tbuckley/cabot-search huggingface dataset:
Dynamic assessment of insulin secretion and insulin resistance in Asians with prediabetes
Authors: Faidon Magkos, Michelle H. Lee, Maybritte Lim, Alex R. Cook, Vanna Chhay, Tze Ping Loh, Kee Seng Chia, Sonia Baig, Ian Yi Han Ang, Joanne Y.Y. Tay, Chin Meng Khoo, Jeffrey B. Halter, Sue-Anne Toh
Journal: Metabolism (2021)

Aims/hypothesisPrediabetes and type 2 diabetes are highly prevalent in Asia. Understanding the pathophysiology of abnormal glucose homeostasis in Asians will have important implications for reducing disease burden, but there have been conflicting reports on the relative contributions of insulin secretion and action in disease progression. In this study, we aimed to assess the contribution of β-cell dysfunction and insulin resistance in the Asian prediabetes phenotype.MethodsWe recruited 1679 Asians with prediabetes (n = 659) or normoglycemia (n = 1020) from a multi-ethnic population in Singapore. Participants underwent an oral glucose tolerance test, an intravenous glucose challenge, and a hyperinsulinemic-euglycemic clamp procedure to determine glucose tolerance, β-cell responsivity, insulin secretion, insulin clearance and insulin sensitivity.ResultsParticipants with prediabetes had significantly higher glucose concentrations in the fasting state and after glucose ingestion than did normoglycemic participants. Insulin sensitivity (M/I ratio) was ~15% lower, acute insulin response (AIR) to intravenous glucose and β-cell responsivity to oral glucose were ~35% lower, but total insulin secretion rate in the fasting state and after glucose ingestion was ~10% greater in prediabetic than in normoglycemic participants. The decrease in β-cell function with worsening glucose homeostasis in Asians with prediabetes was associated with progressively greater defects in AIR rather than M/I. However, analysis using static surrogate measures (HOMA indices) of insulin resistance and β-cell function revealed a different pattern.ConclusionsLower AIR to intravenous glucose and β-cell responsivity to oral glucose, on a background of mild insulin resistance, are the major contributors to the dysregulation of glucose homeostasis in Asians with prediabetes.
A BCL2L1 Armoured BCMA Targeting CAR T Cell to Overcome Exhaustion and Enhance Persistence in Multiple Myeloma
Authors: Ranjan Maity, Sacha Benaoudia, Franz Zemp, Holly Lee, Elie Barakat, Noemie Leblay, Sungwoo Ahn, Douglas Mahoney, Paola Neri, Nizar J. Bahlis
Journal: Blood (2021)
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: Neuro-Oncology (2021)

Abstract 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 &amp;lt; 70 with no systemic therapy options do not derive benefit from radiation therapy. Additional information is available at www.asco.org/neurooncology-guidelines.
CAR T-cell therapy in primary central nervous system lymphoma: the clinical experience of the French LOC network
Authors: Marion Alcantara, Caroline Houillier, Marie Blonski, Marie-Thérèse Rubio, Lise Willems, Agathe Waultier Rascalou, Magali Le Garff-Tavernier, Karim Maloum, Clotilde Bravetti, Laetitia Souchet, Damien Roos-Weil, Véronique Morel, Madalina Uzunov, Carole Metz, Meriem Dhib-Charfi, Stéphanie Nguyen, Natalia Shor, Dimitri Psimaras, Nicolas Weiss, Nathalie Jacque, Silvia Solorzano, Nicolas Gauthier, Marie Le Cann, Françoise Norol, Carole Soussain, Sylvain Choquet
Journal: Blood (2021)
B Cell Numbers Predict Humoral and Cellular Response Upon <scp>SARS</scp>–<scp>CoV</scp>‐2 Vaccination Among Patients Treated With Rituximab
Authors: Ana‐Luisa Stefanski, Hector Rincon‐Arevalo, Eva Schrezenmeier, Kirsten Karberg, Franziska Szelinski, Jacob Ritter, Bernd Jahrsdörfer, Hubert Schrezenmeier, Carolin Ludwig, Arne Sattler, Katja Kotsch, Yidan Chen, Anne Claußnitzer, Hildrun Haibel, Fabian Proft, Gabriela Guerra, Pawel Durek, Frederik Heinrich, Marta Ferreira‐Gomes, Gerd R. Burmester, Andreas Radbruch, Mir‐Farzin Mashreghi, Andreia C. Lino, Thomas Dörner
Journal: Arthritis & Rheumatology (2021)

Objective Patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) therapy are at higher risk of poor COVID‐19 outcomes and show substantially impaired humoral immune response to anti–SARS–CoV‐2 vaccine. However, the complex relationship between antigen‐specific B cells and T cells and the level of B cell repopulation necessary to achieve anti‐vaccine responses remain largely unknown. Methods Antibody responses to SARS–CoV‐2 vaccines and induction of antigen‐specific B and CD4/CD8 T cell subsets were studied in 19 patients with rheumatoid arthritis (RA) or antineutrophil cytoplasmic antibody–associated vasculitis receiving RTX, 12 patients with RA receiving other therapies, and 30 healthy controls after SARS–CoV‐2 vaccination with either messenger RNA or vector‐based vaccines. Results A minimum of 10 B cells per microliter (0.4% of lymphocytes) in the peripheral circulation appeared to be required for RTX‐treated patients to mount seroconversion to anti‐S1 IgG upon SARS–CoV‐2 vaccination. RTX‐treated patients who lacked IgG seroconversion showed reduced receptor‐binding domain–positive B cells ( P = 0.0005), a lower frequency of Tfh‐like cells ( P = 0.0481), as well as fewer activated CD4 ( P = 0.0036) and CD8 T cells ( P = 0.0308) compared to RTX‐treated patients who achieved IgG seroconversion. Functionally relevant B cell depletion resulted in impaired interferon‐γ secretion by spike‐specific CD4 T cells ( P = 0.0112, r = 0.5342). In contrast, antigen‐specific CD8 T cells were reduced in both RA patients and RTX‐treated patients, independently of IgG formation. Conclusion In RTX‐treated patients, a minimum of 10 B cells per microliter in the peripheral circulation is a candidate biomarker for a high likelihood of an appropriate cellular and humoral response after SARS–CoV‐2 vaccination. Mechanistically, the data emphasize the crucial role of costimulatory B cell functions for the proper induction of CD4 responses propagating vaccine‐specific B cell and plasma cell differentiation.
DNA methylation clocks tick in naked mole rats but queens age more slowly than nonbreeders
Authors: Steve Horvath, Amin Haghani, Nicholas Macoretta, Julia Ablaeva, Joseph A. Zoller, Caesar Z. Li, Joshua Zhang, Masaki Takasugi, Yang Zhao, Elena Rydkina, Zhihui Zhang, Stephan Emmrich, Ken Raj, Andrei Seluanov, Chris G. Faulkes, Vera Gorbunova
Journal: Nature Aging (2021)

Abstract Naked mole rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity and are resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging according to a primary hallmark of aging: epigenetic changes. To address this question, we profiled n = 385 samples from 11 tissue types at loci that are highly conserved between mammalian species using a custom array (HorvathMammalMethylChip40). We observed strong epigenetic aging effects and developed seven highly accurate epigenetic clocks for several tissues (pan-tissue, blood, kidney, liver, skin clocks) and two dual-species (human–NMR) clocks. The skin clock correctly estimated induced pluripotent stem cells derived from NMR fibroblasts to be of prenatal age. The NMR epigenetic clocks revealed that breeding NMR queens age more slowly than nonbreeders, a feature that is also observed in some eusocial insects. Our results show that despite a phenotype of negligible senescence, the NMR ages epigenetically.
The health and wellbeing of Indigenous adolescents: a global collective for an equitable and sustainable future
Authors: Alex D H Brown, Sue Crengle, Jordan Tewhaiti-Smith, Seth Westhead, Brittany Bingham, Ngiare Brown, Chenoa Cassidy-Matthews, Terryann Clark, Summer M Finlay, Ketil L Hansen, Matire Harwood, Katarina S H Niia, Kine N Iversen, Jonill M F Knapp, Siv Kvernmo, Crystal Lee, Ricky-Lee T Watts, Melanie Nadeau, Odette Pearson, Jeff Reading, Áigin M F Sarre, Amalie Seljenes, Jon Petter A Stoor, Christian Eckhoff, Elizabeth Saewyc, Miguel San Sebastian, Salenna Elliott, Christina V L Larsen, Andrew Sise, Peter S Azzopardi
Journal: The Lancet (2021)
How Would You Treat This Patient Hospitalized With Community-Acquired Pneumonia?
Authors: Zahir Kanjee, Joshua P. Metlay, Ari Moskowitz, Eileen E. Reynolds
Journal: Annals of Internal Medicine (2021)

Community-acquired pneumonia is a major cause of morbidity and mortality in the United States, leading to 1.5 million hospitalizations and at least 200 000 deaths annually. The 2019 American Thoracic Society/Infectious Diseases Society of America clinical practice guideline on diagnosis and treatment of adults with community-acquired pneumonia provides an evidence-based overview of this common illness. Here, 2 experts, a general internist who served as the co–primary author of the guidelines and a pulmonary and critical care physician, debate the management of a patient hospitalized with community-acquired pneumonia. They discuss disease severity stratification methods, whether to use adjunctive corticosteroids, and when to prescribe empirical treatment for multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.
CTNI-10. ADVANCES IN MANAGEMENT OF LOW-GRADE GLIOMAS
Authors: Ruchi Raval, Aadi Pandya, Jaspreet Behl, Sumul Raval
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Low-grade gliomas (LGGs) are common benign brain tumors that arise from glial cells of the brain. The complex and variable backgrounds of LGGs cause difficulties in assigning therapies. In this report, we compile findings relating to LGG genetics and treatment options in order to create a coherent summary for referential use. METHODS We compiled 70 articles from the past ten years that cover a broad range of topics pertaining to LGGs, including molecular, genetic, epigenetic, morphological, and other diagnostic factors, as well as prognosis and treatment options. RESULTS In order to provide proper treatment, the molecular basis and histology of the tumor must be addressed. The 1p/19q co-deletion indicator has been considered the gold standard of glioma diagnosis, but oft-sighted mutations in the IDH1 and IDH2 genes have given rise to three subgroups of 1p/19q co-deleted tumors, each associated with specific patterns of nervous cells. Other molecular markers and microRNA expression patterns have been studied for possible diagnostic and prognostic methods. Microsurgical resection is the singular treatment with highest overall survival (OS) and quality of life (QOL). Total gross resection is optimal, with patients having a 5-year OS of 100% with 90% tumor resection. Low doses of radiation are as effective as high doses and are better tolerated (with less cognitive deficits). Chemotherapy, specifically temozolomide, offers a favorable toxicity profile and QOL; additionally, seizure reduction is an early and consistent prognostic marker for survival after treatment with temozolomide. CONCLUSIONS The “wait and see” approach for treatment is no longer the standard for LGGs. Immediate treatment after diagnosis is recommended. Gross total resection (if achievable) is the most favorable treatment, with the highest OS and QOL. The use of temozolomide and radiotherapy is recommended. Histological background and genetic markers are vital for determining a treatment plan.
Added to pre-existing inflammation, mRNA-lipid nanoparticles induce inflammation exacerbation (IE)
Authors: Hamideh Parhiz, Jacob S. Brenner, Priyal N. Patel, Tyler E. Papp, Hamna Shahnawaz, Qin Li, Ruiqi Shi, Marco E. Zamora, Amir Yadegari, Oscar A. Marcos-Contreras, Ambika Natesan, Norbert Pardi, Vladimir V. Shuvaev, Raisa Kiseleva, Jacob W. Myerson, Thomas Uhler, Rachel S. Riley, Xuexiang Han, Michael J. Mitchell, Kieu Lam, James Heyes, Drew Weissman, Vladimir R. Muzykantov
Journal: Journal of Controlled Release (2021)
Trav15-dv6 family <i>Tcrd</i> rearrangements diversify the <i>Tcra</i> repertoire
Authors: Danielle J. Dauphars, Ariana Mihai, Liuyang Wang, Yuan Zhuang, Michael S. Krangel
Journal: The Journal of Experimental Medicine (2021)

The Tcra repertoire is generated by multiple rounds of Vα-Jα rearrangement. However, Tcrd recombination precedes Tcra recombination within the complex Tcra-Tcrd locus. Here, by ablating Tcrd recombination, we report that Tcrd rearrangement broadens primary Vα use to diversify the Tcra repertoire in mice. We reveal that use of Trav15-dv6 family V gene segments in Tcrd recombination imparts diversity in the Tcra repertoire by instigating use of central and distal Vα segments. Moreover, disruption of the regions containing these genes and their cis-regulatory elements identifies the Trav15-dv6 family as being responsible for driving central and distal Vα recombinations beyond their roles as substrates for Tcrd recombination. Our study demonstrates an indispensable role for Tcrd recombination in general, and the Trav15-dv6 family in particular, in the generation of a combinatorially diverse Tcra repertoire.
Immune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid cancer
Authors: Annika Fendler, Scott T C Shepherd, Lewis Au, Katalin A Wilkinson, Mary Wu, Andreas M Schmitt, Zayd Tippu, Sheima Farag, Aljosja Rogiers, Ruth Harvey, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Benjamin Shum, Camille L Gerard, Daqi Deng, Svend Kjaer, Ok-Ryul Song, Christophe Queval, Caitlin Kavanagh, Emma C Wall, Edward J Carr, Sina Namjou, Simon Caidan, Mike Gavrielides, James I MacRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O'Flaherty, Robyn L Shea, Gail Gardner, Darren Murray, Nadia Yousaf, Shaman Jhanji, Nicholas Van As, Kate Young, Andrew J S Furness, Lisa Pickering, Rupert Beale, Charles Swanton, Sonia Gandhi, Steve Gamblin, David L V Bauer, George Kassiotis, Michael Howell, Emma Nicholson, Susanna Walker, Robert J Wilkinson, James Larkin, Samra Turajlic
Journal: Cancer Cell (2021)
Variation in State-Level Eviction Moratorium Protections and Mental Health Among US Adults During the COVID-19 Pandemic
Authors: Kathryn M. Leifheit, Craig E. Pollack, Julia Raifman, Gabriel L. Schwartz, Robert D. Koehler, Jackie V. Rodriguez Bronico, Emily A. Benfer, Frederick J. Zimmerman, Sabriya L. Linton
Journal: JAMA Network Open (2021)

Although evictions have been associated with adverse mental health outcomes, it remains unclear which stages of the eviction process are associated with mental distress among renters. Variation in COVID-19 pandemic eviction protections across US states enables identification of intervention targets within the eviction process to improve renters' mental health.
“Spider traction” endoscopic submucosal dissection for colonic lesion
Authors: Borathchakra Oung, Jérémie Albouys, Sophie Geyl, Romain Legros, Thomas Lambin, Mathieu Pioche, Jérémie Jacques
Journal: Endoscopy (2021)

Endoscopic submucosal dissection (ESD) is the preferred and most effective approach for resection of large colonic lesions. Use of a traction strategy has been shown to reduce the technical difficulty and improve the safety of the procedure, especially in nonexpert hands. We previously introduced a double clip and rubber band traction technique (DCT-ESD), which is one of the cheapest and easily-made traction devices [1] [2]. A multitraction strategy for ESD of a deep submucosal colonic carcinoma was recently reported [3]. We call this upgraded traction system “spider traction”.
ALK-Negative Anaplastic Large Cell Lymphomas Encompass Distinct Subgroups Including an ALK-Positive-like Subgroup with Favorable Prognosis
Authors: Kwok Him Rex Au Yeung, Veronica Russell, William Choi, Alice Wong, Lawrence Tsui, Yu Yan Carmen Lee, Jamilla Li, Harinder Gill, Ho-Wan Ip, Yok Lam Kwong, Tushar Dave, Sarah L. Ondrejka, Govind Bhagat, Amy Chadburn, Sarah C. Rutherford, Jean L. Koff, David L Jaye, Magdalena Czader, Abner Louissaint, Shaoying Li, Jie Xu, C. Cameron Yin, Choon Kiat Ong, Chee Leong Cheng, Amir Behdad, Andrew M. Evens, Peter H. Norgaard, Anne Ortved Gang, Sirpa Leppa, Marja-Liisa Karjalainen-Lindsberg, Jennifer R Chapman, Catalina Amador, Javeed Iqbal, Yuri Fedoriw, Agata M. Bogusz, Andrew G Evans, Ridas Juskevicius, Eric D. Hsi, Kikkeri N Naresh, Sandeep S. Dave, Eric Tse
Journal: Blood (2021)
Abstract 13761: Does Targeted Temperature Management Modify the Association Between Increasing Epinephrine Dose and Survival Outcomes Following Out-of-Hospital Cardiac Arrest?
Authors: Betty Yang, Natalie Bulger, Richard Chocron, Catherine Counts, Christopher Drucker, Nona Sootedehnia, Peter Kudenchuk, Michael R Sayre, Thomas Rea
Journal: Circulation (2021)

Introduction: Epinephrine (EPI) improves return of circulation after out of hospital cardiac arrest (OHCA). These beneficial cardiac effects are not accompanied by improved neurological survival possibly due to EPI induced microvascular effects and critical brain ischemia. We hypothesized that these dose-dependent adverse EPI effects may be mitigated by targeted temperature management (TTM) such that the relative benefit of TTM is greater at higher EPI doses. Methods: This was a retrospective cohort study of adult non-traumatic OHCA patients in Seattle and King County, Washington from 2008-2018, who were unconscious at hospital admission. We used logistic regression to assess the relationship among EPI dose, TTM, and survival to hospital discharge, and survival with favorable neurological status (Cerebral Performance Category (CPC) 1 or 2). The model evaluated whether TTM modified the association of increasing EPI dose using an interaction term between TTM and EPI dose. Results were stratified by initial shockable vs non-shockable rhythm. Results: Of 5254 eligible patients, the median EPI dose was 2.0 mg (IQR 1.0 - 3.0); 3052 (58%) received TTM. In all, 2177 (41%) survived to discharge, and 1889 (36%) survived with CPC 1-2. Increasing dose of EPI was associated with a decreasing likelihood of survival (OR 0.58, [95% CI 0.55-0.61] for each additional mg of EPI) and CPC 1-2 (OR 0.56, [0.53-0.59]). The dose-dependent EPI association was modified by TTM. After adjustment for Utstein covariates, for each additional mg of EPI, TTM was associated with a relative stepwise improvement in odds of survival (interaction OR 1.35, [1.23, 1.49]) and CPC 1-2 (OR 1.34, [1.21, 1.50]) (Figure). This interaction was consistent among shockable and non-shockable OHCA (Figure). Conclusions: We observed an interaction between TTM and EPI dose such that the beneficial association of TTM increased with increasing EPI dose, suggesting TTM may attenuate the adverse effects of higher dose EPI.
Role of Income-Lifting Social Programs in Reducing Years of Life Lost to Myocardial Infarction and Sudden Death—Reply
Authors: Adam N. Berman, Ersilia M. DeFilippis, Ron Blankstein
Journal: JAMA Cardiology (2021)

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