tbuckley/cabot-search huggingface dataset:
Global, regional, and national trends in under-5 mortality between 1990 and 2019 with scenario-based projections until 2030: a systematic analysis by the UN Inter-agency Group for Child Mortality Estimation
Authors: David Sharrow, Lucia Hug, Danzhen You, Leontine Alkema, Robert Black, Simon Cousens, Trevor Croft, Victor Gaigbe-Togbe, Patrick Gerland, Michel Guillot, Kenneth Hill, Bruno Masquelier, Colin Mathers, Jon Pedersen, Kathleen L Strong, Emi Suzuki, Jon Wakefield, Neff Walker
Journal: The Lancet Global Health (2022)
Comprehensive assessment of germline pathogenic variant detection in tumor-only sequencing
Authors: P Terraf, F Pareja, D N Brown, O Ceyhan-Birsoy, M Misyura, S Rana, E O'Reilly, M I Carlo, C Aghajanian, Y Liu, F Derakhshan, G Jayakumaran, B Weigelt, M Walsh, Z Stadler, K Offit, M Ladanyi, M Robson, A Zehir, J S Reis-Filho, D Mandelker
Journal: Annals of Oncology (2022)

Highlights•In a cohort of >21 000 patients, tumor-only sequencing failed to detect 10.5% of pathogenic germline variants in 16 CSGs.•18.8%, 12.8% and 7.3% of pathogenic germline variants in MMR, DDR and HRD genes were not detected by tumor-only sequencing.•These undetected P/LP variants may affect the use of targeted therapies, preventative measures and familial surveillance.•For patients with negative tumor sequencing results, genetic testing is needed to guide therapy and genetic counseling.AbstractBackgroundTumor-only sequencing, implemented for the identification of somatic variants, is oftentimes used for the detection of actionable germline variants. We sought to determine whether tumor-only sequencing assays are suitable for detection of actionable germline variants, given their importance for the delivery of targeted therapies and risk-reducing measures.Patients and methodsThe detection of germline variants affecting moderate- and high-penetrance cancer susceptibility genes (CSGs) by tumor-only sequencing was compared to clinical germline testing in 21 333 cancer patients who underwent tumor and germline testing using the Food and Drug Administration (FDA)-authorized Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Targets (MSK-IMPACT) assay. Seven homologous recombination deficiency (HRD), two DNA damage response (DDR) and four mismatch repair (MMR) genes, as well as NF1, RB1 and TP53 were included in the analysis. FDA-authorized and New York State Department of Health-approved sequencing methods for germline, tumor/normal and tumor-only sequencing assays and analytical pipelines were employed.ResultsIn patients who underwent tumor and germline sequencing, as compared to clinical genetic testing, tumor-only sequencing failed to detect 10.5% of clinically actionable pathogenic germline variants in CSGs, including 18.8%, 12.8% and 7.3% of germline variants in MMR, DDR and HRD genes, respectively. The sensitivity for detection of pathogenic germline variants by tumor-only sequencing was 89.5%. Whilst the vast majority of pathogenic germline exonic single-nucleotide variants (SNVs) and small indels were detected by tumor-only sequencing, large percentages of germline copy number variants, intronic variants and repetitive element insertions were not detected.ConclusionsTumor-only sequencing is adequate for the detection of clinically actionable germline variants, particularly for SNVs and small indels; however, a small subset of alterations affecting HRD, DDR and MMR genes may not be detected optimally. Therefore, for high-risk patients with negative tumor-only sequencing results, clinical genetic testing could be considered given the impact of these variants on therapy and genetic counseling.
Thrombin cleaves IL‐33 and modulates IL‐33‐activated allergic lung inflammation
Authors: Yuying Huang, Xuezhen Li, Lin Zhu, Chunrong Huang, Wen Chen, Zhiyang Ling, SongLing Zhu, Xintong Feng, Chunyan Yi, Wangpeng Gu, Chenghua Yan, Jing Wang, Liyan Ma, Xiao Su, Ranran Dai, Guochao Shi, Bing Sun, Yaguang Zhang
Journal: Allergy (2022)

Abstract Background Organisms have orchestrated coagulation and immune systems. Although a link between inflammation and haemostasis has been reported in asthma, the interaction mechanism has not been completely elucidated. Here, we investigated the direct link between the mammalian immune and coagulation systems. Methods Mice were administered protease or antigens intranasally to induce airway inflammation with or without thrombin inhibitors treatment. The effects of thrombin and its inhibitors on interleukin (IL)‐33 were investigated both in vivo and in vitro. Peripheral blood mononuclear cells (PBMCs) and plasma from asthma patients are collected to verify the correlation between thrombin and group 2 innate lymphocytes (ILC2s). Results Low‐molecular‐weight heparin (LMWH, an indirect inhibitor of thrombin) restrained both papain‐ and fungus‐induced type 2 immune responses in mice by inhibiting IL‐33 cleavage. Upon examining the potential thrombin protease consensus sites, we found that IL‐33 was directly cleaved by thrombin at specific amino acids (R48 and R106) to generate a mature form of IL‐33 with potent biological activity. In addition, we found that bivalirudin TFA (a direct inhibitor of thrombin) inhibited a variety of type 2 inflammatory responses, such as those in house dust mite (HDM)‐ and ovalbumin (OVA)‐mediated pulmonary inflammation models. We found that plasma thrombin‐antithrombin complex (TATc) levels in asthma patients were positively associated with the number and function of IL‐33‐responder group 2 innate lymphocytes (ILC2s) among peripheral blood mononuclear cells (PBMCs) from asthma patients. Conclusion The data suggested that thrombin inhibitors administration could be effective in treating lung inflammation by regulating ILC2s via IL‐33 maturation, indicating that targeting thrombin is a potential way to treat allergic diseases.
Development and Validation of a Predictive Model of Severe Fatigue After Breast Cancer Diagnosis: Toward a Personalized Framework in Survivorship Care
Authors: Antonio Di Meglio, Julie Havas, Davide Soldato, Daniele Presti, Elise Martin, Barbara Pistilli, Gwenn Menvielle, Agnes Dumas, Cecile Charles, Sibille Everhard, Anne-Laure Martin, Charles Coutant, Carole Tarpin, Laurence Vanlemmens, Christelle Levy, Olivier Rigal, Suzette Delaloge, Nancy U. Lin, Patricia A. Ganz, Ann H. Partridge, Fabrice André, Stefan Michiels, Ines Vaz-Luis
Journal: Journal of Clinical Oncology (2022)

PURPOSE Fatigue is common and troublesome among breast cancer survivors; however, limited tools exist to predict its risk. PATIENTS AND METHODS Participants with stage I-III breast cancer were prospectively included from CANTO (ClinicalTrials.gov identifier: NCT01993498 ), collecting longitudinal data at diagnosis (before the initiation of any cancer treatment) and 1 (T1), 2 (T2), and 4 (T3) years after diagnosis. The main outcome was severe global fatigue at T2 (score ≥ 40/100, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30). Analyses at T3 were exploratory. Secondary outcomes included physical, emotional, and cognitive fatigue (EORTC Quality of Life Questionnaire-FA12). Multivariable logistic regression models retained associations with severe fatigue by bootstrapped Augmented Backward Elimination. Validation methods included 10-fold internal cross-validation, overoptimism-corrected area under the receiver operating characteristic curves, and external validation. RESULTS Among 5,640, 5,000, and 3,400 patients at T1, T2, and T3, respectively, the prevalence of post-treatment severe global fatigue was 35.6%, 34.0%, and 31.5% in the development cohort. Retained risk factors for severe global fatigue at T2 were severe pretreatment fatigue (adjusted odds ratio v no 3.191 [95% CI, 2.704 to 3.767]); younger age (for 1-year decrement 1.015 [1.009 to 1.022]), higher body mass index (for unit increment 1.025 [1.012 to 1.038]), current smoking behavior ( v never 1.552 [1.291 to 1.866]), worse anxiety ( v noncase 1.265 [1.073 to 1.492]), insomnia (for unit increment 1.005 [1.003 to 1.007]), and pain at diagnosis (for unit increment 1.014 [1.010 to 1.017]), with an area under the receiver operating characteristic curve of 0.73 (95% CI, 0.72 to 0.75). Receipt of hormonal therapy was a risk factor for severe fatigue at T3 ( v no 1.448 [1.165 to 1.799]). Dimension-specific risk factors included body mass index for physical fatigue and emotional distress for emotional and cognitive fatigue. CONCLUSION We propose a predictive model to assess fatigue among breast cancer survivors, within a personalized survivorship care framework. This may help clinicians to provide early management interventions or to correct modifiable risk factors and offer more tailored monitoring and education to patients at risk of severe post-treatment fatigue.
Renal function deterioration assessment in totally endophytic “deep” renal masses treated with robotic partial nephrectomy: Comparison with a whole cohort of cT1-2 renal tumors patients from a multicenter analysis (ROSULA database)
Authors: G. Tuderti, R. Autorino, U. Carbonara, A. Mari, D. Amparore, F. Di Maida, A.T. Beksac, R. Mastroianni, A. Bove, U. Anceschi, D. Franzese, G. Rosiello, L. Bianchi, P. Koukourikis, S. Perdonà, C. Lau, H.R. Koon, C. Leonardo, R. Schiavina, I. Derweesh, F. Porpiglia, M. Alexandre, J. Kaouk, A. Minervini, G. Simone
Journal: European Urology (2021)
Impact of SARS-CoV-2 Pandemic on Vascular Liver Diseases
Authors: Anna Baiges, Eira Cerda, Caroline Amicone, Luis Téllez, Edilmar Alvarado-Tapias, Angela Puente, Jose Ignacio Fortea, Elba Llop, Filipa Rocha, Lara Orts, Oliva Ros-Fargas, Pamela Vizcarra, Kamal Zekrini, Ould Amara Lounes, Ghiles Touati, Natalia Jiménez-Esquivel, Maria Jose Serrano, Angels Falgà, Marta Magaz, Pol Olivas, Fabian Betancourt, Valeria Perez-Campuzano, Fanny Turon, Audrey Payancé, Odile Goria, Pierre-Emmanuel Rautou, Virginia Hernández-Gea, Candid Villanueva, Agustin Albillos, Aurélie Plessier, Juan-Carlos García-Pagán
Journal: Clinical Gastroenterology and Hepatology (2021)
Metastatic tumor antigen 1 contributes to hepatocarcinogenesis posttranscriptionally through RNA‐binding function
Authors: Yung‐Tsung Li, Chun‐Jen Liu, Jia‐Horng Kao, Li‐Feng Lin, Hui‐Chu Tu, Chih‐Chiang Wang, Po‐Hsi Huang, Huei‐Ru Cheng, Pei‐Jer Chen, Ding‐Shinn Chen, Hui‐Lin Wu
Journal: Hepatology (2022)

Background and Aims: Both nuclear and cytoplasmic overexpression of metastatic tumor antigen 1 (MTA1) contributes to tumorigenesis of HCC. Most studies have focused on nuclear MTA1 whose function is mainly a chromatin modifier regulating the expression of various cancer‐promoting genes. By contrast, the molecular mechanisms of cytoplasmic MTA1 in carcinogenesis remain elusive. Here, we reveal a role of MTA1 in posttranscriptional gene regulation. Approach and Results: We conducted the in vitro and in vivo RNA‐protein interaction assays indicating that MTA1 could bind directly to the 3′‐untranslated region of MYC RNA. Mutation at the first glycine of the conserved GXXG loop within a K‐homology II domain‐like structure in MTA1 (G78D) resulted in the loss of RNA‐binding activity. We used gain‐ and loss‐of‐function strategy showing that MTA1, but not the G78D mutant, extended the half‐life of MYC and protected it from the lethal ‐7–mediated degradation. The G78D mutant exhibited lower activity in promoting tumorigenesis than wild‐type in vitro and in vivo. Furthermore, RNA‐immunoprecipitation sequencing analysis demonstrated that MTA1 binds various oncogenesis‐related mRNAs besides MYC . The clinical relevance of cytoplasmic MTA1 and its interaction with MYC were investigated using HBV‐HCC cohorts with or without early recurrence. The results showed that higher cytoplasmic MTA1 level and MTA1‐ MYC interaction were associated with early recurrence. Conclusions: MTA1 is a generic RNA‐binding protein. Cytoplasmic MTA1 and its binding to MYC is associated with early recurrence in patients with HBV‐HCC. This function enables it to regulate gene expression posttranscriptionally and contributes to hepatocarcinogenesis.
Urgent Intervention for Both de Winter and Wellens——Reply
Authors: Yuansong Zhu, Suxin Luo, Bi Huang
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Simplified PADUA Renal (SPARE) nephrometry system: French multi-institutional retrospective validation and comparison for Robot-Assisted Partial Nephrectomy (RAPN)
Authors: C. Klein, C. Michiels, C. Allenet, G. Capon, E. Alezra, V. Estrade, F. Bladou, G. Robert, J.C. Bernhard
Journal: European Urology (2021)
The benefits, costs and feasibility of a low incidence COVID-19 strategy
Authors: Thomas Czypionka, Emil N. Iftekhar, Barbara Prainsack, Viola Priesemann, Simon Bauer, André Calero Valdez, Sarah Cuschieri, Enrico Glaab, Eva Grill, Jenny Krutzinna, Christos Lionis, Helena Machado, Carlos Martins, George N. Pavlakis, Matjaž Perc, Elena Petelos, Martyn Pickersgill, Alexander Skupin, Eva Schernhammer, Ewa Szczurek, Sotirios Tsiodras, Peter Willeit, Paul Wilmes
Journal: The Lancet Regional Health - Europe (2022)

In the summer of 2021, European governments removed most NPIs after experiencing prolonged second and third waves of the COVID-19 pandemic. Most countries failed to achieve immunization rates high enough to avoid resurgence of the virus. Public health strategies for autumn and winter 2021 have ranged from countries aiming at low incidence by re-introducing NPIs to accepting high incidence levels. However, such high incidence strategies almost certainly lead to the very consequences that they seek to avoid: restrictions that harm people and economies. At high incidence, the important pandemic containment measure 'test-trace-isolate-support' becomes inefficient. At that point, the spread of SARS-CoV-2 and its numerous harmful consequences can likely only be controlled through restrictions. We argue that all European countries need to pursue a low incidence strategy in a coordinated manner. Such an endeavour can only be successful if it is built on open communication and trust.
Where are female editors from low-income and middle-income countries? A comprehensive assessment of gender, geographical distribution and country’s income group of editorial boards of top-ranked rehabilitation and sports science journals
Authors: Aamir Raoof Memon, Ishtiaq Ahmed, Nabiha Ghaffar, Kainat Ahmed, Iqra Sadiq
Journal: British Journal of Sports Medicine (2022)

Objective We aimed to examine the gender, geographical region and income group of the country of affiliation for editorial leadership (eg, editor-in-chief, section editor, associate editor) and advisors (eg, editorial board members) in top-ranked rehabilitation and sports science journals. Methods A list of Scopus indexed, Q1 (25% top) rehabilitation and sports science journals, available under four different journal categories, was prepared based on the data from the Scientific Journal Rankings (SJR) website. The information for editorial leadership and advisors for these journals was obtained and their gender was determined through a multistep process. The country of affiliation of editorial leadership and advisors was used to categorise them to World Bank’s different geographical regions and income groups (for countries). Results There were 7248 editors (35.7% leadership and 64.3% advisors) across 113 rehabilitation and sports science journals. Of all editors, 1792 (24.7%) were women. Women represented 24.5% of editorial leadership positions, 24.8% of advisory roles and 10.4% of editors-in-chief. Editors from South Asia (0.5%) and sub-Saharan Africa (0.6%) had the least representation, while those affiliated with institutions from high-income countries represented 93.5% of leadership roles and 93.1% of advisory positions. Moreover, editors affiliated with institutions from North America occupied almost half of all editorial roles. Conclusions Women and researchers affiliated with institutions from low-income and middle-income countries are under-represented on the editorial boards of top-ranked rehabilitation and sports science journals indexed in the Scopus database. Editors are responsible for promoting research in their specific field, and therefore, the current leadership in rehabilitation and sports science journals should consider diversifying their editorial boards by providing equitable opportunities to women and researchers from a broader geographical distribution.
Declining disease burden of HCC in the United States, 1992–2017: A population‐based analysis
Authors: Jianglong Han, Bin Wang, Wenmin Liu, Shijie Wang, Ruyan Chen, Mingkai Chen, Zhenming Fu
Journal: Hepatology (2022)

Abstract Background and Aims The incidence of HCC has recently been consistently reported to decline in the United States. However, decreased overall mortality of HCC has just been suggested and needs further examination. Approach and Results Using data from the Surveillance, Epidemiology, and End Results databases, we assessed HCC incidence, incidence‐based mortality (IBM), and 1‐year survival rates from 1992 through 2017 in the United States. These secular trends were analyzed using the National Cancer Institute’s Joinpoint Regression Program. Age‐period‐cohort analyses were performed to address underlying reasons for the observed temporal trends. The incidence and mortality of liver cancer in the United States by different etiologies were acquired from the Global Burden of Disease study (1990–2019) as a likely validation set. Joinpoint and age‐period‐cohort analyses were performed by etiologies. The incidence rates of HCC increased during 1992–2011 and sharply decreased thereafter by −2.3% annually (95% CI: −3.5% to −1.1%). IBM peaked in 2013 (age‐standardized mortality rate: 6.98 per 100,000 person‐years) in the US population. IBM started to decrease significantly in 2013 by −3.2%/year (95% CI: −5.4% to −1.1% per year) after a continuous increase of 3.5% annually during 1993–2013. Overall, the 1‐year survival of HCC improved from 21.4% to 56.6% over the study period. However, the highest HCC incidence and mortality risk for patients aged 60–69 and born between 1952–1957 were found. Conclusions We found significantly decreased overall HCC‐specific mortality since 2013 in the US population, along with decreased incidence and continuously improved survival. The changing etiologies, advances in screening and diagnosis, and improved treatment modality and allocation might all contribute to the downward trends of the disease burden of HCC in the United States.
Synaptic dysfunction connects autism spectrum disorder and sleep disturbances: A perspective from studies in model organisms
Authors: Fusun Doldur-Balli, Toshihiro Imamura, Olivia J. Veatch, Naihua N. Gong, Diane C. Lim, Michael P. Hart, Ted Abel, Matthew S. Kayser, Edward S. Brodkin, Allan I. Pack
Journal: Sleep Medicine Reviews (2022)
Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry
Authors: Pedro M Machado, Saskia Lawson-Tovey, Anja Strangfeld, Elsa F Mateus, Kimme L Hyrich, Laure Gossec, Loreto Carmona, Ana Rodrigues, Bernd Raffeiner, Catia Duarte, Eric Hachulla, Eric Veillard, Eva Strakova, Gerd R Burmester, Gözde Kübra Yardımcı, Jose A Gomez-Puerta, Julija Zepa, Lianne Kearsley-Fleet, Ludovic Trefond, Maria Cunha, Marta Mosca, Martina Cornalba, Martin Soubrier, Nicolas Roux, Olivier Brocq, Patrick Durez, Richard Conway, Tiphaine Goulenok, Johannes WJ Bijlsma, Iain B McInnes, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2021)

To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD).Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively.The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD).The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.
Regional differences in precipitating factors of hospitalization for acute heart failure: insights from the <scp>REPORT‐HF</scp> registry
Authors: Jasper Tromp, Joost C. Beusekamp, Wouter Ouwerkerk, Peter van der Meer, John G.F. Cleland, Christiane E. Angermann, Ulf Dahlstrom, Georg Ertl, Mahmoud Hassanein, Sergio V. Perrone, Mathieu Ghadanfar, Anja Schweizer, Achim Obergfell, Gerasimos Filippatos, Kenneth Dickstein, Sean P Collins, Carolyn S.P. Lam
Journal: European Journal of Heart Failure (2022)
对于最初对伊赛珠单抗没有完全反应的患者,最佳剂量方案是什么?
Journal: British Journal of Dermatology (2020)

伊赛珠单抗 (Taltzâ) 是一种用于中度至重度银屑病患者的现代注射治疗("生物制剂"),通过抵抗银屑病过程的 一种强大刺激因子白细胞介素 17A (