tbuckley/cabot-search huggingface dataset:
Mixed Sputum Granulocyte Longitudinal Impact on Lung Function in the Severe Asthma Research Program
Authors: Annette T. Hastie, David T. Mauger, Loren C. Denlinger, Andrea Coverstone, Mario Castro, Serpil Erzurum, Nizar Jarjour, Bruce D. Levy, Deborah A. Meyers, Wendy C. Moore, Brenda R. Phillips, Sally E. Wenzel, John V. Fahy, Elliot Israel, Eugene R. Bleecker
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Some reports indicate longitudinal variability in sputum differential cell counts, whereas others describe stability. Highly variable sputum eosinophil percentages are associated with greater lung function loss than persistently elevated eosinophil percentages, but elevated neutrophils are linked to more severe asthma.Objectives: To examine sputum granulocyte stability or variability longitudinally and associations with important clinical characteristics.Methods: The SARP III (Severe Asthma Research Program III) cohort underwent comprehensive phenotype characterization at baseline and annually over 3 years. Adult subjects with acceptable sputum levels were assigned to one of three longitudinal sputum groups: eosinophils predominantly <2%, eosinophils predominantly ≥2%, or highly variable eosinophil percentages (>2 SDs determined from independent, repeated baseline eosinophil percentages). Subjects were similarly assigned to one of three longitudinal neutrophil groups with a 50% cut point.Measurements and Main Results: The group with predominantly <2% sputum eosinophils had the highest lung function (prebronchodilator FEV1% predicted, P < 0.01; FEV1/FVC ratio, P < 0.001) at baseline and throughout 3 years compared with other eosinophil groups. Healthcare use did not differ, although the highly variable eosinophil group reported more asthma exacerbations at Year 3. Longitudinal neutrophil groups showed few differences. However, a combination of predominantly ≥2% eosinophil and ≥50% neutrophil groups resulted in the lowest prebronchodilator FEV1% predicted (P = 0.049) compared with the combination with predominantly <2% eosinophils and<50% neutrophils.Conclusions: Subjects with predominantly ≥2% sputum eosinophils in combination with predominantly ≥50% neutrophils showed greater loss of lung function, whereas those with highly variable sputum eosinophils had greater healthcare use.
Real-World Rapid Response to Mepolizumab in the Uncontrolled T2 Severe Asthma Endotype
Authors: Ruperto Gonzalez Perez, Paloma Poza-Guedes, Elena Mederos-Luís, Victor Matheu-Delgado, Cristina Álava-Cruz, Inmaculada Sánchez-Machín
Journal: Journal of Allergy and Clinical Immunology (2021)
Cell membranes targeted unimolecular prodrug for programmatic photodynamic-chemo therapy
Authors: Jie Yuan, Rong Peng, Dongdong Su, Xingxing Zhang, Hepeng Zhao, Xiujuan Zhuang, Mei Chen, Xiaobing Zhang, Lin Yuan
Journal: Theranostics (2021)

Photodynamic therapy (PDT) has emerged as one of the most up-and-coming non-invasive therapeutic modalities for cancer therapy in rencent years. However, its therapeutic effect was still hampered by the short life span, limited diffusion distance and ineluctable depletion of singlet oxygen (
Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer
Authors: Carmine De Angelis, Xiaoyong Fu, Maria Letizia Cataldo, Agostina Nardone, Resel Pereira, Jamunarani Veeraraghavan, Sarmistha Nanda, Lanfang Qin, Vidyalakshmi Sethunath, Tao Wang, Susan G. Hilsenbeck, Matteo Benelli, Ilenia Migliaccio, Cristina Guarducci, Luca Malorni, Lacey M. Litchfield, Jiangang Liu, Joshua Donaldson, Pier Selenica, David N. Brown, Britta Weigelt, Jorge S. Reis-Filho, Ben H. Park, Sara A. Hurvitz, Dennis J. Slamon, Mothaffar F. Rimawi, Valerie M. Jansen, Rinath Jeselsohn, C. Kent Osborne, Rachel Schiff
Journal: Clinical Cancer Research (2021)

Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor-positive (ER+)/HER2- breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes.Parental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation-resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes.Parental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an "IFN-related palbociclib-resistance Signature" (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER+/HER2- tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis.Aberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i.
Author Correction: Magnitude, demographics and dynamics of the effect of the first wave of the COVID-19 pandemic on all-cause mortality in 21 industrialized countries
Authors: Vasilis Kontis, James E. Bennett, Theo Rashid, Robbie M. Parks, Jonathan Pearson-Stuttard, Michel Guillot, Perviz Asaria, Bin Zhou, Marco Battaglini, Gianni Corsetti, Martin McKee, Mariachiara Di Cesare, Colin D. Mathers, Majid Ezzati
Journal: Nature Medicine (2021)

A Correction to this paper has been published: https://doi.org/10.1038/s41591-021-01254-4.
IMGN779, a Next-Generation CD33-Targeting Antibody-Drug Conjugate (ADC) Demonstrates Initial Antileukemia Activity in Patients with Relapsed or Refractory Acute Myeloid Leukemia
Authors: Jorge E. Cortes, Elie Traer, Eunice S. Wang, Harry P. Erba, William Blum, Cecilia Arana-Yi, Callum M. Sloss, Kerry Culm-Merdek, Jeanette Towles, Patrick A. Zweidler-McKay, Daniel J. DeAngelo
Journal: Blood (2017)
Abstract 9651: Angiotensin-(1-12) Modulation of Cardiomyocyte Functional Performance in Wistar-Kyoto and Spontaneously Hypertensive Rats
Authors: Zhe Chen, Yixi Liu, Heng-Jie Cheng, Jessica VonCannon, Sarfaraz Ahmad, Jasmina Varagic, Carlos M Ferrario, Che Ping Cheng
Journal: Circulation (2019)

Background: In spontaneously hypertensive rats (SHR), increased cardiac angiotensin II (Ang II) and Gi expressions have adversed effects on contractility. Recent characterization of a functional pa...
Evaluation of THC-Related Neuropsychiatric Symptoms Among Adults Aged 50 Years and Older
Authors: Latha Velayudhan, Katie Louise McGoohan, Sagnik Bhattacharyya
Journal: JAMA Network Open (2021)

This systematic review and metaregression analysis estimates the association between the delta-9-tetrahydrocannabinol (THC) dose of cannabinoid-based medicines and neuropsychiatric adverse events among adults aged 50 years and older.
Intracavity rendezvous procedure
Authors: Muhammad Farman, Pauline Kane, Stephen Gregory, Andreas Prachalias, Deepak Joshi
Journal: Endoscopy (2021)

Biliary complications are common after liver transplantation, and the vast majority of these can be managed endoscopically [1] [2]. We describe a case of a spontaneous bile leak after liver transplantation which eventually required an extraductal rendezvous to re-establish recipient and donor bile duct continuity.
Physicians’ Electrocardiogram Interpretations
Authors: Mengyang He, Xiangling Deng, Wenquan Niu
Journal: JAMA Internal Medicine (2021)

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
Once-daily tenofovir disoproxil fumarate in treatment-naive Taiwanese patients with chronic hepatitis B and minimally raised alanine aminotransferase (TORCH-B): a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial
Authors: Yao-Chun Hsu, Chi-Yi Chen, I-Wei Chang, Chi-Yang Chang, Chun-Ying Wu, Teng-Yu Lee, Ming-Shiang Wu, Ming-Jong Bair, Jyh-Jou Chen, Chieh-Chang Chen, Cheng-Hao Tseng, Chi-Ming Tai, Yen-Tsung Huang, Wen-Hui Ku, Lein-Ray Mo, Jaw-Town Lin
Journal: The Lancet Infectious Diseases (2021)
Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma
Authors: E. A. Rozeman, E. P. Hoefsmit, I. L. M. Reijers, R. P. M. Saw, J. M. Versluis, O. Krijgsman, P. Dimitriadis, K. Sikorska, B. A. van de Wiel, H. Eriksson, M. Gonzalez, A. Torres Acosta, L. G. Grijpink-Ongering, K. Shannon, J. B. A. G. Haanen, J. Stretch, S. Ch’ng, O. E. Nieweg, H. A. Mallo, S. Adriaansz, R. M. Kerkhoven, S. Cornelissen, A. Broeks, W. M. C. Klop, C. L. Zuur, W. J. van Houdt, D. S. Peeper, A. J. Spillane, A. C. J. van Akkooi, R. A. Scolyer, T. N. M. Schumacher, A. M. Menzies, G. V. Long, C. U. Blank
Journal: Nature Medicine (2021)
Optimized EGFR Blockade Strategies in <i>EGFR</i> Addicted Gastroesophageal Adenocarcinomas
Authors: Simona Corso, Filippo Pietrantonio, Maria Apicella, Cristina Migliore, Daniela Conticelli, Annalisa Petrelli, Laura D'Errico, Stefania Durando, Daniel Moya-Rull, Sara E. Bellomo, Stefano Ughetto, Maurizio Degiuli, Rossella Reddavid, Uberto Fumagalli, Stefano De Pascale, Giovanni Sgroi, Emanuele Rausa, Gian Luca Baiocchi, Sarah Molfino, Giovanni De Manzoni, Maria Bencivenga, Salvatore Siena, Andrea Sartore-Bianchi, Federica Morano, Salvatore Corallo, Michele Prisciandaro, Maria Di Bartolomeo, Annunziata Gloghini, Silvia Marsoni, Antonino Sottile, Anna Sapino, Caterina Marchiò, Asa Dahle-Smith, Zosia Miedzybrodzka, Jessica Lee, Siraj M. Ali, Jeffrey S. Ross, Brian M. Alexander, Vincent A. Miller, Russell Petty, Alexa B. Schrock, Silvia Giordano
Journal: Clinical Cancer Research (2021)

Gastric and gastroesophageal adenocarcinomas represent the third leading cause of cancer mortality worldwide. Despite significant therapeutic improvement, the outcome of patients with advanced gastroesophageal adenocarcinoma is poor. Randomized clinical trials failed to show a significant survival benefit in molecularly unselected patients with advanced gastroesophageal adenocarcinoma treated with anti-EGFR agents.
Cardiac ryanodine receptor calcium release deficiency syndrome
Authors: Bo Sun, Jinjing Yao, Mingke Ni, Jinhong Wei, Xiaowei Zhong, Wenting Guo, Lin Zhang, Ruiwu Wang, Darrell Belke, Yong-Xiang Chen, Krystien V.V. Lieve, Anders K. Broendberg, Thomas M. Roston, Ivan Blankoff, Janneke A. Kammeraad, Johannes C. von Alvensleben, Julieta Lazarte, Alexander Vallmitjana, Loryn J. Bohne, Robert A. Rose, Raul Benitez, Leif Hove-Madsen, Carlo Napolitano, Robert A. Hegele, Michael Fill, Shubhayan Sanatani, Arthur A.M. Wilde, Jason D. Roberts, Silvia G. Priori, Henrik K. Jensen, S. R. Wayne Chen
Journal: Science Translational Medicine (2021)

Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia, a condition characterized by prominent ventricular ectopy in response to catecholamine stress, which can be reproduced on exercise stress testing (EST). However, reports of sudden cardiac death (SCD) have emerged in EST-negative individuals who have loss-of-function (LOF) RyR2 mutations. The clinical relevance of RyR2 LOF mutations including their pathogenic mechanism, diagnosis, and treatment are all unknowns. Here, we performed clinical and genetic evaluations of individuals who suffered from SCD and harbored an LOF RyR2 mutation. We carried out electrophysiological studies using a programed electrical stimulation protocol consisting of a long-burst, long-pause, and short-coupled (LBLPS) ventricular extra-stimulus. Linkage analysis of RyR2 LOF mutations in six families revealed a combined logarithm of the odds ratio for linkage score of 11.479 for a condition associated with SCD with negative EST. A RyR2 LOF mouse model exhibited no catecholamine-provoked ventricular arrhythmias as in humans but did have substantial cardiac electrophysiological remodeling and an increased propensity for early afterdepolarizations. The LBLPS pacing protocol reliably induced ventricular arrhythmias in mice and humans having RyR2 LOF mutations, whose phenotype is otherwise concealed before SCD. Furthermore, treatment with quinidine and flecainide abolished LBLPS-induced ventricular arrhythmias in model mice. Thus, RyR2 LOF mutations underlie a previously unknown disease entity characterized by SCD with normal EST that we have termed RyR2 Ca
Abstract IA006: Endocrine therapy and ER/PR combinations
Authors: Helen J. MacKay
Journal: Clinical Cancer Research (2021)

Abstract Endocrine therapy is the “original” targeted therapy in endometrial cancer (EC). Despite over 60 years experience with this treatment modality we have yet to answer some key questions including which women derive benefit and how do we identify them? Despite a high proportion of ECs being ER and/or PR positive, endocrine therapy is only associated with modest benefit. Greater understanding of ER and PR biology may help identify patient populations who will derive benefit and assist in optimizing this approach. Favourable toxicity profiles and multiple pathway interactions suggest the potential for combining endocrine and other targeted agents. We discuss the preliminary data and hypothesize on potential strategies to accelerate the pace of development in this area. Citation Format: Helen J. MacKay. Endocrine therapy and ER/PR combinations [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr IA006.
Factors associated with SARS-CoV-2 infection and outbreaks in long-term care facilities in England: a national cross-sectional survey
Authors: Laura Shallcross, Danielle Burke, Owen Abbott, Alasdair Donaldson, Gemma Hallatt, Andrew Hayward, Susan Hopkins, Maria Krutikov, Katie Sharp, Leone Wardman, Sapphira Thorne
Journal: The Lancet Healthy Longevity (2021)
DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy
Authors: Chao Fang, Dong Xu, Jing Su, Jonathan R Dry, Bolan Linghu
Journal: npj Digital Medicine (2021)

Abstract Immuno-oncology (IO) therapies have transformed the therapeutic landscape of non-small cell lung cancer (NSCLC). However, patient responses to IO are variable and influenced by a heterogeneous combination of health, immune, and tumor factors. There is a pressing need to discover the distinct NSCLC subgroups that influence response. We have developed a dee p pa tient graph convolutional n etwork, we call “DeePaN”, to discover NSCLC complexity across data modalities impacting IO benefit. DeePaN employs high-dimensional data derived from both real-world evidence (RWE)-based electronic health records (EHRs) and genomics across 1937 IO-treated NSCLC patients. DeePaN demonstrated effectiveness to stratify patients into subgroups with significantly different ( P -value of 2.2 × 10 −11 ) overall median survival of 20.35 months and 9.42 months post-IO therapy. Significant differences in IO outcome were not seen from multiple non-graph-based unsupervised methods. Furthermore, we demonstrate that patient stratification from DeePaN has the potential to augment the emerging IO biomarker of tumor mutation burden (TMB). Characterization of the subgroups discovered by DeePaN indicates potential to inform IO therapeutic insight, including the enrichment of mutated KRAS and high blood monocyte count in the IO beneficial and IO non-beneficial subgroups, respectively. Our work has proven the concept that graph-based AI is feasible and can effectively integrate high-dimensional genomic and EHR data to meaningfully stratify cancer patients on distinct clinical outcomes, with potential to inform precision oncology.
EEC exposure to mite in allergic asthma induces an increase of function and recruitment molecules on blood Treg.
Authors: Virginie Doyen, Anh Poirot, Myriam Maumy-Bertrand, Nathalie Domis, Naji Khayath, Francis Corazza, Frederic De Blay
Journal: Journal of Allergy and Clinical Immunology (2021)
Comparison of breast cancer and cervical cancer stage distributions in ten newly independent states of the former Soviet Union: a population-based study
Authors: Anton Ryzhov, Marilys Corbex, Marion Piñeros, Anton Barchuk, Diana Andreasyan, Sayde Djanklich, Vadim Ghervas, Olga Gretsova, Dilyara Kaidarova, Konstantin Kazanjan, Fuad Mardanli, Yuriy Michailovich, Elena Ten, Alesya Yaumenenka, Freddie Bray, Ariana Znaor
Journal: The Lancet Oncology (2021)

BackgroundScreening for breast cancer and cervical cancer in the newly independent states of the former Soviet Union is largely opportunistic, and countries in the region have among the highest cervical cancer incidence in the WHO European Region. We aimed to compare the stage-specific distributions and changes over time in breast cancer and cervical cancer incidence in the newly independent states of the former Soviet Union.MethodsWe collected breast cancer and cervical cancer incidence data from official statistics from Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Republic of Moldova, Russian Federation, Ukraine, and Uzbekistan for the years 2008–17 by tumour, node, metastasis (TNM) stage, and by age where population-based cancer registry data were available. We used log-linear regression to quantify the changes over time in age-standardised rates.FindingsDuring the period 2013–17, more than 50% of breast cancer cases across the analysed countries, and more than 75% of breast cancer cases in Belarus, Kazakhstan, and Ukraine, were registered at stages I–II. The proportion of stage I breast cancer cases was highest in the screening age group (50–69 years) compared with other ages in Moldova and the Russian registries, but was highest in those aged 15–49 years in Georgia and Ukraine. Breast cancer stage-specific incidence rates increased over time, most prominently for stage I cancers. For cervical cancer, the proportions of cancers diagnosed at a late stage (stages III and IV) were high, particularly in Moldova and Armenia (>50%). The proportion of stage I cervical cancer cases decreased with age in all countries, whereas the proportions of late stage cancers increased with age. Stage-specific incidence rates of cervical cancer generally increased over the period 2008–17.InterpretationOur results suggest modest progress in early detection of breast cancer in the newly independent states of the former Soviet Union. The high proportions of early-stage disease in the absence of mammography screening (eg, in Belarus) provide a benchmark for what is achievable with rapid diagnosis. For cervical cancer, there is a need to tackle the high burden and unfavourable stage-specific changes over time in the region. A radical shift in national policies away from opportunistic screening toward organised, population-based, quality-assured human papillomavirus vaccination and screening programmes is urgently needed.FundingUnion for International Cancer Control, WHO Regional Office for Europe, and Ministry of Health of Ukraine.
Durable SARS-CoV-2 B cell immunity after mild or severe disease
Authors: Clinton O. Ogega, Nicole E. Skinner, Paul W. Blair, Han-Sol Park, Kirsten Littlefield, Abhinaya Ganesan, Santosh Dhakal, Pranay Ladiwala, Annukka A.R. Antar, Stuart C. Ray, Michael J. Betenbaugh, Andrew Pekosz, Sabra L. Klein, Yukari C. Manabe, Andrea L. Cox, Justin R. Bailey
Journal: Journal of Clinical Investigation (2021)

Multiple studies have shown loss of severe acute respiratory syndrome coronavirus 2–specific (SARS-CoV-2–specific) antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from coronavirus disease 2019 (COVID-19). However, memory B cells (MBCs) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multidimensional flow cytometric analysis of S protein receptor binding domain–specific (S-RBD–specific) MBCs in cohorts of ambulatory patients with COVID-19 with mild disease (n = 7), and hospitalized patients with moderate to severe disease (n = 7), at a median of 54 days (range, 39–104 days) after symptom onset. We detected S-RBD–specific class-switched MBCs in 13 of 14 participants, failing only in the individual with the lowest plasma levels of anti–S-RBD IgG and neutralizing antibodies. Resting MBCs (rMBCs) made up the largest proportion of S-RBD–specific MBCs in both cohorts. FCRL5, a marker of functional memory on rMBCs, was more dramatically upregulated on S-RBD–specific rMBCs after mild infection than after severe infection. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD–specific, class-switched rMBCs that resemble germinal center–derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell–mediated immunity against SARS-CoV-2 after mild or severe disease.