tbuckley/cabot-search huggingface dataset:
Impact of donor vaccination on recipient response to early SARS-CoV-2 mRNA vaccination after allogeneic HSCT
Authors: Mathieu Leclerc, Rabah Redjoul, Anne Le Bouter, Florence Beckerich, Christine Robin, Vincent Parinet, Cécile Pautas, Dehbia Menouche, Selwa Bouledroua, Lydia Roy, Ludovic Cabanne, Yakout Nait-Sidenas, Elham Harfouch, Eric Gautier, Slim Fourati, Sébastien Maury
Journal: The Lancet Haematology (2022)
In older persons at risk for dementia, a multidomain approach reduced stroke and transient ischemic attack
Authors: Konstantin A. Krychtiuk, Christopher B. Granger
Journal: Annals of Internal Medicine (2022)

Source Citation Lehtisalo J, Rusanen M, Solomon A, et al. Effect of a multi-domain lifestyle intervention on cardiovascular risk in older people: the FINGER trial. Eur Heart J. 2022. [Epub ahead of print.] 35051281
Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab, or Nivolumab in Patients with Advanced Solid Tumors
Authors: Diwakar Davar, Roberta Zappasodi, Hong Wang, Girish S. Naik, Takami Sato, Todd Bauer, David Bajor, Olivier Rixe, Walter Newman, Jingjing Qi, Aliya Holland, Phillip Wong, Lianna Sifferlen, Diane Piper, Cynthia A. Sirard, Taha Merghoub, Jedd D. Wolchok, Jason J. Luke
Journal: Clinical Cancer Research (2022)

TRX518 is a mAb engaging the glucocorticoid-induced TNF receptor-related protein (GITR). This open-label, phase I study (TRX518-003) evaluated the safety and efficacy of repeated dose TRX518 monotherapy and in combination with gemcitabine, pembrolizumab, or nivolumab in advanced solid tumors.
Association of Satisfaction With Treatment Decision and Failure of Nonoperative Management of Appendicitis in Children
Authors: Rebecca M. Rentea, Shawn D. St Peter
Journal: JAMA Network Open (2022)

Peter C. Minneci, MD, MHSc; Erinn M. Hade, PhD; Lindsay A. Gil, MD; Gregory A. Metzger, MD; Jacqueline M. Saito, MD; Grace Z. Mak, MD; Ronald B. Hirschl, MD; Samir Gadepalli, MD, MBA; Michael A. Helmrath, MD; Charles M. Leys, MD; Thomas T. Sato, MD; Dave R. Lal, MD, MPH; Matthew P. Landman, MD; Rashmi Kabre, MD; Mary E. Fallat, MD; Jennifer N. Cooper, PhD; Katherine J. Deans, MD, MHSc; Midwest Pediatric Surgery Consortium; Gail Benser; Jessica Kandel; Frederick Rescorla; Daniel von Allmen; Brad Warner; Cynthia Downard; Beth Rymeski; Julia Grabowski; Marleta Reynolds; Carley Lutz; Sarah Fox
Mapping genetic markers of artemisinin resistance in Plasmodium falciparum malaria in Asia: a systematic review and spatiotemporal analysis
Authors: Frank M Kagoro, Karen I Barnes, Kevin Marsh, Nattwut Ekapirat, Chris Erwin G Mercado, Ipsita Sinha, Georgina Humphreys, Mehul Dhorda, Philippe J Guerin, Richard J Maude
Journal: The Lancet Microbe (2022)

The increase in artemisinin resistance threatens malaria elimination in Asia by the target date of 2030 and could derail control efforts in other endemic regions. This study aimed to develop up-to-date spatial distribution visualisations of the kelch13 (K13) gene markers of artemisinin resistance in Plasmodium falciparum for policy makers.In this systematic review and spatiotemporal analysis we used the WorldWide Antimalarial Resistance Network (WWARN) surveyor molecular markers of artemisinin resistance database. We updated the database by searching PubMed and SCOPUS for studies published between Jan 1, 1990, and March 31, 2021. Articles were included if they contained data on K13 markers of artemisinin resistance from patients' samples in Asia and articles already included in the WWARN database were excluded. Data were extracted from the published articles and authors were contacted when information was missing. We used the lowest administrative unit levels for the sampling locations of all the K13 data to describe the spatiotemporal distribution. The numbers of samples tested and those with each molecular marker in each administrative unit level were aggregated by year to calculate the marker prevalence over time.Data were collated from 72 studies comprising K13 markers from 16 613 blood samples collected from 1991 to 2020 from 18 countries. Most samples were from Myanmar (3842 [23·1%]), Cambodia (3804 [22·9%]), and Vietnam (2663 [16·0%]). The median time between data collection and publication was 3·6 years (range 0·9-25·0, IQR 2·7 [2·5-5·2]). There was a steady increase in the prevalence of WHO-validated K13 markers, with the lowest of 4·3% in 2005 (n=47) and the highest of 62·9% in 2018 (n=264). Overall, the prevalence of Cys580Tyr mutation increased from 48·9% in 2002 to 84·9% in 2018.From 2002 to 2018, there has been a steady increase in geographical locations and the proportion of infected people with validated artemisinin resistance markers. More consistent data collection, over more extended periods in the same areas with the rapid sharing of data are needed to map the spread and evolution of resistance to better inform policy decisions. Data in the literature are reported in a heterogeneous way leading to difficulties in pooling and interpretation. We propose here a tool with a set of minimum criteria for reporting future studies.This research was funded in part by the Wellcome Trust.
The interplay between community and hospital Enterococcus faecium clones within health-care settings: a genomic analysis
Authors: Sebastiaan J van Hal, Rob J L Willems, Theodore Gouliouris, Susan A Ballard, Teresa M Coque, Anette M Hammerum, Kristin Hegstad, Mette Pinholt, Benjamin P Howden, Surbhi Malhotra-Kumar, Guido Werner, Katsunori Yanagihara, Ashlee M Earl, Katherine E Raven, Jukka Corander, Rory Bowden
Journal: The Lancet Microbe (2022)
Letter to the editor: Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child‐Pugh A and B cirrhosis: A real‐world study—Should we extend the boundaries?
Authors: Parakh Gulati, Sunil Taneja, Ajay Duseja, Virendra Singh
Journal: Hepatology (2022)
How can we address the ever-pressing need to ‘green up’ surgical practice in the National Health Service?
Authors: Nikolaos-Andreas Anastasopoulos, Vassilios Papalois
Journal: Journal of the Royal Society of Medicine (2022)

Clinical practice has inadvertently changed after the COVID-19 pandemic and currently the need to provide sustainable surgical services is more pressing than ever. The National Health Service has committed to a long-term efficient plan to reduce carbon footprint but there is no detailed plan for surgical practice, the domain that contributes the most to hospital-derived pollution. A series of consecutive steps and measures ought to be taken, starting from a hybrid approach quantifying surgically attributed carbon footprint. Then, a variety of suggested measures can be widely discussed and accordingly applied on a wider or more local level. Appropriate training should always precede implementing new practices to ensure that staff is familiar with these. These measures cover a broad range and should be arranged on a patient-centred basis from preoperative preconditioning to an effective follow-up. The need for more intense research and implementation of enhanced recovery protocols is widely discussed. Also, the necessity of green research and reinvestment of materials and resources is highlighted. A change of philosophy from a cradle-to-grave approach to a repurposing approach is suggested. We are confident that a new era is dawning in surgical practice and teamwork is the key for providing greener surgical services.
New Mutations and Pathogenesis of Pulmonary Hypertension: Progress and Puzzles in Disease Pathogenesis
Authors: Micheala A. Aldred, Nicholas W. Morrell, Christophe Guignabert
Journal: Circulation Research (2022)

Pulmonary arterial hypertension (PAH) is a complex multifactorial disease with poor prognosis characterized by functional and structural alterations of the pulmonary circulation causing marked increase in pulmonary vascular resistance, ultimately leading to right heart failure and death. Mutations in the gene encoding BMPRII-a receptor for the TGF-β (transforming growth factor-beta) superfamily-account for over 70% of families with PAH and ≈20% of sporadic cases. In recent years, however, less common or rare mutations in other genes have been identified. This review will consider how these newly discovered PAH genes could help to provide a better understanding of the molecular and cellular bases of the maintenance of the pulmonary vascular integrity, as well as their role in the PAH pathogenesis underlying occlusion of arterioles in the lung. We will also discuss how insights into the genetic contributions of these new PAH-related genes may open up new therapeutic targets for this, currently incurable, cardiopulmonary disorder.
Venetoclax combined with induction chemotherapy in patients with newly diagnosed acute myeloid leukaemia: a post-hoc, propensity score-matched, cohort study
Authors: Curtis A Lachowiez, Patrick K Reville, Hagop Kantarjian, Elias Jabbour, Gautam Borthakur, Naval Daver, Sanam Loghavi, Ken Furudate, Lianchun Xiao, Sherry Pierce, Nicholas J Short, Abhishek Maiti, Musa Yilmaz, Koji Sasaki, Koichi Takahashi, Marina Konopleva, Naveen Pemmaraju, Uday Popat, Elizabeth Shpall, Guillermo Garcia-Manero, Farhad Ravandi, Courtney D DiNardo, Tapan M Kadia
Journal: The Lancet Haematology (2022)
Parvalbumin neuroplasticity compensates for somatostatin impairment, maintaining cognitive function in Alzheimer’s disease
Authors: Christopher Daniel Morrone, Aaron Yenhsin Lai, Jossana Bishay, Mary Elizabeth Hill, JoAnne McLaurin
Journal: Translational Neurodegeneration (2022)

Abstract Background Patient-to-patient variability in the degree to which β-amyloid, tau and neurodegeneration impact cognitive decline in Alzheimer’s disease (AD) complicates disease modeling and treatment. However, the underlying mechanisms leading to cognitive resilience are not resolved. We hypothesize that the variability in cognitive function and loss relates to neuronal resilience of the hippocampal GABAergic network. Methods We compared TgF344-AD and non-transgenic littermate rats at 9, 12, and 15 months of age. Neurons, β-amyloid plaques and tau inclusions were quantified in hippocampus and entorhinal cortex. Somatostatin (SST) and parvalbumin (PVB) interneurons were traced to examine hippocampal neuroplasticity and cognition was tested in the Barnes maze. Results The 9-month-old TgF344-AD rats exhibited loss of neurons in the entorhinal cortex and hippocampus. Hippocampal neuronal compensation was observed in 12-month TgF344-AD rats, with upregulation of GABAergic interneuronal marker. By 15 months, the TgF344-AD rats had robust loss of excitatory and inhibitory neurons. β-Amyloid and tau pathology accumulated continuously across age. SST interneurons exhibited tau inclusions and atrophy from 9 months, whereas PVB interneurons were resilient until 15 months. The hippocampal PVB circuit underwent neuroplastic reorganization with increased dendritic length and complexity in 9- and 12-month-old TgF344-AD rats, before atrophy at 15 months. Strikingly, 12-month-old TgF344-AD rats were resilient in executive function and cognitive flexibility. Cognitive resilience in TgF344-AD rats occurred as maintenance of function between 9 and 12 months of age despite progressive spatial memory deficits, and was sustained by PVB neuroplasticity. Conclusions Our results demonstrate the inherent neuronal processes leading to cognitive maintenance, and describe a novel finding of endogenous cognitive resilience in an AD model.
Tumor ENPP1 (CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer
Authors: Borja Ruiz-Fernández de Córdoba, Haritz Moreno, Karmele Valencia, Naiara Perurena, Pablo Ruedas, Thomas Walle, Alberto Pezonaga-Torres, Juan Hinojosa, Elisabet Guruceaga, Antonio Pineda-Lucena, Marta Abengózar-Muela, Denis Cochonneau, Carolina Zandueta, Susana Martínez-Canarias, Álvaro Teijeira, Daniel Ajona, Sergio Ortiz-Espinosa, Xabier Morales, Carlos Ortiz de Solórzano, Marta Santisteban, Luis I. Ramos-García, Laura Guembe, Vratislav Strnad, Dominique Heymann, Sandra Hervás-Stubbs, Rubén Pío, María E. Rodríguez-Ruiz, Carlos E. de Andrea, Silvestre Vicent, Ignacio Melero, Fernando Lecanda, Rafael Martínez-Monge
Journal: Cancer Discovery (2022)

Locoregional failure (LRF) in breast cancer patients post-surgery and post-irradiation (IR) is linked to a dismal prognosis. In a refined new model, we identified Enpp1 (Ectonucleotide pyrophosphatase /phosphodiesterase 1/CD203a) to be closely associated with LRF. Enpp1high circulating tumor cells (CTC) contribute to relapse by a self-seeding mechanism. This process requires the infiltration of PMN-MDSC and neutrophil extracellular traps (NET) formation. Genetic and pharmacological Enpp1 inhibition or NET blockade extend relapse-free survival. Furthermore, in combination with fractionated irradiation (FD), Enpp1 abrogation obliterates LRF. Mechanistically, Enpp1-generated adenosinergic metabolites enhance Haptoglobin (Hp) expression. This inflammatory mediator elicits myeloid invasiveness and promotes NET formation. Accordingly, a significant increase in ENPP1 and NET formation is detected in relapsed human breast cancer tumors. Moreover, high ENPP1 or HP levels are associated with poor prognosis. These findings unveil the ENPP1/HP axis as an unanticipated mechanism exploited by tumor cells linking inflammation to immune remodeling favoring local relapse.
Loss of PRMT7 reprograms glycine metabolism to selectively eradicate leukemia stem cells in CML
Authors: Chang Liu, Waiyi Zou, Danian Nie, Shuyi Li, Chen Duan, Min Zhou, Peilong Lai, Shengyong Yang, Sen Ji, Yangqiu Li, Mei Mei, Shilai Bao, Yanli Jin, Jingxuan Pan
Journal: Cell Metabolism (2022)
Autoantibodies against type I IFNs in patients with Ph-negative myeloproliferative neoplasms
Authors: Oscar Borsani, Paul Bastard, Jérémie Rosain, Adrian Gervais, Emanuela Sant’Antonio, Daniele Vanni, Ilaria Carola Casetti, Daniela Pietra, Chiara Trotti, Silvia Catricalà, Virginia Valeria Ferretti, Luca Malcovati, Luca Arcaini, Jean-Laurent Casanova, Alessandro Borghesi, Elisa Rumi
Journal: Blood (2022)
Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial
Authors: Huafeng Wang, Liping Mao, Min Yang, Pengxu Qian, Huan Lu, Hongyan Tong, Wanzhuo Xie, De Zhou, Xin Huang, Yungui Wang, Gaixiang Xu, Ying Lu, Juying Wei, Wenyuan Mai, Xiujin Ye, Haitao Meng, Yaojia Shen, Jian Huang, Wenjuan Yu, Jie Sun, Jianpeng Sheng, Xiaoyan Yan, Jie Jin, Hong-Hu Zhu
Journal: The Lancet Haematology (2022)
HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy
Authors: Shaima Salman, David J. Meyers, Elizabeth E. Wicks, Sophia N. Lee, Emmanuel Datan, Aline M. Thomas, Nicole M. Anders, Yousang Hwang, Yajing Lyu, Yongkang Yang, Walter Jackson, Dominic Dordai, Michelle A. Rudek, Gregg L. Semenza
Journal: Journal of Clinical Investigation (2022)

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and available therapies, including immunotherapies, are ineffective for many patients. HCC is characterized by intratumoral hypoxia, and increased expression of hypoxia-inducible factor 1α (HIF-1α) in diagnostic biopsies is associated with patient mortality. Here we report the development of 32-134D, a low-molecular-weight compound that effectively inhibits gene expression mediated by HIF-1 and HIF-2 in HCC cells, and blocks human and mouse HCC tumor growth. In immunocompetent mice bearing Hepa1-6 HCC tumors, addition of 32-134D to anti-PD1 therapy increased the rate of tumor eradication from 25% to 67%. Treated mice showed no changes in appearance, behavior, body weight, hemoglobin, or hematocrit. Compound 32-134D altered the expression of a large battery of genes encoding proteins that mediate angiogenesis, glycolytic metabolism, and responses to innate and adaptive immunity. This altered gene expression led to significant changes in the tumor immune microenvironment, including a decreased percentage of tumor-associated macrophages and myeloid-derived suppressor cells, which mediate immune evasion, and an increased percentage of CD8+ T cells and natural killer cells, which mediate antitumor immunity. Taken together, these preclinical findings suggest that combining 32-134D with immune checkpoint blockade may represent a breakthrough therapy for HCC.
Pulmonary graft-versus-host disease and chronic lung allograft dysfunction: two sides of the same coin?
Authors: Saskia Bos, Hanne Beeckmans, Arno Vanstapel, Annelore Sacreas, Vincent Geudens, Lynn Willems, Ine Schreurs, Bart M Vanaudenaerde, Hélène Schoemans, Robin Vos
Journal: The Lancet Respiratory Medicine (2022)
Is thermogenesis really needed for brown adipose tissue–mediated metabolic benefit?
Authors: Jin-Seon Yook, Shingo Kajimura
Journal: Journal of Clinical Investigation (2022)

Brown adipose tissue (BAT) dissipates energy in the form of heat and functions as a metabolic sink for lipids, glucose, and branched-chain amino acids. Enhanced BAT thermogenesis is thought to tightly couple with beneficial energy metabolism. However, in this issue of the JCI, Huang et al. report a mouse model in which BAT thermogenesis was impaired, yet systemic glucose and lipid homeostasis were improved, on a high-fat diet compared with what occurred in control mice. The authors showed that BAT-specific deletion of mitochondrial thioredoxin-2 (TRX2) impaired adaptive thermogenesis through elevated mitochondrial reactive oxygen species (ROS) and cytosolic efflux of mitochondrial DNA. On the other hand, TRX2 loss enhanced lipid uptake in the BAT and protected mice from obesity, hypertriglyceridemia, and insulin resistance. This study provides a unique model in which BAT does not require thermogenesis per se to function as a lipid sink that leads to metabolic benefits in vivo.
Gut-derived bacterial toxins impair memory CD4+ T cell mitochondrial function in HIV-1 infection
Authors: Brian Ferrari, Amanda Cabral Da Silva, Ken H. Liu, Evgeniya V. Saidakova, Larisa B. Korolevskaya, Konstantin V. Shmagel, Carey Shive, Gabriela Pacheco Sanchez, Mauricio Retuerto, Ashish Arunkumar Sharma, Khader Ghneim, Laura Noel-Romas, Benigno Rodriguez, Mahmoud A. Ghannoum, Peter P. Hunt, Steven G. Deeks, Adam D. Burgener, Dean P. Jones, Mirela A. Dobre, Vincent C. Marconi, Rafick-Pierre Sekaly, Souheil-Antoine Younes
Journal: Journal of Clinical Investigation (2022)

People living with HIV (PLWH) who are immune nonresponders (INRs) are at greater risk of comorbidity and mortality than are immune responders (IRs) who restore their CD4+ T cell count after antiretroviral therapy (ART). INRs have low CD4+ T cell counts (<350 c/μL), heightened systemic inflammation, and increased CD4+ T cell cycling (Ki67+). Here, we report the findings that memory CD4+ T cells and plasma samples of INRs from several cohorts are enriched in gut-derived bacterial solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) that both negatively correlated with CD4+ T cell counts. In vitro PCS or IS blocked CD4+ T cell proliferation, induced apoptosis, and diminished the expression of mitochondrial proteins. Electron microscopy imaging revealed perturbations of mitochondrial networks similar to those found in INRs following incubation of healthy memory CD4+ T cells with PCS. Using bacterial 16S rDNA, INR stool samples were found enriched in proteolytic bacterial genera that metabolize tyrosine and phenylalanine to produce PCS. We propose that toxic solutes from the gut bacterial flora may impair CD4+ T cell recovery during ART and may contribute to CD4+ T cell lymphopenia characteristic of INRs.
Charges for Initial Visits for Uninsured Patients at Musculoskeletal Urgent Care Centers in the US
Authors: Laurie C. Yousman, Walter R. Hsiang, Akshay Khunte, Michael Najem, Grace Jin, Alison Mosier-Mills, Siddharth Jain, Daniel Wiznia
Journal: JAMA Network Open (2022)

In recent years, specialized musculoskeletal urgent care centers (MUCCs) have opened across the US. Uninsured patients may increasingly turn to these orthopedic-specific urgent care centers as a lower-cost alternative to emergency department or general urgent care center visits.To assess out-of-pocket costs and factors associated with these costs at MUCCs for uninsured and underinsured patients in the US.In this survey study, a national secret shopper survey was conducted in June 2019. Clinics identified as MUCCs in 50 states were contacted by telephone by investigators using a standardized script and posing as uninsured patients seeking information on the out-of-pocket charge for a new patient visit.State Medicaid expansion status, clinic Medicaid acceptance status, state Medicaid reimbursement rate, median income per zip code, and clinic region.The primary outcome was each clinic's out-of-pocket charge for a level 3 visit, defined as a new patient office visit requiring medical decision-making of low complexity. Linear regression was used to examine correlations of price with clinic policy against accepting Medicaid, median income per zip code, and Medicaid reimbursement for a level 3 visit.Of 565 MUCCs identified, 558 MUCCs were able to be contacted (98.8%); 536 of the 558 MUCCs (96.1%) disclosed a new patient visit out-of-pocket charge. Of those, 313 (58.4%) accepted Medicaid insurance and 326 (60.8%) were located in states with expanded Medicaid at the time of the survey. The mean (SD) price of a visit to an MUCC was $250 ($110). Clinic policy against accepting Medicaid (β, 22.91; 95% CI, 12.57-33.25; P < .001), higher median income per zip code (β, 0.00056; 95% CI, 0.00020-0.00092; P = .003), and increased Medicaid reimbursement for a level 3 visit (β, 0.737; 95% CI, 0.158-1.316; P = .01) were positively correlated with visit price. The overall regression was statistically significance (R2 = 0.084; P < .001).In this survey study, MUCCs charged a mean price of $250 for a new patient visit. Medicaid acceptance policy, median income per zip code, and Medicaid reimbursement for a level 3 visit were associated with differences in out-of-pocket charges. These findings suggest that accessibility to orthopedic urgent care at MUCCs may be limited for underinsured and uninsured patients.
The rapid replacement of the SARS-CoV-2 Delta variant by Omicron (B.1.1.529) in England
Authors: Robert S. Paton, Christopher E. Overton, Thomas Ward
Journal: Science Translational Medicine (2022)

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (Omicron) variant caused international concern due to its rapid spread in Southern Africa. It was unknown whether this variant would replace or coexist with (either transiently or long term) the then-dominant Delta variant on its introduction to England. We developed a set of hierarchical logistic growth models to describe changes in the frequency of S gene target failure (SGTF) PCR tests, a proxy for Omicron. The doubling time of SGTF cases peaked at 1.56 days (95% CI: 1.49 to 1.63) on 5 December, whereas triple-positive cases were halving every 5.82 days (95% CI: 5.11 to 6.67) going into Christmas 2021. We were unable to characterize the replacement of Delta by Omicron with a single rate. The replacement rate decreased by 53.56% (95% CrI: 45.38 to 61.01) between 14 and 15 December, meaning the competitive advantage of Omicron approximately halved. Preceding the changepoint, Omicron was replacing Delta 16.24% (95% CrI: 9.72 to 23.41) faster in those with two or more vaccine doses, indicative of vaccine escape being a substantial component of competitive advantage. Despite the slowdown, Delta was almost entirely replaced in England within a month of the first sequenced domestic case. The synchrony of changepoints across regions at various stages of Omicron epidemics suggests that the growth rate advantage was not attenuated because of biological mechanisms related to strain competition. The step change in replacement could have resulted from behavioral changes, potentially elicited by public health messaging or policies, that differentially affected Omicron.