tbuckley/cabot-search huggingface dataset:
Prostate cancer multiparametric magnetic resonance imaging visibility is a tumor-intrinsic phenomena
Authors: Amanda Khoo, Lydia Y. Liu, Taylor Y. Sadun, Amirali Salmasi, Aydin Pooli, Ely Felker, Kathleen E. Houlahan, Vladimir Ignatchenko, Steven S. Raman, Anthony E. Sisk, Robert E. Reiter, Paul C. Boutros, Thomas Kislinger
Journal: Journal of Hematology & Oncology (2022)

Abstract Multiparametric magnetic resonance imaging (mpMRI) is an emerging standard for diagnosing and prognosing prostate cancer, but ~ 20% of clinically significant tumors are invisible to mpMRI, as defined by the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) score of one or two. To understand the biological underpinnings of tumor visibility on mpMRI, we examined the proteomes of forty clinically significant tumors ( i.e. , International Society of Urological Pathology (ISUP) Grade Group 2)—twenty mpMRI-visible and twenty mpMRI-invisible, with matched histologically normal prostate. Normal prostate tissue was indistinguishable between patients with visible and invisible tumors, and invisible tumors closely resembled the normal prostate. These data indicate that mpMRI-visibility arises when tumor evolution leads to large-magnitude proteomic divergences from histologically normal prostate.
Differences in saliva ACE2 activity among infected and non-infected adult and pediatric population exposed to SARS-CoV-2
Authors: Daniel Jiménez, Javier Martínez-Sanz, Talía Sainz, Cristina Calvo, Ana Méndez-Echevarría, Elena Moreno, Daniel Blázquez-Gamero, Pilar Vizcarra, Mario Rodríguez, Robert Jenkins, Matilde Sánchez-Conde, Raquel Ron, Francesca Norman, Santiago Moreno, Manuel Ferrer, Sergio Serrano-Villar
Journal: Journal of Infection (2022)
PHGDH is required for germinal center formation and is a therapeutic target in MYC-driven lymphoma
Authors: Annalisa D’Avola, Nathalie Legrave, Mylène Tajan, Probir Chakravarty, Ryan L. Shearer, Hamish W. King, Katarina Kluckova, Eric C. Cheung, Andrew J. Clear, Arief S. Gunawan, Lingling Zhang, Louisa K. James, James I. MacRae, John G. Gribben, Dinis P. Calado, Karen H. Vousden, John C. Riches
Journal: Journal of Clinical Investigation (2022)

The synthesis of serine from glucose is a key metabolic pathway supporting cellular proliferation in healthy and malignant cells. Despite this, the role that this aspect of metabolism plays in germinal center biology and pathology is not known. Here, we performed a comprehensive characterization of the role of the serine synthesis pathway in germinal center B cells and lymphomas derived from these cells. We demonstrate that upregulation of a functional serine synthesis pathway is a metabolic hallmark of B cell activation and the germinal center reaction. Inhibition of phosphoglycerate dehydrogenase (PHGDH), the first and rate-limiting enzyme in this pathway, led to defective germinal formation and impaired high-affinity antibody production. In addition, overexpression of enzymes involved in serine synthesis was a characteristic of germinal center B cell-derived lymphomas, with high levels of expression being predictive of reduced overall survival in diffuse large B cell lymphoma. Inhibition of PHGDH induced apoptosis in lymphoma cells, reducing disease progression. These findings establish PHGDH as a critical player in humoral immunity and a clinically relevant target in lymphoma.
No minister, a “protective ring” was not thrown around care homes
Authors: Martin McKee
Journal: BMJ (2022)

famously said "Advisers advise, ministers decide." 1 Yet, throughout the covid-19 pandemic this distinction has often seemed blurred.Ministers justified decisions by claiming they were "following the science."But were they?Numerous accounts suggest not. 2 -4 Their defence is that the situation was extremely challenging.There were still many uncertainties about the nature of the new infection and how it was transmitted.Their opportunities to respond were constrained, for example, by limited testing capacity and an already overstretched health system.So, were ministerial decisions reasonable in the circumstances?In at least one area, the discharge of patients from hospitals into care homes, contributing to thousands of avoidable deaths, we can now say with certainty that they were not.
Public health considerations for transitioning beyond the acute phase of the COVID-19 pandemic in the EU/EEA
Authors: Jonathan E Suk, Anastasia Pharris, Julien Beauté, Edoardo Colzani, Howard Needham, John Kinsman, Rene Niehus, Rok Grah, Ajibola Omokanye, Diamantis Plachouras, Agoritsa Baka, Bastian Prasse, Frank Sandmann, Ettore Severi, Erik Alm, Emma Wiltshire, Bruno Ciancio
Journal: Eurosurveillance (2022)

Many countries, including some within the EU/EEA, are in the process of transitioning from the acute pandemic phase. During this transition, it is crucial that countries' strategies and activities remain guided by clear COVID-19 control objectives, which increasingly will focus on preventing and managing severe outcomes. Therefore, attention must be given to the groups that are particularly vulnerable to severe outcomes of SARS-CoV-2 infection, including individuals in congregate and healthcare settings. In this phase of pandemic management, a strong focus must remain on transitioning testing approaches and systems for targeted surveillance of COVID-19, capitalising on and strengthening existing systems for respiratory virus surveillance. Furthermore, it will be crucial to focus on lessons learned from the pandemic to enhance preparedness and to enact robust systems for the preparedness, detection, rapid investigation and assessment of new and emerging SARS-CoV-2 variants. Filling existing knowledge gaps, including behavioural insights, can help guide the response to future resurgences of SARS-CoV-2 and/or the emergence of other pandemics. Finally, 'vaccine agility' will be needed to respond to changes in people's behaviours, changes in the virus, and changes in population immunity, all the while addressing issues of global health equity.
To Comply or Not to Comply With the US Preventive Services Task Force—That Is the Question
Authors: Cornelia J. Baines
Journal: JAMA Network Open (2022)

Breast screening research began in the 1960s with the New York Health Insurance Plan study. Since then, so much research, so many guidelines, and so much controversy and invective have ensued,1 a story made accessible to the lay public in Conspiracy of Hope.2
Pharmaceutical SH2 domain–containing protein tyrosine phosphatase 2 inhibition suppresses primary and metastasized liver tumors by provoking hepatic innate immunity
Authors: Jacey J. Liu, Bing Xin, Li Du, Lydia Chen, Yanyan Long, Gen‐Sheng Feng
Journal: Hepatology (2022)

Background and Aims: SH2 domain–containing protein tyrosine phosphatase 2 (Shp2) is the first identified pro‐oncogenic tyrosine phosphatase that acts downstream of receptor tyrosine kinases (RTKs) to promote Ras–extracellular signal–regulated kinase signaling. However, this phosphatase was also shown to be antitumorigenic in HCC. This study is aimed at deciphering paradoxical Shp2 functions and mechanisms in hepatocarcinogenesis and at exploring its value as a pharmaceutical target in HCC therapy. Approaches and Results: We took both genetic and pharmaceutical approaches to examine the effects of Shp2 inhibition on primary liver cancers driven by various oncogenes and on metastasized liver tumors. We show here that the catalytic activity of Shp2 was essential for relay of oncogenic signals from RTKs in HCC and that chemical inhibition of Shp2 robustly suppressed HCC driven by RTKs. However, in contrast to a tumor‐promoting hepatic niche generated by genetically deleting Shp2 in hepatocytes, treatment with a specific Shp2 inhibitor had a tumor‐suppressing effect on metastasized liver tumor progression. Mechanistically, the Shp2 inhibitor enhanced antitumor innate immunity by down‐regulating inflammatory cytokines, suppressing the chemokine (C‐C motif) receptor 5 signaling axis, but up‐regulating interferon‐β secretion. Conclusions These results unveil complex mechanisms for the tumor‐suppressing effect of pharmaceutical Shp2 inhibition in the liver immune environment. We provide a proof of principle for clinical trials with specific Shp2 inhibitors in patients with primary and metastasized liver cancer.
Precision Probiotic Medicine to Improve ICB Immunotherapy
Authors: Blanda Di Luccia, Marco Colonna
Journal: Cancer Discovery (2022)

The established impact of gut microbiota- and probiotic-derived metabolites on immune-checkpoint blockade (ICB) has spurred extensive efforts to identify strains and druggable bioactive molecules of microbial origin that can improve tumor immune therapy. In this issue, Kawanabe-Matsuda and colleagues show that the exopolysaccharide EPS-R1 produced by the probiotic strain Lactobacillus delbrueckii subsp. bulgaricus augments the response to ICB therapy by expanding the population of Peyer's patches CCR6+ CD8+ T cells, which can subsequently migrate from the gut into CCL20-expressing tumors to enhance antitumor activity. See related article by Kawanabe-Matsuda et al., p. 1336 (10).
Treatment of Menopause Symptoms With Hormone Therapy
Authors: Jill Jin
Journal: JAMA (2022)

Gerald Gartlehner, MD, MPH; Sheila V. Patel, BSPH; Cynthia Feltner, MD, MPH; Rachel Palmieri Weber, PhD, MSPH; Rachel Long, PharmD, BCPS, CPP; Kelly Mullican, PharmD, CPP; Erin Boland, MSPH; Linda Lux, MPA; Meera Viswanathan, PhD
The Eph receptor A4 plays a role in demyelination and depression-related behavior
Authors: Yuan Li, Ping Su, Yuxiang Chen, Jing Nie, Ti-Fei Yuan, Albert H.C. Wong, Fang Liu
Journal: Journal of Clinical Investigation (2022)

Proper myelination of axons is crucial for normal sensory, motor, and cognitive function. Abnormal myelination is seen in brain disorders such as major depressive disorder (MDD), but the molecular mechanisms connecting demyelination with the pathobiology remain largely unknown. We observed demyelination and synaptic deficits in mice exposed to either chronic, unpredictable mild stress (CUMS) or LPS, 2 paradigms for inducing depression-like states. Pharmacological restoration of myelination normalized both synaptic deficits and depression-related behaviors. Furthermore, we found increased ephrin A4 receptor (EphA4) expression in the excitatory neurons of mice subjected to CUMS, and shRNA knockdown of EphA4 prevented demyelination and depression-like behaviors. These animal data are consistent with the decrease in myelin basic protein and the increase in EphA4 levels we observed in postmortem brain samples from patients with MDD. Our results provide insights into the etiology of depressive symptoms in some patients and suggest that inhibition of EphA4 or the promotion of myelination could be a promising strategy for treating depression.
Household Secondary Attack Rates of SARS-CoV-2 by Variant and Vaccination Status
Authors: Zachary J. Madewell, Yang Yang, Ira M. Longini, M. Elizabeth Halloran, Natalie E. Dean
Journal: JAMA Network Open (2022)

<h3>Importance</h3> An overall household secondary attack rate (SAR) of 18.9% (95% CI, 16.2%-22.0%) through June 17, 2021 was previously reported for SARS-CoV-2. Emerging variants of concern and increased vaccination have affected transmission rates. <h3>Objective</h3> To evaluate how reported household SARs changed over time and whether SARs varied by viral variant and index case and contact vaccination status. <h3>Data Sources</h3> PubMed and medRxiv from June 18, 2021, through March 8, 2022, and reference lists of eligible articles. Preprints were included. <h3>Study Selection</h3> Articles with original data reporting the number of infected and total number of household contacts. Search terms included<i>SARS-CoV-2</i>,<i>COVID-19</i>,<i>variant</i>,<i>vaccination</i>,<i>secondary attack rate</i>,<i>secondary infection rate</i>,<i>household</i>,<i>index case, family contacts</i>,<i>close contacts,</i>and<i>family transmission.</i> <h3>Data Extraction and Synthesis</h3> The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline was followed. Meta-analyses used generalized linear mixed models to obtain SAR estimates and 95% CIs. <h3>Main Outcomes and Measures</h3> SAR stratified by covariates according to variant, index case and contact vaccination status, and index case identification period. SARs were used to estimate vaccine effectiveness on the basis of the transmission probability for susceptibility to infection (<i>VES,p</i>), infectiousness given infection (<i>VEI,p</i>), and total vaccine effectiveness (<i>VET,p</i>). <h3>Results</h3> Household SARs were higher for 33 studies with midpoints in 2021 to 2022 (37.3%; 95% CI, 32.7% to 42.1%) compared with 63 studies with midpoints through April 2020 (15.5%; 95% CI, 13.2% to 18.2%). Household SARs were 42.7% (95% CI, 35.4% to 50.4%) for Omicron (7 studies), 36.4% (95% CI, 33.4% to 39.5%) for Alpha (11 studies), 29.7% (95% CI, 23.0% to 37.3%) for Delta (16 studies), and 22.5% (95% CI, 18.6% to 26.8%) for Beta (3 studies). For full vaccination,<i>VES,p</i>was 78.6% (95% CI, 76.0% to 80.9%) for Alpha, 56.4% (95% CI, 54.6% to 58.1%) for Delta, and 18.1% (95% CI, −18.3% to 43.3%) for Omicron;<i>VEI,p</i>was 75.3% (95% CI, 69.9% to 79.8%) for Alpha, 21.9% (95% CI, 11.0% to 31.5%) for Delta, and 18.2% (95% CI, 0.6% to 32.6%) for Omicron; and<i>VET,p</i>was 94.7% (95% CI, 93.3% to 95.8%) for Alpha, 64.4% (95% CI, 58.0% to 69.8%) for Delta, and 35.8% (95% CI, 13.0% to 52.6%) for Omicron. <h3>Conclusions and Relevance</h3> These results suggest that emerging SARS-CoV-2 variants of concern have increased transmissibility. Full vaccination was associated with reductions in susceptibility and infectiousness, but more so for Alpha than Delta and Omicron. The changes in estimated vaccine effectiveness underscore the challenges of developing effective vaccines concomitant with viral evolution.
Regional vs General Anesthesia and Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery
Authors: Chloe Nobuhara, Michael Devinney, Miles Berger
Journal: JAMA (2022)

To the Editor The recently published RAGA trial1 failed to detect a difference in the rate of delirium in older patients following hip fracture repair using general anesthesia vs regional anesthesia without intravenous sedation. However, there are several issues with this study.
Group 3 Pulmonary Hypertension: From Bench to Bedside
Authors: Navneet Singh, Peter Dorfmüller, Oksana A. Shlobin, Corey E. Ventetuolo
Journal: Circulation Research (2022)

Pulmonary hypertension (PH) because of chronic lung disease is categorized as Group 3 PH in the most recent classification system. Prevalence of these diseases is increasing over time, creating a growing need for effective therapeutic options. Recent approval of the first pulmonary arterial hypertension therapy for the treatment of Group 3 PH related to interstitial lung disease represents an encouraging advancement. This review focuses on molecular mechanisms contributing to pulmonary vasculopathy in chronic hypoxia, the pathology and epidemiology of Group 3 PH, the right ventricular dysfunction observed in this population and clinical trial data that inform the use of pulmonary vasodilators in Group 3 PH.
Glycine decarboxylase maintains mitochondrial protein lipoylation to support tumor growth
Authors: Dzmitry Mukha, Mariam Fokra, Alona Feldman, Boris Sarvin, Nikita Sarvin, Keren Nevo-Dinur, Elazar Besser, Elior Hallo, Elina Aizenshtein, Zachary T. Schug, Tomer Shlomi
Journal: Cell Metabolism (2022)
In patients with type 2 diabetes and CKD, finerenone improved CV and kidney outcomes
Authors: Kaitlin J. Mayne, William G. Herrington
Journal: Annals of Internal Medicine (2022)

Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43:474-84. 35023547.
Algorithm-based care versus usual care for the early recognition and management of complications after pancreatic resection in the Netherlands: an open-label, nationwide, stepped-wedge cluster-randomised trial
Authors: F Jasmijn Smits, Anne Claire Henry, Marc G Besselink, Olivier R Busch, Casper H van Eijck, Mark Arntz, Thomas L Bollen, Otto M van Delden, Daniel van den Heuvel, Christiaan van der Leij, Krijn P van Lienden, Adriaan Moelker, Bert A Bonsing, Inne H Borel Rinkes, Koop Bosscha, Ronald M van Dam, Wouter J M Derksen, Marcel den Dulk, Sebastiaan Festen, Bas Groot Koerkamp, Robbert J de Haas, Jeroen Hagendoorn, Erwin van der Harst, Ignace H de Hingh, Geert Kazemier, Marion van der Kolk, Mike Liem, Daan J Lips, Misha D Luyer, Vincent E de Meijer, J Sven Mieog, Vincent B Nieuwenhuijs, Gijs A Patijn, Wouter W te Riele, Daphne Roos, Jennifer M Schreinemakers, Martijn W J Stommel, Fennie Wit, Babs A Zonderhuis, Lois A Daamen, C Henri van Werkhoven, I Quintus Molenaar, Hjalmar C van Santvoort, JG Blomjous, MT de Boer, P van den Boezem, S Bouwense, R Bruijnen, CI Buis, M del Chiaro, PP Coene, M Coolsen, F Daams, K Dejong, W Draaisma, HH Eker, AH Elsen, MF Gerhards, H Hartog, FJ Hoogwater, F Imani, S Jenniskens, KP de Jong, TM Karsten, JM Klaase, RHJ de Kleine, CJ van Laarhoven, H van der Lelij, ER Manusama, M Meerdink, M Meijerink, J Nederend, MW Nijkamp, CL Nota, RJ Porte, J Reef, P de Reuver, C van Rijswijk, T Romkens, C Rupert, GP van der Schelling, JP Serafino, LD Vos, MR Vriens, E Beers-Vural, JM Wagtenberg, JH Wijsman, RF de Wilde, CL Wolfgang, HJ Zeh
Journal: The Lancet (2022)
Dissecting Human Gonadal Cell Lineage Specification and Sex Determination Using a Single-Cell RNA-Seq Approach
Authors: Rui Wang, Xixi Liu, Li Li, Ming Yang, Jun Yong, Fan Zhai, Lu Wen, Liying Yan, Jie Qiao, Fuchou Tang
Journal: Genomics Proteomics & Bioinformatics (2022)

Gonadal somatic cells are the main players in gonad development and are important for sex determination and germ cell development. Here, using a time-series single-cell RNA sequencing (scRNA-seq) strategy, we analyzed fetal germ cells (FGCs) and gonadal somatic cells in human embryos and fetuses. Clustering analysis of testes and ovaries revealed several novel cell subsets, including POU5F1+SPARC+ FGCs and KRT19+ somatic cells. Furthermore, our data indicated that the bone morphogenetic protein (BMP) signaling pathway plays cell type-specific and developmental stage-specific roles in testis development and promotes the gonocyte-to-spermatogonium transition (GST) in late-stage testicular mitotic arrest FGCs. Intriguingly, testosterone synthesis function transitioned from fetal Sertoli cells to adult Leydig cells in a stepwise manner. In our study, potential interactions between gonadal somatic cells were systematically explored and we identified cell type-specific developmental defects in both FGCs and gonadal somatic cells in a Turner syndrome embryo (45, XO). Our work provides a blueprint of the complex yet highly ordered development of and the interactions among human FGCs and gonadal somatic cells.
Greater Excess Mortality in 2020 for People With Dementia
Authors: Anita Slomski
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Impact on emergency and elective hospital-based care in Scotland over the first 12 months of the pandemic: interrupted time-series analysis of national lockdowns
Authors: Syed Ahmar Shah, Rachel H Mulholland, Samantha Wilkinson, Srinivasa Vittal Katikireddi, Jiafeng Pan, Ting Shi, Steven Kerr, Uktarsh Agrawal, Igor Rudan, Colin R Simpson, Sarah J Stock, John Macleod, Josephine-LK Murray, Colin McCowan, Lewis Ritchie, Mark Woolhouse, Aziz Sheikh
Journal: Journal of the Royal Society of Medicine (2022)

Objectives COVID-19 has resulted in the greatest disruption to National Health Service (NHS) care in its over 70-year history. Building on our previous work, we assessed the ongoing impact of pandemic-related disruption on provision of emergency and elective hospital-based care across Scotland over the first year of the pandemic. Design We undertook interrupted time-series analyses to evaluate the impact of ongoing pandemic-related disruption on hospital NHS care provision at national level and across demographics and clinical specialties spanning the period 29 March 2020–28 March 2021. Setting Scotland, UK. Participants Patients receiving hospital care from NHS Scotland. Main outcome measures We used the percentage change of accident and emergency attendances, and emergency and planned hospital admissions during the pandemic compared to the average admission rate for equivalent weeks in 2018–2019. Results As restrictions were gradually lifted in Scotland after the first lockdown, hospital-based admissions increased approaching pre-pandemic levels. Subsequent tightening of restrictions in September 2020 were associated with a change in slope of relative weekly admissions rate: –1.98% (–2.38, –1.58) in accident and emergency attendance, –1.36% (–1.68, –1.04) in emergency admissions and –2.31% (–2.95, –1.66) in planned admissions. A similar pattern was seen across sex, socioeconomic status and most age groups, except children (0–14 years) where accident and emergency attendance, and emergency admissions were persistently low over the study period. Conclusions We found substantial disruption to urgent and planned inpatient healthcare provision in hospitals across NHS Scotland. There is the need for urgent policy responses to address continuing unmet health needs and to ensure resilience in the context of future pandemics.
Treatment outcomes 24 months after initiating short, all-oral bedaquiline-containing or injectable-containing rifampicin-resistant tuberculosis treatment regimens in South Africa: a retrospective cohort study
Authors: Norbert Ndjeka, Jonathon R Campbell, Graeme Meintjes, Gary Maartens, H Simon Schaaf, Jennifer Hughes, Xavier Padanilam, Anja Reuter, Rodolfo Romero, Farzana Ismail, Martin Enwerem, Hannetjie Ferreira, Francesca Conradie, Kogieleum Naidoo, Dick Menzies
Journal: The Lancet Infectious Diseases (2022)
Hyaluronic acid association with bacterial, fungal and viral infections: Can hyaluronic acid be used as an antimicrobial polymer for biomedical and pharmaceutical applications?
Authors: Fernanda Zamboni, Chun Kwok Wong, Maurice N. Collins
Journal: Bioactive Materials (2022)

The relationships between hyaluronic acid (HA) and pathological microorganisms incite new understandings on microbial infection, tissue penetration, disease progression and lastly, potential treatments. These understandings are important for the advancement of next generation antimicrobial therapeutical strategies for the control of healthcare-associated infections. Herein, this review will focus on the interplay between HA, bacteria, fungi, and viruses. This review will also comprehensively detail and discuss the antimicrobial activity displayed by various HA molecular weights for a variety of biomedical and pharmaceutical applications, including microbiology, pharmaceutics, and tissue engineering.