tbuckley/cabot-search huggingface dataset:
Clinical Significance of Additional Cytogenetic Abnormalities (ACA) Acquired at the First Relapse in Adult Patients with Philadelphia Chromosome (Ph)-Negative Acute Lymphoblastic Leukemia (ALL)
Authors: Hiroaki Shimizu, Satoru Takada, Nahoko Hatsumi, Akihiko Yokohama, Takayuki Saitoh, Toru Sakura, Hiroshi Handa
Journal: Blood (2017)
Natural Selection Shapes Maintenance of Orthologous sRNAs in Divergent Host-Restricted Bacterial Genomes
Authors: Margaret W Thairu, Venkata Rama Sravani Meduri, Patrick H Degnan, Allison K Hansen
Journal: Molecular Biology and Evolution (2021)

Historically it has been difficult to study the evolution of bacterial small RNAs (sRNAs) across distantly related species. For example, identifying homologs of sRNAs is often difficult in genomes that have undergone multiple structural rearrangements. Also, some types of regulatory sRNAs evolve at rapid rates. The high degree of genomic synteny among divergent host-restricted bacterial lineages, including intracellular symbionts, is conducive to sRNA maintenance and homolog identification. In turn, symbiont genomes can provide us with novel insights into sRNA evolution. Here, we examine the sRNA expression profile of the obligate symbiont of psyllids, Carsonella ruddii, which has one of the smallest cellular genomes described. Using RNA-seq, we identified 36 and 32 antisense sRNAs (asRNAs) expressed by Carsonella from the psyllids Bactericera cockerelli (Carsonella-BC) and Diaphorina citri (Carsonella-DC), respectively. The majority of these asRNAs were associated with genes that are involved in essential amino acid biosynthetic pathways. Eleven of the asRNAs were conserved in both Carsonella lineages and the majority were maintained by selection. Notably, five of the corresponding coding sequences are also the targets of conserved asRNAs in a distantly related insect symbiont, Buchnera. We detected differential expression of two asRNAs for genes involved in arginine and leucine biosynthesis occurring between two distinct Carsonella-BC life stages. Using asRNAs identified in Carsonella, Buchnera, and Profftella which are all endosymbionts, and Escherichia coli, we determined that regions upstream of these asRNAs encode unique conserved patterns of AT/GC richness, GC skew, and sequence motifs which may be involved in asRNA regulation.
Interleukin-1α Is a Central Regulator of Leukocyte-Endothelial Adhesion in Myocardial Infarction and in Chronic Kidney Disease
Authors: Stefan J. Schunk, Sarah Triem, David Schmit, Stephen Zewinger, Tamim Sarakpi, Ellen Becker, Gregor Hütter, Selina Wrublewsky, Fabienne Küting, Mathias Hohl, Dalia Alansary, Leticia Prates Roma, Peter Lipp, Julia Möllmann, Michael Lehrke, Matthias W. Laschke, Michael D. Menger, Rafael Kramann, Peter Boor, Willi Jahnen-Dechent, Winfried März, Michael Böhm, Ulrich Laufs, Barbara A. Niemeyer, Danilo Fliser, Emmanuel Ampofo, Thimoteus Speer
Journal: Circulation (2021)

Background: Cardiovascular diseases and chronic kidney disease (CKD) are highly prevalent, aggravate each other, and account for substantial mortality. Both conditions are characterized by activation of the innate immune system. The alarmin interleukin-1α (IL-1α) is expressed in a variety of cell types promoting (sterile) systemic inflammation. The aim of the present study was to examine the role of IL-1α in mediating inflammation in the setting of acute myocardial infarction (AMI) and CKD. Methods: We assessed the expression of IL-1α on the surface of monocytes from patients with AMI and patients with CKD and determined its association with atherosclerotic cardiovascular disease events during follow-up in an explorative clinical study. Furthermore, we assessed the inflammatory effects of IL-1α in several organ injury models in Il1a −/ − and Il1b −/ − mice and investigated the underlying mechanisms in vitro in monocytes and endothelial cells. Results: IL-1α is strongly expressed on the surface of monocytes from patients with AMI and CKD compared with healthy controls. Higher IL-1α surface expression on monocytes from patients with AMI and CKD was associated with a higher risk for atherosclerotic cardiovascular disease events, which underlines the clinical relevance of IL-1α. In mice, IL-1α, but not IL-1β, mediates leukocyte-endothelial adhesion as determined by intravital microscopy. IL-1α promotes accumulation of macrophages and neutrophils in inflamed tissue in vivo. Furthermore, IL-1α on monocytes stimulates their homing at sites of vascular injury. A variety of stimuli such as free fatty acids or oxalate crystals induce IL-1α surface expression and release by monocytes, which then mediates their adhesion to the endothelium via IL-1 receptor-1. IL-1α also promotes expression of the VCAM-1 (vascular cell adhesion molecule-1) on endothelial cells, thereby fostering the adhesion of circulating leukocytes. IL-1α induces inflammatory injury after experimental AMI, and abrogation of IL-1α prevents the development of CKD in oxalate or adenine-fed mice. Conclusions: IL-1α represents a key mediator of leukocyte-endothelial adhesion and inflammation in AMI and CKD. Inhibition of IL-1α may serve as a novel anti-inflammatory treatment strategy.
Lymphatic Dysregulation in Patients With Heart Failure
Authors: Marat Fudim, Husam M. Salah, Janarthanan Sathananthan, Mathieu Bernier, Waleska Pabon-Ramos, Robert S. Schwartz, Josep Rodés-Cabau, François Côté, Abubaker Khalifa, Sean A. Virani, Manesh R. Patel
Journal: Journal of the American College of Cardiology (2021)
Hypoxia‐Induced Synovial Fibroblast Activation in Inflammatory Arthritis and the Role of Notch‐1 and Notch‐3 Signaling: Comment on the Article by Chen et al
Authors: Wang‐Dong Xu, An‐Fang Huang
Journal: Arthritis & Rheumatology (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Biodegradation behaviour of Fe-based alloys in Hanks’ Balanced Salt Solutions: Part I. material characterisation and corrosion testing
Authors: Christabelle Tonna, Cheng Wang, Di Mei, Sviatlana V. Lamaka, Mikhail L. Zheludkevich, Joseph Buhagiar
Journal: Bioactive Materials (2021)

Research on Fe-based biodegradable alloys for implant applications has increased considerably over the past decade. However, there is limited information on the influence of testing electrolytes on corrosion product formation and general corrosion progress. In this work, the effect of Hanks' Balanced Salt Solution (HBSS) with or without Ca2+ on the corrosion of Fe, Fe35Mn and (Fe35Mn)5Ag powder-processed coupons has been studied using potentiodynamic polarisation, Electrochemical Impedance Spectroscopy (EIS), and preliminary localised measurement of pH and dissolved oxygen concentration in close proximity to the metal surface. Both Fe35Mn and (Fe35Mn)5Ag alloys showed accelerated corrosion when compared to pure Fe based on potentiodynamic testing results, with FeMnAg exhibiting the highest corrosion rate in Ca2+-containing HBSS. The results indicate that in Ca2+-containing HBSS, the formation of a partially protective Ca/P layer decelerates the corrosion progress, whereas the Fe- and Mn-phosphates formed in Ca2+-free HBSS do not have the same effect. The Ca/P layer on (Fe35Mn)5Ag experienced a reduction in resistance following several hours of testing, indicating partial loss of its protective effect.
Informed Consent: Is It Really?
Authors: Margaret Tempero
Journal: Journal of the National Comprehensive Cancer Network (2021)

Is It Really?I n a rare moment of weakness, I agreed to serve on UCSF's Institutional Review Board.This is a big deal.In addition to meetings every 2 weeks, members need to learn a complex electronic content system (not easy for this Luddite).Members have 3 to 4 assignments involving reams and reams of paper (real or electronic) and each must read the informed consent document in excruciating detail.But I did it because this is important and it was the right thing to do.However, I must say that if I were a patient, sick and afraid, I would find these informed consent documents to be overwhelming.Although I think we have improved our simplification of language, we have lost our course in making this document easy for patients to navigate.Let's take a couple of examples.Any patient with cancer on a clinical trial involving a therapeutic intervention will undergo blood tests and imaging.Current rules require that these procedures be detailed in the informed consent document.Sometimes there are more pages on this than on the risks related to the experimental intervention!It doesn't make sense.Because most of our patients have had these procedures as part of their standard of care, could we simply provide a reference compendium in case a patient wants to know more?That alone might eliminate several pages from each document.Another example is the risk associated with checkpoint inhibitors, such as CTLA-4 inhibitors or PD-1 or PD-L1 inhibitors.The last consent document I looked at included 4 pages of painful details for every possible organ system that could be affected by an autoimmune reaction.Why not just make it simple?We could include something like: "This class of drugs can turn your own immune system against virtually any tissue in your body.Fortunately, this is uncommon and reversible, but the most frequent tissues affected are listed in the following table."Wouldn't that be more straightforward?Other sticky issues are related to biopsies obtained for research purposes, the risks of genetic analysis on tissue, and the ownership and custody of tissue.But those topics need to be saved for another day.Right now, I am focused on a template for a clear and understandable informed consent document that does not require an advanced degree to understand.I think that we can personalize these documents according to the patient experience.For instance, a first-line clinical trial might need more detail on procedures than a second-line trial.For drugs that are already FDA-approved for another indication, do we need to detail every possible adverse event?Couldn't we include a statement such as: "DRUG X is already FDA-approved and in wide use for another form of cancer.The most common side effects are listed in the following table."Finally, I think we need to remember that patients rely more on their trust in us than in an informed consent document.Let's honor that and make this process simpler for everyone!
Abstract 58: Differential Ventricular Remodeling Induced by Thin Filament Mutational Effects on the Tropomyosin Overlap Structure
Authors: Mark McConnell, Lauren Tal-Grinspan, Melissa Lynn, Benjamin Schwartz, Ofer Fass, Hassan-Galaydh Farah, Andrea Deranek, Jayant James Jayasundar, Jil C Tardiff
Journal: Circulation Research (2016)

Inherited mutations in cardiac thin filament proteins create primary alterations in structure. These changes then lead to pathologic remodeling of the heart. We have proposed that two mutations, tropomyosin (Tm) D230N which leads to dilated cardiomyopathy (DCM) and cardiac troponin T (cTnT) R92L, which leads to hypertrophic cardiomyopathy (HCM), directly affect the Tm overlap, a crucial structure regulating myofilament activation. These mutations lead to divergent ventricular remodeling, which we hypothesize is caused by differential effects on the Tm overlap, an inherently dynamic system. In order to investigate this hypothesis, we used time-resolved Forster resonance energy transfer (FRET) to measure discrete distances across the proteins of the overlap, and differential scanning calorimetry (DSC) in order to characterize the baseline structure of this region as well as the effects of mutants. We found that the cTnT R92L mutant increased interprotein distance at the proximal N-terminal end of this region. In contrast, the Tm D230N mutant decreases interprotein distance at the proximal C-terminal end of the overlap. DSC studies showed a significant increase in the association of Tm with actin in the presence of Tm D230N, predicted to increase cooperativity of thin filament activation. These finding are in agreement both with the human population who carry the disease, as well as the mouse lines in our lab, which phenocopy the human disease. Overall, the study further characterized the wild type structure of the Tm overlap, and revealed the differential structural effects of the mutants, thereby, for the first time linking local changes in structure to phenotypic changes and ventricular remodeling leading to HCM and DCM. Further studies will investigate the role of isoform and phosphorylation modifiers, elucidating how these modify human disease in the presence and absence of cardiomyopathy linked mutations.
Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open-label, phase 2 study
Authors: Shun Lu, Jian Fang, Xingya Li, Lejie Cao, Jianying Zhou, Qisen Guo, Zongan Liang, Ying Cheng, Liyan Jiang, Nong Yang, Zhigang Han, Jianhua Shi, Yuan Chen, Hua Xu, Helong Zhang, Gongyan Chen, Rui Ma, Sanyuan Sun, Yun Fan, Jing Li, Xian Luo, Linfang Wang, Yongxin Ren, Weiguo Su
Journal: The Lancet Respiratory Medicine (2021)
Effect of Restrictive or Liberal Blood Transfusion on Major Cardiovascular Events in Patients With Acute Myocardial Infarction and Anemia—Reply
Authors: Gregory Ducrocq, Tabassome Simon, P. Gabriel Steg
Journal: JAMA (2021)

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Despite vaccination, China needs non-pharmaceutical interventions to prevent widespread outbreaks of COVID-19 in 2021
Authors: Juan Yang, Valentina Marziano, Xiaowei Deng, Giorgio Guzzetta, Juanjuan Zhang, Filippo Trentini, Jun Cai, Piero Poletti, Wen Zheng, Wei Wang, Qianhui Wu, Zeyao Zhao, Kaige Dong, Guangjie Zhong, Cécile Viboud, Stefano Merler, Marco Ajelli, Hongjie Yu
Journal: Nature Human Behaviour (2021)

COVID-19 vaccination is being conducted in over 200 countries and regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remains a key question for policy makers. To address this, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that, to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable of keeping the reproduction number (Rt) around 1.3, the synergetic effect of NPIs and vaccination could reduce the COVID-19 burden by up to 99% and bring Rt below the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.
Necrobiosis lipoidica-associated cutaneous malignancy
Authors: Jamison A. Harvey, Kevin J. Severson, Caitlin M. Brumfiel, Meera H. Patel, Richard J. Butterfield, Steven A. Nelson, Aleksandar Sekulic, Mark R. Pittelkow, Aaron R. Mangold
Journal: Journal of the American Academy of Dermatology (2021)
Morphological manifestations of irritable bowel syndrome
Authors: Yu.M. Stepanov, I.Ya. Budzak, Yu.A. Gaidar
Journal: GASTROENTEROLOGY (2021)

The article presents modern data on morphological changes in the intestinal mucosa in patients with irritable bowel syndrome. There were analyzed the studies of different years on the morphological manifestations of irritable bowel syndrome. It has been shown that this pathology has an unusual low-grade inflammation. Mast cells play an important role in these inflammatory disorders, they have an effect on motility disorders, visceral hypersensitivity and other pathogenetic factors of irritable bowel syndrome. Disorders of intercellular tight junctions in this category of patients were also analyzed. The role of proteins involved in intercellular contacts (occludin, claudin, ZO) has been characterized. An analysis of the studies investigating these disorders has been carried out. The article provides examples of the analysis of biopsies in patients with irritable bowel syndrome using various methods of their assessment.
Abstract 14214: ATTRibute-CM: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Global Phase 3 Study of AG10 in Patients With Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Authors: Julian D Gillmore, Pablo Garcia-Pavia, Martha Grogan, Mazen A Hanna, Stephen B Heitner, Daniel Jacoby, Mathew S Maurer, Claudio Rapezzi, Sanjiv J Shah, Jitendra Ganju, Leonid Katz, Jonathan Fox, Daniel Judge
Journal: Circulation (2019)

Background: Transthyretin (TTR) amyloidosis (ATTR) is an under-diagnosed cause of heart failure driven by TTR destabilization due to pathogenic mutations and/or aging. AG10 is a small molecule TTR ...
低好塩基球活性化とピーナッツ特異的IgEに関連した持続的な成功したピーナッツ経口免疫療法【JST・京大機械翻訳】
Authors: Tsai Mindy, Mukai Kaori, Chinthrajah R. Sharon, C Nadeau Kari, J Galli Stephen
Journal: Journal of Allergy and Clinical Immunology (2020)
Covid-19: Should we be worried about reports of myocarditis and pericarditis after mRNA vaccines?
Authors: Jacqui Wise
Journal: BMJ (2021)

Covid-19: Should we be worried about reports of myocarditis and pericarditis after mRNA vaccines?Jacqui Wise looks at the data released by UK and US regulatory agencies this week Jacqui Wise What is the latest?On 23 June the US Centers for Disease Control and Prevention's safety committee said there was a "likely association" between the Pfizer-BioNTech and Moderna covid-19 vaccines and myocarditis and pericarditis in some young adults.The CDC's Advisory Committee on Immunization Practices said there was a higher than expected number of reports of heart inflammation in people aged 16-24 who had received the mRNA vaccines but that the benefits of vaccination still clearly outweighed the risks.
What is sexual wellbeing and why does it matter for public health?
Authors: Kirstin R Mitchell, Ruth Lewis, Lucia F O'Sullivan, J Dennis Fortenberry
Journal: The Lancet Public Health (2021)

Sexual health has provided a guiding framework for addressing sexuality in public health for several decades. Although the WHO definition of sexual health is revolutionary in acknowledging positive sexuality, public health approaches remain focused on risk and adverse outcomes. The long-standing conflation of sexual health and sexual wellbeing has affected our ability to address everyday sexual issues. This Viewpoint provides a way forward to resolve this impasse. We propose sexual wellbeing as a distinct and revolutionary concept that can be operationalised as a seven-domain model. We situate sexual wellbeing alongside sexual health, sexual justice, and sexual pleasure as one of four pillars of public health enquiry. We argue that sexual wellbeing is imperative to public health as a marker of health equity, a meaningful population indicator of wellbeing, a means to capture population trends distinct from sexual health, and an opportunity to refocus the ethics, form, and practices of public health.
Resistance exercise, alone and in combination with aerobic exercise, and obesity in Dallas, Texas, US: A prospective cohort study
Authors: Angelique G. Brellenthin, Duck-chul Lee, Jason A. Bennie, Xuemei Sui, Steven N. Blair
Journal: PLoS Medicine (2021)

Background Obesity is a significant and growing public health problem in high-income countries. Little is known about the relationship between resistance exercise (RE), alone and in combination with aerobic exercise (AE), and the risk of developing obesity. The purpose of this prospective cohort study was to examine the associations between different amounts and frequencies of RE, independent of AE, and incident obesity. Methods and findings Participants were 11,938 healthy adults ages 18–89 years with a BMI &lt; 30 kg/m 2 at baseline who completed at least 2 clinical examinations during 1987–2005 as part of the Aerobics Center Longitudinal Study. Self-reported RE participation in minutes/week and days/week was collected from a standardized questionnaire. Incident obesity was defined as a BMI ≥ 30 kg/m 2 at follow-up. Incident obesity was also defined by waist circumference (WC) &gt; 102/88 cm for men/women and percent body fat (PBF) ≥ 25%/30% for men/women at follow-up in participants who were not obese by WC ( n = 9,490) or PBF ( n = 8,733) at baseline. During the average 6-year follow-up, 874 (7%), 726 (8%), and 1,683 (19%) developed obesity defined by BMI, WC, or PBF, respectively. Compared with no RE, 60–119 min/wk of RE was associated with 30%, 41%, and 31% reduced risk of obesity defined by BMI (hazard ratio [95% CI], 0.70 [0.54–0.92], p = 0.008), WC (0.59 [0.44–0.81], p &lt; 0.001), and PBF (0.69 [0.57–0.83], p &lt; 0.001), respectively, after adjusting for confounders including age, sex, examination year, smoking status, heavy alcohol consumption, hypertension, hypercholesterolemia, diabetes, and AE. Compared with not meeting the RE guidelines of ≥2 d/wk, meeting the RE guidelines was associated with 18%, 30%, and 30% reduced risk of obesity defined by BMI (hazard ratio [95% CI], 0.82 [0.69–0.97], p = 0.02), WC (0.70 [0.57–0.85], p &lt; 0.001), and PBF (0.70 [0.62–0.79], p &lt; 0.001), respectively. Compared with meeting neither guideline, meeting both the AE and RE guidelines was associated with the smallest hazard ratios for obesity. Limitations of this study include limited generalizability as participants were predominantly white men from middle to upper socioeconomic strata, use of self-reported RE, and lack of detailed diet data for the majority of participants. Conclusions In this study, we observed that RE was associated with a significantly reduced risk of obesity even after considering AE. However, meeting both the RE and AE guidelines was associated with the lowest risk of obesity.
Changes Associated With the Entry of a Biosimilar in the Insulin Glargine Market
Authors: Joseph Levy, Zahra M. Chowdhury, Mariana P. Socal, Antonio J. Trujillo
Journal: JAMA Internal Medicine (2021)

This study explores the shifts in total US sales and net prices for all 3 insulin glargine products from quarter 1 of 2010 through quarter 2 of 2020.