tbuckley/cabot-search huggingface dataset:
Dupilumab, severe asthma airway responses, and SARS‐CoV‐2 serology
Authors: Anurag Bhalla, Manali Mukherjee, Katherine Radford, Ishac Nazy, Melanie Kjarsgaard, Dawn M. E. Bowdish, Parameswaran Nair
Journal: Allergy (2020)

Dr Bhalla is supported by the Frederick E. Hargreave fellowship in Airway Diseases. Ms Radford, Ms Kjarsgaard, and Dr Nazy do not have any disclosures. Dr Mukherjee is supported by investigator award from Canadian Institutes of Health Research and Canadian Allergy, Asthma, and Immunology Foundation. She has received grants from Methapharm Specialty Pharmaceuticals and honorarium from AZ. Dr Bowdish is supported by a Canada Research Chair in Aging & Immunity. She has received honoraria from Pfizer, Astra Zeneca, and Abbvie. Dr Nair is supported by the Frederick E. Hargreave Teva Innovation Chair in Airway Diseases. He has received honoraria from AZ, Sanofi, Teva, Merck, Novartis, and Equillium, and his university has received research grants from AZ, Teva, Sanofi, Novartis, BI, and Methapharm.
Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder
Authors: Irene M. Loe, Pooja A. Kakar, Lee M. Sanders
Journal: JAMA Pediatrics (2020)

This article summarizes the American Academy of Pediatrics' Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents.
Loss of the laminin subunit alpha‐3 induces cell invasion and macrophage infiltration in cutaneous squamous cell carcinoma*
Authors: M.P. Caley, V.L. Martins, K. Moore, M. Lashari, L. Nissinen, V.‐M. Kähäri, S. Alexander, E. Jones, C.A. Harwood, J. Jones, M. Donaldson, J.F. Marshall, E.A. O’Toole
Journal: British Journal of Dermatology (2020)

Cutaneous squamous cell carcinoma (cSCC) is a common cancer that invades the dermis through the basement membrane. The role of the basement membrane in poorly differentiated cSCC is not well understood.To study the effect that loss of the laminin subunit alpha-3 (α3) chain from the tumour microenvironment has on tumour invasion and inflammatory cell recruitment.We examined the role of the basement membrane proteins laminin subunits α3, β3 and γ2 in SCC invasion and inflammatory cell recruitment using immunohistochemistry, short hairpin RNA knockdown, RNA-Seq, mouse xenograft models and patient tumour samples.Analysis of SCC tumours and cell lines using antibodies specific to laminin chains α3, β3 and γ2 identified a link between poorly differentiated SCC and reduced expression of laminin α3 but not the other laminin subunits investigated. Knockdown of laminin α3 increased tumour invasion both in vitro and in vivo. Western blot and immunohistochemical staining identified increased phosphorylated myosin light chain with loss of laminin α3. Inhibition of ROCK (rho-associated protein kinase) but not Rac1 significantly reduced the invasive potential of laminin α3 knockdown cells. Knockdown of laminin subunits α3 and γ2 increased monocyte recruitment to the tumour microenvironment. However, only the loss of laminin α3 correlated with increased tumour-associated macrophages both in xenografted tumours and in patient tumour samples.These data provide evidence that loss of the laminin α3 chain in cSCC has an effect on both the epithelial and immune components of cSCC, resulting in an aggressive tumour microenvironment.
ContamLD: estimation of ancient nuclear DNA contamination using breakdown of linkage disequilibrium
Authors: Nathan Nakatsuka, Éadaoin Harney, Swapan Mallick, Matthew Mah, Nick Patterson, David Reich
Journal: Genome biology (2020)

Abstract We report a method called ContamLD for estimating autosomal ancient DNA (aDNA) contamination by measuring the breakdown of linkage disequilibrium in a sequenced individual due to the introduction of contaminant DNA. ContamLD leverages the idea that contaminants should have haplotypes uncorrelated to those of the studied individual. Using simulated data, we confirm that ContamLD accurately infers contamination rates with low standard errors: for example, less than 1.5% standard error in cases with less than 10% contamination and 500,000 sequences covering SNPs. This method is optimized for application to aDNA, taking advantage of characteristic aDNA damage patterns to provide calibrated contamination estimates, and is available at https://github.com/nathan-nakatsuka/ContamLD .
Development and validation of a model for predicting incident type 2 diabetes using quantitative clinical data and a Bayesian logistic model: A nationwide cohort and modeling study
Authors: Lua Wilkinson, Nengjun Yi, Tapan Mehta, Suzanne Judd, W. Timothy Garvey
Journal: PLoS Medicine (2020)

Background Obesity is closely related to the development of insulin resistance and type 2 diabetes (T2D). The prevention of T2D has become imperative to stem the rising rates of this disease. Weight loss is highly effective in preventing T2D; however, the at-risk pool is large, and a clinically meaningful metric for risk stratification to guide interventions remains a challenge. The objective of this study is to predict T2D risk using full-information continuous analysis of nationally sampled data from white and black American adults age ≥45 years. Methods and findings A sample of 12,043 black (33%) and white individuals from a population-based cohort, REasons for Geographic And Racial Differences in Stroke (REGARDS) (enrolled 2003–2007), was observed through 2013–2016. The mean participant age was 63.12 ± 8.62 years, and 43.7% were male. Mean BMI was 28.55 ± 5.61 kg/m2. Risk factors for T2D regularly recorded in the primary care setting were used to evaluate future T2D risk using Bayesian logistic regression. External validation was performed using 9,710 participants (19% black) from Atherosclerotic Risk in Communities (ARIC) (enrolled 1987–1989), observed through 1996–1998. The mean participant age in this cohort was 53.86 ± 5.65 years, and 44.6% were male. Mean BMI was 27.15 ± 4.92 kg/m2. Predictive performance was assessed using the receiver operating characteristic (ROC) curves and area under the curve (AUC) statistics. The primary outcome was incident T2D. By 2016 in REGARDS, there were 1,602 incident cases of T2D. Risk factors used to predict T2D progression included age, sex, race, BMI, triglycerides, high-density lipoprotein, blood pressure, and blood glucose. The Bayesian logistic model (AUC = 0.79) outperformed the Framingham risk score (AUC = 0.76), the American Diabetes Association risk score (AUC = 0.64), and a cardiometabolic disease system (using Adult Treatment Panel III criteria) (AUC = 0.75). Validation in ARIC was robust (AUC = 0.85). Main limitations include the limited generalizability of the REGARDS sample to black and white, older Americans, and no time to diagnosis for T2D. Conclusions Our results show that a Bayesian logistic model using full-information continuous predictors has high predictive discrimination, and can be used to quantify race- and sex-specific T2D risk, providing a new, powerful predictive tool. This tool can be used for T2D prevention efforts including weight loss therapy by allowing clinicians to target high-risk individuals in a manner that could be used to optimize outcomes.
THU0458 HIGH PREVALENCE OF JOINT HYPERMOBILITY IN INFLAMMATORY BOWEL DISEASE PATIENTS WITH PAIN UNRESPONSIVE TO BOWEL-TARGETED THERAPY
Authors: H. Zidany, M. Waterman, K. Toledano, Y. Chowers, D. Markovits, A. Karban, A. Balbir-Gurman, Y. Braun-Moscovici
Journal: Annals of the Rheumatic Diseases (2020)

Background: Musculoskeletal manifestations occur in 20-50% of patients (pts) with inflammatory bowel disease (IBD). A substantial number of patients complain of non-inflammatory musculoskeletal pain. Objectives: To assess the incidence of joint hypermobility (JHM), benign joint hypermobility syndrome (BJHS) among patients with inflammatory bowel disease (IBD) examined in the inter-disciplinary rheumatology service at a tertiary referral center and the impact on IBD manifestations and outcome. Methods: Medical records of 180 consecutive IBD pts referred to the inter-disciplinary clinic were retrospectively reviewed. Data regarding age, gender, diagnosis, disease duration, clinical and laboratory features, previous and current therapy, Harvey-Brandshaw Index were entered into a database and analyzed. Beighton’s scoring of ≥4/9 was used to define patients with JHM. The 1998 Brighton’s criteria were used to identify patients with BJHS. Outcome was defined as improvement of joint pain. The statistical methods used included descriptive statistics, T test, Spearman’s correlation and multiple logistic regression analysis. Results: Forty-six patients (mean(SD) age 36.2(12.4), disease duration 13.9(8.8) years) out of 180 IBD patients (mean(SD) age 40.4(14.3), disease duration 15.7(9.1) years) fulfilled the criteria for JHM. Twelve patients had active inflammatory joint disease (2 with axial involvement, 10 with peripheral joint disease and 2 with axial and peripheral joint involvement). The other 32 answered both major criteria for BJHS. The median Beighton scoring was 7 (range 5-9). Most of them were on biological treatment. Patients with JHM suffered frequently of arthralgia and abdominal pain, in spite of endoscopic remission and normal levels of calprotectin and inflammatory markers (p=0.02, r=0.17). JHM and BJHS were associated with poorer outcome (p=0.004, r=0.2). In a multiple logistic regression analysis, only JHM reached borderline significance for predicting worse outcome. Conclusion: Joint and abdominal pain did not improve with immunomodulatory therapy in IBD patients with JHM. JHM may have a negative impact on achievement of clinical remission, in a significant subset of IBD patients. Rheumatologists and gastroenterologists should be aware of this. Disclosure of Interests: : Haya Zidany: None declared, Matti Waterman: None declared, Kohava Toledano: None declared, Yehuda Chowers: None declared, Doron Markovits: None declared, Amir Karban: None declared, Alexandra Balbir-Gurman Consultant of: Novartis, Yolanda Braun-Moscovici: None declared
Patterns of incidental perineural invasion and prognosis in cutaneous squamous cell carcinoma: A multicenter, retrospective cohort study
Authors: Alberto Conde-Ferreirós, Luis A. Corchete, Ane Jaka, Ángel Santos-Briz, María José Fuente, Rodolfo Posada, Laura Pons, Sebastián Podlipnik, Ramón M. Pujol, Concepción Román-Curto, Agustí Toll, Javier Cañueto
Journal: Journal of the American Academy of Dermatology (2020)
Increased rather than decreased incidence of giant-cell arteritis during the COVID-19 pandemic
Authors: Augustin Lecler, Delphine Villeneuve, Catherine Vignal, Thomas Sené
Journal: Annals of the Rheumatic Diseases (2020)

We read with much interest the article entitled “Impact of delayed diagnoses at the time of COVID-19: increased rate of preventable bilateral blindness in giant cell arteritis”,1 reporting a reduction in the requests for fast-track assessment of giant cell arteritis (GCA) in an Italian centre since the outbreak of the COVID-19 pandemic, as compared with the same time frame in 2019.

Our tertiary centre offers the same type of fast-track GCA pathway. Diagnosis of GCA is made based on clinical presentation of suggestive symptoms, increased C-reactive protein level and typical findings …
SAT0185 Gallium-67 spect scintigraphy in diagnosis of temporal arteritis
Authors: TI Reitblat, C Ben-Horin, A Reitblat
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Temporal Arteritis (TA) is a common syndrome in the elderly, consisting of pain in the temporal area of the head, jaw claudication, sudden visual loss, high erythrocyte sedimentation rate and tenderness on palpation in the temporal area. The diagnosis of this condition is relatively straightforward when the typical symptoms and positive temporal artery biopsy are present. Unfortunately, only one half of patients have positive temporal artery biopsy. Other diagnostic procedures such as colour Doppler sonography or superficial carotid arteriography have been proven to be useful for diagnosis of TA, but these techniques do not discriminate between inflammatory and noninflammatory temporal artery disease.<sup>1</sup> Genereau T. <i>et al</i> proposed that Gallium-67 (Ga67) planar scan may be useful in diagnosis of TA.<sup>2</sup> Quantitative Ga67 Single Photon Emission Computed Tomography (SPECT) scintigraphy may rise the accuracy of TA diagnosis. <h3>Objectives</h3> To assess the effectiveness and usefulness of Ga67 SPECT scintigraphy, two patients with suspected diagnosis of TA were examined. Quantitative estimation of Ga67 uptake was done. <h3>Methods</h3> <h3>Case</h3> 1: 61 years old male patient with biopsy proven TA relapsed after half a year period without prednisolone treatment. Clinical features were: severe headache in left temporal region, jaw claudication, fever and tenderness on palpation in left temporal area and high erythrocyte sedimentation rate. <h3>Case</h3> 2: 79 years old female patient was admitted to the hospital with complaints on severe headache, night shoulder girdle pain and jaw claudication. Objective signs were tenderness on palpation in both temporal areas, limited active shoulder motion, high erythrocyte sedimentation rate. Because of a patient?s severe heart disease it was not possible to perform diagnostic temporal artery biopsy. Both patients underwent Ga67 examination: a planar scan followed by a skull SPECT study. Ga67 uptake ratio was calculated (temporal region/background region) on transaxial and coronary slices after SPECT scan reconstruction. <h3>Results</h3> In both cases the Ga67 planar scan was nondiagnostic for inflammatory process in the area. The SPECT study showed increased uptake in the temporal region, with high Ga67 uptake ratio. <h3>Conclusion</h3> Our data suggests that Ga67 skull SPECT may be useful in the diagnosis of TA especially if Ga67 uptake ratio in the area is calculated. Further studies are needed to confirm these data. <h3>References</h3> Genereau T, Herson S. Les arterites temporales. Elements du diagnostic differentiel de la maladie de Horton [Temporal vasculitides. Differential diagnosis of giant cell arteritis]. <i>Ann Med Intern (Paris)</i> 1993;<b>144</b>:198–211 Genereau T, Lortholary O, Guillevin L, <i>et al</i>. Temporal 67 gallium uptake is increased in temporal arteritis. <i>Rheumatology</i> 1999;<b>38</b>:709–13
In vivo synthesis of triple-loaded albumin conjugate for efficient targeted cancer chemotherapy
Authors: Rémi Châtre, Justin Lange, Elodie Péraudeau, Pauline Poinot, Stéphanie Lerondel, Alain Le Pape, Jonathan Clarhaut, Brigitte Renoux, Sébastien Papot
Journal: Journal of Controlled Release (2020)
Tumour sensitization via the extended intratumoural release of a STING agonist and camptothecin from a self-assembled hydrogel
Authors: Feihu Wang, Hao Su, Dongqing Xu, Wenbing Dai, Weijie Zhang, Zongyuan Wang, Caleb F. Anderson, Mengzhen Zheng, Richard Oh, Fengyi Wan, Honggang Cui
Journal: Nature Biomedical Engineering (2020)
Temporal Factors Associated With Opioid Prescriptions for Patients With Pain Conditions in an Urban Emergency Department
Authors: Ben C. Smith, Andrew D. Vigotsky, A. Vania Apkarian, Thomas J. Schnitzer
Journal: JAMA Network Open (2020)

Opioid prescriptions for treatment of pain in emergency departments (EDs) are associated with long-term opioid use. The temporal pattern of opioid prescribing in the context of the opioid epidemic remains unknown.To examine the temporal pattern of opioid prescribing within an ED for varying pain conditions between 2009 and 2018.A population-based, cross-sectional study was conducted at the ED of an urban academic medical center. All patients treated within that ED between January 1, 2009, and December 31, 2018, were included.The proportion of patients prescribed an opioid for treatment of pain in the ED temporally by condition, condition type, patient demographics, and physician prescriber.Between 2009 and 2018, 556 176 patient encounters took place in the ED, with 70 218 unique opioid prescriptions ordered. A total of 316 632 patients (55.9%) were female, 45 070 (42.6%) were of white race, and 43 412 (40.6%) were privately insured; the median age group was 41 to 45 years. Yearly opioid prescriptions decreased by 66.3% (from 16.3 to 5.5 opioids per 100 encounters) between 2013 and 2018, with a yearly adjusted odds ratio (aOR) of 0.808 (95% CI, 0.802-0.814) compared with the prior year. In patients with musculoskeletal pain (back, joint, limb, and neck pain), opioid prescribing decreased by 71.1% (from 36.7 to 10.6 opioids per 100 encounters between 2013 and 2018; aOR, 0.758; 95% CI, 0.744-0.773). In patients with musculoskeletal trauma (fracture, sprain, contusion, and injury), opioid prescribing decreased by 58.0% (from 34.2 to 14.8 opioids per 100 encounters; aOR, 0.811; 95% CI, 0.797-0.824). In patients with nonmusculoskeletal pain (abdominal pain, kidney stone, respiratory distress, and pharyngitis) opioid prescribing decreased by 53.7% (from 20.1 to 9.3 opioids per 100 encounters; aOR, 0.850; 95% CI, 0.834-0.868). Between 2009 and 2018, patients who were black (aOR, 0.760; 95% CI, 0.741-0.779) and those who were Asian (aOR, 0.714; 95% CI, 0.665-0.764) had the lowest odds of receiving an opioid compared with other racial/ethnic groups.There was a substantial temporal decrease in the number of opioid prescriptions within this ED during the study period. This decrease was associated with substantial relative reductions in opioid prescribing for treatment of musculoskeletal pain compared with fractures and kidney stones.
Abstract P078: Gestational Weight Gain Modifies the Effect of the Circadian Rhythms Related <i>MTNR1B</i> Genotype on Postpartum Glycemic Changes: A Longitudinal Study in Women With Prior Gestational Diabetes
Authors: Hoirun Nisa, Junhong Leng, Tao Zhou, Huikun Liu, Weiqin Li, Leishen Wang, Nan Li, Dianjianyi Sun, Xiang Li, Xiaoyun Shang, Gang Hu, Lu Qi
Journal: Circulation (2018)

Context: Gestational diabetes mellitus (GDM) affects postpartum glucose metabolism and future risk of type 2 diabetes. Pregnancy and GDM are related to disturbed circadian rhythms and sleeping, which are determined by genetic variations in genes such as Melatonin receptor 1B ( MTNR1B ). Objective: We prospectively assessed whether the circadian rhythms related MTNR1B genotype was related to on 1-5 years of postpartum glycemic changes among women with a history of GDM, and whether gestational weight gain modified such associations. Design: The established circadian rhythms-associated MTNR1B genetic variant (rs10830963) was genotyped in 1025 Chinese women with a history of GDM. Body weight and glycemic traits during and after pregnancy were longitudinally collected. Results: The frequency of MTNR1B rs10830963 was not different among the three categories of gestational weight gain (inadequate, adequate, and excessive). We found women carrying different MTNR1B genotype showed distinct postpartum changes in 2-h glucose (OGTT) – 0.36, 0.20, and -0.19 mmol/L per additional copy of the G allele in women with inadequate, adequate, and excessive gestational weight gain, respectively ( p for interaction=0.028). The corresponding changes in fasting glucose were 0.14, 0.13, and 0.01, though the modification effects of gestational weight gain on the genetic association was marginal ( p for interaction= 0.067). Conclusions: Our findings suggest that gestational weight gain may modify the circadian rhythms related MTNR1B genetic variant on long term glycemic changes, highlighting the significance of gestational weight management in diabetes prevention among women with GDM.
Digital technologies in the public-health response to COVID-19
Authors: Jobie Budd, Benjamin S. Miller, Erin M. Manning, Vasileios Lampos, Mengdie Zhuang, Michael Edelstein, Geraint Rees, Vincent C. Emery, Molly M. Stevens, Neil Keegan, Michael J. Short, Deenan Pillay, Ed Manley, Ingemar J. Cox, David Heymann, Anne M. Johnson, Rachel A. McKendry
Journal: Nature Medicine (2020)

Digital technologies are being harnessed to support the public-health response to COVID-19 worldwide, including population surveillance, case identification, contact tracing and evaluation of interventions on the basis of mobility data and communication with the public. These rapid responses leverage billions of mobile phones, large online datasets, connected devices, relatively low-cost computing resources and advances in machine learning and natural language processing. This Review aims to capture the breadth of digital innovations for the public-health response to COVID-19 worldwide and their limitations, and barriers to their implementation, including legal, ethical and privacy barriers, as well as organizational and workforce barriers. The future of public health is likely to become increasingly digital, and we review the need for the alignment of international strategies for the regulation, evaluation and use of digital technologies to strengthen pandemic management, and future preparedness for COVID-19 and other infectious diseases. The COVID-19 pandemic has resulted in an accelerated development of applications for digital health, including symptom monitoring and contact tracing. Their potential is wide ranging and must be integrated into conventional approaches to public health for best effect.
Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial
Authors: Evdoxia Kyriazopoulou, Lydia Liaskou-Antoniou, George Adamis, Antonia Panagaki, Nikolaos Melachroinopoulos, Elina Drakou, Konstantinos Marousis, Georgios Chrysos, Andronikos Spyrou, Nikolaos Alexiou, Styliani Symbardi, Zoi Alexiou, Styliani Lagou, Virginia Kolonia, Theologia Gkavogianni, Miltiades Kyprianou, Ioannis Anagnostopoulos, Garyfallia Poulakou, Malvina Lada, Anna Makina, Efrosyni Roulia, Marina Koupetori, Vasileios Apostolopoulos, Dimitra Petrou, Thomas Nitsotolis, Anastasia Antoniadou, Evangelos J. Giamarellos-Bourboulis
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear.Objectives: To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis.Methods: In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 μg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by Clostridioides difficile or multidrug-resistant organisms, or any death attributed to baseline C. difficile or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization.Measurements and Main Results: The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8–13.1%; 9/125) versus 15.3% (95% CI, 10.1–22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20–0.98; P = 0.045); 28-day mortality 15.2% (95% CI, 10–22.5%; 19/125) versus 28.2% (95% CI, 21.2–36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29–0.89; P = 0.02); and median length of antibiotic therapy 5 (range, 5–7) versus 10 (range, 7–15) days (P < 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm.Conclusions: In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization.Clinical trial registered with www.clinicaltrials.gov (NCT03333304).