tbuckley/cabot-search huggingface dataset:
Adult-onset autoinflammation caused by somatic mutations in UBA1: A Dutch case series of patients with VEXAS
Authors: Caspar I. van der Made, Judith Potjewijd, Annemiek Hoogstins, Huub P.J. Willems, Arjan J. Kwakernaak, Ruud G.L. de Sevaux, Paul L.A. van Daele, Annet Simons, Marloes Heijstek, David B. Beck, Mihai G. Netea, Pieter van Paassen, A. Elizabeth Hak, Lars T. van der Veken, Marielle E. van Gijn, Alexander Hoischen, Frank L. van de Veerdonk, Helen L. Leavis, Abraham Rutgers
Journal: Journal of Allergy and Clinical Immunology (2021)
Trait-like nocturnal sleep behavior identified by combining wearable, phone-use, and self-report data
Authors: Stijn A. A. Massar, Xin Yu Chua, Chun Siong Soon, Alyssa S. C. Ng, Ju Lynn Ong, Nicholas I. Y. N. Chee, Tih Shih Lee, Arko Ghosh, Michael W. L. Chee
Journal: npj Digital Medicine (2021)

Abstract Using polysomnography over multiple weeks to characterize an individual’s habitual sleep behavior while accurate, is difficult to upscale. As an alternative, we integrated sleep measurements from a consumer sleep-tracker, smartphone-based ecological momentary assessment, and user-phone interactions in 198 participants for 2 months. User retention averaged &gt;80% for all three modalities. Agreement in bed and wake time estimates across modalities was high (rho = 0.81–0.92) and were adrift of one another for an average of 4 min, providing redundant sleep measurement. On the ~23% of nights where discrepancies between modalities exceeded 1 h, k-means clustering revealed three patterns, each consistently expressed within a given individual. The three corresponding groups that emerged differed systematically in age, sleep timing, time in bed, and peri-sleep phone usage. Hence, contrary to being problematic, discrepant data across measurement modalities facilitated the identification of stable interindividual differences in sleep behavior, underscoring its utility to characterizing population sleep and peri-sleep behavior.
Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration
Authors: Siva P. Kambhampati, Imran A. Bhutto, Tony Wu, Katie Ho, D. Scott McLeod, Gerard A. Lutty, Rangaramanujam M. Kannan
Journal: Journal of Controlled Release (2021)
OP0167 THE ROLE OF LUNG ULTRASOUND IN THE DIAGNOSIS OF INTERSTITIAL LUNG DISEASE IN CHILDREN WITH DERMATOMYOSISTIS
Authors: R. Dertkgil, C. Cappello, S. Dertkigil, R. Marini, S. Appenzeller
Journal: Annals of the Rheumatic Diseases (2021)

Background: Dermatomyositis is a multi organ autoimmune disease wich is commonly complicated with interstitial lung disease. Chest high-resolution computed tomography (HRCT) is still considered the diagnostic gold standard for interstitial lung disease and is quantification, however he increasing use of lung ultrasound may play an important role in the future. Objectives: The aim of our study was to determine the diagnostic value of lung ultrasound in the detection and progression of interstitial pulmonary disease in patients with dermatomyositis. Methods: Twenty two subjects with dermatomyositis diagnosed according to the American College of Rheumatology criteria were enrolled (6 males, 16 females; mean age: 15,8 ± 8.8 years; range: 6 to 29 years). All subjects underwent high resolution computed tomography followed by transthoracic ultrasound for comet tail sign detection and pleural irregularity in order to predict the degree of interstitial lung disease. The modified transthoracic ultrasound assessment was performed at 06 thoracic regions each side. The Warrick score was calculated according standard high-resolution chest computed tomography images that were evaluated independently from each other by two thoracics radiologists. Results: A significantly positive correlation between transthoracic ultrasound and the severity of pulmonary involvement, as seen by the number of B lines (Spearman ‘s correlation coefficient = 0.80, p &lt; 0.001), and the number of positive areas (regions wih more than 3 B lines) (Spearman ‘s correlation coefficient = 0.75, p &lt; 0.001) were found. When compared with high-resolution chest computed tomography as the gold standard method, the sensitivity, specificity, of transthoracic ultrasound was 96.4%, 83,3% respectively. Addicionally the number of B lines (sum of 35 or more B lines) and a number of B lines positive areas (7 or more regions with at least 3 B lines) cut of allowed to discriminate the inflamatory pattern (ground glass) to those with structural pattern (honeycomb and pulmonary cysts). Conclusion: Our study showed that transthoracic ultrasound comet tails scoring system could be useful in the assessment of the pulmonary involvement in patients with dermatomyositis, and should be considered as a primary screening exam to exclude lung involvement, rather than routine chest CT scans in assimptomatic patients. Disclosure of Interests: None declared
Chimeric antigen receptor <scp>T</scp>‐cells safety: A pharmacovigilance and meta‐analysis study
Authors: Charles Dolladille, Stéphane Ederhy, Emilien Ezine, Sylvain Choquet, Lee S Nguyen, Joachim Alexandre, Javid J Moslehi, Agnès Dechartres, Joe-Elie Salem, Diane Picard, Rebecca Leroy, Tifany Poussy, Frederic Tankere, Peggy Gatignol
Journal: American Journal of Hematology (2021)

Chimeric-antigen-receptor T cells directed against CD19 (CAR-T) are emerging hematological therapeutics with scarce data on its overall safety profile spectrum. To determine the clinical features and incidence of adverse-drug reactions (ADR) associated with CAR-T. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase and meta-analysis of data from CAR-T trials and cohorts in the literature was also performed through March, 2020. The primary objective was to identify ADR associated with approved CAR-T (axicabtagene-ciloleucel; tisagenlecleucel). We conducted a Bayesian disproportionate analysis with the 95% lower credibility-interval of information component (IC025 , significance > 0). We also performed a systematic-review and meta-analysis of CAR-T trials and cohorts in the literature to evaluate ADR incidence. Nine ADR classes were associated with CAR-T: Cytokine release syndrome (CRS, n = 1378, IC025 = 4.24), neurological disorders (n = 963, IC025 = 2.42), hematological disorders (n = 532, IC025 = 3.32), infections (n = 287, IC025 = 2.38), cardiovascular disorders (n = 256, IC025 = 2.81), pulmonary disorders (n = 186, IC025 = 3.80), reno-metabolic disorders (n = 123, IC025 = 1.89), hemophagocytic-lymphohistiocytosis (n = 36, IC025 = 5.01) and hepatic disorders (n = 32, IC025 = 2.49). ADR-related fatalities accounted for 99/1783 (5.5%) of the reports and 262/1783 (14.7%) for all-cause mortality. These ADR-related fatalities were associated with hemophagocytic-lymphohistiocytosis, cerebral vascular disorder, infections, and respiratory failure. In meta-analyses, the most frequent any-grade ADRs were CRS, hematological disorders, and neurological disorders. Fatal ADR were most found with neurological disorders, CRS, and infections. Note, CAR-T infusion may be associated with severe ADR mainly following the week of administration, though rarely fatal. Infections, hemophagocytic-lymphohistiocytosis and end organ failures including neurological or lung involvements require scrutiny.
Junior doctors call for 15% pay rise and censure BMA for inaction over pay review body
Authors: Abi Rimmer
Journal: BMJ (2021)

Junior doctors have called on the BMA to lobby the UK governments for a 15% pay rise.

Delegates attending the association’s junior doctors conference online on 8 May also voted to censure the BMA for failing to withdraw from the Review Body on Doctors’ and Dentists’ Remuneration (DDRB).

At the BMA’s annual representative meeting (ARM) in September 2020, delegates passed a motion that called on the association to withdraw from the DDRB before the end of 2020. However, at a subsequent meeting in November, the BMA Council voted to defer the motion because a number of representatives said that not submitting evidence to the DDRB “would result in them not being best able to lobby on pay increases for doctors.”1 …
Abstract 14879: Using Predictive Machine Learning Modeling for the Nursing Triage of Acute Chest Pain at the Emergency Department
Authors: Stephanie O Frisch, Hongjin Li, Ziad Faramand, Christian Martin-Gill, Clifton W Callaway, Ervin Sejdic, Salah S Al-Zaiti
Journal: Circulation (2019)

Introduction: Emergency nurses triage nearly 137 million patients every year. Chest pain is a common complaint at the emergency department but it frequently lacks specificity, which makes the recog...
In HFrEF, adding empagliflozin to medical therapy reduced a composite outcome, regardless of CKD status
Authors: Carlos G. Santos-Gallego, Harriette G.C. Van Spall
Journal: Annals of Internal Medicine (2021)

Source Citation Zannad F, Ferreira JP, Pocock SJ, et al. Cardiac and kidney benefits of empagliflozin in heart failure across the spectrum of kidney function: insights from EMPEROR-Reduced. Circulation. 2021;143:310-21. 33095032
Long-term Follow-up and Correlative Analysis of Two Phase II Trials of Rituximab and Lenalidomide Followed by Continuous Lenalidomide in Untreated and Relapsed/Refractory Indolent Lymphoma
Authors: Joseph M. Tuscano, Christina Poh, Paul Kaesberg, Guilluame Luxardi, Alexander Merleev, Alina Marusina, Ann Brunson, Aaron Rosenberg, Brian Jonas, Emanual Maverakis
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Rituximab and lenalidomide are effective for previously untreated and relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). However, long-term survival and predictive biomarkers are not well described. Patients and Methods: We conducted two phase II open-label trials involving 60 patients with previously untreated and R/R advanced-stage iNHL. Patients received lenalidomide and rituximab induction followed by continuous lenalidomide until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Correlative studies included plasma cytokine monitoring, flow cytometry of peripheral blood mononuclear cells (PBMC; days 0, 15, 30, and 60), and RNA sequencing (RNA-seq) of pretreatment tumor biopsies. Results: At a median follow-up of 63 months for previously untreated and 100 months for R/R, ORR was 82% for both. The 11 R/R patients who achieved complete remission remained in continuous remission for 16 to 141 months, thereafter. Median overall survival (OS) was not reached in the previously untreated and was 140 months (95% confidence interval, 53.4–140) in the R/R group. A mixed-effects linear regression model identified significant associations between Granzyme B+ (GranB+) CD8+ T cells and long-term complete response (LTCR; P = 5.3e-4). Furthermore, prior to start of therapy, treatment response could be predicted by B-cell and GranB+ CD8+ T-cell levels (% total lymphocytes). Conclusions: Rituximab plus lenalidomide followed by continuous lenalidomide is effective with manageable toxicity in patients with previously untreated and R/R iNHL. This regimen produces durable remissions, even in heavily pretreated patients, with some lasting greater than 10 years. GranB+ CD8+ T cells, B cells, and plasma IFNγ allowed prediction of LTCR but need validation in larger trials.
Evidence of air pollution exposure and new asthma onset: further justification for cleaner air
Authors: George D. Thurston, Alison Lee
Journal: European Respiratory Journal (2021)

<b>Further evidence that new onset asthma can occur from air pollution, even below prevailing air quality standards. It is time the ERS and ATS release a formal statement on the evidence for the link between long-term air pollution and new incident asthma.</b>https://bit.ly/30uAjNN
Association of Psychobehavioral Variables With HOMA-IR and BMI Differs for Men and Women With Prediabetes in the PREVIEW Lifestyle Intervention
Authors: Tanja C. Adam, Mathijs Drummen, Ian Macdonald, Elli Jalo, Pia Siig-Vestentoft, J. Alfredo Martinez, Teodora Handjiev-Darlenska, Jennie Brand-Miller, Sally Poppitt, Gareth Stratton, Mikael Fogelholm, Kirsi H. Pietiläinen, Moira Taylor, Santiago Navas-Carretero, Bjorn Winkens, Svetoslav Handjiev, Roslyn Muirhead, Marta Silvestre, Nils Swindell, Maija Huttunen-Lenz, Wolfgang Schlicht, Tony Lam, Jouko Sundvall, Laura Råman, Edith Feskens, Thomas-Meinert Larssen, Angelo Tremblay, Anne Raben, Margriet Westerterp-Plantenga
Journal: Diabetes Care (2021)

Stress, sleep, eating behavior, and physical activity are associated with weight change and insulin resistance (IR). The aim of this analysis was the assessment of the overall and sex-specific associations of psychobehavioral variables throughout the 3-year PREVIEW intervention using the homeostatic model assessment of IR (HOMA-IR), BMI, and length of time in the study.Associations of psychobehavioral variables, including stress, mood, eating behavior, physical activity (PA), and sleep, with BMI, HOMA-IR, and time spent in the study were assessed in 2,184 participants with prediabetes and overweight/obesity (n = 706 men; n = 1,478 women) during a 3-year lifestyle intervention using linear mixed modeling and general linear modeling. The study was a randomized multicenter trial using a 2 × 2 diet-by-PA design.Overall, cognitive restraint and PA increased during the intervention compared with baseline, whereas BMI, HOMA-IR, disinhibition, hunger, and sleepiness decreased (all P < 0.05). Cognitive restraint and PA were negatively, whereas disinhibition, hunger, stress, and total mood disturbance were positively, associated with both BMI and HOMA-IR. Sleep duration, low sleep quality, total mood disturbance, disinhibition, and hunger scores were positively associated with HOMA-IR for men only. Participants who dropped out at 6 months had higher stress and total mood disturbance scores at baseline and throughout their time spent in the study compared with study completers.Eating behavior and PA, control of stress, mood disturbance, and sleep characteristics were associated with BMI, HOMA-IR, and time spent in the study, with different effects in men and women during the PREVIEW lifestyle intervention study.
Behavioral Interventions for Healthy Weight Gain During Pregnancy
Authors: Jill Jin
Journal: JAMA (2021)

US Preventive Services Task Force; Karina W. Davidson, PhD, MASc; Michael J. Barry, MD; Carol M. Mangione, MD, MSPH; Michael Cabana, MD, MA, MPH; Aaron B. Caughey, MD, PhD; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Chyke A. Doubeni, MD, MPH; Alex H. Krist, MD, MPH; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Lori Pbert, PhD; Michael Silverstein, MD, MPH; Melissa Simon, MD, MPH; James Stevermer, MD, MSPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
Correction to: Exosomal miR-21 regulates the TETs/PTENp1/PTEN pathway to promote hepatocellular carcinoma growth
Authors: Liang-qi Cao, Xue-wei Yang, Yu-bin Chen, Da-wei Zhang, Xiao-Feng Jiang, Ping Xue
Journal: Molecular Cancer (2020)

Following the publication of article [1], the authors found that the images of Transwell Matrigel invasion (Fig. 7d) are incorrect.
Uncovering Modifier Genes of X-Linked Alport Syndrome Using a Novel Multiparent Mouse Model
Authors: Yuka Takemon, Valerie Wright, Bernard Davenport, Daniel M. Gatti, Susan M. Sheehan, Kelsey Letson, Holly S. Savage, Rachel Lennon, Ron Korstanje
Journal: Journal of the American Society of Nephrology (2021)

Mutations in COL4A5 are responsible for 80% of cases of X-linked Alport Syndrome (XLAS). Although genes that cause AS are well characterized, people with AS who have similar genetic mutations present with a wide variation in the extent of kidney impairment and age of onset, suggesting the activities of modifier genes.We created a cohort of genetically diverse XLAS male and female mice using the Diversity Outbred mouse resource and measured albuminuria, GFR, and gene expression. Using a quantitative trait locus approach, we mapped modifier genes that can best explain the underlying phenotypic variation measured in our diverse population.Genetic analysis identified several loci associated with the variation in albuminuria and GFR, including a locus on the X chromosome associated with X inactivation and a locus on chromosome 2 containing Fmn1. Subsequent analysis of genetically reduced Fmn1 expression in Col4a5 knockout mice showed a decrease in albuminuria, podocyte effacement, and podocyte protrusions in the glomerular basement membrane, which support the candidacy of Fmn1 as a modifier gene for AS.With this novel approach, we emulated the variability in the severity of kidney phenotypes found in human patients with Alport Syndrome through albuminuria and GFR measurements. This approach can identify modifier genes in kidney disease that can be used as novel therapeutic targets.
Covid-19 pilot events: the pursuit of outcomes
Authors: Keely McCarthy, Llion Davies
Journal: BMJ (2021)

As covid-19 incidence rates decrease and vaccination coverage increases, the UK is looking to re-commence large events such as business meetings and crowd attendance at sports venues. We note the image of the spectator crowd attending the English League Cup final on 25 April 2021 alongside an article in the 1 May edition of The BMJ .1 This event occurred as part of the government’s events research programme as a pilot event to investigate the safe return of supporters to …
Genomics, Transcriptomics, and Minimal Residual Disease Detection: The Winning Team to Guide Treatment of Acute Lymphoblastic Leukemia
Authors: Heidi Segers, Jan Cools
Journal: Blood Cancer Discovery (2021)

Cytogenetics supported by additional molecular analyses and minimal residual disease detection have been successfully combined to improve the outcome of childhood acute lymphoblastic leukemia (ALL). Results from the St. Jude Total Therapy Study 16 demonstrate that some of the recently identified ALL subtypes can further guide risk stratification.See related article by Jeha et al., p. 326.
Abstract 15641: Lymphopenia is a Marker for Hepatic Disease Severity and Heart Failure Independent of Hemodynamics in Fontan Subjects
Authors: Anna L Scandinaro, Michael McCann, Anisa Chaudhry, William R Davidson
Journal: Circulation (2019)

Fontan patients develop lymphopenia. The prevalence and clinical significance of lymphopenia in Fontan patients is poorly understood. The purpose of this study was to determine the prevalence of ly...
POS1119 A SINGLE DOSE OF ZOLEDRONATE INDUCES MODIFICATIONS OF SERUM VEGF IN OSTEOPOROTIC POSTMENOPAUSAL WOMEN
Authors: F. Bellone, N. Morabito, A. Gaudio, A. Sottile, S. Loddo, F. Corica, A. Catalano
Journal: Annals of the Rheumatic Diseases (2021)

Background: Zoledronate (Zol) is an aminobisphosphonate commonly used to treat osteoporosis and other benign and malignant skeletal diseases. Exposure to bisphosphonates has been previously associated with the risk of osteonecrosis of the jaw (BRONJ), a rare but serious side effect. In cancer patients, the Vascular Endothelial Growth Factor (VEGF) has been advocated to take part to BRONJ pathogenesis via interfering with angiogenesis. No information is currently available on the VEGF concentrations after Zol administration for osteoporosis. Objectives: To explore change of VEGF concentrations after Zol administration in postmenopausal women with osteoporosis. Methods: A total of twenty-eight postmenopausal women with osteopenia or osteoporosis and at least one prevalent vertebral fracture were recruited and randomized in two groups. Eighteen women received a single i.v. dose of Zol 5 mg, while the other ten served as controls. Serum samples were collected at baseline, after 3 and 30 days, for repeated measurements of VEGF, and measurement of bone turn over markers and 25-hydroxyvitamin D (25(OH)D). Results: VEGF levels increased significantly after 3 days in women receiving Zol; then levels decreased after 30 days compared with VEGF concentrations at both day-3 and baseline (-18% at day-30 vs. baseline, p=0.01). 25(OH)D level, a surrogate of vitamin D status, was associated with VEGF change at the end of the study (r=0.29, p=0.028), and this association was maintained also after correcting for age, BMI, time since menopause, femoral neck BMD, osteocalcin, C-terminal telopeptide of collagen type 1 and baseline levels of VEGF (β=1.7, SE=0.71, p=0.03). Conclusion: Zol administration induced a reduction of circulating VEGF in postmenopausal women treated for osteoporosis, and vitamin D status has been showed to modulate this change. Further studies in this setting of women are needed to define whether VEGF modifications may predict the risk of BRONJ. Disclosure of Interests: None declared.
Integrative omics provide biological and clinical insights into acute respiratory distress syndrome
Authors: Mulong Du, Joe G. N. Garcia, Jason D. Christie, Junyi Xin, Guoshuai Cai, Nuala J. Meyer, Zhaozhong Zhu, Qianyu Yuan, Zhengdong Zhang, Li Su, Sipeng Shen, Xuesi Dong, Hui Li, John N. Hutchinson, Paula Tejera, Xihong Lin, Meilin Wang, Feng Chen, David C. Christiani
Journal: Intensive Care Medicine (2021)
Contacts with Macrophages Promote an Aggressive Nanomechanical Phenotype of Circulating Tumor Cells in Prostate Cancer
Authors: Pawel A. Osmulski, Alessandra Cunsolo, Meizhen Chen, Yusheng Qian, Chun-Lin Lin, Chia-Nung Hung, Devalingam Mahalingam, Nameer B. Kirma, Chun-Liang Chen, Josephine A. Taverna, Michael A. Liss, Ian M. Thompson, Tim H.-M. Huang, Maria E. Gaczynska
Journal: Cancer Research (2021)

Aggressive tumors of epithelial origin shed cells that intravasate and become circulating tumor cells (CTC). The CTCs that are able to survive the stresses encountered in the bloodstream can then seed metastases. We demonstrated previously that CTCs isolated from the blood of prostate cancer patients display specific nanomechanical phenotypes characteristic of cell endurance and invasiveness and patient sensitivity to androgen deprivation therapy. Here we report that patient-isolated CTCs are nanomechanically distinct from cells randomly shed from the tumor, with high adhesion as the most distinguishing biophysical marker. CTCs uniquely coisolated with macrophage-like cells bearing the markers of tumor-associated macrophages (TAM). The presence of these immune cells was indicative of a survival-promoting phenotype of "mechanical fitness" in CTCs based on high softness and high adhesion as determined by atomic force microscopy. Correlations between enumeration of macrophages and mechanical fitness of CTCs were strong in patients before the start of hormonal therapy. Single-cell proteomic analysis and nanomechanical phenotyping of tumor cell-macrophage cocultures revealed that macrophages promoted epithelial-mesenchymal plasticity in prostate cancer cells, manifesting in their mechanical fitness. The resulting softness and adhesiveness of the mechanically fit CTCs confer resistance to shear stress and enable protective cell clustering. These findings suggest that selected tumor cells are coached by TAMs and accompanied by them to acquire intermediate epithelial/mesenchymal status, thereby facilitating survival during the critical early stage leading to metastasis. SIGNIFICANCE: The interaction between macrophages and circulating tumor cells increases the capacity of tumor cells to initiate metastasis and may constitute a new set of blood-based targets for pharmacologic intervention.