tbuckley/cabot-search huggingface dataset:
Association of Plasma Tau With Mortality and Long-term Neurocognitive Impairment in Survivors of Pediatric Cerebral Malaria and Severe Malarial Anemia
Authors: Dibyadyuti Datta, Paul Bangirana, Robert O. Opoka, Andrea L. Conroy, Katrina Co, Caitlin Bond, Yi Zhao, Keisuke Kawata, Andrew J. Saykin, Chandy C. John
Journal: JAMA Network Open (2021)

Cerebral malaria (CM) and severe malarial anemia (SMA) are associated with persistent neurocognitive impairment (NCI) among children in Africa. Identifying blood biomarkers of acute brain injury that are associated with future NCI could allow early interventions to prevent or reduce NCI in survivors of severe malaria.To investigate whether acutely elevated tau levels are associated with future NCI in children after CM or SMA.This prospective cohort study was conducted at Mulago National Referral Hospital in Kampala, Uganda, from March 2008 to October 2015. Children aged 1.5 to 12 years with CM (n = 182) or SMA (n = 162) as well as community children (CC; n = 123) were enrolled in the study. Data analysis was conducted from January 2020 to May 2021.CM or SMA.Enrollment plasma tau levels were measured using single-molecule array detection technology. Overall cognition (primary) and attention and memory (secondary) z scores were measured at 1 week and 6, 12, and 24 months after discharge using tools validated in Ugandan children younger than 5 years or 5 years and older.A total of 467 children were enrolled. In the CM group, 75 (41%) were girls, and the mean (SD) age was 4.02 (1.92) years. In the SMA group, 59 (36%) were girls, and the mean (SD) age was 3.45 (1.60) years. In the CC group, 65 (53%) were girls, and the mean (SD) age was 3.94 (1.92) years. Elevated plasma tau levels (>95th percentile in CC group; >6.43 pg/mL) were observed in 100 children (55%) with CM and 69 children (43%) with SMA (P < .001). In children with CM who were younger than 5 years, elevated plasma tau levels were associated with increased mortality (odds ratio [OR], 3.06; 95% CI, 1.01-9.26; P = .048). In children with CM who were younger than 5 years at both CM episode and follow-up neurocognitive testing, plasma tau levels (log10 transformed) were associated with worse overall cognition scores over 24-month follow-up (β = -0.80; 95% CI, -1.32 to -0.27; P = .003). In children with CM who were younger than 5 years at CM episode and 5 years or older at follow-up neurocognitive testing, plasma tau was associated with worse scores in attention (β = -1.08; 95% CI, -1.79 to -0.38; P = .003) and working memory (β = -1.39; 95% CI, -2.18 to -0.60; P = .001).In this study, plasma tau, a marker of injury to neuronal axons, was elevated in children with CM or SMA and was associated with mortality and persistent NCI in children with CM younger than 5 years.
Alcohol consumption as a risk factor for oesophageal squamous cell carcinoma risk in sub-Saharan Africa
Authors: Violet Kayamba
Journal: The Lancet Global Health (2021)

Epidemiological studies from many parts of the world have reported alcohol consumption as a risk factor for oesophageal squamous cell carcinoma (ESCC) and that this relationship is dose-dependent,1 but evidence from Africa has been inconsistent.2 In sub-Saharan Africa, the burden of ESCC is substantially higher in the eastern regions than western regions,3 but reasons for this difference are yet to be established. There is evidence that the total adult consumption of alcohol per capita is higher in western Africa than eastern Africa, suggesting that alcohol consumption on its own is unlikely to be driving these observed differences in disease burden.
Epidemiological trends and trajectories of MAFLD-associated hepatocellular carcinoma 2002–2033: the ITA.LI.CA database
Authors: Alessandro Vitale, Gianluca Svegliati-Baroni, Alessio Ortolani, Monica Cucco, Giulio V Dalla Riva, Edoardo G Giannini, Fabio Piscaglia, Gianludovico Rapaccini, Mariella Di Marco, Eugenio Caturelli, Marco Zoli, Rodolfo Sacco, Giuseppe Cabibbo, Fabio Marra, Andrea Mega, Filomena Morisco, Antonio Gasbarrini, Francesco Giuseppe Foschi, Gabriele Missale, Alberto Masotto, Gerardo Nardone, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Filippo Oliveri, Filippo Pelizzaro, Rafael Ramirez Morales, Umberto Cillo, Franco Trevisani, Luca Miele, Giulio Marchesini, Fabio Farinati
Journal: Gut (2021)

Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort.We analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC.MAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002-2003, to 77.3% and 28.9% in 2018-2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006).The prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.
Errors in Results Section and Figure 2
Journal: JAMA Psychiatry (2021)

Psychiatry, 1 errors occurred in the text and Figure 2. In the PRS Analyses subsection of the Results section, the last 2 sentences of the last paragraph should have appeared as follows: "These results suggest that individuals with the higher PRSs for schizophrenia, bipolar disorder, anorexia nervosa, and autism spectrum disorder and the lower PRSs for ADHD preferentially moved from the rural environment to cities. Individuals with the higher PRSs for major depressive disorder were born and stayed in cities."In Figure 2E, the part label should have been shown as "Autism spectrum disorder."This article was corrected.
Characterization of novel CTNNB1 mutation in Craniopharyngioma by whole-genome sequencing
Authors: Juan He, Zhen Zeng, Yuelong Wang, Jiaojiao Deng, Xin Tang, Fujun Liu, Jianhan Huang, Hongxu Chen, Ruichao Liang, Xin Zan, Zhiyong Liu, Aiping Tong, Gang Guo, Jianguo Xu, Xiaofeng Zhu, Liangxue Zhou, Yong Peng
Journal: Molecular Cancer (2021)

Abstract Background Craniopharyngioma (CP) is rare histologically benign but clinically challenging tumor because of its intimate relationship with the critical structure in the central brain. CP can be divided into two major histologic subtypes: adamantinomatous-type CP (ACP) and papillary-type CP (PCP). Although some genetic aberrations for both categories have been revealed in previous studies, the complete spectrum of genetic changes of this tumor remains unknown. Methods In this study, we conducted whole genome sequencing (WGS) on twenty-six CPs including 16 ACPs and 10 PCPs together with their matched blood samples. Somatic variants (SNVs, InDels, SVs and CNVs) were identified and mutational signatures were characterized for each patient. We investigated the impact of a novel CTNNB1 mutant on its protein stability, ubiquitination and Wnt pathway activity. Cell proliferation ability of the CTNNB1 mutant in ACP primary cells was additionally analyzed by CCK8 and colony formation assays. Results We found that CPs had showed less complexity with fewer somatic mutations compared with malignant tumors. Moreover, mutations in CTNNB1 (68.75% of ACP) and BRAF V600E (70.00% of PCP) are mutually exclusive in ACP and PCP, consolidating that the driving roles of these two genes in ACP and PCP, respectively. A novel mutation in the exon 3 of CTNNB1 which compromised both a transversion and in-frame deletion was identified in ACP. This mutation was experimentally validated to confer β-catenin increased stability by inhibiting its ubiquitination, thus activating Wnt-signaling pathway and promoting cell proliferation. Conclusions Whole genome landscape for CP was revealed by WGS analysis, and a novel mutation in the exon 3 of CTNNB1 was identified. This novel mutation activates Wnt-signaling pathway through increasing the stability of β-catenin. Our findings provided us with more comprehensive insight into the spectrum of genetic alterations in CP.
Clinical manifestations and treatment outcomes of pyoderma gangrenosum following rituximab exposure: A systematic review
Authors: David Croitoru, Nikki Nathanielsz, Kyle Seigel, Rawaan Elsawi, Cathryn Sibbald, Afsaneh Alavi, Jon Zipursky, Vincent Piguet
Journal: Journal of the American Academy of Dermatology (2021)
6P Pembrolizumab plus chemotherapy vs chemotherapy in Asian patients with PD-L1 negative advanced NSCLC: Pooled analysis of KN021G, KN189 and KN407
Authors: Y. Cheng, J.C-H. Yang, I. Okamoto, L. Zhang, J. Hu, D. Wang, C. Hu, J. Zhou, L. Wu, L. Cao, J. Liu, H. Zhang, H. Sun, Z. Wang, H. Gao, Y. Yan, S. Xiao, J. Lin, M.C. Pietanza, T. Kurata
Journal: Annals of Oncology (2021)
Portal hypertensive biliopathy presenting as acute jaundice with suspected intrahepatic biliary strictures and stones
Authors: Simon Phillpotts, Tareq El Menabawey, Harry Martin, Michael Chapman
Journal: Endoscopy (2021)

A 58-year-old woman with liver cirrhosis, previously decompensation with ascites, presented with jaundice. Abdominal ultrasound identified a shrunken, cirrhotic liver with intrahepatic duct dilatation within the left liver lobe, gallbladder calculi, and a normal bile duct. Subsequent magnetic resonance cholangiopancreatography identified dilated left and right intrahepatic ducts containing several filling defects, with stricturing of the left main duct and a normal-caliber common bile duct ([Fig. 1]). Endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy was performed to assess the stricture and remove presumed intrahepatic stones.
Advisory Board and Contents
Authors: Alexander Stahn, Simone Kühn, M Landi, Elizabeth Buffalo, Brian Lucas, Loran Nordgren, Moritz Ingendahl, Tobias Vogel, Sascha Topolinski, Andromachi Tsouli, Ben Harvey, Shir Hofstetter, Yuxuan Cai, Maarten Van Der Smagt, Susan Te Pas, Serge Dumoulin, Louisa Bogaerts, Noam Siegelman, Morten Christiansen, Ram Frost, Martin Dahl, Mara Mather, Markus Werkle-Bergner, James Kragel, Joel Voss, Lindsey Drayton, Jessica Miles, Rolf Van Der Sanden, Patrick Scheffmann, Ralph Adolphs, Renee Baillargeon, Nick Chater, Peter Dayan, Stanislas Dehaene, Daniel Dennett, Yadin Dudai, Andreas Engel, Martha Farah, Angela Friederici, Okihide Hikosaka, Ray Jackendoff, Philip Johnson-Laird, Nancy Kanwisher, Christof Koch, Marta Kutas, Nikos Logothetis, James Mcclelland, Earl Miller, Elizabeth Phelps, Russell Poldrack, Marcus Raichle, Trevor Robbins, Anthony Wagner, Vincent Walsh
Journal: Trends in Cognitive Sciences (2021)
Toward noninvasive brain stimulation 2.0 in Alzheimer’s disease
Authors: Arianna Menardi, Simone Rossi, Giacomo Koch, Harald Hampel, Andrea Vergallo, Michael A. Nitsche, Yaakov Stern, Barbara Borroni, Stefano F. Cappa, Maria Cotelli, Giulio Ruffini, Georges El-Fakhri, Paolo M. Rossini, Brad Dickerson, Andrea Antal, Claudio Babiloni, Jean-Pascal Lefaucheur, Bruno Dubois, Gustavo Deco, Ulf Ziemann, Alvaro Pascual-Leone, Emiliano Santarnecchi
Journal: Ageing Research Reviews (2021)
Abstract 9450: Shockable Rhythm at Hospital Arrival as the Predictor of Favorable Neurological Outcome in Out-of-Hospital Cardiac Arrest Patients Receiving Extracorporeal Cardiopulmonary Resuscitation
Authors: Pei-I Su
Journal: Circulation (2021)

Introduction: For OHCA patients without ROSC under standard ALS, extracorporeal cardiopulmonary resuscitation (ECPR) was the only chance. However, ECPR was invasive and costed tremendous resources. This study aimed to analyze the predictor of favorable neurological outcome at hospital discharge (FO, cerebral performance category 1-2). Hypothesis: In OHCA patients receiving ECPR, shockable rhythm at hospital arrival could serve as predictor of FO. Method: This was a single center retrospective study which enrolled 126 OHCA patients receiving ECPR between January 2012 to December 2019. Primary outcome was FO at hospital discharge. Predictors of FO were assessed by multiple logistic regression. Patients with initial shockable rhythm were analyzed according to the cardiac rhythm at hospital arrival. Result: Among OHCA patients receiving ECPR, FO at hospital discharge was 21%. Certain variables were associated with FO: witnessed collapse (P=0.014), bystander CPR (P=0.05), shorter no flow time(P=0.008), and shockable rhythm at hospital arrival (78% vs. 49%;P=0.009). Initial shockable rhythm did not differ significantly (85% vs. 71% ;P=0.15). Multiple logistic regression showed that shockable rhythm at hospital arrival was the only predictor of FO (OR, 3.012; 95% CI, 1.06-8.53; P=0.038). Patients with initial shockable rhythm represented a heterogenous group. The group with shockable rhythm at hospital arrival had 30% of FO, which was significantly higher than 17% in PEA group, and 6% in asystole group (Graph 1). Patients who remained shockable had higher percentage of witnessed arrest, shorter arrest-hospital time, less metabolic disturbance, and hence higher percentage of FO. Conclusion: In OHCA patients receiving ECPR, shockable rhythm at hospital arrival could predict favorable neurological outcome at discharge more precisely than initial shockable rhythm. ECPR selection criteria should take the rhythm at hospital arrival into consideration.
Reply to Marc Furrer, Niranjan J. Sathianathen, and Nathan Lawrentschuk’s Letter to the Editor re: Pietro Piazza, Luca Sarchi, Stefano Puliatti, Carlo Andrea Bravi, Sophie Knipper, Alexandre Mottrie. The Unsolved Issue of Reporting of Late Complications in Urology. Eur Urol 2021;80:527–528
Authors: Pietro Piazza, Luca Sarchi, Stefano Puliatti, Alexandre Mottrie
Journal: European Urology (2021)
ERS/ATS technical standard on interpretive strategies for routine lung function tests
Authors: Sanja Stanojevic, David A. Kaminsky, Martin R. Miller, Bruce Thompson, Andrea Aliverti, Igor Barjaktarevic, Brendan G. Cooper, Bruce Culver, Eric Derom, Graham L. Hall, Teal S. Hallstrand, Joerg D. Leuppi, Neil MacIntyre, Meredith McCormack, Margaret Rosenfeld, Erik R. Swenson
Journal: European Respiratory Journal (2021)

Appropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, integrating knowledge of physiological determinants of test results into functional classifications and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society (ATS) and European Respiratory Society (ERS) jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standards for PFT interpretation.
Combinatorial immunotherapy induces tumor-infiltrating CD8<sup>+</sup>T cells with distinct functional, migratory, and stem-like properties
Authors: Natalija Van Braeckel-Budimir, Joseph Samuel Dolina, Jie Wei, Xiao Wang, Shih-Hsun Chen, Pamela Santiago, Guanghuan Tu, Luca Micci, Amir A Al-Khami, Sophia Pfister, Sripad Ram, Purnima Sundar, Graham Thomas, Hua Long, Wenjing Yang, Shobha Potluri, Shahram Salek-Ardakani
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Programmed death (ligand) 1 (PD-(L)1) blockade and OX40/4-1BB costimulation have been separately evaluated in the clinic to elicit potent antitumor T cell responses. The precise mechanisms underlying single agent activity are incompletely understood. It also remains unclear if combining individual therapies leads to synergism, elicits novel immune mechanisms, or invokes additive effects. Methods We performed high-dimensional flow cytometry and single-cell RNA sequencing-based immunoprofiling of murine tumor-infiltrating lymphocytes (TILs) isolated from hosts bearing B16 or MC38 syngeneic tumors. This baseline infiltrate was compared to TILs after treatment with either anti-PD-(L)1, anti-OX40, or anti-4-1BB as single agents or as double and triple combinatorial therapies. Fingolimod treatment and CXCR3 blockade were used to evaluate the contribution of intratumoral versus peripheral CD8 + T cells to therapeutic efficacy. Results We identified CD8 + T cell subtypes with distinct functional and migratory signatures highly predictive of tumor rejection upon treatment with single agent versus combination therapies. Rather than reinvigorating terminally exhausted CD8 + T cells, OX40/4-1BB agonism expanded a stem-like PD-1 lo KLRG-1 + Ki-67 + CD8 + T cell subpopulation, which PD-(L)1 blockade alone did not. However, PD-(L)1 blockade synergized with OX40/4-1BB costimulation by dramatically enhancing stem-like TIL presence via a CXCR3-dependent mechanism. Conclusions Our findings provide new mechanistic insights into the interplay between components of combinatorial immunotherapy, where agonism of select costimulatory pathways seeds a pool of stem-like CD8 + T cells more responsive to immune checkpoint blockade (ICB).
Fatal police violence by race and state in the USA, 1980–2019: a network meta-regression
Journal: The Lancet (2021)

The burden of fatal police violence is an urgent public health crisis in the USA. Mounting evidence shows that deaths at the hands of the police disproportionately impact people of certain races and ethnicities, pointing to systemic racism in policing. Recent high-profile killings by police in the USA have prompted calls for more extensive and public data reporting on police violence. This study examines the presence and extent of under-reporting of police violence in US Government-run vital registration data, offers a method for correcting under-reporting in these datasets, and presents revised estimates of deaths due to police violence in the USA.
Lenalidomide Versus Thalidomide or Bortezomib As Maintenance Regimens for Non-Transplant Patients with Multiple Myeloma: Multi-Center Real World Experience in China
Authors: Zhe Zhuang, Lei Shi, Ying Tian, Dongmei Zou, Ru Feng, Fei Dong, Yanping Ma, Hong Yu, Wei-wei Tian, Shuangjiao Liu, Liangming Ma, Rong Fu, Hongmei Jing, Hui Liu, Wanling Sun, Chen Wenming, Yin Wu, Li Bao, Junling Zhuang
Journal: Blood (2021)
Hepatology Highlights
Authors: Alyson Kaplan, Robert S. Brown, Adam Buckholz, Thuy‐Van P. Hang, Preeti A. Reshamwala, Jessica L. Maiers, Robert E. Schwartz, Wei Zhang, Shalil Khanal, Enis Kostallari, Adebowale O. Bamidele, Amani Lee, Enis Kostallari, Mati Ullah Dad Ullah, Daryl T.Y. Lau, Davide Povero, Nabeel Wahid, Russell Rosenblatt
Journal: Hepatology (2021)
Injuries in elite women’s ski jumping: a cohort study following three International Ski Federation (FIS) World Cup seasons from 2017–2018 to 2019–2020
Authors: Oleane Marthea Rebne Stenseth, Sindre Fløtlien Barli, R Kyle Martin, Lars Engebretsen
Journal: British Journal of Sports Medicine (2021)

To define incidence and injury patterns of International Ski Federation (FIS) World Cup (WC) women ski jumpers over three seasons.Ski jump athletes competing in the Women's FIS WC were recruited for prospective injury surveillance from 2017-2018 to 2019-2020. Team representatives recruited the athletes annually and prospectively recorded all injuries requiring medical attention. Retrospective end-of-season interviews corroborated injury surveillance. Medical doctors collected and processed the data. The 4-month competitive season was used to calculate the annual incidence of injuries per 100 athletes per season. Injury type, location, severity and aetiology were reported.Athletes from 19 nations were enrolled equalling 205 athlete-seasons. Mean age was 21.2 years (SD=3.8). Thirty-nine injury events resulted in 54 total injuries (26.3 injuries/100 athletes/season). Injuries were mostly acute (83%) and occurred on the ski jump hill (78%). The most common injury location was the knee (n=18, 33%). Crash landings were the most common cause of injury events (70%). Nearly half of the acute ski jump injury events occurred in snowy, windy or cloudy conditions (44%) and/or during telemark landings (46%), and most jumps (96%) were shorter than hill size. One third of the injuries were severe, and 78% of severe injuries involved the knee.Acute injury events occur relatively frequently in elite women ski jumpers, most resulting in time-loss from sport and a significant proportion involving serious knee injuries. Crash landing was the leading cause of injury. This baseline information can be used to guide and evaluate future efforts at injury prevention.
Diabetes and pre‐diabetes in patients with heart failure and preserved ejection fraction
Authors: Alice M. Jackson, Rasmus Rørth, Jiankang Liu, Søren Lund Kristensen, Inder S. Anand, Brian L. Claggett, John G.F. Cleland, Vijay K. Chopra, Akshay S. Desai, Junbo Ge, Jianjian Gong, Carolyn S.P. Lam, Martin P. Lefkowitz, Aldo P. Maggioni, Felipe Martinez, Milton Packer, Marc A. Pfeffer, Burkert Pieske, Margaret M. Redfield, Adel R. Rizkala, Jean L. Rouleau, Petar M. Seferović, Jasper Tromp, Dirk J. Van Veldhuisen, Mehmet B. Yilmaz, Faiez Zannad, Michael R. Zile, Lars Køber, Mark C. Petrie, Pardeep S. Jhund, Scott D. Solomon, John J.V. McMurray
Journal: European Journal of Heart Failure (2021)

There is an association between heart failure with preserved ejection fraction (HFpEF) and insulin resistance, but less is known about the diabetic continuum, and in particular about pre-diabetes, in HFpEF. We examined characteristics and outcomes of participants with diabetes or pre-diabetes in PARAGON-HF.Patients aged ≥50 years with left ventricular ejection fraction ≥45%, structural heart disease and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) were eligible. Patients were classified according to glycated haemoglobin (HbA1c): (i) normal HbA1c, <6.0%; (ii) pre-diabetes, 6.0%-6.4%; (iii) diabetes, ≥6.5% or history of diabetes. The primary outcome was a composite of cardiovascular (CV) death and total heart failure hospitalizations (HFH). Of 4796 patients, 50% had diabetes and 18% had pre-diabetes. Compared to patients with normal HbA1c, patients with pre-diabetes and diabetes more often were obese, had a history of myocardial infarction and had lower Kansas City Cardiomyopathy Questionnaire scores, while patients with diabetes had more clinical evidence of congestion, but similar NT-proBNP concentrations. The risks of the primary composite outcome (rate ratio [RR] 1.59, 95% confidence interval [CI] 1.35-1.88), total HFH (RR 1.67, 95% CI 1.39-2.02) and CV death (hazard ratio [HR] 1.35, 95% CI 1.07-1.71) were higher among patients with diabetes, compared to those with normal HbA1c. Patients with pre-diabetes had a higher risk (which was intermediate between that of patients with diabetes and those with normal HbA1c) of the primary outcome (HR 1.27, 95% CI 1.00-1.60) and HFH (HR 1.35, 95% CI 1.03-1.77), but not of CV death (HR 1.02, 95% CI 0.75-1.40). Patients with diabetes treated with insulin had worse outcomes than those not, and those with 'lean diabetes' had similar mortality rates to those with a higher body mass index, but lower rates of HFH.Pre-diabetes is common in patients with HFpEF and is associated with worse clinical status and greater risk of HFH.ClinicalTrials.gov Identifier NCT01920711.