tbuckley/cabot-search huggingface dataset:
The State of Our Understanding of the Pathophysiology and Optimal Treatment of Depression: Glass Half Full or Half Empty?
Authors: Charles B. Nemeroff
Journal: American Journal of Psychiatry (2020)

Major depressive disorder is a remarkably common and often severe psychiatric disorder associated with high levels of morbidity and mortality. Patients with major depression are prone to several comorbid psychiatric conditions, including posttraumatic stress disorder, anxiety disorders, obsessive-compulsive disorder, and substance use disorders, and medical conditions, including cardiovascular disease, diabetes, stroke, cancer, which, coupled with the risk of suicide, result in a shortened life expectancy. The goal of this review is to provide an overview of our current understanding of major depression, from pathophysiology to treatment. In spite of decades of research, relatively little is known about its pathogenesis, other than that risk is largely defined by a combination of ill-defined genetic and environmental factors. Although we know that female sex, a history of childhood maltreatment, and family history as well as more recent stressors are risk factors, precisely how these environmental influences interact with genetic vulnerability remains obscure. In recent years, considerable advances have been made in beginning to understand the genetic substrates that underlie disease vulnerability, and the interaction of genes, early-life adversity, and the epigenome in influencing gene expression is now being intensively studied. The role of inflammation and other immune system dysfunction in the pathogenesis of major depression is also being intensively investigated. Brain imaging studies have provided a firmer understanding of the circuitry involved in major depression, providing potential new therapeutic targets. Despite a broad armamentarium for major depression, including antidepressants, evidence-based psychotherapies, nonpharmacological somatic treatments, and a host of augmentation strategies, a sizable percentage of patients remain nonresponsive or poorly responsive to available treatments. Investigational agents with novel mechanisms of action are under active study. Personalized medicine in psychiatry provides the hope of escape from the current standard trial-and-error approach to treatment, moving to a more refined method that augurs a new era for patients and clinicians alike.
Focused Transesophageal Echocardiography During Cardiac Arrest Resuscitation
Authors: Felipe Teran, Michael I. Prats, Bret P. Nelson, Ross Kessler, Michael Blaivas, Mary Ann Peberdy, Sasha K. Shillcutt, Robert T. Arntfield, David Bahner
Journal: Journal of the American College of Cardiology (2020)
AB0182 EVALUATION OF THE SOCIO-PROFESSIONAL IMPACT OF ANKYLOSING SPONDYLITIS AND RHEUMATOID ARTHRITIS IN TUNISIA: DATA FROM THE BINAR REGISTRY
Authors: H. Hachfi, N. Ben Chekaya, D. Khalifa, M. Brahem, H. Themri, L. Abdelmoula, S. Baklouti, N. Bergaoui, E. Bouajina, M. Elleuch, I. Gharssallah, M. M. Kchir, S. Kochbati, A. Laatar, Y. Mohamed
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are disabling and common chronic inflammatory rheumatic diseases. Objectives: The aim of our study was to evaluate the socio-professional impact of RA and AS. Methods: Using the Biological National Registry (BINAR) data, which includes ten tunisian rheumatology centers,we identified patients≥18 years with AS and RA according to the ACR and EULAR 2010 criteria(RA) and ASAS 2009 (AS), receiving biotherapy for less than two years. Results: 298 patients were included in the study. The percentage of patients with RA was 58.7 % and those with AS 41.3%. The sex ratio was 0.6. The average age of the onset of the disease was 49.1 years ± 14.1 years [18–79]. For marital status, 72% were married, single (25%), widowed (2.6%) and divorced (0.4%). 22.4% of patients were illiterate, 32.7 % (primary), 28.3% (secondary) and 16.6% had an university level. For the RA population, a high disease activity (DAS28-ESR &gt;5.1) was detected in 36% of patients, an erosive arthritis in 73.1% and 7.2% had a coxitis. In the AS group, an elevate BASDAI (BASDAI≥4) was detected in 56.9% of patients and 39% had coxitis. All patients have received Biological therapy concomitant with corticosteroids (59.1%), methotrexate (42.6%), salazopirine (20.8%) and leflunomide (4.7%). 54% of patients had a comorbidity, of which 1.7% was depression. More than half of our patients (54.3%) were unemployed, 40 % were professionally active, and 5.7% were retired due to the rheumatic condition. Absence from work was observed in 15.1% of cases with a total duration exceeding three months in 55.5% of cases. 37.9 % of patients were physically active: regularly (9.8%), irregularly (28.1%) and (62.1%) were sedentary. For the functional impact, HAQ score was 1.31± 0.7 for RA and BASFI was 5.2 ± 4.8 for AS. The working abandonment is significantly associated to: marital status (p=0.039), low level of education (p=0.04),depression (p&lt;0.001), high activity of AS (p=0.004) and BASFI&gt;4 (p=0,001). Conclusion: RA or AS requiring biotherapy have a high socio-economic impact and are responsible for absenteeism at work and even for early working abandonment. Early therapeutic management and a global assessment are essential in order to improve quality of life and working conditions. Longitudinal studies are needed to assess the effect of biological therapy on the socio-professional impact of these chronic inflammatory rheumatic disease. Disclosure of Interests: None declared
Lessons of COVID-19: Virtual conferences
Authors: Stephanie Houston
Journal: The Journal of Experimental Medicine (2020)

COVID-19 abruptly halted scientific conferences and seminars in mid-March, forcing the scientific community to either postpone or adapt to a virtual format. We caught up with Carla V. Rothlin, Elina I. Zúñiga, Hongbo Chi, Rino Rappuoli, and Matthew Krummel to find out about the pros and cons of virtual conferences and seminars and how these could change the nature of scientific conferences. Carla (CVR) and Elina (EIZ) established Global ImmunoTalks in April this year; Hongbo (HC) helped organize the Immunometabolism Mini-Symposia series in May and June; Rino (RR) was one of the scientific organizers of the Transforming Vaccinology Keystone, which moved to a virtual format in June; and Matthew (MK) has been organizing Eco Seminars at the University of California, San Francisco since 2019.
AB0189 ASSESSMENT OF POWER DOPPLER SYNOVITIS IN RHEUMATOID ARTHRITIS PATIENTS WITH CLINICAL REMISSION
Authors: R. Fakhfakh, N. El Amri, K. Baccouche, H. Zeglaoui, E. Bouajina
Journal: Annals of the Rheumatic Diseases (2020)

Background: Ultrasound-detected synovitis, mainly synovial Doppler signal, has shown predictive value in relation to radiographic damage progression and disease flare or relapse in rheumatoid arthritis (RA) patients with clinical remission. Objectives: The aim of the study was to analyze the correlation between power Doppler scores and clinical/laboratory and radiographic data in clinical remission RA patients. Methods: Cross-sectional study including patients with RA in clinical remission defined by: DAS28ESR ≤ 2.6, without disease flare or changes in therapy in the previous 6 months. Each patient underwent ultrasound: B-mode and PD assessments of 36 joints and 20 tendons in the Rheumatology Department over a period of 6 month. Synovitis and tenosynovitis were defined and scored according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT). Radiological measurements included the modified Sharp/van der Heijde method (SHS). Functional capacity was assessed by the Health Assessment Questionnaire (HAQ). Results: Thirty two patients were enrolled, the mean age was 53.7±13.4 and 75% were female. The mean disease duration was 15 years ± 8.8. Subclinical synovitis were the most frequent in wrist (56.3%), 2 nd metacarpophalangeal joints (28.1%) and 2 nd metatarsophalangeal joints (29%). The mean subclinical synovitis/ tenosynovitis numbers was 4±3.1 per patient. Synovial hypertrophy and B mode tenosynovitis were detected in 93.8%: 71.3% had a grade = 2 and 9.8% had a grade= 3. Total B mode score was correlated only with the SHS score in the feet (r: 0.4, p: 0.03). PD signal was detected in 62.5% of patients: 37.5% had a grade =2 and 9.4% had a grade= 3. Total PD score was correlated with DAS28 (r:0.42, p:0.02), the SHS score in the hands (r:0.39, p:0.03) and in the feet (r:0.5, p:0.007), synovial hypertrophy (r:0.6, p:0.0001) and HAQ (r:0.32, p:0.06). No correlation was found with CDAI, SDAI, swollen joint counts, tender joint counts, patient global health assessment, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor and anti-cyclic citrullinated peptide, biologic treatment. Conclusion: Synovial hypertrophy and PD signal were frequent in RA remission. PD signal was associated with RA activity, radiologic damage and functional capacity. References: [1]Yan Geng &amp; Jingjing Han &amp; Xuerong Deng and al. Presence of power Doppler synovitis in rheumatoid arthritis patients with synthetic and/or biological disease-modifying anti-rheumatic drug-induced clinical remission: experience from a Chinese cohort. Clinical Rheumatology 2014. DOI 10.1007/s10067-014-2634-y Disclosure of Interests: None declared
Assessing Telemedicine Unreadiness Among Older Adults in the United States During the COVID-19 Pandemic
Authors: Kenneth Lam, Amy D. Lu, Ying Shi, Kenneth E. Covinsky
Journal: JAMA Internal Medicine (2020)

This cross-sectional study uses 2018 data from the National Health and Aging Trends Study to assess the prevalence among older adults in the United States of unreadiness to access video or telephone telemedicine because of disability or inexperience with technology.
A mouse model of asthma‐chronic obstructive pulmonary disease overlap induced by intratracheal papain
Authors: Kensuke Fukuda, Hirotaka Matsuzaki, Yu Mikami, Kosuke Makita, Kazuko Miyakawa, Naoya Miyashita, Keisuke Hosoki, Takashi Ishii, Satoshi Noguchi, Hirokazu Urushiyama, Masafumi Horie, Akihisa Mitani, Yasuhiro Yamauchi, Eri Shimura, Susumu Nakae, Akira Saito, Takahide Nagase, Yoshihisa Hiraishi
Journal: Allergy (2020)

TitleA mouse model of asthma­–chronic obstructive pulmonary disease overlap induced by intratracheal papain
In Amateur Athletes With Type 1 Diabetes, a 9-Day Period of Cycling at Moderate-to-Vigorous Intensity Unexpectedly Increased the Time Spent in Hyperglycemia, Which Was Associated With Impairment in Heart Rate Variability
Authors: Elodie Lespagnol, Olivia Bocock, Joris Heyman, François-Xavier Gamelin, Serge Berthoin, Bruno Pereira, Julien Boissière, Martine Duclos, Elsa Heyman
Journal: Diabetes Care (2020)

OBJECTIVE In type 1 diabetes, autonomic dysfunction may occur early as a decrease in heart rate variability (HRV). In populations without diabetes, the positive effects of exercise training on HRV are well-documented. However, exercise in individuals with type 1 diabetes, particularly if strenuous and prolonged, can lead to sharp glycemic variations, which can negatively impact HRV. This study explores the impact of a 9-day cycling tour on HRV in this population, with a focus on exercise-induced glycemic excursions. RESEARCH DESIGN AND METHODS Twenty amateur athletes with uncomplicated type 1 diabetes cycled 1,500 km. HRV and glycemic variability were measured by heart rate and continuous glucose monitoring. Linear mixed models were used to test the effects of exercise on HRV, with concomitant glycemic excursions and subject characteristics considered as covariates. RESULTS Nighttime HRV tended to decrease with the daily distance traveled. The more time the subjects spent in hyperglycemia, the lower the parasympathetic tone was. This result is striking given that hyperglycemic excursions progressively increased throughout the 9 days of the tour, and to a greater degree on the days a longer distance was traveled, while time spent in hypoglycemia surprisingly decreased. This phenomenon occurred despite no changes in insulin administration and a decrease in carbohydrate intake from snacks. CONCLUSIONS In sports enthusiasts with type 1 diabetes, multiday prolonged exercise at moderate-to-vigorous intensity worsened hyperglycemia, with hyperglycemia negatively associated with parasympathetic cardiac tone. Considering the putative deleterious consequences on cardiac risks, future work should focus on understanding and managing exercise-induced hyperglycemia.
Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories
Authors: Kirby D. Johnson, Daniel J. Conn, Evgenia Shishkova, Koichi R. Katsumura, Peng Liu, Siqi Shen, Erik A. Ranheim, Sean G. Kraus, Weixin Wang, Katherine R. Calvo, Amy P. Hsu, Steven M. Holland, Joshua J. Coon, Sunduz Keles, Emery H. Bresnick
Journal: The Journal of Experimental Medicine (2020)

Stem and progenitor cell fate transitions constitute key decision points in organismal development that enable access to a developmental path or actively preclude others. Using the hematopoietic system, we analyzed the relative importance of cell fate–promoting mechanisms versus negating fate-suppressing mechanisms to engineer progenitor cells with multilineage differentiation potential. Deletion of the murine Gata2−77 enhancer, with a human equivalent that causes leukemia, downregulates the transcription factor GATA2 and blocks progenitor differentiation into erythrocytes, megakaryocytes, basophils, and granulocytes, but not macrophages. Using multiomics and single-cell analyses, we demonstrated that the enhancer orchestrates a balance between pro- and anti-fate circuitry in single cells. By increasing GATA2 expression, the enhancer instigates a fate-promoting mechanism while abrogating an innate immunity–linked, fate-suppressing mechanism. During embryogenesis, the suppressing mechanism dominated in enhancer mutant progenitors, thus yielding progenitors with a predominant monocytic differentiation potential. Coordinating fate-promoting and -suppressing circuits therefore averts deconstruction of a multifate system into a monopotent system and maintains critical progenitor heterogeneity and functionality.
Safety and Anti-Tumour Activity of RP6530, Dual PI3K δ/γ Inhibitor, in Relapsed/Refractory T-Cell Lymphoma: Updated Results from the Dose Expansion Cohort of an on-Going Phase I/Ib Study
Authors: Yasuhiro Oki, Jasmine Zain, Bradley M. Haverkos, Neil Korman, Lauren Pinter-Brown, Sumana Devata, Rod Ramchandren, Mary Jo Lechowicz, Prajak Barde, Ajit Nair, Auris Huen
Journal: Blood (2017)
Tension pneumomediastinum in patients with COVID-19
Authors: Alessio Campisi, Venerino Poletti, Angelo Paolo Ciarrocchi, Maurizio Salvi, Franco Stella
Journal: Thorax (2020)

A 65-year-old obese male, with no other comorbidities, was admitted to our intensive care unit for acute respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient was mechanically ventilated (intermittent positive pressure ventilation autoflow mode with tidal volume of 6 mL/kg, positive end expiratory pressure (PEEP) 12 cmH2O, respiratory rate 20 breaths/min and fractional inspired oxygen (FiO2) to the lowest level to maintain arterial pO2 in a range of 55–60 mm Hg) for 7 days before his condition abruptly worsened. He became haemodynamically unstable with changes in the cardiac electrical activity and hypotension unresponsive to catecholamines. An initial plain chest X-ray revealed widespread subcutaneous emphysema. Chest-CT demonstrated a massive tension pneumomediastinum. Mediastinal decompression was performed via two incisions, one at the sternal notch and one below the xiphoid process (figure 1). The posterior wall of …
Animal-to-human transmission of <i>Mycobacterium pinnipedii</i>
Authors: Rita Macedo, Joana Isidro, Maria Conceição Gomes, Ana Botelho, Teresa Albuquerque, Arlete Sogorb, Rui Bernardino, Teresa Lobo Fernandes, Teresa Mourato, Mário Durval, João Paulo Gomes
Journal: European Respiratory Journal (2020)

<b>Use of culture isolation and whole-genome sequencing analysis to report the first confirmed case of animal-to-human transmission of <i>Mycobacterium pinnipedii</i> involving a sea lion and a keeper in a zoo</b>https://bit.ly/3hEYu3s
THU0214 Effect of triamcinolone diacetate injections in early dupuytren’s contracture and stenosing tenosynovitis of the hand
Authors: B Mukerji
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Dupuytren's contracture and other fibrosing conditions of the hand are generally progressive, causing limitation of function and decreasing grip strength. Long term results of surgical procedures are less than optimal with high recurrence and extension rates. Other non-operative therapies such as slow skeletal traction, radiation, splinting, ultrasound and enzymatic fasciotomy have not proven to be clinically useful. <h3>Objectives</h3> The objective of this study was to determine the effectiveness of steroid injections in slowing the progression of fibrosis and contractures in early Dupuytren's disease and conditions causing stenosing tenosynovitis of the hand. <h3>Methods</h3> Twenty-three patients were studied. There were 12 men and 11 women with an age range of 35 to 72 years. Of these patients four also had diabetes mellitus and three had rheumatoid arthritis. Eighteen patients had Dupuytrens' contracture. Fifteen had bilateral contractures and three in one hand only. None of them had contractures in the proximal interphalangeal joints. One had mild flexion contracture at the second, third and fourth metacarpophalangeal joints. Two had bilateral De Quervain's tenosynovitis and three had isolated fibrous nodules in one flexor tendon in the hand. All patients received one or two triamcinolone diacetate injections in the fibrous nodules, cords and tendon sheaths. Additionally, five patients received oral non-steroidal antiinflammatory agents for one to two weeks. Patients with Dupuytren's contracture demonstrated softening of the symptomatic chords, improvement of grip strength and partial resolution of nodules. The other patients had complete resolution of their condition. <h3>Results</h3> Patients were followed for one to seven years and maintained their functional improvement. No patient's contracture progressed or required surgery or radiotherapy. There were no complications such as hematoma, skin necrosis, infection, granuloma formation, decrease in grip strength, transient paresthesia or flexion deformity of the fingers. <h3>Conclusion</h3> In conclusion, early Dupuytren's disease and other fibrosing tenosynovitis of the hands can be safely and effectively treated with injections of triamcinolone diacetate and this appears to prevent progression of these conditions.
X- and Y-Linked Chromatin-Modifying Genes as Regulators of Sex-Specific Cancer Incidence and Prognosis
Authors: Rossella Tricarico, Emmanuelle Nicolas, Michael J. Hall, Erica A. Golemis
Journal: Clinical Cancer Research (2020)

Abstract Biological sex profoundly conditions organismal development and physiology, imposing wide-ranging effects on cell signaling, metabolism, and immune response. These effects arise from sex-specified differences in hormonal exposure, and from intrinsic genetic and epigenetic differences associated with the presence of an XX versus XY chromosomal complement. In addition, biological sex is now recognized to be a determinant of the incidence, presentation, and therapeutic response of multiple forms of cancer, including cancers not specifically associated with male or female anatomy. Although multiple factors contribute to sex-based differences in cancer, a growing body of research emphasizes a role for differential activity of X- and Y-linked tumor-suppressor genes in males and females. Among these, the X-linked KDM6A/UTX and KDM5C/JARID1C/SMCX, and their Y-linked paralogs UTY/KDM6C and KDM5D/JARID1D/SMCY encode lysine demethylases. These epigenetic modulators profoundly influence gene expression, based on enzymatic activity in demethylating H3K27me3 and H3K4me3, and nonenzymatic scaffolding roles for large complexes that open and close chromatin for transcription. In a growing number of cases, mutations affecting these proteins have been recognized to strongly influence cancer risk, prognosis, and response to specific therapies. However, sex-specific patterns of mutation, expression, and activity of these genes, coupled with tissue-specific requirement for their function as tumor suppressors, together exemplify the complex relationship between sex and cancer vulnerabilities. In this review, we summarize and discuss the current state of the literature on the roles of these proteins in contributing to sex bias in cancer, and the status of clinical agents relevant to their function.
A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma
Authors: Nancy L. Bartlett, Alex F. Herrera, Eva Domingo-Domenech, Amitkumar Mehta, Andres Forero-Torres, Ramon Garcia-Sanz, Philippe Armand, Sumana Devata, Antonia Rodriguez Izquierdo, Izidore S. Lossos, Craig Reeder, Taimur Sher, Robert Chen, Sylvia E. Schwarz, Leila Alland, Andras Strassz, Kim Prier, Cassandra Choe-Juliak, Stephen M. Ansell
Journal: Blood (2020)
Sixty seconds on . . . waves
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The pandemic friendly greeting?No. We're talking about the "second wave of the [covid-19] pandemic" that Boris Johnson said shows signs of coming to Europe, which caused a tsunami of protest after he announced new travel restrictions for people coming to the UK from Spain. Batten down the hatches!You might think of waves as peaks and troughs, but there is no set definition of a wave in terms of infectious disease.Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said, "Much of the thinking about second waves is derived from previous influenza epidemics and pandemics, and the patterns may not be the same for covid-19: SARS-Cov-2 is a very different virus to the different influenza viruses."1 Centre for Evidence-Based Medicine.Covid 19-epidemic "waves".30 Apr 2020.https://www.cebm.net/covid-19/covid-19-epidemic-waves/.