tbuckley/cabot-search huggingface dataset:
Examining Natural History through the Lens of Palaeogenomics
Authors: Kieren J. Mitchell, Nicolas J. Rawlence
Journal: Trends in Ecology & Evolution (2021)

The many high-resolution tools that are uniquely applicable to specimens from the Quaternary period (the past ~2.5 Ma) provide an opportunity to cross-validate data and test hypotheses based on the morphology and distribution of fossils. Among these tools is palaeogenomics - the genome-scale sequencing of genetic material from ancient specimens - that can provide direct insight into ecology and evolution, potentially improving the accuracy of inferences about past ecological communities over longer timescales. Palaeogenomics has revealed instances of over- and underestimation of extinct diversity, detected cryptic faunal migration and turnover, allowed quantification of widespread sex biases and sexual dimorphism in the fossil record, revealed past hybridisation events and hybrid individuals, and has highlighted previously unrecognised routes of zoonotic disease transfer.
The impact of COVID-19 on rare and complex connective tissue diseases: the experience of ERN ReCONNET
Authors: Rosaria Talarico, Silvia Aguilera, Tobias Alexander, Zahir Amoura, Ana M. Antunes, Laurent Arnaud, Tadej Avcin, Lorenzo Beretta, Stefano Bombardieri, Gerd R. Burmester, Sara Cannizzo, Lorenzo Cavagna, Benjamin Chaigne, Alain Cornet, Nathalie Costedoat-Chalumeau, Andrea Doria, Alessandro Ferraris, Rebecca Fischer-Betz, João E. Fonseca, Charissa Frank, Andrea Gaglioti, Ilaria Galetti, Jürgen Grunert, Vera Guimarães, Eric Hachulla, Frederic Houssiau, Luca Iaccarino, Thomas Krieg, Marteen Limper, Fransiska Malfait, Xavier Mariette, Diana Marinello, Thierry Martin, Lisa Matthews, Marco Matucci-Cerinic, Alain Meyer, Carlomaurizio Montecucco, Luc Mouthon, Ulf Müller-Ladner, Simona Rednic, Vasco C. Romão, Matthias Schneider, Vanessa Smith, Alberto Sulli, Farah Tamirou, Domenica Taruscio, Anna V. Taulaigo, Enrique Terol, Angela Tincani, Simone Ticciati, Giuseppe Turchetti, P. Martin van Hagen, Jacob M. van Laar, Ana Vieira, Jeska K. de Vries-Bouwstra, Maurizio Cutolo, Marta Mosca
Journal: Nature Reviews Rheumatology (2021)

During the COVID-19 pandemic, the need to provide high-level care for a large number of patients with COVID-19 has affected resourcing for, and limited the routine care of, all other conditions. The impact of this health emergency is particularly relevant in the rare connective tissue diseases (rCTDs) communities, as discussed in this Perspective article by the multi-stakeholder European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET). The clinical, organizational and health economic challenges faced by health-care providers, institutions, patients and their families during the SARS-CoV-2 outbreak have demonstrated the importance of ensuring continuity of care in the management of rCTDs, including adequate diagnostics and monitoring protocols, and highlighted the need for a structured emergency strategy. The vulnerability of patients with rCTDs needs to be taken into account when planning future health policies, in preparation for not only the post-COVID era, but also any possible new health emergencies. In this Perspective article, members of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases discuss clinical and organizational challenges in this community caused by the COVID-19 pandemic and what lessons might be learned for the future.
A Systematic Review of Patients’ Values, Preferences, and Expectations for the Diagnosis and Treatment of Male Lower Urinary Tract Symptoms
Authors: Sachin Malde, Roland Umbach, Jessica R. Wheeler, Lyubov Lytvyn, Jean-Nicholas Cornu, Mauro Gacci, Christian Gratzke, Thomas R.W. Herrmann, Charalampos Mamoulakis, Malte Rieken, Mark J. Speakman, Stavros Gravas, Marcus J. Drake, Gordon H. Guyatt, Kari A.O. Tikkinen
Journal: European Urology (2021)
Risk Characterization and Probabilistic Concentration–Response Modeling of Complex Environmental Mixtures Using New Approach Methodologies (NAMs) Data from Organotypic <i>in Vitro</i> Human Stem Cell Assays
Authors: Nan-Hung Hsieh, Zunwei Chen, Ivan Rusyn, Weihsueh A. Chiu
Journal: Environmental Health Perspectives (2021)

Background: Risk assessment of chemical mixtures or complex substances remains a major methodological challenge due to lack of available hazard or exposure data. Therefore, risk assessors usually infer hazard or risk from data on the subset of constituents with available toxicity values. Objectives: We evaluated the validity of the widely used traditional mixtures risk assessment paradigms, Independent Action (IA) and Concentration Addition (CA), with new approach methodologies (NAMs) data from human cell-based in vitro assays. Methods: A diverse set of 42 chemicals was tested both individually and as mixtures for functional and cytotoxic effects in vitro. A panel of induced pluripotent stem cell (iPSCs)-derived models (hepatocytes, cardiomyocytes, endothelial, and neurons) and one primary cell type (HUVEC) were used. Bayesian concentration–response modeling of individual chemicals or their mixtures was performed for a total of 47 phenotypes to derive point-of-departure (POD) values. Probabilistic IA or CA was conducted to estimate the mixture effects based on the bioactivity profiles from the individual chemicals and compared with mixture bioactivity. Results: All mixtures showed significant bioactivity, even though some were constructed using individual chemical concentrations considered "low" or "safe." Even though CA is much more accurate as a predictor of mixture effects in comparison with IA, with CA-based POD typically within an order of magnitude of the actual mixture, in some cases, the bioactivity of the mixtures appeared to be much greater than that of their components under either additivity assumption. Discussion: These results suggest that CA is a preferred first approximation for predicting mixture toxicity when data for all constituents are available. However, because the accuracy of additivity assumptions varies greatly across phenotypes, we posit that mixtures and complex substances need to be directly tested for their hazard potential. NAMs provide a practical solution that rapidly yields highly informative data for mixtures risk assessment. https://doi.org/10.1289/EHP7600
The association between tumor mutational burden and prognosis is dependent on treatment context
Authors: Cristina Valero, Mark Lee, Douglas Hoen, Jingming Wang, Zaineb Nadeem, Neal Patel, Michael A. Postow, Alexander N. Shoushtari, George Plitas, Vinod P. Balachandran, J. Joshua Smith, Aimee M. Crago, Kara C. Long Roche, Daniel W. Kelly, Robert M. Samstein, Satshil Rana, Ian Ganly, Richard J. Wong, A. Ari Hakimi, Michael F. Berger, Ahmet Zehir, David B. Solit, Marc Ladanyi, Nadeem Riaz, Timothy A. Chan, Venkatraman E. Seshan, Luc G. T. Morris
Journal: Nature Genetics (2021)
Cancer Screening Tests and Cancer Diagnoses During the COVID-19 Pandemic
Authors: Ziad Bakouny, Marco Paciotti, Andrew L. Schmidt, Stuart R. Lipsitz, Toni K. Choueiri, Quoc-Dien Trinh
Journal: JAMA Oncology (2021)

This cohort study describes the number of patients undergoing cancer screening tests and of ensuing cancer diagnoses during the COVID-19 pandemic in 1 health care system in the northeastern United States.
Chimeric Antigen Receptor T-Cell Therapy in the Management of Relapsed Non-Hodgkin Lymphoma
Authors: Krishna V. Komanduri
Journal: Journal of Clinical Oncology (2021)

Article Tools REVIEW ARTICLES Immunotherapy for Hematologic Malignancies Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.20.01749 Journal of Clinical Oncology - published online before print January 12, 2021 PMID: 33434079 Chimeric Antigen Receptor T-Cell Therapy in the Management of Relapsed Non-Hodgkin Lymphoma Krishna V. Komanduri , MD1xKrishna V. KomanduriSearch for articles by this author Show More 1Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL https://doi.org/10.1200/JCO.20.01749 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologyCONTEXTKey ObjectiveWho should receive therapy for relapsed and refractory non-Hodgkin lymphoma with autologous chimeric antigen receptor modified T (CAR-T) cells?Knowledge GeneratedT cells engineered to express chimeric antigen receptors recognizing CD19 have revolutionized the therapy of relapsed and refractory lymphomas. Three products have been approved by the US Food and Drug Administration to treat several subsets of high-risk lymphomas that failed multiple prior therapies, with additional products likely to receive approval in the coming year.RelevanceDespite their transformative impact, notable challenges of current CAR-T therapies include underutilization, the potential for serious toxicities after therapy, and large rates of relapse in patients who experience a response to therapy. Ongoing trials are addressing the role of novel autologous and allogeneic CAR-T therapies across histologic subtypes of lymphoma and in earlier phases of disease.SUPPORTSupported in part by the Kalish Family Chair in Stem Cell Transplantation.AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTChimeric Antigen Receptor T-Cell Therapy in the Management of Relapsed Non-Hodgkin LymphomaThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Krishna V. KomanduriHonoraria: Takeda, Kadmon, Kite, Gilead, Kiadis Pharma, Novartis, Incyte, Autolus, Genentech, Gamida CellConsulting or Advisory Role: Kiadis Pharma, Kite, Gilead, Novartis, Takeda, Incyte, Autolus, Kadmon, Genentech, Gamida CellExpert Testimony: Kite, GileadNo other potential conflicts of interest were reported.
Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people
Authors: Nicholas S Hopkinson, Niccolo Rossi, Julia El-Sayed_Moustafa, Anthony A Laverty, Jennifer K Quint, Maxim Freidin, Alessia Visconti, Ben Murray, Marc Modat, Sebastien Ourselin, Kerrin Small, Richard Davies, Jonathan Wolf, Tim D Spector, Claire J Steves, Mario Falchi
Journal: Thorax (2021)

Background The association between current tobacco smoking, the risk of developing symptomatic COVID-19 and the severity of illness is an important information gap. Methods UK users of the Zoe COVID-19 Symptom Study app provided baseline data including demographics, anthropometrics, smoking status and medical conditions, and were asked to log their condition daily. Participants who reported that they did not feel physically normal were then asked by the app to complete a series of questions, including 14 potential COVID-19 symptoms and about hospital attendance. The main study outcome was the development of ‘classic’ symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness and their association with current smoking. The number of concurrent COVID-19 symptoms was used as a proxy for severity and the pattern of association between symptoms was also compared between smokers and non-smokers. Results Between 24 March 2020 and 23 April 2020, data were available on 2 401 982 participants, mean (SD) age 43.6 (15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834 437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to report symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR (95% CI) 1.14 (1.10 to 1.18); &gt;5 symptoms 1.29 (1.26 to 1.31); &gt;10 symptoms 1.50 (1.42 to 1.58). The pattern of association between reported symptoms did not vary between smokers and non-smokers. Interpretation These data are consistent with people who smoke being at an increased risk of developing symptomatic COVID-19.
Second opinion needed: communicating uncertainty in medical machine learning
Authors: Benjamin Kompa, Jasper Snoek, Andrew L. Beam
Journal: npj Digital Medicine (2021)

Abstract There is great excitement that medical artificial intelligence (AI) based on machine learning (ML) can be used to improve decision making at the patient level in a variety of healthcare settings. However, the quantification and communication of uncertainty for individual predictions is often neglected even though uncertainty estimates could lead to more principled decision-making and enable machine learning models to automatically or semi-automatically abstain on samples for which there is high uncertainty. In this article, we provide an overview of different approaches to uncertainty quantification and abstention for machine learning and highlight how these techniques could improve the safety and reliability of current ML systems being used in healthcare settings. Effective quantification and communication of uncertainty could help to engender trust with healthcare workers, while providing safeguards against known failure modes of current machine learning approaches. As machine learning becomes further integrated into healthcare environments, the ability to say “I’m not sure” or “I don’t know” when uncertain is a necessary capability to enable safe clinical deployment.
A MET Targeting Antibody–Drug Conjugate Overcomes Gemcitabine Resistance in Pancreatic Cancer
Authors: Alex Cazes, Oscar Betancourt, Edgar Esparza, Evangeline S. Mose, Dawn Jaquish, Eric Wong, Alexis A. Wascher, Hervé Tiriac, Marco Gymnopoulos, Andrew M. Lowy
Journal: Clinical Cancer Research (2021)

Pancreatic cancer is an aggressive disease associated with a poor 5-year overall survival. Most patients are ineligible for surgery due to late diagnosis and are treated primarily with chemotherapy with very limited success. Pancreatic cancer is relatively insensitive to chemotherapy due to multiple factors, including reduced bioavailability of drugs to tumor cells. One strategy to improve drug efficacy with reduced toxicity is the development of antibody-drug conjugates (ADC), which have now been used successfully to treat both solid and liquid tumors. Here, we evaluate the efficacy of TR1801-ADC, a newly developed ADC composed of a MET antibody conjugated to the highly potent pyrrolobenzodiazepine toxin-linker, tesirine.We first evaluated MET expression and subcellular localization in pancreatic cancer cell lines, human tumors, and patient-derived xenografts (PDX). We then tested TR1801-ADC efficacy in vitro in pancreatic cancer cell lines. Preclinical evaluation of TR1801-ADC efficacy was conducted on PDXs selected on the basis of their MET expression level.We show that MET is highly expressed and located at the plasma membrane of pancreatic cancer cells. We found that TR1801-ADC induces a specific cytotoxicity in pancreatic cancer cell lines and a profound tumor growth inhibition, even in a gemcitabine-resistant tumor. We also noted synergism between TR1801-ADC and gemcitabine in vitro and an improved response to the combination in vivo.Together, these results suggest the promise of agents such as TR1801-ADC as a novel approach to the treatment of pancreatic cancer.
Entire Bilateral Kidneys Enhanced by Air Contrast after Ventilation-induced Alveolar Rupture
Authors: Hsin Tseng, Alexander Lee Wang, Hsin-Ti Lin, Chi Chan Lee, Wei-Cheng Chen
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Entire Bilateral Kidneys Enhanced by Air Contrast after Ventilation-induced Alveolar Rupture." American Journal of Respiratory and Critical Care Medicine, 203(9), pp. e31–e32
An isocaloric moderately high-fat diet extends lifespan in male rats and Drosophila
Authors: Dan Shi, TianShu Han, Xia Chu, Huimin Lu, Xue Yang, TianQi Zi, YanHe Zhao, XinYue Wang, ZhiPeng Liu, JingQi Ruan, Xin Liu, Hua Ning, MaoQing Wang, Zhen Tian, Wei Wei, Yue Sun, YinLing Li, Rui Guo, Yu Wang, Fan Ling, Yue Guan, Da Shen, YuCun Niu, Ying Li, ChangHao Sun
Journal: Cell Metabolism (2021)
Abstract 13134: A Novel Device for Detecting Anaerobic Threshold Using Sweat Lactate Acid During Exercise
Authors: Yuta Seki, Daisuke Nakashima, Ryuzaki Toshinobu, Hidehiko Ikura, Kotaro Miura, Yasuyuki Shiraishi, Keiichi Fukuda, Yoshinori Katsumata
Journal: Circulation (2020)

Background: Continuous monitoring of lactate acid (LA) levels during exercise has not been possible. We aimed to visualize real-time changes in LA levels in sweat during exercise and to investigate the relationship between the lactate threshold in sweat (sLT) and LT in blood (bLT) and the ventilatory threshold (VT). Methods: Twenty-three healthy subjects (age: median; 20 [interquartile range; 20, 21] years old) and 22 consecutive patients (age: 65 [57, 73] years old) with cardiovascular diseases (CVDs) underwent exercise tests with a RAMP protocol ergometer, simultaneously monitoring changes in the LA values in sweat using a wearable lactate sensor. The sLT was identified as the first significant increase in LA above baseline based on the graphical plots and change finder scores calculated by the Change Finder algorithm using the time-series data of the LA values during exercise. We applied the Bland-Altman method to verify similarities for each threshold. Results: During exercise, the dynamic changes in LA values in sweat were successfully visualized in real-time with a sharp continuous increase up to volitional exhaustion and a gradual decrease in the recovery period. In healthy subjects, the work rate (WR) at the sLT (WR-sLT) was substantially correlated with the WR at the bLT (r=0.90). The Bland-Altman plot described a strong agreement (the mean difference: -3.0 watt). Among 22 patients, there were 8 patients whose LA values in sweat were not measured due to a non-response in the sensor. In the remaining 13 cases, except for a patient in whom the VT could not be detected, the sLT was well correlated with bLT and VT (r=0.81 and 0.65, respectively); the mean differences were -8.3 and 3.4, and there was no bias between the mean values. Finally, the logistic regression analysis revealed that a non-response in the sensor was associated with NYHA 3/4 and low peak VO2 (Odds ratio [OR] 0.01 [95% confidence interval (CI); 0.00-0.13], OR 1.45 [95% CI; 1.09-2.20], respectively) Conclusions: Our wearable device enabled a continuous and real-time LA measurement in sweat during incremental exercise in a subset of patients with CVDs as well as healthy subjects. This can provide additional information for detecting the VT.
Chemotherapy in Combination With Radiotherapy for Definitive-Intent Treatment of Stage II-IVA Nasopharyngeal Carcinoma: CSCO and ASCO Guideline
Authors: Yu-Pei Chen, Nofisat Ismaila, Melvin L. K. Chua, A. Dimitrios Colevas, Robert Haddad, Shao Hui Huang, Joseph T. S. Wee, Alexander C. Whitley, Jun-Lin Yi, Sue S. Yom, Anthony T. C. Chan, Chao-Su Hu, Jin-Yi Lang, Quynh-Thu Le, Anne W. M. Lee, Nancy Lee, Jin-Ching Lin, Brigette Ma, Thomas J. Morgan, Jatin Shah, Ying Sun, Jun Ma
Journal: Journal of Clinical Oncology (2021)

The aim of this joint guideline is to provide evidence-based recommendations to practicing physicians and other healthcare providers on definitive-intent chemoradiotherapy for patients with stage II-IVA nasopharyngeal carcinoma (NPC).The Chinese Society of Clinical Oncology (CSCO) and ASCO convened an expert panel of radiation oncology, medical oncology, surgery, and advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2020. Outcomes of interest included survival, distant and locoregional disease control, and quality of life. Expert panel members used this evidence and informal consensus to develop evidence-based guideline recommendations.The literature search identified 108 relevant studies to inform the evidence base for this guideline. Five overarching clinical questions were addressed, which included subquestions on radiotherapy (RT), chemotherapy sequence, and concurrent, induction, and adjuvant chemotherapy options.Evidence-based recommendations were developed to address aspects of care related to chemotherapy in combination with RT for the definitive-intent treatment of stage II to IVA NPC.Additional information is available at www.asco.org/head-neck-cancer-guidelines.
Household acquisition and transmission of extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae after hospital discharge of ESBL-positive index patients
Authors: Maria E. Riccio, Tess Verschuuren, Nadine Conzelmann, Daniel Martak, Alexandre Meunier, Elena Salamanca, Mercedes Delgado, Julia Guther, Silke Peter, Julian Paganini, Romain Martischang, Julien Sauser, Marlieke E.A. de Kraker, Abdessalam Cherkaoui, Ad C. Fluit, Ben S. Cooper, Didier Hocquet, Jan A.J.W. Kluytmans, Evelina Tacconelli, Jesús Rodriguez-Baño, Stephan Harbarth, Caroline Brossier, Elodie von Dach, Gesuele Renzi, Jacques Schrenzel, Stefanie Bunk, Siri Goepel, Florian Hölzl, Michael Eib, Ingo B. Autenrieth, Álvaro Pascual, Xavier Bertrand, Jelle Scharringa, Patrick Musicha
Journal: Clinical Microbiology and Infection (2021)

This study aimed to determine rates and risk factors of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) acquisition and transmission within households after hospital discharge of an ESBL-PE-positive index patient.Two-year prospective cohort study in five European cities. Patients colonized with ESBL-producing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp), and their household contacts were followed up for 4 months after hospital discharge of the index case. At each follow up, participants provided a faecal sample and personal information. ESBL-PE whole-genome sequences were compared using pairwise single nucleotide polymorphism-based analysis.We enrolled 71 index patients carrying ESBL-Ec (n = 45), ESBL-Kp (n = 20) or both (n = 6), and 102 household contacts. The incidence of any ESBL-PE acquisition among household members initially free of ESBL-PE was 1.9/100 participant-weeks at risk. Nineteen clonally related household transmissions occurred (case to contact: 13; contact to case: 6), with an overall rate of 1.18 transmissions/100 participant-weeks at risk. Most of the acquisition and transmission events occurred within the first 2 months after discharge. The rate of ESBL-Kp household transmission (1.16/100 participant-weeks) was higher than of ESBL-Ec (0.93/100 participant-weeks), whereas more acquisitions were noted for ESBL-Ec (1.06/100 participant-weeks) compared with ESBL-Kp (0.65/100 participant-weeks). Providing assistance for urinary and faecal excretion to the index case by household members increased the risk of ESBL-PE transmission (adjusted prevalence ratio 4.3; 95% CI 1.3-14.1).ESBL-PE cases discharged from the hospital are an important source of ESBL-PE transmission within households. Most acquisition and transmission events occurred during the first 2 months after hospital discharge and were causally related to care activities at home, highlighting the importance of hygiene measures in community settings.German Clinical Trials Register, DRKS-ID: DRKS00013250.