tbuckley/cabot-search huggingface dataset:
Abstract A40: The SIAMCAT R package enables statistical and machine learning analyses for case-control microbiome datasets
Authors: Jakob Wirbel, Konrad Zych, Morgan Essex, Nicolai Karcher, Ece Kartal, Guillem Salazar, Peer Bork, Shinichi Sunagawa, Georg Zeller
Journal: Cancer Research (2020)

Abstract Alterations in microbiome composition have been linked to many human diseases, including colorectal cancer or precancerous liver diseases. Findings from microbiome-association studies are increasingly explored as promising avenues for clinical applications due to their diagnostic or therapeutic potential. However, microbiome data complexity and the lack of integrated computational tools make it difficult to arrive at robust associations and predictive disease models. Here, we present the SIAMCAT R package as a modular and user-friendly toolbox for machine learning workflows, statistical analysis, and confounder detection for case-control microbiome datasets. Previously, we conducted a machine learning meta-analysis of colorectal cancer metagenomics studies (Wirbel, Pyl et al., Nat Med 2019) using the functionalities of SIAMCAT, which is now available to the wider community via Bioconductor. We showcase how SIAMCAT is a versatile tool by applying it to a large set of metagenomic datasets that have been processed with a wide variety of taxonomic and functional profiling tools. We furthermore demonstrate how SIAMCAT can help to detect confounding factors in microbiome association studies. By making stringent machine learning workflows and analysis pipelines available through a user-friendly and flexible interface, SIAMCAT will facilitate microbiome data analyses, biomarker discovery, and thus the translation of microbiome research to clinical applications, while simultaneously improving statistical rigor and safeguarding against common machine learning pitfalls. Citation Format: Jakob Wirbel, Konrad Zych, Morgan Essex, Nicolai Karcher, Ece Kartal, Guillem Salazar, Peer Bork, Shinichi Sunagawa, Georg Zeller. The SIAMCAT R package enables statistical and machine learning analyses for case-control microbiome datasets [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A40.
Single-Therapy Androgen Suppression in Men with Advanced Prostate Cancer
Authors: Jerome Seidenfeld, David J. Samson, Vic Hasselblad, Naomi Aronson, Peter C. Albertsen, Charles L. Bennett, Timothy J. Wilt
Journal: Annals of Internal Medicine (2000)

Purpose: To compare luteinizing hormone-releasing hormone (LHRH) agonists with orchiectomy or diethylstilbestrol, and to compare antiandrogens with any of these three alternatives. Data Sources: A search of the MEDLINE, Cancerlit, EMBASE, and Cochrane Library databases from 1966 to March 1998 and Current Contents to 24 August 1998 for articles comparing the outcomes of the specified treatments. The search was limited to studies on prostatic neoplasms in humans. Total yield was 1477 studies. Study Selection: Reports of efficacy outcomes were limited to randomized, controlled trials. Twenty-four trials involving more than 6600 patients, phase II studies that reported on withdrawals from therapy (the most reliable indicator of adverse effects), and all studies reporting on quality of life were abstracted. Data Extraction: Two independent reviewers abstracted each article by following a prospectively designed protocol. The meta-analysis combined data on 2-year overall survival by using a random-effects model and reported results as a hazard ratio relative to orchiectomy. Data Synthesis: Ten trials of LHRH agonists involving 1908 patients reported no significant difference in overall survival. The hazard ratio showed LHRH agonists to be essentially equivalent to orchiectomy (hazard ratio, 1.262 [95% CI, 0.915 to 1.386]). There was no evidence of difference in overall survival among the LHRH agonists, although CIs were wider for leuprolide (hazard ratio, 1.0994 [CI, 0.207 to 5.835]) and buserelin (hazard ratio, 1.1315 [CI, 0.533 to 2.404]) than for goserelin (hazard ratio, 1.1172 [CI, 0.898 to 1.390]). Evidence from 8 trials involving 2717 patients suggests that nonsteroidal antiandrogens were associated with lower overall survival. The CI for the hazard ratio approached statistical significance (hazard ratio, 1.2158 [CI, 0.988 to 1.496]). Treatment withdrawals were less frequent with LHRH agonists (0% to 4%) than with nonsteroidal antiandrogens (4% to 10%). Conclusions: Survival after therapy with an LHRH agonist was equivalent to that after orchiectomy. No evidence shows a difference in effectiveness among the LHRH agonists. Survival rates may be somewhat lower if a nonsteroidal antiandrogen is used as monotherapy.
Triggering itch in laboratory studies using histamine or audio‐visual materials
Authors: R. Marzell, G. Reichwein, U. Gieler, J. Kupfer, C. Schut
Journal: British Journal of Dermatology (2020)

Itch is a major symptom of many skin diseases, and in some scientific studies, researchers want to deliberately trigger an itch on volunteers’ skin. There are different methods to induce itch in laboratory settings. One possibility is to transfer an itch inducing substance produced by the body, called histamine, into the skin by use of a light current. This method is called histamine‐iontophoresis and requires ‘direct skin manipulation’. A different, ‘non‐skin manipulating’ method is providing the volunteers with itch‐related audio‐visual material (for example, slides or videos of crawling insects). From other studies it is well‐known that the experience of itch also depends on the person's attention. With this study researchers from Germany aimed to find out whether itch induced (triggered) by audio‐visual material is comparable to itch induced by histamine‐iontophoresis in two situations: not focusing on the skin before itch induction (study 1a) and focusing on the skin before itch induction (study 1b). In study 1a, all 80 subjects rested for 10 minutes. Then 40 of them were shown the itch inducing video, while in the other 40 histamine was applied. Study 1b was the same as 1a, except that instead of resting for 10 minutes, all 80 subjects watched a non‐itch inducing video on the skin before receiving either histamine itch‐induction (40 people) or watching itch‐related audio‐visual material (40 people). Itch was measured by asking the participants how intense their maximum itch was, and how intense the itch was immediately after it was induced. The researchers found that the maximum itch induced by audio‐visual material was comparable to the maximum itch induced by histamine, but only when subjects watched a non‐itch inducing video on the skin before itch induction (study 1b). However, histamine‐induced itch was actually more intense when volunteers did not focus on the skin before itch induction (study 1a). This suggests that channelling the attention of the volunteers before itch induction is important when researchers would like to use itch‐related stimuli (such as audio‐visual materials) in their studies as an alternative to histamine‐iontophoresis. This is a summary of the study: Itch induction by audiovisual stimuli and histamine iontophoresis: a randomized, controlled, noninferiority study.
Phase 1 trial of oral MAC-321 in subjects with advanced malignant solid tumors
Authors: A. X. Zhu, R. Bukowski, A. C. Lockhart, K. K. Wang, W. Cooper, J. Grover, M. Cohen, L. Appleman, M. Shapiro, M. L. Rothenberg
Journal: Journal of Clinical Oncology (2004)

2040 Background: MAC-321 is a novel taxane that has demonstrated exceptional activity in human xenograft models when administered intravenously and orally. Preclinical studies of MAC-321 have shown antitumor activity in MDR-expressing and paclitaxel-resistant tumors. Methods: This phase 1 ascending-dose study was performed to determine the safety and tolerability of orally administered MAC-321 given once every 21 days. Preliminary antitumor activity of MAC-321 was also examined. Key eligibility criteria included adult patients with refractory solid tumors, good performance status (ECOG ≤ 2), and adequate hematologic, hepatic, and renal function. Plasma pharmacokinetic (PK) sampling was performed during the first cycle of therapy. Results: 18 patients (4 females, 14 males) were evaluated at 5 dose levels ranging from 25 to 75 mg/m2. Treatment was well tolerated at the first 3 dose levels (25, 37, 50 mg/m2). Two patients developed dose-limiting toxicities (DLTs) at 75 mg/m2 (1 patient with grade 3 neutropenia with fever, another patient had grade 4 neutropenia with fever). Three patients were treated at an intermediate dose level of 60 mg/m2 without DLTs. Other common toxicities included grade 1–2 fatigue and grade 1–2 diarrhea. Disease stabilization was seen in 4 patients with the following tumors: mesothelioma (14 cycles), chondrosarcoma (12 cycles), small cell carcinoma (10 cycles), and prostate carcinoma (6 cycles). There was substantial interpatient variability in the PK parameters. MAC-321 was absorbed rapidly with mean Tmax less than 1 hour. Mean Cmax and AUC values generally increased in a dose-related manner. The elimination half-life ranged from 20–228 hours. Conclusions: MAC-321 can be safely administered orally once every 21 days up to a dose of 60 mg/m2. The major DLT was neutropenic fever. Four patients had disease stabilization. This study is ongoing to confirm 60 mg/m2 as the maximum tolerated dose and to determine the oral bioavailability of MAC-321. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Taxolog, Inc.; Wyeth
The rise in appendix cancer incidence: 2000-2009.
Authors: Schelomo Marmor, Pamela R. Portschy, Todd M. Tuttle, Beth A. Virnig
Journal: Journal of Clinical Oncology (2013)

e12506 Background: Cancer of the appendix is a rare and potentially aggressive malignancy. The objectives of this study were to characterize secular demographic patterns of disease and to determine survival by using a population-based data source. Methods: Using the Surveillance Epidemiology and End Results database we identified all appendiceal neoplasms reported to the registry between 2000 and 2009.Tumors were classified as carcinoid, adenocarcinoma, mucinous and signet ring cell carcinoma. We compared overall incidence, age distribution by tumor type and overall survival rates by extent of disease at diagnosis. To assess whether the incidence rate, tumor size, and cancer stage changed over time, the Cochrane-Armitage trend test was used. Logistic regression models were used to determine the odds of distant disease at diagnosis and Cox proportional-hazards modeling was used to identify the factors associated with overall survival rates. Results: We identified 4,765 patients with appendix cancer. The incidence of appendiceal cancer increased by 54% from 2000 (0.63 per 100,000) to 2009 (0.97 per 100,000). Incidence rates increased across all tumor types, stages, age groups and gender. The most common malignancies were mucinous (38%), followed by carcinoids (28%) adenocarcinoma (27%), and signet ring cell carcinoma (7%). Distant stage at diagnosis was most common among, signet ring cell tumors (60%). Larger tumor size and older patient age were significantly associated with higher relative odds of distant disease at diagnosis (P &lt; .0001). Tumor type, older age, black race, males, tumor size of 2 cm and greater, cancer stage and registry were significantly associated with higher relative hazard of death (P&lt; .0001). Mean 5-year survival was 55% for carcinoid patients, 49% for adenocarcinoma, 50% for mucinous and 38% for the signet ring cell cohort. Conclusions: Although appendiceal cancer is rare, the incidence increased significantly in the U.S. from 2000 to 2009. The cause of this trend is not obvious. We did not see increases differentially associated with stage, histology, registry or demographic characteristics. Further investigation is needed to examine factors underlying this increase. This research was generously supported by the Betti Boers Maloney Appendix Cancer Research Fund at the University of Minnesota Foundation.
Immunity-related GTPase induces lipophagy to prevent excess hepatic lipid accumulation
Authors: Kristin Schwerbel, Anne Kamitz, Natalie Krahmer, Nicole Hallahan, Markus Jähnert, Pascal Gottmann, Sandra Lebek, Tanja Schallschmidt, Danny Arends, Fabian Schumacher, Burkhard Kleuser, Tom Haltenhof, Florian Heyd, Sofiya Gancheva, Karl W. Broman, Michael Roden, Hans-Georg Joost, Alexandra Chadt, Hadi Al-Hasani, Heike Vogel, Wenke Jonas, Annette Schürmann
Journal: Journal of Hepatology (2020)

Currently, only a few genetic variants explain the heritability of fatty liver disease. Quantitative trait loci (QTL) analysis of mouse strains has identified the susceptibility locus Ltg/NZO (liver triglycerides from New Zealand obese [NZO] alleles) on chromosome 18 as associating with increased hepatic triglycerides. Herein, we aimed to identify genomic variants responsible for this association.
Association of Behavioral Nudges With High-Value Evidence-Based Prescribing in Oncology
Authors: Samuel U. Takvorian, Vrushabh P. Ladage, E. Paul Wileyto, Drew S. Mace, Rinad S. Beidas, Lawrence N. Shulman, Justin E. Bekelman
Journal: JAMA Oncology (2020)

This interrupted time series analysis evaluates the association of nudges with zoledronate prescription vs more expensive denosumab.
Natural history of naevi: a two‐wave study
Authors: S. Ribero, D. Zugna, T. Spector, V. Bataille
Journal: British Journal of Dermatology (2020)

Background Naevi number changes with age. Thus, a better understanding of naevus biology will shed more light on the genetic and environmental factors involved in melanoma development. Objectives To use a two-wave study to better understand the evolution of naevi in healthy adults. Methods This study is a prospective two-wave study based on adult twins from the TwinsUK registry (n = 414) who underwent total body naevus counts with an interval of at least 15 years. A negative binomial hierarchical model with two levels, the individual and the twin pair, was used to estimate expected changes in naevus count between the first and second visit, at any specific body site and on the whole body. The model was adjusted for age, calendar year at the first visit, height and skin type. Results The mean age of participants was 46 years at the first visit and 63 years at the second visit (the mean elapsed time between visits was 17 years). An increase in naevus count was observed in 235 (57%) participants and a decrease was observed in 166 (40%). The mean difference in total naevus count between the two visits was nine. The expected total body naevus count increased, on a logarithmic scale, by 0·28 [95% confidence interval (CI) 0·16–0·40] with a change in the incidence rate of total body naevus count of 32% (95% CI 17–49%). However, the observed increase in naevus count over time was observed only on the upper parts of the body, whereas there was no evidence of an increase on the lower parts. Conclusions Naevus counts increased slightly over time at older ages, but this was dependent on body site. The overall decrease in naevus counts previously reported in cross-sectional studies has not been confirmed by this longitudinal study.
Reply to: “Comparison of daily dosing vs. Monday through Friday dosing of vismodegib for locally advanced basal cell carcinoma (laBCC) and basal cell nevus syndrome: A retrospective case series”
Authors: Alessia Villani, Claudia Costa, Gabriella Fabbrocini, Milena Cappello, Massimiliano Scalvenzi
Journal: Journal of the American Academy of Dermatology (2020)
Skp2 in the ubiquitin‐proteasome system: A comprehensive review
Authors: Moges Dessale Asmamaw, Ying Liu, Yi‐Chao Zheng, Xiao‐Jing Shi, Hong‐Min Liu
Journal: Medicinal Research Reviews (2020)

Abstract The ubiquitin‐proteasome system (UPS) is a complex process that regulates protein stability and activity by the sequential actions of E1, E2 and E3 enzymes to influence diverse aspects of eukaryotic cells. However, due to the diversity of proteins in cells, substrate selection is a highly critical part of the process. As a key player in UPS, E3 ubiquitin ligases recruit substrates for ubiquitination specifically. Among them, RING E3 ubiquitin ligases which are the most abundant E3 ubiquitin ligases contribute to diverse cellular processes. The multisubunit cullin‐RING ligases (CRLs) are the largest family of RING E3 ubiquitin ligases with tremendous plasticity in substrate specificity and regulate a vast array of cellular functions. The F‐box protein Skp2 is a component of CRL1 (the prototype of CRLs) which is expressed in many tissues and participates in multiple cellular functions such as cell proliferation, metabolism, and tumorigenesis by contributing to the ubiquitination and subsequent degradation of several specific tumor suppressors. Most importantly, Skp2 plays a pivotal role in a plethora of cancer‐associated signaling pathways. It enhances cell growth, accelerates cell cycle progression, promotes migration and invasion, and inhibits cell apoptosis among others. Hence, targeting Skp2 may represent a novel and attractive strategy for the treatment of different human cancers overexpressing this oncogene. In this review article, we summarized the known roles of Skp2 both in health and disease states in relation to the UPS.
Lactation improves pancreatic β cell mass and function through serotonin production
Authors: Joon Ho Moon, Hyeongseok Kim, Hyunki Kim, Jungsun Park, Wonsuk Choi, Wongun Choi, Hyun Jung Hong, Hyun-Joo Ro, Sangmi Jun, Sung Hee Choi, Ronadip R. Banerjee, Minho Shong, Nam Han Cho, Seung K. Kim, Michael S. German, Hak Chul Jang, Hail Kim
Journal: Science Translational Medicine (2020)

Lactation benefits women’s metabolic health by improving pancreatic β cell mass and function through serotonin production in β cells.
External heated humidification during non-invasive ventilation set up: results from a pilot cross-over clinical trial
Authors: Swapna Mandal, Michelle Ramsay, Eui-Sik Suh, Rachel Harding, April Thompson, Abdel Douiri, John Moxham, Patrick Brian Murphy, Nicholas Hart
Journal: European Respiratory Journal (2020)

Patient comfort is important in ensuring adherence to domiciliary non-invasive ventilation (NIV). Oronasal dryness is often reported with NIV use [1], but the use of heated humidification in clinical practice is not uniform [2]. As there are limited data to currently guide clinical practice, we investigated the effect of external heated humidification on neural respiratory drive (NRD), patient–ventilator asynchrony (PVA), patient-reported outcomes, ventilator performance and adherence in a pilot randomised crossover trial in patients with chronic respiratory failure during NIV set up. Short-term heated humidification has limited effect on physiological and clinical outcomes during non-invasive ventilation set up <http://bit.ly/31cFfGt> A. Douiri and N. Hart acknowledge the support of the National Institute for Health Research (NIHR) Clinical Research Facility at Guy's and St Thomas' NHS Foundation Trust and NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals
Authors: Ling Ni, Fang Ye, Meng-Li Cheng, Yu Feng, Yong-Qiang Deng, Hui Zhao, Peng Wei, Jiwan Ge, Mengting Gou, Xiaoli Li, Lin Sun, Tianshu Cao, Pengzhi Wang, Chao Zhou, Rongrong Zhang, Peng Liang, Han Guo, Xinquan Wang, Cheng-Feng Qin, Fang Chen, Chen Dong
Journal: Immunity (2020)
Effect of Epicardial or Biventricular Pacing to Prolong QT Interval and Increase Transmural Dispersion of Repolarization
Authors: Victor A. Medina-Ravell, Ramarao S. Lankipalli, Gan-Xin Yan, Charles Antzelevitch, Napoleon A. Medina-Malpica, Otto A. Medina-Malpica, Christopher Droogan, Peter R. Kowey
Journal: Circulation (2003)

Background— The present study examined pacing site–dependent changes in QT interval and transmural dispersion of repolarization (TDR) and their potential role in the development of torsade de pointes (TdP). Methods and Results— In humans, the QT interval, JT interval, and TDR were measured in 29 patients with heart failure during right ventricular endocardial pacing (RVEndoP), biventricular pacing (BiVP), and left ventricular epicardial pacing (LVEpiP). In animal experiments, pacing site–dependent changes in ventricular repolarization were examined with a rabbit left ventricular wedge preparation in which action potentials from endocardium and epicardium could be simultaneously recorded with a transmural ECG. In humans, LVEpiP and BiVP led to significant QT and JT prolongation. LVEpiP also enhanced TDR. Frequent R-on-T extrasystoles generated by BiVP and LVEpiP but completely inhibited by RVEndoP occurred in 4 patients, of whom 1 developed multiple episodes of nonsustained polymorphic ventricular tachycardia and another suffered incessant TdP. In rabbit experiments, switching from endocardial to epicardial pacing produced a net increase in QT interval and TDR by 17±5 and 22±5 ms, respectively (n=6, P &lt;0.01), without parallel increases in ventricular transmembrane action potential durations. Epicardial pacing facilitated transmural propagation of early afterdepolarization, leading to the development of R-on-T extrasystoles and TdP in the presence of action potential duration–prolonging agents. Conclusions— LVEpiP and BiVP increase QT, JT, and TDR by altering the transmural sequence of activation of the intrinsically heterogeneous ventricular myocardium. Our data suggest that the resultant exaggeration of arrhythmic substrates can lead to the development of TdP in a subset of patients.
Effects of IGF2BP2, KCNQ1, and GCKR polymorphisms on clinical outcome in metastatic gastric cancer treated with EOF regimen.
Authors: Xin Liu, Zhiyu Chen, Xiaoying Zhao, Mingzhu Huang, Chenchen Wang, Wei Peng, Ji Liang Yin, Jin Li, Guang He, Xin Li, Xiaodong Zhu
Journal: Journal of Clinical Oncology (2015)

64 Background: Genetic variants of T2D (type 2 diabetes mellitus)-related genes may increase the risk of gastric cancer (GC), but its role in predicting chemotherapy efficacy and GC outcome has not been investigated. The present study analyzed the polymorphisms of T2D-related genes and their impacts on the response to chemotherapy and survival of patients with metastatic gastric cancer (MGC). Methods: 108 consecutive patients with MGC treated with first-line chemotherapy of EOF regimen (epirubicin, oxaliplatin and 5Fu) were enrolled in the present retrospective study. The genomic DNA was extracted from blood samples, and eleven single nucleotide polymorphisms (SNPs) of five T2D-related genes (IGF2BP2, CDKAL1, FTO, KCNQ1 and GCKR) were determined using a polymerase chain reaction–restriction fragment length polymorphism assay. Results: Among the 11 SNPs, 3 SNPs (IGF2BP2 rs4402960, IGF2BP2 rs6769511 and KCNQ1 rs163182) were significantly associated with the disease control rate; 2 GCKR SNPs rs780093 and rs780094 were significantly associated with the PFS and OS. The genotype frequencies of rs4402960, rs6769511 and rs163182 showed significant differences between disease control (CR+PR+SD) and disease progressive (PD) patients (p = 0.031, p = 0.034 and P =0.020, respectively). After adjustment for clinical features in a multivariate Cox model, the GCKR SNPs rs780093 and rs780094 showed statistically significant impact on PFS (rs780093: HR,.477; 95% CI,.278-.820 and P =.007; rs780094: HR,.458; 95% CI,.266-.791 and P =.005) and OS (rs780093: HR,.471; 95% CI,.244-.910 and P =.025; rs780094: HR,.442; 95% CI,.228-.858 and P =.016). Conclusions: Our results firstly suggest that IGF2BP2 and KCNQ1 polymorphisms might be independent predictors of the response to chemotherapy and GCKR polymorphisms might be independent predictors of the PFS and OS in patients with MGC treated with first-line chemotherapy of EOF regimen in the Chinese Han population.