tbuckley/cabot-search huggingface dataset:
Circulating microbial small RNAs are altered in patients with rheumatoid arthritis
Authors: Michelle J Ormseth, Qiong Wu, Shilin Zhao, Ryan M Allen, Joseph Solus, Quanhu Sheng, Yan Guo, Fei Ye, Marisol Ramirez-Solano, S Louis Bridges, Jeffrey R Curtis, Kasey Vickers, C Michael Stein
Journal: Annals of the Rheumatic Diseases (2020)

To determine if plasma microbial small RNAs (sRNAs) are altered in patients with rheumatoid arthritis (RA) compared with control subjects, associated with RA disease-related features, and altered by disease-modifying antirheumatic drugs (DMARDs).sRNA sequencing was performed on plasma from 165 patients with RA and 90 matched controls and a separate cohort of 70 patients with RA before and after starting a DMARD. Genome alignments for RA-associated bacteria, representative bacterial and fungal human microbiome genomes and environmental bacteria were performed. Microbial genome counts and individual sRNAs were compared across groups and correlated with disease features. False discovery rate was set at 0.05.Genome counts of Lactobacillus salivarius, Anaerobaculum hydrogeniformans, Staphylococcus epidermidis, Staphylococcus aureus, Paenisporosarcina spp, Facklamia hominis, Sphingobacterium spiritivorum, Lentibacillus amyloliquefaciens, Geobacillus spp, and Pseudomonas fluorescens were significantly decreased in the plasma of RA compared with control subjects. Three microbial transfer RNA-derived sRNAs were increased in RA versus controls and inversely associated with disease activity. Higher total microbial sRNA reads were associated with lower disease activity in RA. Baseline total microbial sRNAs were threefold higher among patients who improved with DMARD versus those who did not but did not change significantly after 6 months of treatment.Plasma microbial sRNA composition is altered in RA versus control subjects and associated with some measures of RA disease activity. DMARD treatment does not alter microbial sRNA abundance or composition, but increased abundance of microbial sRNAs at baseline was associated with disease activity improvement at 6 months.
Perinatal mental health: a review of progress and challenges
Authors: Louise M. Howard, Hind Khalifeh
Journal: World Psychiatry (2020)

Perinatal mental health has become a significant focus of interest in recent years, with investment in new specialist mental health services in some high‐income countries, and inpatient psychiatric mother and baby units in diverse settings. In this paper, we summarize and critically examine the epidemiology and impact of perinatal mental disorders, including emerging evidence of an increase of their prevalence in young pregnant women. Perinatal mental disorders are among the commonest morbidities of pregnancy, and make an important contribution to maternal mortality, as well as to adverse neonatal, infant and child outcomes. We then review the current evidence base on interventions, including individual level and public health ones, as well as service delivery models. Randomized controlled trials provide evidence on the effectiveness of psychological and psychosocial interventions at the individual level, though it is not yet clear which women with perinatal mental disorders also need additional support for parenting. The evidence base on psychotropic use in pregnancy is almost exclusively observational. There is little research on the full range of perinatal mental disorders, on how to improve access to treatment for women with psychosocial difficulties, and on the effectiveness of different service delivery models. We conclude with research and clinical implications, which, we argue, highlight the need for an extension of generic psychiatric services to include preconception care, and further investment into public health interventions, in addition to perinatal mental health services, potentially for women and men, to reduce maternal and child morbidity and mortality.
Canonical Wnt Pathway Is Activated in Myeloid Leukemia Stem Cells Via Hematopoietic Cell Kinase That Is Phosphorylated By an Autocrine TIM-3/Galectin-9 Signaling
Authors: Teppei Sakoda, Yoshikane Kikushige, Toshihiro Miyamoto, Koichi Akashi
Journal: Blood (2017)
Oral SARS-CoV-2 Inoculation Establishes Subclinical Respiratory Infection with Virus Shedding in Golden Syrian Hamsters
Authors: Andrew Chak-Yiu Lee, Anna Jinxia Zhang, Jasper Fuk-Woo Chan, Can Li, Zhimeng Fan, Feifei Liu, Yanxia Chen, Ronghui Liang, Siddharth Sridhar, Jian-Piao Cai, Vincent Kwok-Man Poon, Chris Chung-Sing Chan, Kelvin Kai-Wang To, Shuofeng Yuan, Jie Zhou, Hin Chu, Kwok-Yung Yuen
Journal: Cell Reports Medicine (2020)

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is transmitted largely by respiratory droplets or airborne aerosols. Despite being frequently found in the immediate environment and feces of patients, evidence supporting the oral acquisition of SARS-CoV-2 is unavailable. Using the Syrian hamster model, we demonstrate that the severity of pneumonia induced by the intranasal inhalation of SARS-CoV-2 increases with virus inoculum. SARS-CoV-2 retains its infectivity in vitro in simulated human-fed-gastric and fasted-intestinal fluid after 2 h. Oral inoculation with the highest intranasal inoculum (105 PFUs) causes mild pneumonia in 67% (4/6) of the animals, with no weight loss. The lung histopathology score and viral load are significantly lower than those infected by the lowest intranasal inoculum (100 PFUs). However, 83% of the oral infections (10/12 hamsters) have a level of detectable viral shedding from oral swabs and feces similar to that of intranasally infected hamsters. Our findings indicate that the oral acquisition of SARS-CoV-2 can establish subclinical respiratory infection with less efficiency.
18F-Fluciclovine Uptake in Thymoma Demonstrated on PET/MRI
Authors: Lucas Tsikitas, Shawn Karls, Anca-Oana Kranz, Kent P. Friedman, Sonia Mahajan
Journal: Clinical Nuclear Medicine (2020)

A 68-year-old man with a history of prostate cancer post-primary treatment presented with rising prostate-specific antigen levels and was referred for 18F-fluciclovine PET/MRI to localize recurrent disease. PET/MRI revealed a solitary focus of uptake in a soft tissue nodule in the anterior mediastinum, which was resected and found to be a type B2 thymoma. 18F-fluciclovine uptake is mediated by amino acid transporters, primarily alanine-serine-cysteine transporter 2 and l-type amino acid transporter 1, previously demonstrated to be expressed on thymic carcinomas. This case highlights the possibility of overexpression of amino acid transporters in thymomas as well, rarely described before.
Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate
Authors: Reiner K. Mailer, Mikel Allende, Marco Heestermans, Michaela Schweizer, Carsten Deppermann, Maike Frye, Giordano Pula, Jacob Odeberg, Mathias Gelderblom, Stefan Rose-John, Albert Sickmann, Stefan Blankenberg, Tobias B. Huber, Christian Kubisch, Coen Maas, Stepan Gambaryan, Dmitri Firsov, Evi X. Stavrou, Lynn M. Butler, Thomas Renné
Journal: Blood (2020)
Preoperative immunotherapy for resectable hepatocellular carcinoma: Toward a paradigm shift?
Authors: Florian Seckler, Alexandre Doussot, Prudence Colpart, Célia Turco, Paul Calame, François Aubin, Marie Paule Algros, Christophe Borg, Charlée Nardin, Bruno Heyd
Journal: Journal of Hepatology (2020)
Genetic Confirmation of Monogenic Familial Hypercholesterolemia Advises a More Intensive Lipid-Lowering Approach
Authors: Carlos Guijarro, Fernando Civeira, Luis Masana
Journal: JAMA Cardiology (2020)

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Re: Medical Event: Accidental Oral Administration of 177Lu-PSMA to a Patient With Hyperthyroidism
Authors: Kambiz Rahbar, Hojjat Ahmadzadehfar
Journal: Clinical Nuclear Medicine (2020)

∗Department of Nuclear Medicine University Hospital Muenster, Germany [email protected] †Department of Nuclear Medicine Klinikum Westfalen, Dortmund, Germany Conflicts of interest and sources of funding: none declared.
Interventions to Improve Statin Tolerance and Adherence in Patients at Risk for Cardiovascular Disease
Authors: James T. Reston, Andrew Buelt, Mark P. Donahue, Brian Neubauer, Elena Vagichev, Kristy McShea
Journal: Annals of Internal Medicine (2020)

Strategies to improve patients' tolerance of and adherence to statins may enhance the effectiveness of dyslipidemia treatment in those at risk for cardiovascular disease (CVD).To assess the benefits and harms of interventions to improve statin adherence in patients at risk for CVD.MEDLINE, EMBASE, PubMed, and the Cochrane Library from December 2013 through May 2019 (English language only).Systematic reviews (SRs), randomized controlled trials (RCTs), and cohort studies that addressed interventions for improving statin tolerance and adherence.One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy.One SR, 1 RCT, and 4 cohort studies were included. The SR found that intensified patient care improved adherence and decreased levels of total serum cholesterol and low-density lipoprotein cholesterol (LDL-C) at 6 months or more of follow-up. Compared with statin treatment discontinuation, nondaily statin dosing lowered total cholesterol and LDL-C levels. One large cohort study suggested that more than 90% of patients who discontinued statin treatment could be rechallenged with the same or a different statin and be adherent 1 year after a statin-related adverse event led to discontinuation. Two small cohort studies reported that more than 90% of patients who were previously intolerant to statins and who had low baseline levels of vitamin D were able to adhere to statins 1 year after vitamin D supplementation.This is a qualitative synthesis of new evidence with existing meta-analyses, and studies had several methodological shortcomings.Although the strength of evidence for most interventions was low or very low, intensified patient care and rechallenge with the same or a different statin (or a lower dose) seem to be favorable options for improving statin adherence.U.S. Department of Veterans Affairs.
TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls
Authors: Jeremy Howick, Rebecca K. Webster, Jonathan L. Rees, Richard Turner, Helen Macdonald, Amy Price, Andrea W. M. Evers, Felicity Bishop, Gary S. Collins, Klara Bokelmann, Sally Hopewell, André Knottnerus, Sarah Lamb, Claire Madigan, Vitaly Napadow, Andrew N. Papanikitas, Tammy Hoffmann
Journal: PLoS Medicine (2020)

Placebo or sham controls are the standard against which the benefits and harms of many active interventions are measured. Whilst the components and the method of their delivery have been shown to affect study outcomes, placebo and sham controls are rarely reported and often not matched to those of the active comparator. This can influence how beneficial or harmful the active intervention appears to be. Without adequate descriptions of placebo or sham controls, it is difficult to interpret results about the benefits and harms of active interventions within placebo-controlled trials. To overcome this problem, we developed a checklist and guide for reporting placebo or sham interventions.
Neoantigen-specific CD4<sup>+</sup>T-cell response is critical for the therapeutic efficacy of cryo-thermal therapy
Authors: Peng Peng, Hongming Hu, Ping Liu, Lisa X Xu
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Traditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined. Methods The long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice treated with RFA or cryo-thermal therapy were coincubated with tumor antigen peptides to detect the frequency of antigen specific CD4 + and CD8 + T-cells by flow cytometry. Splenocytes were then stimulated and expanded by αCD3 or peptides and adoptive T-cell therapy experiments were performed to identify the antitumor efficacy of T-cells induced by RFA and cryo-thermal therapy. Naïve mice and tumor-bearing mice were used as control groups. Results Local cryo-thermal therapy generated a stronger systematic antitumor immune response than RFA and a long-lasting antitumor immunity that protected against tumor rechallenge. In vitro studies showed that the antigen-specific CD8 + T-cell response was induced by both cryo-thermal therapy and RFA, but the strong neoantigen-specific CD4 + T-cell response was only induced by cryo-thermal therapy. Cryo-thermal therapy-induced strong antitumor immune response was mainly mediated by CD4 + T-cells, particularly neoantigen-specific CD4 + T-cells. Conclusion Cryo-thermal therapy induced a stronger and broader antigen-specific memory T-cells. Specifically, cryo-thermal therapy, but not RFA, led to a strong neoantigen-specific CD4 + T-cell response that mediated the resistance to tumor challenge.
Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma
Authors: Evon Poon, Tong Liang, Yann Jamin, Susanne Walz, Colin Kwok, Anne Hakkert, Karen Barker, Zuzanna Urban, Khin Thway, Rhamy Zeid, Albert Hallsworth, Gary Box, Marli E. Ebus, Marco P. Licciardello, Yordan Sbirkov, Glori Lazaro, Elizabeth Calton, Barbara M. Costa, Melanie Valenti, Alexis De Haven Brandon, Hannah Webber, Nicolas Tardif, Gilberto S. Almeida, Rossitza Christova, Gunther Boysen, Mark W. Richards, Giuseppe Barone, Anthony Ford, Richard Bayliss, Paul A. Clarke, Johann De Bono, Nathanael S. Gray, Julian Blagg, Simon P. Robinson, Suzanne A. Eccles, Daniella Zheleva, James E. Bradner, Jan Molenaar, Igor Vivanco, Martin Eilers, Paul Workman, Charles Y. Lin, Louis Chesler
Journal: Journal of Clinical Investigation (2020)

The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show that CYC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuroblastoma via multiple mechanisms. CDK9 — a component of the transcription elongation complex P-TEFb — bound to the MYCN-amplicon superenhancer, and its inhibition resulted in selective loss of nascent MYCN transcription. MYCN loss led to growth arrest, sensitizing cells for apoptosis following CDK2 inhibition. In MYCN-amplified neuroblastoma, MYCN invaded active enhancers, driving a transcriptionally encoded adrenergic gene expression program that was selectively reversed by CYC065. MYCN overexpression in mesenchymal neuroblastoma was sufficient to induce adrenergic identity and sensitize cells to CYC065. CYC065, used together with temozolomide, a reference therapy for relapsed neuroblastoma, caused long-term suppression of neuroblastoma growth in vivo, highlighting the clinical potential of CDK9/2 inhibition in the treatment of MYCN-amplified neuroblastoma.
The self-fulfilling prophecy of pulmonary fibrosis: a selective inspection of pathological signalling loops
Authors: Ashley R. Rackow, David J. Nagel, Claire McCarthy, Jennifer Judge, Shannon Lacy, Margaret A.T. Freeberg, Thomas H. Thatcher, R. Matthew Kottmann, Patricia J. Sime
Journal: European Respiratory Journal (2020)

Pulmonary fibrosis is a devastating, progressive disease and carries a prognosis worse than most cancers. Despite ongoing research, the mechanisms that underlie disease pathogenesis remain only partially understood. However, the self-perpetuating nature of pulmonary fibrosis has led several researchers to propose the existence of pathological signalling loops. According to this hypothesis, the normal wound-healing process becomes corrupted and results in the progressive accumulation of scar tissue in the lung. In addition, several negative regulators of pulmonary fibrosis are downregulated and, therefore, are no longer capable of inhibiting these feed-forward loops. The combination of pathological signalling loops and loss of a checks and balances system ultimately culminates in a process of unregulated scar formation. This review details specific signalling pathways demonstrated to play a role in the pathogenesis of pulmonary fibrosis. The evidence of detrimental signalling loops is elucidated with regard to epithelial cell injury, cellular senescence and the activation of developmental and ageing pathways. We demonstrate where these loops intersect each other, as well as common mediators that may drive these responses and how the loss of pro-resolving mediators may contribute to the propagation of disease. By focusing on the overlapping signalling mediators among the many pro-fibrotic pathways, it is our hope that the pulmonary fibrosis community will be better equipped to design future trials that incorporate the redundant nature of these pathways as we move towards finding a cure for this unrelenting disease.
Nature and prevalence of combinations of mental disorders and their association with excess mortality in a population‐based cohort study
Authors: Oleguer Plana‐Ripoll, Katherine L. Musliner, Søren Dalsgaard, Natalie C. Momen, Nanna Weye, Maria K. Christensen, Esben Agerbo, Kim Moesgaard Iburg, Thomas Munk Laursen, Preben Bo Mortensen, Carsten Bøcker Pedersen, Liselotte Vogdrup Petersen, Damian F. Santomauro, Bjarni J. Vilhjálmsson, Harvey A. Whiteford, John J. McGrath
Journal: World Psychiatry (2020)

The nature and prevalence of combinations of mental disorders and their associations with premature mortality have never been reported in a comprehensive way. We describe the most common combinations of mental disorders and estimate excess mortality associated with these combinations. We designed a population‐based cohort study including all 7,505,576 persons living in Denmark at some point between January 1, 1995 and December 31, 2016. Information on mental disorders and mortality was obtained from national registers. A total of 546,090 individuals (10.5%) living in Denmark on January 1, 1995 were diagnosed with at least one mental disorder during the 22‐year follow‐up period. The overall crude rate of diagnosis of mental disorders was 9.28 (95% CI: 9.26‐9.30) per 1,000 person‐years. The rate of diagnosis of additional mental disorders was 70.01 (95% CI: 69.80‐70.26) per 1,000 person‐years for individuals with one disorder already diagnosed. At the end of follow‐up, two out of five individuals with mental disorders were diagnosed with two or more disorder types. The most prevalent were neurotic/stress‐related/somatoform disorders (ICD‐10 F40‐F48) and mood disorders (ICD‐10 F30‐F39), which – alone or in combination with other disorders – were present in 64.8% of individuals diagnosed with any mental disorder. Mortality rates were higher for people with mental disorders compared to those without mental disorders. The highest mortality rate ratio was 5.97 (95% CI: 5.52‐6.45) for the combination of schizophrenia (ICD‐10 F20‐F29), neurotic/stress‐related/somatoform disorders and substance use disorders (ICD‐10 F10‐F19). Any combination of mental disorders was associated with a shorter life expectancy compared to the general Danish population, with differences in remaining life expectancy ranging from 5.06 years (95% CI: 5.01‐5.11) to 17.46 years (95% CI: 16.86‐18.03). The largest excess mortality was observed for combinations that included substance use disorders. This study reports novel estimates related to the “force of comorbidity” and provides new insights into the contribution of substance use disorders to premature mortality in those with comorbid mental disorders.
Assessment of Opioid Prescribing Patterns in a Large Network of US Community Health Centers, 2009 to 2018
Authors: John Muench, Katie Fankhauser, Robert W. Voss, Nathalie Huguet, Daniel M. Hartung, Jean O’Malley, Steffani R. Bailey, Stuart Cowburn, Dagan Wright, Gordon Barker, Maria Ukhanova, Irina Chamine
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Understanding opioid prescribing patterns in community health centers (CHCs) that disproportionately serve low-income patients may help to guide strategies to reduce opioid-related harms. <h3>Objective</h3> To assess opioid prescribing patterns between January 1, 2009, and December 31, 2018, in a network of safety-net clinics serving high-risk patients. <h3>Design, Setting, and Participants</h3> Cross-sectional study of 3 227 459 opioid prescriptions abstracted from the electronic health records of 2 129 097 unique primary care patients treated from 2009 through 2018 at a network of CHCs that included 449 clinic sites in 17 states. All age groups were included in the analysis. <h3>Main Outcomes and Measures</h3> The following measures were described at the population level for each study year: (1) percentage of patients with at least 1 prescription for an opioid by age and sex, (2) number of opioid prescriptions per 100 patients, (3) number of long-acting opioid prescriptions per 100 patients, (4) mean annual morphine milligram equivalents (MMEs) per patient, (5) mean MME per prescription, (6) number of chronic opioid users, and (7) mean of high-dose opioid users. <h3>Results</h3> The study population included 2 129 097 patients (1 158 413 women [54.4%]) with a mean (SD) age of 32.2 (21.1) years and a total of 3 227 459 opioid prescriptions. The percentage of patients receiving at least 1 opioid prescription in a calendar year declined 67.4% from 15.9% in 2009 to 5.2% in 2018. Over the 10-year study period, a greater percentage of women received a prescription (13.1%) compared with men (10.9%), and a greater percentage of non-Hispanic White patients (18.1%) received an opioid prescription compared with non-Hispanic Black patients (9.5%), non-Hispanic patients who self-identified as other races (8.0%), and Hispanic patients (6.9%). The number of opioid prescriptions for every 100 patients decreased 73.7% from 110.8 in 2009 to 29.1 in 2018. The number of long-acting opioids for every 100 patients decreased 85.5% during the same period, from 22.0 to 3.2. The MMEs per patient decreased from 1682.7 in 2009 to 243.1 in 2018, a decline of 85.6%. <h3>Conclusions and Relevance</h3> In this cross-sectional study, the opioid prescribing rate in 2009 in the CHC network was higher than national population estimates but began to decline earlier and more precipitously. This finding likely reflects harm mitigation policies and efforts at federal, state, and clinic levels and strong clinical quality improvement strategies within the CHCs.