tbuckley/cabot-search huggingface dataset:
AB0140 BAFF NEUTRALIZATION HAS JANUS-FACED EFFECT ON ATHEROSCLEROSIS ASSOCIATED WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: F. Saidoune, N. Charles, J. Chezel, B. Escoubet, T. Papo, A. Nicoletti, K. Sacre
Journal: Annals of the Rheumatic Diseases (2020)

Background: Cardiovascular diseases (CVD) are the leading cause of death in systemic lupus erythematosus (SLE). B cells play a key role in the pathogenesis of lupus and anti-BAFF therapy has been approved in SLE. Since mature B cells also promote atherosclerosis, BAFF neutralization is expected to have an atheroprotective effect in SLE. Objectives: The aim of our study was to test this hypothesis using a new mouse model with a mix susceptibility to lupus and atherosclerosis that received or not an anti-BAFF treatment, and in a cohort of SLE patients in whom we monitored carotid plaques, the B cell compartment and BAFF levels. Methods: The effect of BAFF on atherosclerosis associated with lupus was investigated in the atherosclerosis- and lupus-prone Apoe°D227K mouse model and in a cohort of SLE patients. Mice were treated with a blocking anti-BAFF monoclonal antibody (Ab), while fed with a standard chow diet. Carotid plaque and carotid intima media thickness were assessed by ultrasound at baseline and during follow-up in SLE patients asymptomatic for CVD. Results: Anti-BAFF Ab in Apoe°D227K mice i/ induced a B cell depletion, ii/ efficiently treated lupus , iii/ improved atherosclerosis lesions in mice that had low plasma cholesterol levels but worsened the lesions in mice with high cholesterol levels. In that case, the atheroprotective effect of the BAFF-BAFFR signaling inhibition on B cells was counterbalanced by the proatherogenic effect of the BAFF-TACI signaling inhibition on macrophages. In SLE patients, BAFF blood levels were associated with subclinical atherosclerosis. Anti-BAFF Ab treatment had a differential effect on the intima media thickness progression in SLE patients depending on the body mass index Conclusion: Depending on the balance between metabolic- and B cell-induced proatherogenic conditions, anti-BAFF could be respectively detrimental or beneficial on atherosclerosis development in SLE Acknowledgments: Guillaume Even, Yasmine Lamri, Anh-Thu Gaston, Disclosure of Interests: Fanny Saidoune Grant/research support from: supported by a research partnerships between the academic and GlaxoSmithKline France. Anti-BAFF mAb (IgG1, clone 10F4B) in mice was provided by Glaxosmithkline, Nicolas Charles: None declared, Julie Chezel: None declared, Brigitte Escoubet: None declared, Thomas Papo: None declared, Antonino Nicoletti: None declared, karim sacre: None declared
Exploring the human hair follicle microbiome*
Authors: M.B. Lousada, T. Lachnit, J. Edelkamp, T. Rouillé, D. Ajdic, Y. Uchida, A. Di Nardo, T.C.G. Bosch, R. Paus
Journal: British Journal of Dermatology (2020)

Human hair follicles (HFs) carry complex microbial communities that differ from the skin surface microbiota. This likely reflects that the HF epithelium differs from the epidermal barrier in that it provides a moist, less acidic, and relatively ultraviolet light-protected environment, part of which is immune-privileged, thus facilitating microbial survival. Here we review the current understanding of the human HF microbiome and its potential physiological and pathological functions, including in folliculitis, acne vulgaris, hidradenitis suppurativa, alopecia areata and cicatricial alopecias. While reviewing the main human HF bacteria (such as Propionibacteria, Corynebacteria, Staphylococci and Streptococci), viruses, fungi and parasites as human HF microbiome constituents, we advocate a broad view of the HF as an integral part of the human holobiont. Specifically, we explore how the human HF may manage its microbiome via the regulated production of antimicrobial peptides (such as cathelicidin, psoriasin, RNAse7 and dermcidin) by HF keratinocytes, how the microbiome may impact on cytokine and chemokine release from the HF, and examine hair growth-modulatory effects of antibiotics, and ask whether the microbiome affects hair growth in turn. We highlight major open questions and potential novel approaches to the management of hair diseases by targeting the HF microbiome.
Teeter-totter effect: a new mechanism to understand shoe-related improvements in long-distance running
Authors: Benno M Nigg, Sasa Cigoja, Sandro R Nigg
Journal: British Journal of Sports Medicine (2020)

The effect of shoe mid-sole construction on running performance was discussed with reference to the Nike Vaporfly 4%.1 Drs Burns and Tam described the mid-sole thickness as the major running shoe characteristic that contributes to changes in performance. Here, we highlight the role of the curved carbon fibre plate embedded in the mid-sole, and introduce a new effect on running mechanics, the ‘ teeter-totter effect ’.

During ground contact in running, the point of application of the ground reaction force moves anteriorly during the second half of ground contact towards the front end of the curved carbon fibre plate. We suggest that, in this position, the ground reaction force produces a ‘reaction’ force at the heel in upward direction (perpendicular to the direction of the plate; figure 1).



Figure 1 
Schematic illustration of the teeter-totter effect including the application point of the ground reaction force (red full circle) and its translation (red broken circle and line), the applied force of the runner (black arrow) at the front part of the shoe and the reaction force at the heel of the foot (red arrow) during early/mid-stance (left orientation) and push-off (right orientation). Image modified from nike.com.



If the curvature of the plate is designed correctly, the teeter-totter effect …
Long-term trends of asthma, allergic rhinitis and atopic eczema in young Finnish men: a retrospective analysis, 1926–2017
Authors: Jere Reijula, Jari Latvala, Mika Mäkelä, Simo Siitonen, Mari Saario, Tari Haahtela
Journal: European Respiratory Journal (2020)

The aim of this study was to assess the long-term time trends of the prevalence of asthma, allergic rhinitis and atopic eczema in young Finnish men.A retrospective analysis was carried out on cross-sectional data from the Finnish Defence Forces taken from call-up examinations of candidates for military conscription and examinations of conscripts discharged from service because of poor health. Roughly 1.7 million men aged 18‒19 years (98% of men of conscription age) were examined from 1966 to 2017. A proportional but unknown number of young men were examined from 1926 to 1961.The main outcome measures were asthma recorded at call-up examination as the main diagnosis in 1926‒2017 and any diagnosis in 1997‒2017, exemption or discharge from military service due to asthma, and allergic rhinitis and atopic eczema recorded as the main diagnosis in 1966‒2017 and any diagnosis in 1997‒2017.During 1926-1961 the prevalence of asthma remained low at between 0.02% and 0.08%. A linear rise began between 1961 and 1966, with a 12-fold increase in the prevalence from 0.29% in 1966 to 3.44% in 2001. Thereafter, the prevalence of asthma as the main diagnosis stabilised but continued to increase to 5.19% in 2017 if secondary diagnoses of asthma were included. Exemption rates from military service due to asthma have similarly increased but fluctuated more. The prevalence of allergic rhinitis increased from 0.06% to 10.70% and atopic eczema from 0.15% to 2.90% during the period 1966‒2017.In Finland, an increase in asthma and allergic conditions among young men became evident in the mid-1960s. The increase slowed in the 2000s and may be levelling off in the 2020s.
Association between hydrochlorothiazide and the risk of in situ and invasive squamous cell skin carcinoma and basal cell carcinoma: A population-based case-control study
Authors: Jonas A. Adalsteinsson, Sonal Muzumdar, Reid Waldman, Chaoran Hu, Rong Wu, Désirée Ratner, Jonathan Ungar, Jonathan I. Silverberg, Gudridur H. Olafsdottir, Arni Kjalar Kristjansson, Laufey Tryggvadottir, Jon Gunnlaugur Jonasson
Journal: Journal of the American Academy of Dermatology (2020)
Ibrutinib Disrupts IL-4R - IL-4 Axis By Inhibiting IL-4R Signaling and Reversing Th2/Th1 Polarization through Diminished CLECL1 in CLL B Cells
Authors: Shih-Shih Chen, Priyadarshini Ravichandran, Gerardo Ferrer, Andrea Nicola Mazzarello, Florencia Palacios, Michael Ibrahim, Yasmine Kieso, Jacqueline C. Barrientos, Edward Clark, Barbara Sherry, Jan A. Burger, Kanti Rai, Nicholas Chiorazzi
Journal: Blood (2017)
Abstract B42: Mutant RAS represses CASZ1, a novel regulator of MYOD and MYOG, to inhibit embryonal rhabdomyosarcoma differentiation
Authors: Zhihui Liu, Xiyuan Zhang, Haiyan Lei, Norris Lam, Oliver Yockey, Max Xu, Arnulfo Mendoza, Jun S Wei, Javed Khan, Marielle E. Yohe, Jack F. Shern, Carol J. Thiele
Journal: Cancer Research (2020)

Abstract Embryonal rhabdomyosarcoma (ERMS) is a childhood cancer that expresses myogenic master regulatory factor MYOD but fails to differentiate. Zinc finger transcription factor CASZ1 is a tumor suppressor and orchestrates cell-fate specification, commitment, and differentiation in many cell types during development. CASZ1 is expressed during skeletal myogenesis; however, whether CASZ1 plays a role in skeletal muscle cell differentiation and RMS pathogenesis is unknown. Here we uncover that CASZ1 crosstalks with myogenic regulatory factors Myf5, MyoD, and Myog to regulate myogenesis in C2C12 cells. Public transcriptome data show that CASZ1 mRNA levels are lower in ERMS compared to normal muscle (p&amp;lt;0.001). CASZ1 levels decrease upon oncogenic activation of RAS-MEK pathway and increase when ERMS undergoes terminal differentiation after MEK inhibitor trametinib (MEKi) treatment. Analysis of super-enhancer landscape in MEKi-induced differentiated ERMS cells reveals a core transcriptional regulatory circuitry (CRC) including CASZ1, MYOD, and MYOG. Loss of CASZ1 attenuates MEKi-induced myogenic programming in ERMS. Restoration of CASZ1 in ERMS cells induces muscle differentiation. ChIP-seq, ATAC-seq, and RNA-seq results show that CASZ1 directly upregulates expression of skeletal muscle differentiation genes and represses non-muscle genes through affecting chromatin accessibility, enhancer maintenance, and super-enhancer activity. Next-generation sequencing of primary RMS tumors identified a nonsynonymous single-nucleotide variant causing an arginine-to-cysteine switch (R25C). When evaluated in 293T and ERMS cells, R25C impairs CASZ1 nuclear localization and fails to activate target genes’ transcription. Tumor xenograft studies show that CASZ1 suppresses RMS tumor growth (p&amp;lt;0.005), while the CASZ1-R25C mutant has no effect. Taken together, loss of CASZ1 activity, due to RAS-MEK signaling or genetic alteration, impairs ERMS differentiation, contributing to RMS tumorigenesis. Citation Format: Zhihui Liu, Xiyuan Zhang, Haiyan Lei, Norris Lam, Oliver Yockey, Max Xu, Arnulfo Mendoza, Jun S Wei, Javed Khan, Marielle E. Yohe, Jack F. Shern, Carol J. Thiele. Mutant RAS represses CASZ1, a novel regulator of MYOD and MYOG, to inhibit embryonal rhabdomyosarcoma differentiation [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B42.
Surveillance Functional Imaging Has Limited Role in Solitary Plasmacytomas: International Multi-Centre Study of Clinical Outcomes
Authors: Faye A Sharpley, Pedro Neffa, Fotis Panitsas, Jaimal Kothari, David Cutter, Roberta Shcolnik Szor, Manil Subesinghe, Gracia Martinez, Vanderson Rocha, Karthik Ramasamy
Journal: Blood (2017)
Associations of Socioeconomic Status, Public vs Private Insurance, and Race/Ethnicity With Metastatic Sarcoma at Diagnosis
Authors: Brandon J. Diessner, Brenda J. Weigel, Paari Murugan, Lin Zhang, Jenny N. Poynter, Logan G. Spector
Journal: JAMA Network Open (2020)

Approximately 10% to 30% of patients with sarcoma present with detectable metastases at diagnosis. However, the extent to which presentation with metastases is due to delayed diagnosis vs other factors remains unclear.To evaluate whether socioeconomic status, insurance status, or race/ethnicity were associated with the presence of metastases at diagnosis of sarcoma.This cross-sectional study used data from the population-based Surveillance, Epidemiology, and End Results program. Adult and pediatric patients with an initial diagnosis of soft-tissue and bone sarcoma between 2001 and 2015 were stratified by age group (pediatric, <20 years; adult, 20-65 years; older adult, >65 years) and sarcoma subtype. Statistical analyses were performed between August 2019 and January 2020.Surveillance, Epidemiology, and End Results Census tract-level socioeconomic status index, insurance status, and race/ethnicity.The odds of presenting with metastases at diagnosis were calculated.A total of 47 337 patients with first primary malignant sarcoma were included (24 343 male patients [51.4%]), with 29 975 non-Hispanic White patients (63.3%), 5673 non-Hispanic Black patients (12.0%), 7504 Hispanic patients (15.8%), and 4185 American Indian-Alaskan Native and Asian Pacific Islander patients (8.8%). Liposarcoma in adults was the only subtype and age group combination that demonstrated a significant trend in incidence across socioeconomic status levels (odds ratio, 0.85; 99% CI, 0.76-0.96; P = .001). However, compared with having non-Medicaid insurance, having Medicaid or no insurance in adults was associated with an increased odds of metastases at diagnosis for 6 of the 8 sarcoma subtypes evaluated; osteosarcoma and Ewing sarcoma were the only 2 subtypes in adults for which metastases were not associated with insurance status. In addition, there was an increased risk of presenting with metastases among non-Hispanic Black adults diagnosed with leiomyosarcoma (odds ratio, 1.87; 99% CI, 1.41-2.48) and unclassified sarcomas (odds ratio, 1.65; 99% CI, 1.01-2.67) compared with non-Hispanic White adults that was independent of socioeconomic and insurance status.These findings suggest that delayed access to care is associated with advanced stage at diagnosis for several soft-tissue sarcoma subtypes in adults, whereas other factors may be associated with the metastatic progression of osteosarcoma and Ewing sarcoma, as well as the racial disparities observed with metastatic leiomyosarcoma and unclassified sarcomas.
Improvement of Signs and Symptoms of Nonradiographic Axial Spondyloarthritis in Patients Treated With Secukinumab: Primary Results of a Randomized, Placebo‐Controlled Phase III Study
Authors: Atul Deodhar, Ricardo Blanco, Eva Dokoupilová, Stephen Hall, Hideto Kameda, Alan J. Kivitz, Denis Poddubnyy, Marleen van de Sande, Anna S. Wiksten, Brian O. Porter, Hanno B. Richards, Sibylle Haemmerle, Jürgen Braun
Journal: Arthritis & Rheumatology (2020)

Objective To report the primary (1‐year) results from PREVENT, the first phase III study evaluating secukinumab in patients with active nonradiographic axial spondyloarthritis (SpA). Methods A total of 555 patients were randomized (1:1:1) to receive subcutaneous secukinumab 150 mg with a loading dose (loading dose [LD] group), secukinumab 150 mg without a loading dose (non–loading dose [NL] group), or placebo weekly and then every 4 weeks starting at week 4. The NL group received placebo at weeks 1, 2, and 3 to maintain blinding. Switch to open‐label secukinumab or standard of care was permitted after week 20. The study had 2 independent analysis plans, per European Union and non‐US (plan A; week 16) and US (plan B; week 52) regulatory requirements. The primary end point was 40% improvement in disease activity according to the Assessment of SpondyloArthritis international Society (ASAS40) criteria at week 16 (in the LD group) and at week 52 (in the NL group) in tumor necrosis factor inhibitor (TNFi)–naive patients. Safety analyses included all patients who received ≥1 dose of study treatment. Results Overall, 481 patients completed 52 weeks of treatment, including 84.3% (156 of 185) in the LD group, 89.7% (165 of 184) in the NL group, and 86.0% (160 of 186) in the placebo group. The proportion of patients who switched to open‐label or standard of care between weeks 20 and 48 was 50.8% in the LD group, 47.3% in the NL group, and 64.0% in the placebo group. Both primary and all secondary end points were met at week 16. The proportion of TNFi‐naive patients who met ASAS40 was significantly higher for LD at week 16 (41.5%) and NL at week 52 (39.8%) versus placebo (29.2% at week 16 and 19.9% at week 52; both P &lt; 0.05). No new safety findings were reported. Conclusion Our findings indicate that secukinumab 150 mg provides significant and sustained improvement in signs and symptoms of nonradiographic axial SpA through 52 weeks. Safety was consistent with previous reports.
Role of glia in optic nerve
Authors: Meysam Yazdankhah, Peng Shang, Sayan Ghosh, Stacey Hose, Haitao Liu, Joseph Weiss, Christopher S. Fitting, Imran A. Bhutto, J. Samuel Zigler, Jiang Qian, José-Alain Sahel, Debasish Sinha, Nadezda A. Stepicheva
Journal: Progress in Retinal and Eye Research (2020)
Elevated Expression of the S100A8/S100A9 Complex in AML Correlates with Reduced Sensitivity to the BCL2 Inhibitor Venetoclax
Authors: Riikka Karjalainen, Minxia Liu, Ashwini Kumar, Alun Parsons, Mika Kontro, Kimmo Porkka, Caroline A Heckman
Journal: Blood (2017)
Abstract 16511: Time-to-controlled De-escalation Of Dual Antiplatelet Therapy Does Not Impact The Change Of Laboratory Level Of Platelet Inhibition In Primary Angioplasty
Authors: Zuzana J Motovska, Robin Kralik, Martin Kamenik, Jiri Knot, Michal Svoboda, Roman Miklik, Petr Kala, Jiri Jarkovsky
Journal: Circulation (2019)

Background: Controlled de-escalation after AMI presents a real option for personalized dual antiplatelet therapy (DAPT). The randomized PRAGUE 18 study (prasugrel vs. ticagrelor in primary PCI, N 1...
CB-058. REGULATION OF CANCER PROMOTING TRYPTOPHAN CATABOLISM IN GLIOBLASTOMA BY THE GLUCOCORTICOID RECEPTOR
Authors: Martina Ott, Ulrike Litzenburger, Katharina Rauschenbach, Lukas Bunse, Stefan Pusch, Katharina Ochs, Felix Sahm, Christiane Opitz, Andreas von Deimling, Wolfgang Wick, Michael Platten
Journal: Neuro-Oncology (2013)

The immunosuppressive microenvironment is a major obstacle for the treatment of glioblastoma. Recently, we identified a novel signaling pathway in glioblastoma and other types of cancer involving the degradation of tryptophan to kynurenine by tryptophan-2,3-dioxygenase (TDO), which leads to the inhi
Thematic Analysis of Hospice Mentions in the Health Records of Veterans with Advanced Kidney Disease
Authors: Ann M. O’Hare, Catherine R. Butler, Janelle S. Taylor, Susan P.Y. Wong, Elizabeth K. Vig, Ryan S. Laundry, Melissa W. Wachterman, Paul L. Hebert, Chuan-Fen Liu, Nilka Rios-Burrows, Claire A. Richards
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Little is known regarding how decisions about hospice referral among patients with advanced kidney disease unfold in real-world clinical settings. The authors identified three dominant themes in their qualitative analysis of documentation pertaining to hospice in the electronic medical records of members of a national sample of veterans with advanced kidney disease. First, hospice and usual care seemed to function as conflicting rather than complementary models of care. Second, patients were usually referred to hospice late in the course of illness after all other options had been exhausted. Third, patients’ complex care needs sometimes complicated transitions to hospice, stretched the limits of home hospice, and fostered reliance on the acute medical system. These findings highlight the need to improve hospice transitions for patients with advanced kidney disease. Background Patients with advanced kidney disease are less likely than many patients with other types of serious illness to enroll in hospice. Little is known about real-world clinical decision-making related to hospice for members of this population. Methods We used a text search tool to conduct a thematic analysis of documentation pertaining to hospice in the electronic medical record system of the Department of Veterans Affairs, for a national sample of 1000 patients with advanced kidney disease between 2004 and 2014 who were followed until October 8, 2019. Results Three dominant themes emerged from our qualitative analysis of the electronic medical records of 340 cohort members with notes containing hospice mentions: ( 1 ) hospice and usual care as antithetical care models: clinicians appeared to perceive a sharp demarcation between services that could be provided under hospice versus usual care and were often uncertain about hospice eligibility criteria. This could shape decision-making about hospice and dialysis and made it hard to individualize care; ( 2 ) hospice as a last resort: patients often were referred to hospice late in the course of illness and did not so much choose hospice as accept these services after all treatment options had been exhausted; and ( 3 ) care complexity: patients’ complex care needs at the time of hospice referral could complicate transitions to hospice, stretch the limits of home hospice, and promote continued reliance on the acute care system. Conclusions Our findings underscore the need to improve transitions to hospice for patients with advanced kidney disease as they approach the end of life.
After 62 years of regulating immunity, dexamethasone meets COVID-19
Authors: Derek W. Cain, John A. Cidlowski
Journal: Nature reviews. Immunology (2020)

Six months into the COVID-19 pandemic, effective treatments have been frustratingly sparse. The RECOVERY clinical trial, however, revealed that treatment with dexamethasone, a classic synthetic glucocorticoid, enhanced survival of critically ill patients with COVID-19. In this Comment, we discuss the immunological impacts of glucocorticoid therapy for COVID-19. The corticosteroid dexamethasome has been shown to reduce mortality in patients hospitalized with COVID-19 who require mechanical ventilation. Here, the authors describe how this immunosuppressive drug might work.
Monophyletic Origin and Divergent Evolution of Animal Telomerase RNA
Authors: Dhenugen Logeswaran, Yang Li, Joshua D Podlevsky, Julian J -L Chen
Journal: Molecular Biology and Evolution (2020)

Abstract Telomerase RNA (TR) is a noncoding RNA essential for the function of telomerase ribonucleoprotein. TRs from vertebrates, fungi, ciliates, and plants exhibit extreme diversity in size, sequence, secondary structure, and biogenesis pathway. However, the evolutionary pathways leading to such unusual diversity among eukaryotic kingdoms remain elusive. Within the metazoan kingdom, the study of TR has been limited to vertebrates and echinoderms. To understand the origin and evolution of TR across the animal kingdom, we employed a phylogeny-guided, structure-based bioinformatics approach to identify 82 novel TRs from eight previously unexplored metazoan phyla, including the basal-branching sponges. Synthetic TRs from two representative species, a hemichordate and a mollusk, reconstitute active telomerase in vitro with their corresponding telomerase reverse transcriptase components, confirming that they are authentic TRs. Comparative analysis shows that three functional domains, template-pseudoknot (T-PK), CR4/5, and box H/ACA, are conserved between vertebrate and the basal metazoan lineages, indicating a monophyletic origin of the animal TRs with a snoRNA-related biogenesis mechanism. Nonetheless, TRs along separate animal lineages evolved with divergent structural elements in the T-PK and CR4/5 domains. For example, TRs from echinoderms and protostomes lack the canonical CR4/5 and have independently evolved functionally equivalent domains with different secondary structures. In the T-PK domain, a P1.1 stem common in most metazoan clades defines the template boundary, which is replaced by a P1-defined boundary in vertebrates. This study provides unprecedented insight into the divergent evolution of detailed TR secondary structures across broad metazoan lineages, revealing ancestral and later-diversified elements.