tbuckley/cabot-search huggingface dataset:
Research on peer review and biomedical publication
Authors: Sara Schroter, Elizabeth Loder, Fiona Godlee
Journal: BMJ (2020)

At The BMJ we try to practise what we preach-just as in healthcare, our decisions should be based on solid evidence.Of course, solid evidence can only be generated by solid research that is well conceived, executed, and disseminated.Paradoxically, the processes underlying the generation, dissemination, and implementation of research have not been well studied: we need more and better research on research.Journals amass huge amounts of data from authors, reviewers, and editors.Each year The BMJ alone receives around 3500 research submissions, which annually generate over 2000 reviews.And as the publisher of a broad portfolio of over 70 general and specialty journals, BMJ Publishing Group's manuscript tracking systems hold considerably more data.Journal publishers and editors hold this wealth of data but have limited time or expertise to analyse them, whereas researchers have the skills but no access.Some publishers are concerned about data protection and privacy issues, others are just secretive.Attracting funding for conducting research on research is challenging, yet evidence of serious problems with the quality of research is stacking up.
A phase I study of MGCD0103 given as a twice weekly oral dose in patients with advanced leukemias or myelodysplastic syndromes (MDS)
Authors: J. E. Lancet, G. Nichols, S. Assouline, M. Ward, M. Burton, M. Mintz, C. Rousseau, A. Kalita, P. J. Brabant, O. Odenike
Journal: Journal of Clinical Oncology (2007)

2516 Background: Small molecule inhibitors of histone deacetylase (HDAC) have emerged as novel anticancer agents. MGCD0103 is an oral isotype selective small molecule inhibitor of HDAC. Methods: Eligible patients had relapsed/refractory (RR) AML or MDS (or newly diagnosed disease in patients &gt;60 yrs, ineligible for induction chemotherapy); RR ALL; RR CML. MGCD0103 was administered 2x/weekly for 3 weeks, with no recovery period between cycles. Patients with stable disease or better were eligible to continue therapy indefinitely. Results: Patients have been treated at 4 dose levels: 40, 53, 66 and 83 mg/m 2 /day, including 19 enrolled patients with the following demographics: M:F = 15:4, median age (range) = 75 (52–83), ECOG 0:1:2 = 5:12:2, diagnosis of RR MDS= 7, RR AML or RR ALL=8: untreated AML or MDS = 4. Cytogenetics (n=12): Diploid = 3, Complex = 4, Del 7 = 3, Del 12 = 1, Del Y = 1. Nineteen patients are evaluable for safety. A total of 38 cycles have been administered with a median of 2 per patient (range, 1–6); 13 patients have completed =2 cycles. One patient experienced grade 3 fatigue at 53 mg/m 2 and 2 patients had grade 3 weakness/fatigue at 83 mg/m 2 (exceeded the Maximum Tolerated Dose [MTD]) Non-dose-limiting toxicities included lower grade fatigue, diarrhea, and nausea. Plasma PK in 14 patients revealed t 1/2 of 7–12 hr, t max 0.6- 1 hr, and a dose proportional average C max of 155 ng/mL at 40 mg/m 2 and 225 ng/mL at 53 mg/m 2 . Significant inhibition of whole cell total HDAC activity within PBMC was observed in a majority of patients, at all dosing levels. Four patients have experienced stable disease. Conclusions: MGCD0103 has been well-tolerated in patients with advanced leukemias or MDS. MTD has been reached, and the recommended phase II 2x/week dose is being confirmed. At all dose levels, significant HDAC inhibition was observed. [Table: see text]
Use of microsatellite instability in non-hereditary advanced colorectal cancer to predict response to chemotherapy and overall survival: A study of the Dutch Colorectal Cancer Group (DCCG)
Authors: M. Koopman, G. A. Kortman, L. Mekenkamp, M. J. Ligtenberg, N. Hoogerbrugge, L. Mol, N. F. Antonini, C. J. Punt, J. H. van Krieken
Journal: Journal of Clinical Oncology (2007)

4118 Background: Microsatellite instability (MSI) is present in 10–20% of patients (pts) with non-hereditary colorectal cancer (CRC) and is generally associated with improved overall survival. The effect of chemotherapy in such pts is uncertain, and most data are derived from early stage CRC. Therefore the outcome of treatment in relation to presence or absence of MSI was studied in pts with non- hereditary advanced CRC. Methods: Data were collected from previously untreated advanced CRC pts randomized between 1 st line capecitabine (Cap), 2 nd line irinotecan (Iri), and 3 rd line Cap + oxaliplatin (CapOx) vs 1 st line CapIri and 2 nd line CapOx. Formalin-fixed, paraffin embedded blocks of primary tumors and normal tissue were collected and tissue microarrays were made. Expression of the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 was examined by immunohistochemistry. Additionally MSI analysis and hypermethylation of the MLH1-promoter were performed. Pts with a tumor showing MSI caused by hypermethylation of the MLH1-promoter were included to study the correlation between MSI status and response to 1 st line treatment and overall survival. Results: MSI caused by hypermethylation of the MLH1-promoter was found in 14 (3%) of 512 eligible pts. In 461 evaluable pts, disease control (CR+PR+SD=4 months) in 12 pts with MSI was 58% [95% CI 28%- 85%] and in 449 without MSI 83% [95% CI 79%-86%, p= 0.03].The median OS in pts with MSI was 7 months [95% CI 4–17] and in pts without MSI 18 months [95% CI 16–19, log rank p=0.08]. Conclusions: MSI in advanced non-hereditary CRC is very rare, and predicts a significantly worse outcome in terms of response to chemotherapy with a trend towards a decreased OS. No significant financial relationships to disclose.
Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study
Authors: Lisi Deng, Chunna Li, Qi Zeng, Xi Liu, Xinghua Li, Haitang Zhang, Zhongsi Hong, Jinyu Xia
Journal: Journal of Infection (2020)

BackgroundCorona Virus Disease 2019 (COVID-19) due to the 2019 novel coronavirus (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China. We aimed to compare arbidol and lopinavir/ritonavir(LPV/r) treatment for patients with COVID-19 with LPV/r only.MethodsIn this retrospective cohort study, we included adults (age≥18years) with laboratory-confirmed COVID-19 without Invasive ventilation, diagnosed between Jan 17, 2020, and Feb 13, 2020. Patients, diagnosed after Jan 17, 2020, were given oral arbidol and LPV/r in the combination group and oral LPV/r only in the monotherapy group for 5–21 days. The primary endpoint was a negative conversion rate of coronavirus from the date of COVID-19 diagnosis(day7, day14), and assessed whether the pneumonia was progressing or improving by chest CT (day7).ResultsWe analyzed 16 patients who received oral arbidol and LPV/r in the combination group and 17 who oral LPV/r only in the monotherapy group, and both initiated after diagnosis. Baseline clinical, laboratory, and chest CT characteristics were similar between groups. The SARS-CoV-2 could not be detected for 12(75%) of 16 patients' nasopharyngeal specimens in the combination group after seven days, compared with 6 (35%) of 17 in the monotherapy group (p < 0·05). After 14 days, 15 (94%) of 16 and 9 (52·9%) of 17, respectively, SARS-CoV-2 could not be detected (p < 0·05). The chest CT scans were improving for 11(69%) of 16 patients in the combination group after seven days, compared with 5(29%) of 17 in the monotherapy group (p < 0·05).ConclusionIn patients with COVID-19, the apparent favorable clinical response with arbidol and LPV/r supports further LPV/r only.
MKL1 deficiency results in a severe neutrophil motility defect due to impaired actin polymerization
Authors: Evelien G. G. Sprenkeler, Stefanie S. V. Henriet, Anton T. J. Tool, Iris C. Kreft, Ivo van der Bijl, Cathelijn E. M. Aarts, Michel van Houdt, Paul J. J. H. Verkuijlen, Koen van Aerde, Gerald Jaspers, Arno van Heijst, Wouter Koole, Thatjana Gardeitchik, Judy Geissler, Martin de Boer, Simon Tol, Christine W. Bruggeman, Floris P. J. van Alphen, Han J. M. P. Verhagen, Emile van den Akker, Hans Janssen, Robin van Bruggen, Timo K. van den Berg, Kian D. Liem, Taco W. Kuijpers
Journal: Blood (2020)
Abstract 27: Group- Plus Home-based Tai Chi Program Improves Physical Function and Psychosocial Well-being Among Patients With Coronary Heart Disease
Authors: Ting Liu, Sek Ying Chair, Aileen W Chan
Journal: Circulation (2020)

Introduction: Substantial evidences demonstrate impaired physical health and decreased psychosocial well-being among patients with coronary heart disease (CHD). Tai Chi is an effective exercise option in cardiac rehabilitation to manage CHDs. There has been an increasing focus on home-based cardiac rehabilitation to improve participation rate, while none of studies emphasized the effect of home-based Tai Chi program. Hypothesis: A group- plus home-based Tai Chi program improves physical function (aerobic endurance, lower-body strength, lower-body flexibility, and agility and dynamic balance), and psychosocial well-being (perceived stress, social support, exercise self-efficacy) among CHD patients. Methods: In this randomized controlled trial, 98 community-dwelling patients with CHD (mean age: 69.2±4.68 years; 69 women; 29 men) were randomized to Tai Chi (n=49) or control group (n=49). Participants in Tai Chi group first attended 6 weeks supervised group-based Tai Chi classes that were scheduled as follows: 2 times/week for week 1 and 2, 3 times/week for weeks 3 and 4, and then 4 times/week for week 5 and 6, with 60 minutes/class. After that, participants in Tai Chi group practiced home-based Tai Chi 4 times/week, 60 minutes for each time, for another 6 weeks. Outcomes, namely, aerobic endurance, lower-body strength, lower-body flexibility, and agility and dynamic balance were tested by 2-Minute Step Test (steps), Chair Stand Test (times), Chair Sit-and-Reach Test (cm), and 8-Foot Up-and-Go Test (seconds), respectively. Other outcomes included perceived stress, social support, and exercise self-efficacy. Data were collected at baseline, post group-based Tai Chi training at 6-week, post Tai Chi intervention at 12-week, and at 24-week follow-up assessment. Generalized estimating equations models were used to compare changes in outcomes over time between groups. Results: Compared to changes in control group, Tai Chi showed significant improvements in aerobic endurance (+12 steps), lower-body strength (+3 times), agility and dynamic balance (log-transformed score: -0.058s), perceived stress, emotional support, belonging support, tangible support, and exercise self-efficacy at 24-week. Significant improvement in lower-body flexibility (4 cm) was only achieved at 12-week, compared to changes in control group. No significant changes in self-esteem support over time between groups were observed. Intervention adherence: Tai Chi=79.6% (39 of 49) (attending ≥75% of total Tai Chi sessions). Attrition rate: Tai Chi=20.4% (10 of 49), control=24.5% (12 of 49). Conclusions: This Tai Chi program significantly improve physical function and psychosocial well-being among CHD patients, indicating that Tai Chi could be taught in group sessions and then continued independently as a home exercise routine for health promotion in CHD patients.
Long-lived T follicular helper cells retain plasticity and help sustain humoral immunity
Authors: Marco Künzli, David Schreiner, Tamara C. Pereboom, Nivedya Swarnalekha, Ludivine C. Litzler, Jonas Lötscher, Yusuf I. Ertuna, Julien Roux, Florian Geier, Roman P. Jakob, Timm Maier, Christoph Hess, Justin J. Taylor, Carolyn G. King
Journal: Science Immunology (2020)

CD4+ memory T cells play an important role in protective immunity and are a key target in vaccine development. Many studies have focused on T central memory (Tcm) cells, whereas the existence and functional significance of long-lived T follicular helper (Tfh) cells are controversial. Here, we show that Tfh cells are highly susceptible to NAD-induced cell death (NICD) during isolation from tissues, leading to their underrepresentation in prior studies. NICD blockade reveals the persistence of abundant Tfh cells with high expression of hallmark Tfh markers to at least 400 days after infection, by which time Tcm cells are no longer found. Using single-cell RNA-seq, we demonstrate that long-lived Tfh cells are transcriptionally distinct from Tcm cells, maintain stemness and self-renewal gene expression, and, in contrast to Tcm cells, are multipotent after recall. At the protein level, we show that folate receptor 4 (FR4) robustly discriminates long-lived Tfh cells from Tcm cells. Unexpectedly, long-lived Tfh cells concurrently express a distinct glycolytic signature similar to trained immune cells, including elevated expression of mTOR-, HIF-1-, and cAMP-regulated genes. Late disruption of glycolysis/ICOS signaling leads to Tfh cell depletion concomitant with decreased splenic plasma cells and circulating antibody titers, demonstrating both unique homeostatic regulation of Tfh and their sustained function during the memory phase of the immune response. These results highlight the metabolic heterogeneity underlying distinct long-lived T cell subsets and establish Tfh cells as an attractive target for the induction of durable adaptive immunity.
Under Our Very Eyes
Authors: Alan Koff, Maricar Malinis, Santiago Delgado, Matthew Grant, Tariq Ahmad
Journal: New England Journal of Medicine (2020)

A 64-year-old man with a history of ischemic cardiomyopathy presented to the emergency department in the summer with intermittent high fevers that had begun 7 weeks after he underwent heart transplantation at that hospital. He also reported chills, nausea, and headaches.
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
Authors: Fei Zhou, Ting Yu, Ronghui Du, Guohui Fan, Ying Liu, Zhibo Liu, Jie Xiang, Yeming Wang, Bin Song, Xiaoying Gu, Lulu Guan, Yuan Wei, Hui Li, Xudong Wu, Jiuyang Xu, Shengjin Tu, Yi Zhang, Hua Chen, Bin Cao
Journal: The Lancet (2020)
The microbiome modulating activity of bile acids
Authors: Yuan Tian, Wei Gui, Imhoi Koo, Philip B. Smith, Erik L. Allman, Robert G. Nichols, Bipin Rimal, Jingwei Cai, Qing Liu, Andrew D. Patterson
Journal: Gut Microbes (2020)

Bile acids are potent antibacterial compounds and play an important role in shaping the microbial ecology of the gut. Here, we combined flow cytometry, growth rate measurements (OD600), and NMR- and mass spectrometry-based metabolomics to systematically profile the impact of bile acids on the microbiome using in vitro and in vivo models. This study confirmed that (1) unconjugated bile acids possess more potent antibacterial activity than conjugated bile acids; (2) Gram-positive bacteria are more sensitive to bile acids than Gram-negative bacteria; (3) some probiotic bacteria such as Lactobacillus and Bifidobacterium and 7α-dehydroxylating bacteria such as Clostridium scindens show bile acid resistance that is associated with activation of glycolysis. Moreover, we demonstrated that (4) as one of most hydrophobic bile acids, lithocholic acid (LCA) shows reduced toxicity to bacteria in the cecal microbiome in both in vivo and in vitro models; (5) bile acids directly and rapidly affect bacterial global metabolism including membrane damage, disrupted amino acid, nucleotide, and carbohydrate metabolism; and (6) in vivo, short-term exposure to bile acids significantly affected host metabolism via alterations of the bacterial community structure. This study systematically profiled interactions between bile acids and gut bacteria providing validation of previous observation and new insights into the interaction of bile acids with the microbiome and mechanisms related to bile acid tolerance.
Abstract P555: Plasma Lipids And The Risk For Stroke In The Reasons For Geographic And Racial Differences In Stroke Study (regards).
Authors: Neil Zakai, Jessica Minnier, Monika M Safford, Lisandro Colantonio, Marguerite M Irvin, Sergio Fazio, Mary Cushman, Virginia J Howard, Nathalie Pamir
Journal: Circulation (2020)

Introduction: Whether plasma lipid levels are associated with stroke risk remains controversial, with even less data for American blacks versus whites. Hypothesis: We hypothesized that abnormal lipid levels are not associated with stroke incidence in either blacks or whites. Methods: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study recruited 30,283 black and white individuals aged 45+ from the contiguous U.S. between 2003 to 2007, participants with a history of stroke at baseline were excluded. Participants were followed until 2018 for stroke events following the WHO definition and confirmed by review of medical records. The association of lipid measures with stroke were assessed using Cox regression models adjusted for traditional CVD risk factors and an age-x-race interaction term. Results: With 27,714 participants (mean age 64.85± 9.43, 59.5% white and 55.4% female), over a median of 11 years of follow up, 1,415 stroke events occurred, of which 599 among blacks. After adjusting for traditional stroke risk factors, there were modest associations between higher total cholesterol and higher LDL, but not higher triglycerides, with stroke risk. There was no evidence of a race interaction. Overall, HDL levels were not associated with stroke risk. However, when stratified by race, whites had a reduced risk of stroke with higher HDL-C, whereas no association was seen among blacks (p-interaction 0.09). Conclusion: In REGARDs, there was a modest association of cholesterol measures with stroke risk. The association for HDL with stroke may be influenced by race, with a less strong association among blacks than among whites.
Abstract P137: Women Experience A Greater Decline In Brachial Artery Distensibility With Age Than Men
Authors: Martin Cech, Amena Keshawarz, Janet Snell-bergeon
Journal: Circulation (2020)

Introduction: Brachial artery distensibility is reduced in type 1 diabetes and can predict future coronary artery disease (CAD). Although women generally have reduced cardiovascular risk as compared with men, type 1 diabetes increases cardiovascular risk to a greater degree in women such that their cardiovascular risk matches that in men. Sex differences in arterial distensibility may contribute to the increased cardiovascular risk in women with type 1 diabetes. Hypothesis: We tested the hypothesis that brachial distensibility differed by sex and by diabetes status in a cohort of adults with and without type 1 diabetes. Methods: We measured brachial distensibility via DynaPulse instrument (PulseMetric, San Diego, CA) in 268 adults with type 1 diabetes (mean age 44±9 years) and 373 adults without diabetes (mean age 47 ±8 years) who completed clinical study visits 8±0.89 years apart. A linear mixed model was used to calculate mean brachial distensibility by age at the study visits in men and women by diabetes status. This model was adjusted for age, sex, diabetes status, and visit number. An age group*sex*diabetes interaction was used to calculate least squares means (LSmeans) brachial distensibility and examine trends in each stratum of interest. Results: Brachial distensibility decreases with increasing age (Figure 1). This reduction is greatest for women with type 1 diabetes and smallest for men without diabetes, with decreases from the oldest to youngest age group of 2.6 %/mmHg and 0.98 %/mmHg, respectively. Prior to the age of 40 years, women have better brachial distensibility than men regardless of diabetes status, while men have better brachial distensibility than women beginning in the 40-45 years age group. Conclusions: Women experience a steeper decline in their brachial distensibility than men regardless of diabetes status. Rapid reduction in brachial distensibility may contribute to the increases in cardiovascular risk in women with type 1 diabetes.
Evaluation of<i> POLE/POLD1</i> Variants as Potential Biomarkers for Immune Checkpoint Inhibitor Treatment Outcomes
Authors: Lisa Golmard, Jean-Louis Golmard, Dominique Stoppa-Lyonnet
Journal: JAMA Oncology (2020)

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Current and future treatments for tuberculosis
Authors: Anthony Lee, Yingda Linda Xie, Clifton E Barry, Ray Y Chen
Journal: BMJ (2020)

Guidelines on the treatment of tuberculosis (TB) have essentially remained the same for the past 35 years, but are now starting to change. Ongoing clinical trials will hopefully transform the landscape for treatment of drug sensitive TB, drug resistant TB, and latent TB infection. Multiple trials are evaluating novel agents, repurposed agents, adjunctive host directed therapies, and novel treatment strategies that will increase the probability of success of future clinical trials. Guidelines for HIV-TB co-infection treatment continue to be updated and drug resistance testing has been revolutionized in recent years with the shift from phenotypic to genotypic testing and the concomitant increased speed of results. These coming changes are long overdue and are sorely needed to address the vast disparities in global TB incidence rates. TB is currently the leading cause of death globally from a single infectious agent, but the work of many researchers and the contributions of many patients in clinical trials will reduce the substantial global morbidity and mortality of the disease.
Abstract P156: Recruitment and Retention of an American Indian Cohort - The Strong Heart Study Reducing Disparities Through Research
Authors: Marcia O'Leary, Tauqeer Ali, Cynthia West, Marie Gross
Journal: Circulation (2020)

Tribal communities have legitimate reasons for being wary of research. The Strong Heart Study works to coordinate multi-disciplinary efforts towards bidirectional partnerships, with an ethos of respect and capacity development. Best practices are being developed through iterative processes including co-development of survey research through translating/communicating data analysis and applying CBPR practices. Information translation and CBPR throughout the research process also includes participating in community-based research symposia, developing site specific information through informational venues (e.g. Red Talks), formal reporting to Tribal councils and health committees, informal interaction by participating in local Native American community events, engaging Community Advisory groups, and supporting local students through hands-on internships. These activities also enhance transition of traditional public health research to a support a more autonomous, individualized system for the Tribal partners toward greater self-determining their own health. This approach encourages health literacy, promotes Institutional memory and automates longitudinal surveillance of local health issues to reduce disparities in Tribal nations.