tbuckley/cabot-search huggingface dataset:
Island Biogeography Revisited: Museomics Reveals Affinities of Shelf Island Birds Determined by Bathymetry and Paleo-Rivers, Not by Distance to Mainland
Authors: Kritika M Garg, Balaji Chattopadhyay, Emilie Cros, Suzanne Tomassi, Suzan Benedick, David P Edwards, Frank E Rheindt
Journal: Molecular Biology and Evolution (2021)

Island biogeography is one of the most powerful subdisciplines of ecology: its mathematical predictions that island size and distance to mainland determine diversity have withstood the test of time. A key question is whether these predictions follow at a population-genomic level. Using rigorous ancient-DNA protocols, we retrieved approximately 1,000 genomic markers from approximately 100 historic specimens of two Southeast Asian songbird complexes from across the Sunda Shelf archipelago collected 1893-1957. We show that the genetic affinities of populations on small shelf islands defy the predictions of geographic distance and appear governed by Earth-historic factors including the position of terrestrial barriers (paleo-rivers) and persistence of corridors (Quaternary land bridges). Our analyses suggest that classic island-biogeographic predictors may not hold well for population-genomic dynamics on the thousands of shelf islands across the globe, which are exposed to dynamic changes in land distribution during Quaternary climate change.
Abstract 14456: Rethinking The Treatment Of Cardiac Arrest To Include Non-oxygen Metabolite Supplementation: Plasma Lysophosphatidylcholine Level Maintenance After Cardiac Arrest Is Critical For Survival
Authors: Muhammad Shoaib, Mitsuaki Nishikimi, Rishabh Choudhary, Tai Yin, Kei Hayashida, Santiago Miyara, Nancy Kim, Lance B Becker, Junhwan Kim
Journal: Circulation (2021)

Cardiac arrest (CA) is a loss of circulation that curtails the supply of oxygen and non-oxygen metabolites to the whole body resulting in ischemia and death. Subsequent resuscitation is vital for survival, but also causes reperfusion injury. Oxygen deprivation as one arm of ischemia-reperfusion injury and its relationship with death is well-established, but its counterpart, metabolite dysfunction, is overlooked and poorly understood. We have previously shown that many metabolites are not normalized as efficiently or rapidly after resuscitation especially, particularly those that are severely decreased after CA. As such, we hypothesize that appropriate replenishment of certain metabolites is essential for survival. Lysophosphatidylcholine (LPC), an important family of phospholipids, is an example of such non-oxygen metabolites required post-CA. With multifactorial roles for maintaining homeostasis, such as acting as an energy substrate, maintaining membrane integrity, and functioning in inter- and intra-cellular signaling, decreased levels of LPC post-CA disrupts the various physiologic responsibilities resulting in profound systemic effects causing cellular and organ system injury. In this analysis, 1) phospholipid screening using HPLS-MS on plasma samples obtained from asphyxial-CA rats and human CA patients shows that LPC significantly decreases post-CA, especially during the reperfusion phase, and is strongly correlated with the duration of preceding CA and poor neurological/survival outcomes, and 2) individual supplementation of three species of LPC (LPC 18:0, LPC 18:1, and LPC 22:6) following resuscitation after 10 and 12 min rat CA helps improve survival and brain function as compared with vehicle. Overall, our study highlights that LPC is an essential, non-oxygen metabolite that is necessary to help promote survival after CA in rats that has therapeutic potential for human translation.
Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline
Authors: Michael A. Vogelbaum, Paul D. Brown, Hans Messersmith, Priscilla K. Brastianos, Stuart Burri, Dan Cahill, Ian F. Dunn, Laurie E. Gaspar, Na Tosha N. Gatson, Vinai Gondi, Justin T. Jordan, Andrew B. Lassman, Julia Maues, Nimish Mohile, Navid Redjal, Glen Stevens, Erik Sulman, Martin van den Bent, H. James Wallace, Jeffrey S. Weinberg, Gelareh Zadeh, David Schiff
Journal: Journal of Clinical Oncology (2021)

PURPOSE To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. METHODS ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. RECOMMENDATIONS Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non–small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status &lt; 70 with no systemic therapy options do not derive benefit from radiation therapy. Additional information is available at www.asco.org/neurooncology-guidelines .
Biliary colic
Authors: Sandra Hapca, George Ramsay, Peter Murchie, Irfan Ahmed
Journal: BMJ (2021)

### What you need to know A 30 year old woman presents to her general practice with abdominal pain. It started suddenly yesterday evening and lasted for a few hours, but then it came on again in the morning. She says it feels like a tight band around her upper abdomen. She had a similar, less painful, episode a few weeks ago which resolved with over-the-counter analgesia. She is otherwise healthy and has intentionally lost 5 kg in the past six weeks. This article outlines how to assess and manage a patient with suspected biliary colic in primary care. Areas covered include criteria for referral, investigations, and discussion of management options. Abdominal pain is a common presenting symptom with many causes, as outlined in box 1. Gallstone pathology is an important differential. Box 2 describes the spectrum of clinical syndromes that can arise from gallstones. Box 1 ### Differential diagnoses in a patient presenting with epigastric/right upper quadrant painRETURN TO TEXT Box 2 ### Spectrum of clinical syndromes caused by gallstonesRETURN TO TEXT
Herpes zoster reactivation after mRNA-1273 vaccination in patients with rheumatic diseases
Authors: Tai-Ju Lee, Cheng-Hsun Lu, Song-Chou Hsieh
Journal: Annals of the Rheumatic Diseases (2021)

<h3>Abstract</h3> Pancreatic cancers are typically diagnosed at late stage where disease prognosis is poor as exemplified by a 5-year survival rate of 8.2%. Earlier diagnosis would be beneficial by enabling surgical resection or earlier application of therapeutic regimens. We investigated the detection of pancreatic ductal adenocarcinoma (PDAC) in a non-invasive manner by interrogating changes in 5-hydroxymethylation cytosine status (5hmC) of circulating cell free DNA in the plasma of a PDAC cohort (n=51) in comparison with a non-cancer cohort (n=41). We found that 5hmC sites are enriched in a disease and stage specific manner in exons, 3'UTRs and transcription termination sites. Our data show that 5hmC density in H3K4me3 sites is reduced in progressive disease suggesting increased transcriptional activity. 5hmC density is differentially represented in thousands of genes, and a stringently filtered set of the most significant genes exhibited biology related to pancreas (GATA4, GATA6, PROX1, ONECUT1) and/or cancer development (YAP1, TEAD1, PROX1, ONECUT1, ONECUT2, IGF1 and IGF2). Regularized regression models were built using 5hmC densities in statistically filtered genes or a comprehensive set of highly variable gene counts and performed with an AUC = 0.94-0.96 on training data. We were able to test the ability to classify PDAC and non-cancer samples with the elastic net and lasso models on two external pancreatic cancer 5hmC data sets and found validation performance to be AUC = 0.74-0.97. The findings suggest that 5hmC changes enable classification of PDAC patients with high fidelity and are worthy of further investigation on larger cohorts of patient samples.
Decision-tree derivation and external validation of a new clinical decision rule (DISCERN-FN) to predict the risk of severe infection during febrile neutropenia in children treated for cancer
Authors: Mathilde Delebarre, Fanny Gonzales, Hélène Behal, Aude Tiphaine, Hélène Sudour-Bonnange, Anne Lutun, Samuel Abbou, Sophie Pertuisel, Sandrine Thouvenin-Doulet, Isabelle Pellier, Ludovic Mansuy, Christophe Piguet, Catherine Paillard, Laurence Blanc, Estelle Thebaud, Dominique Plantaz, Pascale Blouin, Pascale Schneider, Cécile Guillaumat, Pauline Simon, Carine Domenech, Hélène Pacquement, Marion Le Meignen, Claire Pluchart, Cécile Vérite, Geneviève Plat, Alain Martinot, Alain Duhamel, François Dubos
Journal: The Lancet Child & Adolescent Health (2021)
Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART, IFCT 0503): an open-label, randomised, phase 3 trial
Authors: Cecile Le Pechoux, Nicolas Pourel, Fabrice Barlesi, Delphine Lerouge, Delphine Antoni, Bruno Lamezec, Ursula Nestle, Pierre Boisselier, Eric Dansin, Amaury Paumier, Karine Peignaux, François Thillays, Gerard Zalcman, Jeannick Madelaine, Eric Pichon, Anne Larrouy, Armelle Lavole, Delphine Argo-Leignel, Marc Derollez, Corinne Faivre-Finn, Matthew Q Hatton, Oliver Riesterer, Emilie Bouvier-Morel, Ariane Dunant, John G Edwards, Pascal Alexandre Thomas, Olaf Mercier, Aurelie Bardet
Journal: The Lancet Oncology (2021)
Underdiagnosis bias of artificial intelligence algorithms applied to chest radiographs in under-served patient populations
Authors: Laleh Seyyed-Kalantari, Haoran Zhang, Matthew B. A. McDermott, Irene Y. Chen, Marzyeh Ghassemi
Journal: Nature Medicine (2021)

Abstract Artificial intelligence (AI) systems have increasingly achieved expert-level performance in medical imaging applications. However, there is growing concern that such AI systems may reflect and amplify human bias, and reduce the quality of their performance in historically under-served populations such as female patients, Black patients, or patients of low socioeconomic status. Such biases are especially troubling in the context of underdiagnosis, whereby the AI algorithm would inaccurately label an individual with a disease as healthy, potentially delaying access to care. Here, we examine algorithmic underdiagnosis in chest X-ray pathology classification across three large chest X-ray datasets, as well as one multi-source dataset. We find that classifiers produced using state-of-the-art computer vision techniques consistently and selectively underdiagnosed under-served patient populations and that the underdiagnosis rate was higher for intersectional under-served subpopulations, for example, Hispanic female patients. Deployment of AI systems using medical imaging for disease diagnosis with such biases risks exacerbation of existing care biases and can potentially lead to unequal access to medical treatment, thereby raising ethical concerns for the use of these models in the clinic.
Anticancer drug resistance: An update and perspective
Authors: Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Journal: Drug Resistance Updates (2021)

Driver mutations promote initiation and progression of cancer. Pharmacological treatment can inhibit the action of the mutant protein; however, drug resistance almost invariably emerges. Multiple studies revealed that cancer drug resistance is based upon a plethora of distinct mechanisms. Drug resistance mutations can occur in the same protein or in different proteins; as well as in the same pathway or in parallel pathways, bypassing the intercepted signaling. The dilemma that the clinical oncologist is facing is that not all the genomic alterations as well as alterations in the tumor microenvironment that facilitate cancer cell proliferation are known, and neither are the alterations that are likely to promote metastasis. For example, the common KRas
The parasitophorous vacuole nutrient channel is critical for drug access in malaria parasites and modulates the artemisinin resistance fitness cost
Authors: Paolo Mesén-Ramírez, Bärbel Bergmann, Mourad Elhabiri, Lei Zhu, Heidrun von Thien, Carolina Castro-Peña, Tim-Wolf Gilberger, Elisabeth Davioud-Charvet, Zbynek Bozdech, Anna Bachmann, Tobias Spielmann
Journal: Cell Host & Microbe (2021)
Influenza A(H3N2) Outbreak on a University Campus — Michigan, October–November 2021
Authors: Miranda J. Delahoy, Lindsey Mortenson, Laura Bauman, Juan Marquez, Natasha Bagdasarian, Joseph Coyle, Kelsey Sumner, Nathaniel M. Lewis, Adam S. Lauring, Brendan Flannery, Manish M. Patel, Emily T. Martin
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

On November 10, 2021, the Michigan Department of Health and Human Services (MDHHS) was notified of a rapid increase in influenza A(H3N2) cases by the University Health Service (UHS) at the University of Michigan in Ann Arbor. Because this outbreak represented some of the first substantial influenza activity during the COVID-19 pandemic, CDC, in collaboration with the university, MDHHS, and local partners conducted an investigation to characterize and help control the outbreak. Beginning August 1, 2021, persons with COVID-19-like* or influenza-like illness evaluated at UHS received testing for SARS-CoV-2, influenza, and respiratory syncytial viruses by rapid multiplex molecular assay.† During October 6-November 19, a total of 745 laboratory-confirmed influenza cases were identified.§ Demographic information, genetic characterization of viruses, and influenza vaccination history data were reviewed. This activity was conducted consistent with applicable federal law and CDC policy.¶.
108P PICTuRE: Real-world treatment pathways in stage III non-small cell lung cancer in Portugal
Authors: M.E. Teixeira, M.G. Oliveira Fernandes, M.L.S. Ferreira, F. Estevinho, J.A. Lopes, A. Araújo, M.M. Pacheco Figueiredo, M.L. Barradas Lopes, M. Lopes, U. Brito, A.M.P. Barroso, C. Camacho, B. Parente, M.M. Felizardo, A. Meleiro, M. Bernardo, F. Bernardo, S. Figueiredo
Journal: Annals of Oncology (2021)
Abstract 10936: Gender Disparities in In-Hospital Management of Out-of-Hospital Cardiac Arrest Patients: A Propensity Score Matching Analysis
Authors: Jooyeong Kim, Kim Sung Jin, Sejoong Ahn, Jonghak Park, Juhyun Song, Hanjin Cho
Journal: Circulation (2021)

Background: Gender differences of outcomes of out-of-hospital cardiac arrest (OHCA) were reported in previous studies and still remains uncertainty. Furthermore, gender disparities in in-hospital management are not well studied. Hypothesis: We hypothesized there is differences in in-hospital management in OHCA patients by gender in Korea. Method: This is an observational study using Korean Cardiac Arrest Research Consortium (KoCARC) data. Adult (age over 18 years) OHCA patients from October 2015 to June 2020 were included. The main variable of interest was gender. Primary outcomes were whether in-hospital managements such as coronary angiography (CAG), percutaneous coronary intervention (PCI), target temperature management (TTM), and extracorporeal membrane oxygenation (ECMO) were performed. Secondary outcomes were clinical outcomes such as survival to admission, survival to discharge, and good neurologic outcome (cerebral performance category 1 or 2) at discharge. The propensity score matching (PSM) method was performed to minimize differences in baselines demographics and characteristics. Results: Total 8,177 OHCA patients were enrolled. After PSM, 6564 patients (female: 2782, male: 2782) were obtained. In unmatched cohort, female patients were less likely receive CAG, PCI, TTM, ECMO and less likely to survive to admit, survive to discharge, and discharge as good neurologic outcome. In PSM cohort, female patients were less likely to receive CAG, PCI than male (179 (6.4%) vs 252 (9.1%), p&lt;0.001 and 54 (1.9%) vs 104 (8.2%), p&lt;0.001, respectively). The proportion of TTM, ECMO, and clinical outcomes were not statistically different among gender. Conclusions: CAG, PCI were less likely to performed in female OHCA patients. Further studies are needed for gender disparities in in-hospital management of OHCA patients.
38P The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors
Authors: D.C. Guven, O.H. Aktepe, M.S. Aksun, T.K. Sahin, G. Kavgaci, E. Ucgul, I.Y. Cakir, H.C. Yildirim, G. Guner, S. Akin, N. Kertmen, O. Dizdar, S. Aksoy, M. Erman, S. Yalcin, S. Kilickap
Journal: Annals of Oncology (2021)
TDP-43 Pathology in Alzheimer’s Disease
Authors: Axel Meneses, Shunsuke Koga, Justin O’Leary, Dennis W. Dickson, Guojun Bu, Na Zhao
Journal: Molecular Neurodegeneration (2021)

Abstract Transactive response DNA binding protein of 43 kDa (TDP-43) is an intranuclear protein encoded by the TARDBP gene that is involved in RNA splicing, trafficking, stabilization, and thus, the regulation of gene expression. Cytoplasmic inclusion bodies containing phosphorylated and truncated forms of TDP-43 are hallmarks of amyotrophic lateral sclerosis (ALS) and a subset of frontotemporal lobar degeneration (FTLD). Additionally, TDP-43 inclusions have been found in up to 57% of Alzheimer’s disease (AD) cases, most often in a limbic distribution, with or without hippocampal sclerosis. In some cases, TDP-43 deposits are also found in neurons with neurofibrillary tangles. AD patients with TDP-43 pathology have increased severity of cognitive impairment compared to those without TDP-43 pathology. Furthermore, the most common genetic risk factor for AD, apolipoprotein E4 ( APOE4 ), is associated with increased frequency of TDP-43 pathology. These findings provide strong evidence that TDP-43 pathology is an integral part of multiple neurodegenerative conditions, including AD. Here, we review the biology and pathobiology of TDP-43 with a focus on its role in AD. We emphasize the need for studies on the mechanisms that lead to TDP-43 pathology, especially in the setting of age-related disorders such as AD.
Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study
Authors: Saad Z Usmani, Hang Quach, Maria-Victoria Mateos, Ola Landgren, Xavier Leleu, David Siegel, Katja Weisel, Maria Gavriatopoulou, Albert Oriol, Neil Rabin, Ajay Nooka, Ming Qi, Meral Beksac, Andrzej Jakubowiak, Bifeng Ding, Anita Zahlten-Kumeli, Akeem Yusuf, Meletios Dimopoulos
Journal: The Lancet Oncology (2021)
Association of Weight Loss Achieved Through Metabolic Surgery With Risk and Severity of COVID-19 Infection
Authors: Ali Aminian, Chao Tu, Alex Milinovich, Kathy E. Wolski, Michael W. Kattan, Steven E. Nissen
Journal: JAMA Surgery (2021)

Obesity is an established risk factor for severe COVID-19 infection. However, it is not known whether losing weight is associated with reduced adverse outcomes of COVID-19 infection.To investigate the association between a successful weight loss intervention and improved risk and severity of COVID-19 infection in patients with obesity.This cohort study involved adult patients with a body mass index of 35 or higher (calculated as weight in kilograms divided by height in meters squared) who underwent weight loss surgery between January 1, 2004, and December 31, 2017, at the Cleveland Clinic Health System (CCHS). Patients in the surgical group were matched 1:3 to patients who did not have surgical intervention for their obesity (control group). The source of data was the CCHS electronic health record. Follow-up was conducted through March 1, 2021.Weight loss surgery including Roux-en-Y gastric bypass and sleeve gastrectomy.Distinct outcomes were examined before and after COVID-19 outbreak on March 1, 2020. Weight loss and all-cause mortality were assessed between the enrollment date and March 1, 2020. Four COVID-19-related outcomes were analyzed in patients with COVID-19 diagnosis between March 1, 2020, and March 1, 2021: positive SARS-CoV-2 test result, hospitalization, need for supplemental oxygen, and severe COVID-19 infection (a composite of intensive care unit admission, need for mechanical ventilation, or death).A total of 20 212 patients (median [IQR] age, 46 [35-57] years; 77.6% female individuals [15 690]) with a median (IQR) body mass index of 45 (41-51) were enrolled. The overall median (IQR) follow-up duration was 6.1 (3.8-9.0) years. Before the COVID-19 outbreak, patients in the surgical group compared with control patients lost more weight (mean difference at 10 years from baseline: 18.6 [95% CI, 18.4-18.7] percentage points; P < .001) and had a 53% lower 10-year cumulative incidence of all-cause non-COVID-19 mortality (4.7% [95% CI, 3.7%-5.7%] vs 9.4% [95% CI, 8.7%-10.1%]; P < .001). Of the 20 212 enrolled patients, 11 809 were available on March 1, 2020, for an assessment of COVID-19-related outcomes. The rates of positive SARS-CoV-2 test results were comparable in the surgical and control groups (9.1% [95% CI, 7.9%-10.3%] vs 8.7% [95% CI, 8.0%-9.3%]; P = .71). However, undergoing weight loss surgery was associated with a lower risk of hospitalization (adjusted hazard ratio [HR], 0.51; 95% CI, 0.35-0.76; P < .001), need for supplemental oxygen (adjusted HR, 0.37; 95% CI, 0.23-0.61; P < .001), and severe COVID-19 infection (adjusted HR, 0.40; 95% CI, 0.18-0.86; P = .02).This cohort study found that, among patients with obesity, substantial weight loss achieved with surgery was associated with improved outcomes of COVID-19 infection. The findings suggest that obesity can be a modifiable risk factor for the severity of COVID-19 infection.
Aging disrupts circadian gene regulation and function in macrophages
Authors: Eran Blacher, Connie Tsai, Lev Litichevskiy, Zohar Shipony, Chinyere Agbaegbu Iweka, Kai Markus Schneider, Bayarsaikhan Chuluun, H. Craig Heller, Vilas Menon, Christoph A. Thaiss, Katrin I. Andreasson
Journal: Nature Immunology (2021)