tbuckley/cabot-search huggingface dataset:
26248 Efficacy of secukinumab and adalimumab in psoriatic arthritis patients with moderate-to-severe plaque psoriasis: Results from the EXCEED study
Authors: Alice B. Gottlieb, Joseph F. Merola, Kristian Reich, Frank Behrens, Weibin Bao, Pascale Pellet, Luminita Pricop, Iain B. McInnes
Journal: Journal of the American Academy of Dermatology (2021)
O-8 Final overall survival for the phase 3 KN177 study: Pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer
Authors: T. André, K. Shiu, T. Kim, B. Jensen, L. Jensen, C. Punt, D. Smith, R. Garcia-Carbonero, J. Alcaide García, P. Gibbs, C. De la Fouchardière, F. Rivera Herrero, E. Elez, J. Bendell, D. Le, T. Yoshino, W. Zhong, D. Fogelman, P. Marinello, L. Diaz
Journal: Annals of Oncology (2021)
Rapid Shifts in Mitochondrial tRNA Import in a Plant Lineage with Extensive Mitochondrial tRNA Gene Loss
Authors: Jessica M Warren, Thalia Salinas-Giegé, Deborah A Triant, Douglas R Taylor, Laurence Drouard, Daniel B Sloan
Journal: Molecular Biology and Evolution (2021)

In most eukaryotes, transfer RNAs (tRNAs) are one of the very few classes of genes remaining in the mitochondrial genome, but some mitochondria have lost these vestiges of their prokaryotic ancestry. Sequencing of mitogenomes from the flowering plant genus Silene previously revealed a large range in tRNA gene content, suggesting rapid and ongoing gene loss/replacement. Here, we use this system to test longstanding hypotheses about how mitochondrial tRNA genes are replaced by importing nuclear-encoded tRNAs. We traced the evolutionary history of these gene loss events by sequencing mitochondrial genomes from key outgroups (Agrostemma githago and Silene [=Lychnis] chalcedonica). We then performed the first global sequencing of purified plant mitochondrial tRNA populations to characterize the expression of mitochondrial-encoded tRNAs and the identity of imported nuclear-encoded tRNAs. We also confirmed the utility of high-throughput sequencing methods for the detection of tRNA import by sequencing mitochondrial tRNA populations in a species (Solanum tuberosum) with known tRNA trafficking patterns. Mitochondrial tRNA sequencing in Silene revealed substantial shifts in the abundance of some nuclear-encoded tRNAs in conjunction with their recent history of mt-tRNA gene loss and surprising cases where tRNAs with anticodons still encoded in the mitochondrial genome also appeared to be imported. These data suggest that nuclear-encoded counterparts are likely replacing mitochondrial tRNAs even in systems with recent mitochondrial tRNA gene loss, and the redundant import of a nuclear-encoded tRNA may provide a mechanism for functional replacement between translation systems separated by billions of years of evolutionary divergence.
COVID-19: stewardship of diagnostic tests for bacterial co-infection
Authors: Tom G S Williams, Luke B Snell, Jonathan D Edgeworth, Geraldine A O'Hara
Journal: The Lancet Microbe (2021)

diagnostic testing, particularly for hospital acquired infection, to improve antimicrobial stewardship.This is now feasible given widespread introduction of point of care SARS-CoV-2 diagnostics that can give confidence in diagnosis leading to tailored management, including of antimicrobial prescriptions.We declare no competing interests.
Correspondence on “Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: results from the COVID-19 Global Rheumatology Alliance physician registry” by Sparks<i>et al</i>
Authors: Elisa Gremese, Gianfranco Ferraccioli
Journal: Annals of the Rheumatic Diseases (2021)

<h3>Abstract</h3> Atherosclerotic plaque calcification directly contributes to the leading cause of morbidity and mortality by affecting the plaque vulnerability and rupture risk. Small microcalcifications can increase plaque stress and promote rupture, whereas large calcifications can stabilize plaques. Drugs that target bone mineralization may lead to unintended consequences on ectopic plaque calcification and cardiovascular outcomes. Bisphosphonates, common anti-osteoporotic agents, elicited unexpected cardiovascular events in clinical trials. Here, we investigated the role of bisphosphonates treatment and timing on the disruption or promotion of vascular calcification and bone mineral in a mouse model of atherosclerosis. We started the bisphosphonate treatment either before plaque formation, at early plaque formation times associated with the onset of calcification, or at late stages of plaque development. Our data indicate that long term bisphosphonate treatment (beginning prior to plaque development) leads to higher levels of plaque calcification, with a narrower mineral size distribution. When given later in plaque development, we measured a wider distribution of mineral size. These morphological alterations may associate with higher risk of plaque rupture by creating stress foci. Yet, bone mineral density positively correlated with the duration of bisphosphonate treatment.
Blood leukocyte transcriptomes in Gram-positive and Gram-negative community-acquired pneumonia
Authors: Liza Pereverzeva, Fabrice Uhel, Hessel Peters Sengers, Joe Butler, Lonneke A. van Vught, Katie L. Burnham, Emma E. Davenport, Julian C. Knight, Olaf L. Cremer, Marcus J. Schultz, Marc M.J. Bonten, Brendon P. Scicluna, Tom van der Poll
Journal: European Respiratory Journal (2021)

Background Gram-positive and Gram-negative bacteria are the most common causative pathogens in community-acquired pneumonia (CAP) on the intensive care unit (ICU). The aim of this study was to determine whether the host immune response differs between Gram-positive and Gram-negative CAP upon ICU admission. Methods 16 host response biomarkers providing insight into pathophysiological mechanisms implicated in sepsis and blood leukocyte transcriptomes were analysed in patients with CAP upon ICU admission in two tertiary hospitals in the Netherlands. Results 309 patients with CAP with a definite or probable likelihood (determined by predefined criteria) were included. A causative pathogen was determined in 74.4% of admissions. Patients admitted with Gram-positive CAP (n=90) were not different from those admitted with Gram-negative CAP (n=75) regarding demographics, chronic comorbidities, severity of disease and mortality. Host response biomarkers reflective of systemic inflammation, coagulation activation and endothelial cell function, as well as blood leukocyte transcriptomes, were largely similar between Gram-positive and Gram-negative CAP. Blood leukocyte transcriptomes were also similar in Gram-positive and Gram-negative CAP in two independent validation cohorts. On a pathogen-specific level, Streptococcus pneumoniae and Escherichia coli induced the most distinct host immune response. Conclusion Outcome and host response are similar in critically ill patients with CAP due to Gram-positive bacteria compared with Gram-negative bacteria.
Call for abstracts: HIV and Healthy Longevity
Authors: Cassandra Coburn, Peter Hayward, Amy C Justice
Journal: The Lancet Healthy Longevity (2021)

We invite submission of abstracts for oral presentation at The Lancet Summit: HIV and Healthy Longevity, a virtual meeting to be held Feb 24–25, 2022. Earlier this year, The Lancet journals marked the 40th anniversary of the first cases of HIV/AIDS being described in medical literature and the incredible advances in the understanding, management, treatment, and prevention of HIV in the past four decades. While helping to curtail HIV transmission and substantially increasing healthy life expectancy, the phenomenal success of antiretroviral therapy around the world has led to more people living and ageing with HIV than ever before. These individuals face major challenges including multimorbidity, complications from polypharmacy, and stigma associated with both age and HIV. Their pathophysiology may offer important insights regarding the role of immune dysfunction and chronic inflammation in ageing more generally. Additionally, HIV has been viewed as a highly morbid condition affecting young people, but as management has improved, many people ageing with HIV remain healthy and sexually active and may continue to use substances. This combined with substantial delays in diagnosis among older individuals, leads to risk of HIV transmission often unappreciated by the individual or their health-care provider. As global populations age more older people will be at risk of acquiring HIV and outreach may need to be better tailored to this group. In recognition of this demographic shift in people affected by HIV, The Lancet Healthy Longevity and The Lancet HIV will host The Lancet Summit: HIV and Health Longevity. This virtual meeting aims to bring together key opinion leaders in HIV and geroscience to present new research, analysis, and discussion, and to nurture cross-boundary collaboration. At The Lancet Summit, we hope to inspire new work that will help address specific challenges in HIV prevention, diagnosis, and treatment among older individuals. To facilitate this, we invite submission of research abstracts for presentation at the meeting on any topic related to HIV and longevity. We are particularly interested in clinical and implementation research that will help to guide practice and policy in the coming decades in a variety of health-care settings. Abstracts accepted for presentation will be published in one of the two journals. Deadline for submission is Oct 15.
27885 An optimized formulation of retinol with a specific sensory profile upregulates antiaging biomarkers for both prevention and rejuvenation of the skin
Authors: Daphne Meza, Ruchi Patel, Anisa Rahim, Melissa Tang, Jasmine Tan, Wen Ni Tan, Josh Zhang, Ramine Parsa
Journal: Journal of the American Academy of Dermatology (2021)
Reply
Authors: Terry Cheuk‐Fung Yip, Vincent Wai‐Sun Wong, Grace Lai‐Hung Wong
Journal: Hepatology (2021)

1Medical Data Analytics CentreThe Chinese University of Hong KongHong Kong SARChina 2Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong Kong SARChina 3Institute of Digestive DiseaseThe Chinese University of Hong KongHong Kong SARChina *Correspondence Grace Lai‐Hung Wong, Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30‐32 Ngan Shing Street, Shatin, Hong Kong. Email: [email protected]
Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections
Authors: Yahiya Y. Syed
Journal: Drugs (2021)

Intravenous cefiderocol (Fetroja®; Fetcroja®) is the first siderophore cephalosporin approved for the treatment of adults with serious Gram-negative bacterial infections. Cefiderocol is stable against all four Ambler classes of β-lactamases (including metallo-β-lactamases) and exhibits excellent in vitro activity against many clinically relevant Gram-negative pathogens, including multidrug resistant strains. In randomized, double-blind clinical trials, cefiderocol was noninferior to imipenem/cilastatin for the treatment of complicated urinary tract infections (cUTI) and to meropenem for nosocomial pneumonia. Furthermore, in a pathogen-focused clinical trial in patients with carbapenem-resistant (CR) infections, cefiderocol showed comparable efficacy to best available therapy (BAT), albeit all-cause mortality rate was higher in the cefiderocol arm, the cause of which has not been established. Cefiderocol had a good tolerability and safety profile in clinical trials. Thus cefiderocol is a novel, emerging, useful addition to the current treatment options for adults with susceptible Gram-negative bacterial infections (including cUTI and nosocomial pneumonia) for whom there are limited treatment options. Infections caused by carbapenem-resistant (CR) Enterobacterales and nonfermenters (such as Pseudomonas, Acinetobacter, Stenotrophomonas, Burkholderia) are a major global health threat. Cefiderocol, a cephalosporin with activity against CR Enterobacterales and nonfermenters, uses the bacteria's own iron uptake system to gain cell entry, like a Trojan horse. Once inside, the drug disrupts the formation of the bacterial cell wall, killing the bacteria. Cefiderocol is approved for the treatment of serious Gram-negative bacterial infections. In clinical trials, cefiderocol was effective versus carbapenems or best available therapy for complicated urinary tract infections, nosocomial pneumonia and bloodstream infections/sepsis, including those caused by CR bacteria. The drug had a good tolerability and safety profile. Thus, cefiderocol is a useful addition to the current treatment options for adults with cefiderocol-susceptible Gram-negative bacterial infections for whom there are limited treatment options.
Abstract 14932: Adult Cardiac Fibroblasts Are Not Terminally Differentiated and Possess Mesenchymal Stem Cell Like Properties With Aberrant Differentiation Contributing to Myocardial Calcification
Authors: Indulekha C. L. Pillai, Bhavesh K Ahir, Denny Liu, Eric S Ubil, Jucheng Gong, Arjun Deb
Journal: Circulation (2013)

Cardiac fibroblasts (CFs) form the stromal skeleton of the adult heart. Stromal cells in bone marrow and adipose tissue exhibit stem cell like properties. However CFs are thought to be terminally d...
NHS recovery plan for Scotland is “unrealistic,” doctors’ leaders warn
Authors: Bryan Christie
Journal: BMJ (2021)

Medical leaders have questioned the feasibility of a £1bn (€1.17bn; $1.37bn) government recovery plan for the NHS in Scotland that is promising a huge increase in capacity.

The five year plan1 aims to increase NHS capacity by at least 10% as quickly as possible to reduce the backlog in care caused by the covid pandemic, as well as meeting the continuing needs of patients around the country.

The plan identifies the restoration of face-to-face GP consultations as a priority and promises to increase spending on primary care by at least …
iCOVID: interpretable deep learning framework for early recovery-time prediction of COVID-19 patients
Authors: Jun Wang, Chen Liu, Jingwen Li, Cheng Yuan, Lichi Zhang, Cheng Jin, Jianwei Xu, Yaqi Wang, Yaofeng Wen, Hongbing Lu, Biao Li, Chang Chen, Xiangdong Li, Dinggang Shen, Dahong Qian, Jian Wang
Journal: npj Digital Medicine (2021)

Abstract Most prior studies focused on developing models for the severity or mortality prediction of COVID-19 patients. However, effective models for recovery-time prediction are still lacking. Here, we present a deep learning solution named iCOVID that can successfully predict the recovery-time of COVID-19 patients based on predefined treatment schemes and heterogeneous multimodal patient information collected within 48 hours after admission. Meanwhile, an interpretable mechanism termed FSR is integrated into iCOVID to reveal the features greatly affecting the prediction of each patient. Data from a total of 3008 patients were collected from three hospitals in Wuhan, China, for large-scale verification. The experiments demonstrate that iCOVID can achieve a time-dependent concordance index of 74.9% (95% CI: 73.6-76.3%) and an average day error of 4.4 days (95% CI: 4.2-4.6 days). Our study reveals that treatment schemes, age, symptoms, comorbidities, and biomarkers are highly related to recovery-time predictions.
Abstract 16030: Mitochondrial Membrane Potential Oscillations Persist During Reperfusion After Ischemia in MCU-KO Myocytes
Authors: Deepthi Ashok, Kyriakos Papanicolaou, Ting Liu, Brian O’Rourke
Journal: Circulation (2019)

Ca2+ entry via the Mitochondrial Calcium Uniporter (MCU) participates in energetic adaption to workload under physiological conditions but is thought to contribute to cell death during ischemia-rep...
Abstract 11989: Impact of Thoracentesis on the Outcome of Acute Congestive Heart Failure for In-hospitalized Patients in the United States
Authors: Suchith Shetty, Aaqib Malik, Wilbert S Aronow, Alexandros Briasoulis, Paulino Alvarez
Journal: Circulation (2019)

Background: Observational studies have reported conflicting results on in-hospital mortality for patients who undergo thoracentesis (THR) for pleural effusion of all-cause. To our knowledge, no stu...
Error in Figure 1
Journal: JAMA Neurology (2021)

Tom Aschman, MD; Julia Schneider, MSc; Selina Greuel, MD; Jenny Meinhardt, MD; Simon Streit, MD; Hans-Hilmar Goebel, MD; Ivana Büttnerova, MD; Sefer Elezkurtaj, MD; Franziska Scheibe, MD; Josefine Radke, MD; Christian Meisel, MD; Christian Drosten, MD; Helena Radbruch, MD; Frank L. Heppner, MD; Victor Max Corman, MD; Werner Stenzel, MD
Anti-PD-1/L1 lead-in before MAPK inhibitor combination maximizes antitumor immunity and efficacy
Authors: Yujue Wang, Sixue Liu, Zhentao Yang, Alain P. Algazi, Shirley H. Lomeli, Yan Wang, Megan Othus, Aayoung Hong, Xiaoyan Wang, Chris E. Randolph, Alexis M. Jones, Marcus W. Bosenberg, Stephanie D. Byrum, Alan J. Tackett, Henry Lopez, Clayton Yates, David B. Solit, Antoni Ribas, Marco Piva, Gatien Moriceau, Roger S. Lo
Journal: Cancer Cell (2021)

Rationally sequencing and combining PD-1/L1-and MAPK-targeted therapies may overcome innate and acquired resistance. Since increased clinical benefit of MAPK inhibitors (MAPKi) is associated with previous immune checkpoint therapy, we compare the efficacies of sequential and/or combinatorial regimens in subcutaneous murine models of melanoma driven by BrafV600, Nras, or Nf1 mutations as well as colorectal and pancreatic carcinoma driven by KrasG12C. Anti-PD-1/L1 lead-in preceding MAPKi combination optimizes response durability by promoting pro-inflammatory polarization of macrophages and clonal expansion of interferon-γhi, and CD8+ cytotoxic and proliferative (versus CD4+ regulatory) T cells that highly express activation genes. Since therapeutic resistance of melanoma brain metastasis (MBM) limits patient survival, we demonstrate that sequencing anti-PD-1/L1 therapy before MAPKi combination suppresses MBM and improves mouse survival with robust T cell clonal expansion in both intracranial and extracranial metastatic sites. We propose clinically testing brief anti-PD-1/L1 (± anti-CTLA-4) dosing before MAPKi co-treatment to suppress therapeutic resistance.
Use of Antimicrobials in a Cohort of US Nursing Homes
Authors: Fumiya Omata, Mitsuaki Oura, Yoshitaka Nishikawa
Journal: JAMA (2021)

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A case of ANCA-associated vasculitis after AZD1222 (Oxford–AstraZeneca) SARS-CoV-2 vaccination: casualty or causality?
Authors: Miguel Villa, Francisco Díaz-Crespo, Ana Pérez de José, Úrsula Verdalles, Eduardo Verde, Fernando Almeida Ruiz, Adriana Acosta, Antonia Mijaylova, Marian Goicoechea
Journal: Kidney International (2021)
Toxicology of the Fluoroalkenes: Review and Research Needs
Authors: J. Wesley Clayton
Journal: Environmental Health Perspectives (1977)

In this review of the published literature on the toxicology of fluoroalkenes several features emerge and research needs are evident. The fluoroalkenes vary widely in acute inhalation toxicity. Those, such as perfluoroisobutylene, PFIB, the most highly toxic member, attacks the pulmonary epithelium of rats eventuating in edema and death after a delay of about one day. Other fluoroalkenes, such as hexafluoropropylene (HFP) or chlorotrifluoroethylene (CTFE), also cause pulmonary injury but at lower concentrations produce concentration dependent changes in the renal concentrating mechanism of the rat. Changes in the CNS of rats and rabbits have also been reported for CTFE. CTFE, in repeated exposures, has produced blood pressure changes in dogs, CNS effects and changes in the erythropoietic system. This variety of responses indicates the need for investigation. Chronic effects have not been sufficiently studied for PFIB and HFP. Thus pointing up the desirability for study. Mechanisms of action research for fluoroalkenes is an important area of need. While several ideas have been suggested, there are no data to support them. The nucleophilic sensitivity of the fluoroalkenes and the potential carcinogenic effects stemming therefrom suggests a need field for investigation. We also can readily perceive the needs for the evaluation of effects on reproduction (including mutagenesis and teratogenesis), metabolism pulmonary functions, cellular function and structure. Epidemiologic studies on occupationally exposed populations are desirable in order to adequately define human health hazard from these fluorocarbons.
Human circadian variations
Authors: Nicholas W. Gentry, Liza H. Ashbrook, Ying-Hui Fu, Louis J. Ptáček
Journal: Journal of Clinical Investigation (2021)

Circadian rhythms, present in most phyla across life, are biological oscillations occurring on a daily cycle. Since the discovery of their molecular foundations in model organisms, many inputs that modify this tightly controlled system in humans have been identified. Polygenic variations and environmental factors influence each person's circadian rhythm, contributing to the trait known as chronotype, which manifests as the degree of morning or evening preference in an individual. Despite normal variation in chronotype, much of society operates on a "one size fits all" schedule that can be difficult to adjust to, especially for certain individuals whose endogenous circadian phase is extremely advanced or delayed. This is a public health concern, as phase misalignment in humans is associated with a number of adverse health outcomes. Additionally, modern technology (such as electric lights and computer, tablet, and phone screens that emit blue light) and lifestyles (such as shift or irregular work schedules) are disrupting circadian consistency in an increasing number of people. Though medical and lifestyle interventions can alleviate some of these issues, growing research on endogenous circadian variability and sensitivity suggests that broader social changes may be necessary to minimize the impact of circadian misalignment on health.