tbuckley/cabot-search huggingface dataset:
Evaluation and Management After Acute Left-Sided Colonic Diverticulitis
Authors: Ethan M. Balk, Gaelen P. Adam, Wangnan Cao, Shivani Mehta, Nishit Shah
Journal: Annals of Internal Medicine (2022)

The value of interventions used after acute colonic diverticulitis is unclear. To evaluate postdiverticulitis colonoscopy and interventions to prevent recurrent diverticulitis. MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, CINAHL, and ClinicalTrials.gov from 1 January 1990 through 16 November 2020. Comparative studies of interventions of interest reporting critical or important outcomes, and larger single-group studies to evaluate prevalence of colonoscopy findings and harms. 6 researchers extracted study data and risk of bias. The team assessed strength of evidence. 19 studies evaluated colonoscopy. Risk for prevalent colorectal cancer (CRC) compared with the general population is unclear. Based on low-strength evidence, long-term CRC diagnosis is similar with or without colonoscopy. High-strength evidence indicates that risk for prevalent CRC is higher among patients with complicated diverticulitis and colonoscopy complications are rare. Based on high-strength evidence, mesalamine does not reduce recurrence risk (6 randomized controlled trials [RCTs]). Evidence on other nonsurgical interventions is insufficient. For patients with prior complicated or smoldering or frequently recurrent diverticulitis, elective surgery is associated with reduced recurrence (3 studies; high strength). In 19 studies, serious surgical complications were uncommon. Few RCTs provided evidence. Heterogeneity of treatment effect was not adequately assessed. It is unclear whether patients with recent acute diverticulitis are at increased risk for prevalent CRC, but those with complicated diverticulitis are at increased risk. Mesalamine is ineffective in preventing recurrence; other nonsurgical treatments have inadequate evidence. Elective surgery reduces recurrence in patients with prior complicated or smoldering or frequently recurrent diverticulitis, but it is unclear which of these patients may benefit most. Agency for Healthcare Research and Quality and American College of Physicians. (PROSPERO: CRD42020151246).
A multiple membership multilevel negative binomial model for intersection crash analysis
Authors: Ho-Chul Park, Byung-Jung Park, Peter Y. Park
Journal: Analytic Methods in Accident Research (2022)

Many intersections belong to more than one zone, but most research has not considered the effects of multiple zones in intersection crash analysis. This issue is known as a boundary problem. Unobserved heterogeneity between zones can lead to model misspecification which can result in biased parameter estimates and poor model fitting performance. This study investigated the issue using five years of intersection crash data from the City of Regina, Saskatchewan, Canada. The study developed three multiple membership multilevel negative binomial models to reduce unobserved zonal-level heterogeneity. Each multiple membership multilevel model used a different weight strategy. When the fitting performance of the three multiple membership multilevel models was compared with two additional models, a traditional single level model and a conventional multilevel model, all three multiple membership multilevel models had a better fitting performance. Five individual-level and seven group-level variables were statistically significant (90% confidence level) in all the models with five of the individual-level and four of the group-level variables statistically significant at the 99% confidence level. The multiple membership multilevel models also helped to prevent the underestimation of group-level variance and type I statistical errors that tend to occur with single level models and conventional multilevel models. In particular, the three multiple membership multilevel models produced more accurate results for intersections with a large AADT. As intersections with a large AADT are known to have more crashes, multiple membership multilevel models are likely to be more useful than single level models and conventional multilevel models when selecting intersections for safety improvement. The study recommends the adoption of a multiple membership multilevel model to improve fitting performance and reduce the boundary problem for intersections affected by more than one zone.
Selenium and tellurium in the development of novel small molecules and nanoparticles as cancer multidrug resistance reversal agents
Authors: Enrique Domínguez-Álvarez, Bálint Rácz, Małgorzata Anna Marć, Muhammad Jawad Nasim, Nikoletta Szemerédi, Jitka Viktorová, Claus Jacob, Gabriella Spengler
Journal: Drug Resistance Updates (2022)

Selenium is an essential trace element that is crucial for cellular antioxidant defense against reactive oxygen species (ROS). Recently, many selenium-containing compounds have exhibited a wide spectrum of biological activities that make them promising scaffolds in Medicinal Chemistry, and, in particular, in the search for novel compounds with anticancer activity. Similarly, certain tellurium-containing compounds have also exhibited substantial biological activities. Here we provide an overview of the biological activities of seleno- and tellurocompounds including chemopreventive activity, antioxidant or pro-oxidant activity, modulation of the inflammatory processes, induction of apoptosis, modulation of autophagy, inhibition of multidrug efflux pumps such as P-gp, inhibition of cancer metastasis, selective targeting of tumors and enhancement of the cytotoxic activity of chemotherapeutic drugs, as well as overcoming tumor drug resistance. A review of the chemistry of the most relevant seleno- or tellurocompounds with activity against resistant cancers is also presented, paying attention to the synthesis of these compounds and to the preparation of bioactive selenium or tellurium nanoparticles. Based on these data, the use of these seleno- and tellurocompounds is a promising approach in the development of strategies that can drive forward the search for novel therapies or adjuvants of current therapies against drug-resistant cancers.
Switch maintenance endocrine therapy plus bevacizumab after bevacizumab plus paclitaxel in advanced or metastatic oestrogen receptor-positive, HER2-negative breast cancer (BOOSTER): a randomised, open-label, phase 2 trial
Authors: Shigehira Saji, Naruto Taira, Masahiro Kitada, Toshimi Takano, Masahiro Takada, Tohru Ohtake, Tatsuya Toyama, Yuichiro Kikawa, Yoshie Hasegawa, Tomomi Fujisawa, Masahiro Kashiwaba, Takanori Ishida, Rikiya Nakamura, Yutaka Yamamoto, Uhi Toh, Hiroji Iwata, Norikazu Masuda, Satoshi Morita, Shinji Ohno, Masakazu Toi
Journal: The Lancet Oncology (2022)
Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
Authors: Heidi Hautakangas, Bendik S. Winsvold, Sanni E. Ruotsalainen, Gyda Bjornsdottir, Aster V. E. Harder, Lisette J. A. Kogelman, Laurent F. Thomas, Raymond Noordam, Christian Benner, Padhraig Gormley, Ville Artto, Karina Banasik, Anna Bjornsdottir, Dorret I. Boomsma, Ben M. Brumpton, Kristoffer Sølvsten Burgdorf, Julie E. Buring, Mona Ameri Chalmer, Irene de Boer, Martin Dichgans, Christian Erikstrup, Markus Färkkilä, Maiken Elvestad Garbrielsen, Mohsen Ghanbari, Knut Hagen, Paavo Häppölä, Jouke-Jan Hottenga, Maria G. Hrafnsdottir, Kristian Hveem, Marianne Bakke Johnsen, Mika Kähönen, Espen S. Kristoffersen, Tobias Kurth, Terho Lehtimäki, Lannie Lighart, Sigurdur H. Magnusson, Rainer Malik, Ole Birger Pedersen, Nadine Pelzer, Brenda W. J. H. Penninx, Caroline Ran, Paul M. Ridker, Frits R. Rosendaal, Gudrun R. Sigurdardottir, Anne Heidi Skogholt, Olafur A. Sveinsson, Thorgeir E. Thorgeirsson, Henrik Ullum, Lisanne S. Vijfhuizen, Elisabeth Widén, Ko Willems van Dijk, Irene de Boer, Arn M. J. M. van den Maagdenberg, Arpo Aromaa, Andrea Carmine Belin, Tobias Freilinger, M. Arfan Ikram, Marjo-Riitta Järvelin, Olli T. Raitakari, Gisela M. Terwindt, Mikko Kallela, Maija Wessman, Jes Olesen, Daniel I. Chasman, Dale R. Nyholt, Hreinn Stefánsson, Kari Stefansson, Arn M. J. M. van den Maagdenberg, Thomas Folkmann Hansen, Samuli Ripatti, John-Anker Zwart, Aarno Palotie, Matti Pirinen
Journal: Nature Genetics (2022)

Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
Historically High Excess Mortality During the COVID-19 Pandemic in Switzerland, Sweden, and Spain
Authors: Kaspar Staub, Radoslaw Panczak, Katarina L. Matthes, Joël Floris, Claudia Berlin, Christoph Junker, Rolf Weitkunat, Svenn-Erik Mamelund, Marcel Zwahlen, Julien Riou
Journal: Annals of Internal Medicine (2022)

Background: Excess mortality quantifies the overall mortality impact of a pandemic. Mortality data have been accessible for many countries in recent decades, but few continuous data have been available for longer periods. Objective: To assess the historical dimension of the COVID-19 pandemic in 2020 for 3 countries with reliable death count data over an uninterrupted span of more than 100 years. Design: Observational study. Setting: Switzerland, Sweden, and Spain, which were militarily neutral and not involved in combat during either world war and have not been affected by significant changes in their territory since the end of the 19th century. Participants: Complete populations of these 3 countries. Measurements: Continuous series of recorded deaths (from all causes) by month from the earliest available year (1877 for Switzerland, 1851 for Sweden, and 1908 for Spain) were jointly modeled with annual age group–specific death and total population counts using negative binomial and multinomial models, which accounted for temporal trends and seasonal variability of prepandemic years. The aim was to estimate the expected number of deaths in a pandemic year for a nonpandemic scenario and the difference in observed and expected deaths aggregated over the year. Results: In 2020, the number of excess deaths recorded per 100 000 persons was 100 (95% credible interval [CrI], 60 to 135) for Switzerland, 75 (CrI, 40 to 105) for Sweden, and 155 (CrI, 110 to 195) for Spain. In 1918, excess mortality was 6 to 7 times higher. In all 3 countries, the peaks of monthly excess mortality in 2020 were greater than most monthly excess mortality since 1918, including many peaks due to seasonal influenza and heat waves during that period. Limitation: Historical vital statistics might be affected by minor completeness issues before the beginning of the 20th century. Conclusion: In 2020, the COVID-19 pandemic led to the second-largest infection-related mortality disaster in Switzerland, Sweden, and Spain since the beginning of the 20th century. Primary Funding Source: Foundation for Research in Science and the Humanities at the University of Zurich, Swiss National Science Foundation, and National Institute of Allergy and Infectious Diseases.
Single-Cell RNA Sequencing Reveals a Distinct Immune Landscape of Myeloid Cells in Coronary Culprit Plaques Causing Acute Coronary Syndrome
Authors: Takuo Emoto, Hiroyuki Yamamoto, Tomoya Yamashita, Tomofumi Takaya, Takahiro Sawada, Shintaro Takeda, Masayuki Taniguchi, Naoto Sasaki, Naofumi Yoshida, Yoshihiro Saito, Tharini Sivasubramaniyam, Hiromasa Otake, Tomoyuki Furuyashiki, Clinton S. Robbins, Hiroya Kawai, Ken-ichi Hirata
Journal: Circulation (2022)
The Association of Excess Body Weight with Risk of ESKD Is Mediated Through Insulin Resistance, Hypertension, and Hyperuricemia
Authors: Josef Fritz, Wolfgang Brozek, Hans Concin, Gabriele Nagel, Julia Kerschbaum, Karl Lhotta, Hanno Ulmer, Emanuel Zitt
Journal: Journal of the American Society of Nephrology (2022)

Insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia are hypothesized to be important intermediates in the relationship between excess body weight and CKD risk. However, the magnitude of the total effect of excess body weight on ESKD mediated through these four pathways remains to be quantified.
Treatment Efficacy Score—continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials
Authors: M. Marczyk, A. Mrukwa, C. Yau, D. Wolf, Y.-Y. Chen, R. Balassanian, R. Nanda, B.A. Parker, G. Krings, H. Sattar, J.C. Zeck, K.S. Albain, J.C. Boughey, M.C. Liu, A.D. Elias, A.S. Clark, S.J. Venters, S. Shad, A. Basu, S.M. Asare, M. Buxton, A.L. Asare, H.S. Rugo, J. Perlmutter, A.M. DeMichele, D. Yee, D.A. Berry, L. van’t Veer, W.F. Symmans, L. Esserman, L. Pusztai
Journal: Annals of Oncology (2022)
Nivolumab, nivolumab–ipilimumab, and VEGFR-tyrosine kinase inhibitors as first-line treatment for metastatic clear-cell renal cell carcinoma (BIONIKK): a biomarker-driven, open-label, non-comparative, randomised, phase 2 trial
Authors: Yann-Alexandre Vano, Réza Elaidi, Mostefa Bennamoun, Christine Chevreau, Delphine Borchiellini, Diane Pannier, Denis Maillet, Marine Gross-Goupil, Christophe Tournigand, Brigitte Laguerre, Philippe Barthélémy, Elodie Coquan, Gwenaëlle Gravis, Nadine Houede, Mathilde Cancel, Olivier Huillard, Philippe Beuzeboc, Laure Fournier, Arnaud Méjean, Xavier Cathelineau, Nicolas Doumerc, Philippe Paparel, Jean-Christophe Bernhard, Alexandre de la Taille, Karim Bensalah, Thibault Tricard, Thibaut Waeckel, Géraldine Pignot, Elena Braychenko, Stefano Caruso, Cheng-Ming Sun, Virginie Verkarre, Guillaume Lacroix, Marco Moreira, Maxime Meylan, Antoine Bougouïn, Letuan Phan, Christelle Thibault-Carpentier, Jessica Zucman-Rossi, Wolf Herman Fridman, Catherine Sautès-Fridman, Stéphane Oudard
Journal: The Lancet Oncology (2022)
Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy
Authors: Kaleen N. Hayes, Kevin A. Brown, Angela M. Cheung, Sandra A. Kim, David N. Juurlink, Suzanne M. Cadarette
Journal: Annals of Internal Medicine (2022)

An osteoporosis drug holiday is recommended for most patients after 3 to 5 years of therapy. Risedronate has a shorter half-life than alendronate, and thus the residual length of fracture protection may be shorter. To examine the comparative risks of drug holidays after long-term (≥3 years) risedronate versus alendronate therapy. Population-based, matched, cohort study. Province-wide health care administrative databases providing comprehensive coverage to Ontario residents aged 65 years or older between November 2000 and March 2020. Persons aged 66 years or older who had long-term risedronate therapy and a drug holiday were matched 1:1 on propensity score to those who had long-term alendronate therapy and a drug holiday. The primary outcome was hip fracture within 3 years after a 120-day ascertainment period. Secondary analyses included shorter follow-up and sex-specific estimates. Cox proportional hazards models were used to estimate hazard ratios (HRs) for fracture risk between groups. A total of 25 077 propensity score-matched pairs were eligible (mean age, 81 years; 81% women). Hip fracture rates were higher among risedronate than alendronate drug holidays (12.4 and 10.6 events, respectively, per 1000 patient-years; HR, 1.18 [95% CI, 1.04 to 1.34]; 915 total hip fractures). The association was attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00 to 1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85 to 1.24]; 2 years: HR, 1.14 [CI, 0.96 to 1.32]). Analyses were limited to health care administrative data (potential unmeasured confounding), and some secondary analyses contained few events. Drug holidays after long-term therapy with risedronate were associated with a small increase in risk for hip fracture compared with alendronate drug holidays. Future research should examine how best to mitigate this risk. Canadian Institutes of Health Research.
Recombinant programmed cell death protein 1 functions as an immune check point blockade and enhances anti-cancer immunity
Authors: Juyoung Hwang, Eun-Koung An, Wei Zhang, Hae-Bin Park, So-Jung Kim, Dhananjay Yadav, Jihoe Kim, Inho Choi, Minseok Kwak, Peter CW. Lee, Xiaoyan Zhang, Jianqing Xu, Jun-O Jin
Journal: Biomaterials (2022)
Health-related quality-of-life outcomes in patients with advanced renal cell carcinoma treated with lenvatinib plus pembrolizumab or everolimus versus sunitinib (CLEAR): a randomised, phase 3 study
Authors: Robert Motzer, Camillo Porta, Boris Alekseev, Sun Young Rha, Toni K Choueiri, Maria Jose Mendez-Vidal, Sung-Hoo Hong, Anil Kapoor, Jeffrey C Goh, Masatoshi Eto, Lee Bennett, Jinyi Wang, Jie Janice Pan, Todd L Saretsky, Rodolfo F Perini, Cixin Steven He, Kalgi Mody, David Cella
Journal: The Lancet Oncology (2022)
Unusual complications in the management of <scp>chronic lymphocytic leukemia</scp>
Authors: Max J. Gordon, Alessandra Ferrajoli
Journal: American Journal of Hematology (2022)

Abstract Chronic lymphocytic leukemia (CLL) is a common, indolent disease that typically presents with a proliferation of mature, immunologically dysfunctional CD5+ B‐cells which preferentially occupy the bone marrow, peripheral blood and lymphoid organs. Immune dysfunction leads to an increase in autoimmune diseases which occur in approximately 10% of patients with CLL. Autoimmune cytopenias are the most common, but other organs may be affected as well. The treatment of these conditions typically depends on the extent of CLL and severity of symptoms, but generally consists of CLL‐directed therapies, immunosuppression or both. CLL may also infiltrate extranodal sites in the body. Symptomatic extranodal CLL or extranodal disease which threatens normal organ function is an indication for initiation of CLL‐directed therapy. The following review summarizes autoimmune and extranodal complications that can occur in patients with CLL and our suggested approach to their treatment.
Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study
Authors: Sean McPhail, Ruth Swann, Shane A Johnson, Matthew E Barclay, Hazem Abd Elkader, Riaz Alvi, Andriana Barisic, Oliver Bucher, Gavin R C Clark, Nicola Creighton, Bolette Danckert, Cheryl A Denny, David W Donnelly, Jeff J Dowden, Norah Finn, Colin R Fox, Sharon Fung, Anna T Gavin, Elba Gomez Navas, Steven Habbous, Jihee Han, Dyfed W Huws, Christopher G C A Jackson, Henry Jensen, Bethany Kaposhi, S Eshwar Kumar, Alana L Little, Shuang Lu, Carol A McClure, Bjørn Møller, Grace Musto, Yngvar Nilssen, Nathalie Saint-Jacques, Sabuj Sarker, Luc te Marvelde, Rebecca S Thomas, Robert J S Thomas, Catherine S Thomson, Ryan R Woods, Bin Zhang, Georgios Lyratzopoulos, Brooke Filsinger, Katharina Forster, Leon May, David S Morrison, A. Ffion Thomas, Janet L Warlow, Hui You
Journal: The Lancet Oncology (2022)

Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries.
Antithrombotic Therapy After Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation
Authors: James V. Freeman, Angela Y. Higgins, Yongfei Wang, Chengan Du, Daniel J. Friedman, Usama A. Daimee, Karl E. Minges, Lucy Pereira, Andrew M. Goldsweig, Matthew J. Price, Vivek Y. Reddy, Douglas Gibson, Shephal K. Doshi, Paul D. Varosy, Frederick A. Masoudi, Jeptha P. Curtis
Journal: Journal of the American College of Cardiology (2022)
Plasma proteome analyses in individuals of European and African ancestry identify cis-pQTLs and models for proteome-wide association studies
Authors: Jingning Zhang, Diptavo Dutta, Anna Köttgen, Adrienne Tin, Pascal Schlosser, Morgan E. Grams, Benjamin Harvey, Bing Yu, Eric Boerwinkle, Josef Coresh, Nilanjan Chatterjee
Journal: Nature Genetics (2022)
Phase Ib study of anlotinib combined with TQB2450 in pretreated advanced biliary tract cancer and biomarker analysis
Authors: Jun Zhou, Yongkun Sun, Wen Zhang, Jiajia Yuan, Zhi Peng, Wei Wang, Jifang Gong, Lin Yang, Yanshuo Cao, Hong Zhao, Chao Chen, Weifeng Wang, Lin Shen, Aiping Zhou
Journal: Hepatology (2022)

Background and Aims: We evaluated the efficacy and safety of the antiangiogenic tyrosine kinase inhibitor anlotinib plus TQB2450, a programmed death‐ligand 1 inhibitor in pretreated advanced biliary tract cancers (BTCs). Approach and Results: In this pooled analysis of two single‐center, phase Ib clinical trials (TQB2450‐Ib‐05 and TQB2450‐Ib‐08 trials), 66 patients with advanced BTCs who had progressed or declined or were ineligible for first‐line chemotherapy were included. With the treatment of anlotinib plus TQB2450, two patients achieved complete response, and 12 had a partial response assessed by Response Evaluation Criteria in Solid Tumors 1.1, yielding an objective response rate of 21.21%, a disease control rate (DCR) of 72.73%, and a clinical benefit rate (CBR) of 42.42%. With a median follow‐up of 19.68 months, median progression‐free survival (PFS) and overall survival (OS) were 6.24 (95% confidence interval [CI], 4.11–8.25) and 15.77 (95% CI, 10.74–19.71) months, respectively. Adverse events (AEs) were reported in 64 (96.97%) patients, and the most common grade 3 or worse treatment‐related AEs included elevated levels of aspartate aminotransferase (7.58%), alanine aminotransferase (6.06%), and hypertension (6.06%). Patients with high tumor mutational burden (TMB; ≥5 mutations/Mbp) had a better CBR (70.8% vs. 22.2%), longer OS (14.32 vs. 9.64 months), and a trend toward longer PFS (7.03 vs. 4.06 months). Patients with kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations showed a lower CBR (12.5% vs. 58.8%) and shorter PFS (2.02 vs. 6.80 months) and OS (10.53 vs. 13.13 months). Conclusions: Anlotinib combined with TQB2450 showed promising efficacy and was well tolerated in advanced BTCs. KRAS mutation and high TMB might serve as predictors of treatment efficacy.
High-Intensity Statin Use Among Patients With Atherosclerosis in the U.S.
Authors: Adam J. Nelson, Kevin Haynes, Sonali Shambhu, Zubin Eapen, Mark J. Cziraky, Michael G. Nanna, Sara B. Calvert, Kerrin Gallagher, Neha J. Pagidipati, Christopher B. Granger
Journal: Journal of the American College of Cardiology (2022)
Erratum to ‘Ribonuclease 7-driven activation of ROS1 is a potential therapeutic target in hepatocellular carcinoma’ [J Hepatol 2021 (907-918)]
Authors: Chunxiao Liu, Zhengyu Zha, Chenhao Zhou, Yeh Chen, Weiya Xia, Ying-Nai Wang, Heng-Huan Lee, Yirui Yin, Meisi Yan, Chiung-Wen Chang, Li-Chuan Chan, Yufan Qiu, Hui Li, Chia-Wei Li, Jung-Mao Hsu, Jennifer L. Hsu, Shao-Chun Wang, Ning Ren, Mien-Chie Hung
Journal: Journal of Hepatology (2022)