E. Drummer, Eleanor Barnes
Journal: Hepatology (2022)

A prophylactic vaccine targeting multiple HCV genotypes (gt) is urgently required to meet World Health Organization elimination targets. Neutralizing antibodies (nAbs) and CD4
Ixazomib with cyclophosphamide and dexamethasone in relapsed or refractory myeloma: MUKeight phase II randomised controlled trial results
Authors: Holger W. Auner, Sarah R. Brown, Katrina Walker, Jessica Kendall, Bryony Dawkins, David Meads, Gareth J. Morgan, Martin F. Kaiser, Mark Cook, Sadie Roberts, Christopher Parrish, Gordon Cook
Journal: Blood Cancer Journal (2022)

Abstract The all-oral combination of ixazomib, cyclophosphamide, and dexamethasone (ICD) is well tolerated and effective in newly diagnosed and relapsed multiple myeloma (MM). We carried out MUKeight, a randomised, controlled, open, parallel group, multi-centre phase II trial in patients with relapsed MM after prior treatment with thalidomide, lenalidomide, and a proteasome inhibitor (ISRCTN58227268), with the primary objective to test whether ICD has improved clinical activity compared to cyclophosphamide and dexamethasone (CD) in terms of progression-free survival (PFS). Between January 2016 and December 2018, 112 participants were randomised between ICD ( n = 58) and CD ( n = 54) in 33 UK centres. Patients had a median age of 70 years and had received a median of four prior lines of therapy. 74% were classed as frail. Median PFS in the ICD arm was 5.6 months, compared to 6.7 months with CD (hazard ratio (HR) = 1.21, 80% CI 0.9–1.6, p = 0.3634). Response rates and overall survival were not significantly different between ICD and CD. Dose modifications or omissions, and serious adverse events (SAEs), occurred more often in the ICD arm. In summary, the addition of ixazomib to cyclophosphamide and dexamethasone did not improve outcomes in the comparatively frail patients enroled in the MUKeight trial.
Heme Oxygenase-1 targeting exosomes for temozolomide resistant glioblastoma synergistic therapy
Authors: Fawad Ur Rehman, Yang Liu, Qingshan Yang, Haoying Yang, Runhan Liu, Dongya Zhang, Pir Muhammad, Yanjie Liu, Sumaira Hanif, Muhammad Ismail, Meng Zheng, Bingyang Shi
Journal: Journal of Controlled Release (2022)
IMPACT OF BASELINE LV VOLUME ON LV REVERSE REMODELING AFTER CRT
Authors: Xavier Galloo, Jan Stassen, Kensuke Hirasawa, Surenjav Chimed, Bernard Cosyns, Nina Ajmone Marsan, Victoria Delgado, Pieter van der Bijl, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2022)
TRENDS IN EPIDEMIOLOGY, CLINICAL CHARACTERISTICS, AND OUTCOMES OF INFECTIVE ENDOCARDITIS: A 16-YEAR NATIONWIDE COHORT STUDY
Authors: William Kim, Iksung Cho, Seonhwa Lee, Kyu-Yong Ko, Dae-Young Kim, Ji Won Seo, Chi Young Shim, Geu-Ru Hong, Jong-Won Ha
Journal: Journal of the American College of Cardiology (2022)
CLO22-073: Familial Nevoid Basal Cell Carcinoma Syndrome (NBCCS) Associated to Novel PTCH1 Mutation c.1067 + 2T&gt;C of Paternal Origin in Somatic Mosaicism With Marked Phenotypic Variation in the Children
Authors: Enrique Nogueira, Concepción Lobo, Carmen Garma, Génesis Vizuete, Beatriz del Olmo
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-073: Familial Nevoid Basal Cell Carcinoma Syndrome (NBCCS) Associated to Novel PTCH1 Mutation c.1067 + 2T>C of Paternal Origin in Somatic Mosaicism With Marked Phenotypic Variation in the Children" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Dasiglucagon Effectively Mitigates Postbariatric Postprandial Hypoglycemia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial
Authors: Casper K. Nielsen, Caroline C. Øhrstrøm, Urd L. Kielgast, Dorte L. Hansen, Bolette Hartmann, Jens J. Holst, Asger Lund, Tina Vilsbøll, Filip K. Knop
Journal: Diabetes Care (2022)

OBJECTIVE To investigate the efficacy and safety of dasiglucagon, a novel stable glucagon analog in a liquid formulation, in Roux-en-Y gastric bypass (RYGB)–operated individuals suffering from postbariatric hypoglycemia (PBH). RESEARCH DESIGN AND METHODS In a randomized, double-blind, placebo-controlled, crossover trial, 10 RYGB-operated participants with continuous glucose monitoring–verified PBH were randomly assigned to 3 trial days, each consisting of a 240-min standardized liquid mixed-meal test with the subcutaneous injection of placebo or 80 μg or 200 μg dasiglucagon. RESULTS Compared with placebo, treatment with both 80 and 200 μg dasiglucagon raised nadir plasma glucose (PG) (placebo: 3.0 ± 0.2 mmol/L [mean ± SEM]; 80 μg dasiglucagon: 3.9 ± 0.3 mmol/L, P = 0.002; 200 μg dasiglucagon: 4.5 ± 0.2 mmol/L, P = 0.0002) and reduced time in hypoglycemia (PG &amp;lt;3.9 mmol/L) by 70.0 min (P = 0.030 and P = 0.008). CONCLUSIONS Single-dose administration of dasiglucagon effectively mitigated postprandial hypoglycemia.
Fungal sensing enhances neutrophil metabolic fitness by regulating antifungal Glut1 activity
Authors: De-Dong Li, Chetan V Jawale, Chunsheng Zhou, Li Lin, Giraldina J Trevejo-Nunez, Syed A Rahman, Steven J Mullet, Jishnu Das, Stacy G Wendell, Greg M Delgoffe, Michail S Lionakis, Sarah L Gaffen, Partha S Biswas
Journal: Cell Host & Microbe (2022)
Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study
Authors: H.S. Rugo, J. O’Shaughnessy, F. Boyle, M. Toi, R. Broom, I. Blancas, M. Gumus, T. Yamashita, Y.-H. Im, P. Rastogi, F. Zagouri, C. Song, M. Campone, B. San Antonio, A. Shahir, M. Hulstijn, J. Brown, A. Zimmermann, R. Wei, S.R.D. Johnston, M. Reinisch, S.M. Tolaney
Journal: Annals of Oncology (2022)

In monarchE, abemaciclib plus endocrine therapy (ET) as adjuvant treatment of hormone receptor-positive, human epidermal growth factor 2-negative, high-risk, early breast cancer (EBC) demonstrated a clinically meaningful improvement in invasive disease-free survival versus ET alone. Detailed safety analyses conducted at a median follow-up of 27 months and key patient-reported outcomes (PROs) are presented.The safety population included all patients who received at least one dose of study treatment (n = 5591). Safety analyses included incidence, management, and outcomes of common and clinically relevant adverse events (AEs). Patient-reported health-related quality of life, ET symptoms, fatigue, and side-effect burden were assessed.The addition of abemaciclib to ET resulted in higher incidence of grade ≥3 AEs (49.7% versus 16.3% with ET alone), predominantly laboratory cytopenias [e.g. neutropenia (19.6%)] without clinical complications. Abemaciclib-treated patients experienced more serious AEs (15.2% versus 8.8%). Discontinuation of abemaciclib and/or ET due to AEs occurred in 18.5% of patients, mainly due to grade 1/2 AEs (66.8%). AEs were managed with comedications (e.g. antidiarrheals), abemaciclib dose holds (61.7%), and/or dose reductions (43.4%). Diarrhea was generally low grade (grade 1/2: 76%); grade 2/3 events were highest in the first month (20.5%), most were short-lived (≤7 days) and did not recur. Venous thromboembolic events (VTEs) were higher with abemaciclib + ET (2.5%) versus ET (0.6%); in the abemaciclib arm, increased VTE risk was observed with tamoxifen versus aromatase inhibitors (4.3% versus 1.8%). PROs were similar between arms, including being 'bothered by side-effects of treatment', except for diarrhea. At ≥3 months, most patients reporting diarrhea reported 'a little bit' or 'somewhat'.In patients with high-risk EBC, adjuvant abemaciclib + ET has an acceptable safety profile and tolerability is supported by PRO findings. Most AEs were reversible and manageable with comedications and/or dose modifications, consistent with the known abemaciclib toxicity profile.
Perception and attitudes towards COVID-19 vaccination among urban slum dwellers in Dhaka, Bangladesh
Authors: Wafa Alam, Farzana Manzoor, Nadia Farnaz, Bachera Aktar, Sabina Faiz Rashid
Journal: The Lancet Global Health (2022)

Vaccine hesitancy was identified as a major threat to global health by WHO in 2019. This hesitancy was also observed with COVID-19 vaccination rollout in many countries including Bangladesh, where it began on Feb 7, 2021. Reasons for this include lack of knowledge, misinformation, low trust in health systems, and so on. Vaccine hesitancy is context specific and varies across time, place, and socioeconomic groups. People living in urban slums should be prioritised for COVID-19 vaccination because they are more prone to COVID-19 infection due to their poor living conditions and inability to practice preventive measures. Therefore, we aimed to understand the perceptions and attitudes of urban slum dwellers in Dhaka, Bangladesh, towards COVID-19 vaccination through time.This qualitative study was done in three urban slums of Dhaka city, Bangladesh. In-depth telephone interviews were done with 36 adults (25 women and 11 men) from Oct 21, 2020 to Jan 12, 2021, using a semi-structured guideline. Participants were selected by use of snowballing and opportunistic sampling techniques. Follow-up interviews were done in April and August, 2021. We did thematic analysis on the collected data. Informed verbal consent was obtained from the participants, and ethical clearance was obtained from BRAC James P Grant School of Public Health (Dhaka, Bangladesh; 2019-034-IR).Before COVID-19 vaccine rollout, doubts, fears, and rumours about safety and effectiveness of the vaccine lead to hesitancy among many participants. With time, more people were willing to get COVID-19 vaccines when they found that many in their communities were getting vaccinated and that it was free of cost. Women knew more about the vaccine compared with men, due to the awareness sessions in courtyard meetings of non-governmental organisations (NGOs) attended by women. Trusted information sources were television news, community health workers, and government loudspeaker announcements. Youths (aged 18-24 years) in the slums were more interested in getting vaccinated as they had exposure to technology and social media where they learned about the benefits of vaccination, compared with people from older age groups. Besides structural inequities in the vaccination drive, such as the complicated online registration system, long queues at vaccination centres also meant many urban poor couldn't access COVID-19 vaccination as they worried about missing a day's work.This study highlighted the importance of using sources such as NGO workers and television news to debunk myths and disseminate COVID-19 vaccine information to ensure compliance with vaccination among urban slum dwellers. Community perceptions shape individual practices, which can help policy makers design effective communication and strategies aimed at people who are poor to improve COVID-19 vaccine uptake.GCRF UKRI funded ARISE Consortium.
Artificial intelligence-assisted staging in Barrett’s carcinoma
Authors: Mate Knabe, Lukas Welsch, Tobias Blasberg, Elisa Müller, Myriam Heilani, Christoph Bergen, Eva Herrmann, Andrea May
Journal: Endoscopy (2022)

Artificial intelligence (AI) is increasingly being used to detect neoplasia and interpret endoscopic images. The T stage of Barrett's carcinoma is a major criterion for subsequent treatment decisions. Although endoscopic ultrasound is still the standard for preoperative staging, its value is debatable. Novel tools are required to assist with staging, to optimize results. This study aimed to investigate the accuracy of T stage of Barrett's carcinoma by an AI system based on endoscopic images.1020 images (minimum one per patient, maximum three) from 577 patients with Barrett's adenocarcinoma were used for training and internal validation of a convolutional neural network. In all, 821 images were selected to train the model and 199 images were used for validation.AI recognized Barrett's mucosa without neoplasia with an accuracy of 85 % (95 %CI 82.7-87.1). Mucosal cancer was identified with a sensitivity of 72 % (95 %CI 67.5-76.4), specificity of 64 % (95 %CI 60.0-68.4), and accuracy of 68 % (95 %CI 64.6-70.7). The sensitivity, specificity, and accuracy for early Barrett's neoplasia < T1b sm2 were 57 % (95 %CI 51.8-61.0), 77 % (95 %CI 72.3-80.2), and 67 % (95 %CI 63.4-69.5), respectively. More advanced stages (T3/T4) were diagnosed correctly with a sensitivity of 71 % (95 %CI 65.1-76.7) and specificity of 73 % (95 %CI 69.7-76.5). The overall accuracy was 73 % (95 %CI 69.6-75.5).The AI system identified esophageal cancer with high accuracy, suggesting its potential to assist endoscopists in clinical decision making.
Suicide Risk and Lithium
Authors: Mirko Manchia, Gabriele Sani, Martin Alda
Journal: JAMA Psychiatry (2022)

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Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19
Authors: Tom Norris, Cameron Razieh, Thomas Yates, Francesco Zaccardi, Clare L. Gillies, Yogini V. Chudasama, Alex Rowlands, Melanie J. Davies, Gerry P. McCann, Amitava Banerjee, Annemarie B. Docherty, Peter J.M. Openshaw, J. Kenneth Baillie, Malcolm G. Semple, Claire A. Lawson, Kamlesh Khunti
Journal: Diabetes Care (2022)

OBJECTIVE To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. RESEARCH DESIGN AND METHODS In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. RESULTS Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8–8.7) (120.6 mg/dL [104.4–156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age &amp;lt;69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. CONCLUSIONS Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.
CAUSES AND PREDICTORS OF 90-DAY READMISSION AFTER PACEMAKER INSERTION FOR SICK SINUS SYNDROME: AN ANALYSIS OF THE NATIONAL READMISSIONS DATABASE
Authors: Ramtej Atluri, Omar Khdeir, Mukunthan Murthi, Sujitha Velagapudi, Bharosa Sharma, Hafeez Shaka
Journal: Journal of the American College of Cardiology (2022)
Field performance of three Ebola rapid diagnostic tests used during the 2018–20 outbreak in the eastern Democratic Republic of the Congo: a retrospective, multicentre observational study
Authors: Daniel Mukadi-Bamuleka, Junior Bulabula-Penge, Anja De Weggheleire, Bart K M Jacobs, François Edidi-Atani, Fabrice Mambu-Mbika, Placide Mbala-Kingebeni, Sheila Makiala-Mandanda, Martin Faye, Cheick T Diagne, Moussa M Diagne, Oumar Faye, Masahiro Kajihara, Ousmane Faye, Ayato Takada, Amadou A Sall, Jean-Jacques Muyembe-Tamfum, Johan van Griensven, Kevin K Ariën, Steve Ahuka-Mundeke
Journal: The Lancet Infectious Diseases (2022)
CLO22-085: A Dual-Center Retrospective Cohort Validation of the 2021 NCCN Risk Stratification for Cutaneous Squamous Cell Carcinoma
Authors: Jacqueline S. Stevens, Fadi Murad, Timothy D. Smile, Shlomo Koyfman, Abigail B. Waldman, Emily S. Ruiz, Chrysalyne D. Schmults
Journal: Journal of the National Comprehensive Cancer Network (2022)