tbuckley/cabot-search huggingface dataset:
CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability
Authors: Yu Zhang, Jiajia Jiang, Jiayin Zhang, Han Shen, Maoye Wang, Zhen Guo, Xueyan Zang, Hui Shi, Jiayan Gao, Hui Cai, Xinjian Fang, Hui Qian, Wenrong Xu, Xu Zhang
Journal: Molecular Cancer (2021)

Abstract Background Circular RNAs (circRNAs) play important roles in cancer development and progression. The purpose of this study is to identify aberrantly expressed circRNAs in gastric cancer (GC), unravel their roles in GC progression, and provide new targets for GC diagnosis and therapy. Methods Bioinformatic analyses were performed to identify the aberrantly expression of hsa_circ_0061137 (termed as circDIDO1) in GC. Gain- and loss-of-function studies were performed to examine the biological roles of circDIDO1 in GC progression. Tagged RNA affinity purification, mass spectrometry, immunofluorescence, co-immunoprecipitation, and Western blot were used to identify circRNA-interacting and circRNA-encoded proteins. RNA sequencing, qRT-PCR, and Western blot were performed to analyze circRNA-regulated downstream target genes and signaling pathways. Mouse tumor models were used to analyze the effects of circDIDO1 on GC growth and metastasis. Results CircDIDO1 was transcribed from human DIDO1 (death-inducer obliterator 1) gene and formed by back-splicing of exons 2–6 of the linear transcript. circDIDO1 was down-regulated in GC tissues and its low levels were associated with larger tumor size, distal metastasis, and poor prognosis. CircDIDO1 overexpression inhibited while knockdown promoted GC cell proliferation, migration and invasion . CircDIDO1 overexpression suppressed GC growth and metastasis in mouse tumor models. Mechanistically, circDIDO1 encoded a novel 529aa protein that directly interacted with poly ADP-ribose polymerase 1 (PARP1) and inhibited its activity. CircDIDO1 also specifically bound to peroxiredoxin 2 (PRDX2) and promoted RBX1-mediated ubiquitination and degradation of PRDX2, which led to the inactivation of its downstream signaling pathways. Conclusions CircDIDO1 is a new circRNA that has tumor suppressor function in GC and it may serve as a potential prognostic biomarker and therapeutic target for GC.
Perceptions on Barriers and Facilitators to Colonoscopy Completion After Abnormal Fecal Immunochemical Test Results in a Safety Net System
Authors: Rachel B. Issaka, Ari Bell-Brown, Cyndy Snyder, Dana L. Atkins, Lisa Chew, Bryan J. Weiner, Lisa Strate, John M. Inadomi, Scott D. Ramsey
Journal: JAMA Network Open (2021)

The effectiveness of stool-based colorectal cancer (CRC) screening, including fecal immunochemical tests (FITs), relies on colonoscopy completion among patients with abnormal results, but in safety net systems and federally qualified health centers, in which FIT is frequently used, colonoscopy completion within 1 year of an abnormal result rarely exceeds 50%. Clinician-identified factors in follow-up of abnormal FIT results are understudied and could lead to more effective interventions to address this issue.To describe clinician-identified barriers and facilitators to colonoscopy completion among patients with abnormal FIT results in a safety net health care system.This qualitative study was conducted using semistructured key informant interviews with primary care physicians (PCPs) and staff members in a large safety net health care system in Washington state. Eligible clinicians were recruited through all-staff meetings and clinic medical directors. Interviews were conducted from February to December 2020 through face-to-face interactions or digital meeting platforms. Interview transcripts were analyzed deductively and inductively using a content analysis approach. Data were analyzed from September through December 2020.Barriers and facilitators to colonoscopy completion after an abnormal FIT result were identified by PCPs and staff members.Among 21 participants, there were 10 PCPs and 11 staff members; 20 participants provided demographic information. The median (interquartile range) age was 38.5 (33.0-51.5) years, 17 (85.0%) were women, and 9 participants (45.0%) spent more than 75% of their working time engaging in patient care. All participants identified social determinants of health, organizational factors, and patient cognitive factors as barriers to colonoscopy completion. Participants suggested that existing resources that addressed these factors facilitated colonoscopy completion but were insufficient to meet national follow-up colonoscopy goals.In this qualitative study, responses of interviewed PCPs and staff members suggested that the barriers to colonoscopy completion in a safety net health system may be modifiable. These findings suggest that interventions to improve follow-up of abnormal FIT results should be informed by clinician-identified factors to address multilevel challenges to colonoscopy completion.
Biomarker Analysis of the Phase III NALA Study of Neratinib + Capecitabine versus Lapatinib + Capecitabine in Patients with Previously Treated Metastatic Breast Cancer
Authors: Cristina Saura, Judit Matito, Mafalda Oliveira, Hans Wildiers, Adam M. Brufksy, Simon H. Waters, Sara A. Hurvitz, Beverly Moy, Sung-Bae Kim, William J. Gradishar, Geraldo Silva Queiroz, Eduardo Cronemberger, Gerald J. Wallweber, Judith Bebchuk, Kiana Keyvanjah, Alshad S. Lalani, Richard Bryce, Ana Vivancos, Lisa D. Eli, Suzette Delaloge
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Neratinib plus capecitabine (N+C) demonstrated significant progression-free survival (PFS) benefit in NALA (NCT01808573), a randomized phase III trial comparing N+C with lapatinib + capecitabine (L+C) in 621 patients with HER2-positive (HER2+) metastatic breast cancer (MBC) who had received ≥2 prior HER2-directed regimens in the metastatic setting. We evaluated correlations between exploratory biomarkers and PFS. Patients and Methods: Somatic mutations were evaluated by next-generation sequencing on primary or metastatic samples. HER2 protein expression was evaluated by central IHC, H-score, and VeraTag/HERmark. p95 expression (truncated HER2) was measured by VeraTag. HRs were estimated using unstratified Cox proportional hazards models. Results: Four hundred and twenty samples had successful sequencing: 34.0% had PIK3CA mutations and 5.5% had HER2 (ERBB2) mutations. In the combined patient populations, PIK3CA mutations trended toward shorter PFS [wild-type vs. mutant, HR = 0.81; 95% confidence interval (CI), 0.64–1.03], whereas HER2 mutations trended toward longer PFS [HR = 1.69 (95% CI, 0.97–3.29)]. Higher HER2 protein expression was associated with longer PFS [IHC 3+ vs. 2+, HR = 0.67 (0.54–0.82); H-score ≥240 versus &amp;lt;240, HR = 0.77 (0.63–0.93); HERmark positive vs. negative, HR = 0.76 (0.59–0.98)]. Patients whose tumors had higher HER2 protein expression (any method) derived an increased benefit from N+C compared with L+C [IHC 3+, HR = 0.64 (0.51–0.81); H-score ≥ 240, HR = 0.54 (0.41–0.72); HERmark positive, HR = 0.65 (0.50–0.84)], as did patients with high p95 [p95 ≥2.8 relative fluorescence (RF)/mm2, HR = 0.66 (0.50–0.86) vs. p95 &amp;lt; 2.8 RF/mm2, HR = 0.91 (0.61–1.36)]. Conclusions: PIK3CA mutations were associated with shorter PFS whereas higher HER2 expression was associated with longer PFS. Higher HER2 protein expression was also associated with a greater benefit for N+C compared with L+C.
Efficacy and safety of switching to dolutegravir plus lamivudine versus continuing triple antiretroviral therapy in virologically suppressed adults with HIV at 48 weeks (DOLAM): a randomised non-inferiority trial
Authors: Jhon Rojas, Elisa de Lazzari, Eugenia Negredo, Pere Domingo, Juan Tiraboschi, Esteve Ribera, Nadia Abdulghani, Jordi Puig, Maria G Mateo, Daniel Podzamczer, Maria M Gutierrez, Roger Paredes, Bonaventura Clotet, Jose M Gatell, Jose L Blanco, Esteban Martínez
Journal: The Lancet HIV (2021)
만성 B 형 간염환자에서 B 형 간염 바이러스 유전자형의 빈도
Authors: 조일현(Il Hyun Cho), 송정엽(Jung Youp Song), 김덕기(Deog Ki Kim), 임홍석(Hong Seok Lim), 신승수(Seung Soo Sheen), 김원석(Won Seok Kim), 이기명(Kee Myeong Lee), 함기백(Ki Baik Hahm), 김진홍(Jin Hong Kim), 조성원(Sung Won Cho)
Journal: Clinical and Molecular Hepatology (2001)

Background / Aims : Hepatitis B virus(HBV) genotype have distinct geographic distributions. The possibility of pathogenic difference among HBV genotypes has been suggested. We investigated the prevalence of HBV genotypes in Korea and the association between distinct genotypes and clinical outcomes. Methods : Using a PCR-RFLP and sequencing, HBV genotypes were determined in 136 patients with chronic type B hepatitis. Results : The genotype C was detected in 131 patients(96.3%), and other 5 patients(3.7%) had genotype B. There were no significant differences in sex, age, disease duration, ALT level, HBeAg/anti-HBe status, or HBeAg loss between genotype B and C patients. Conclusion : These results suggest that almost all patients with chronic hepatitis B are infected with genotype C. Genotypes do not influence the outcome of chronic hepatitis B patients in Korea.
28456 Efficacy and tolerability of oral antibiotics for cetuximab-induced acneiform eruption
Authors: YoungHwan Choi, Jaihee Bae Dong Min Shin, Donghwi Jang, Dokyoung Yoon, Jongeun Lee, Se Jin Oh, Hyun Je Kim, Ji-Hye Park
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 15934: Automatic Segmentation of Left Ventricular Myocardium and Scar From Lge-cmr Images Utilizing Deep Learning With Weighted Categorical Cross Entropy Loss Function Weight Initialization
Authors: Vivek P Jani, Mohammad R Ostovaneh, Ela Chamera, Joao A Lima, Bharath Ambale-Venkatesh
Journal: Circulation (2019)

Introduction: Myocardial fibrosis is associated with worsening left ventricular (LV) systolic function and has been found to increase with age. Clinical assessment of myocardial replacement fibrosi...
Review of Surgical Therapy of Adrenal Tumors in Guidelines From the German Association of Endocrine Surgeons
Authors: Kimberly M. Ramonell, Jessica Fazendin, Brenessa Lindeman
Journal: JAMA Surgery (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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Surgery journal
Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update
Authors: Andrew M. Veitch, Franco Radaelli, Raza Alikhan, Jean-Marc Dumonceau, Diane Eaton, Jo Jerrome, Will Lester, David Nylander, Mo Thoufeeq, Geoffroy Vanbiervliet, James R. Wilkinson, Jeanin E. van Hooft
Journal: Endoscopy (2021)

Abstract This is a collaboration between the British Society of Gastroenterology (BSG) and the European Society of Gastrointestinal Endoscopy (ESGE), and is a scheduled update of their 2016 guideline on endoscopy in patients on antiplatelet or anticoagulant therapy. The guideline development committee included representatives from the British Society of Haematology, the British Cardiovascular Intervention Society, and two patient representatives from the charities Anticoagulation UK and Thrombosis UK, as well as gastroenterologists. The process conformed to AGREE II principles, and the quality of evidence and strength of recommendations were derived using GRADE methodology. Prior to submission for publication, consultation was made with all member societies of ESGE, including BSG. Evidence-based revisions have been made to the risk categories for endoscopic procedures, and to the categories for risks of thrombosis. In particular a more detailed risk analysis for atrial fibrillation has been employed, and the recommendations for direct oral anticoagulants have been strengthened in light of trial data published since the previous version. A section has been added on the management of patients presenting with acute GI haemorrhage. Important patient considerations are highlighted. Recommendations are based on the risk balance between thrombosis and haemorrhage in given situations.
Teaching Careers Clinic
Authors: Grace George, Abhishek Srivastava, Holly Melvin, Uchechukwu Okwu
Journal: BMJ (2021)

Near-peer teaching has long been a key part of medical education. Over the past 18 months, those running these sessions have had to step up to master the relevant technology and keep their peers engaged from a distance. <b>BMJ Student</b> spoke to students and junior doctors across the country about their experiences
Midcareer Medical School Research Faculty Perspectives on Vitality and Professionalism During the COVID-19 Pandemic
Authors: Linda H. Pololi, Vasilia Vasiliou, Kimberly Bloom-Feshbach
Journal: JAMA Network Open (2021)

As medical faculty have central roles during the COVID-19 pandemic, it is important to study the pandemic's association with the vitality and careers of medical school faculty.To examine how the COVID-19 pandemic affected midcareer research faculty in academic medicine.This qualitative study included medical school faculty who participated in the C-Change Mentoring and Leadership Institute. All US medical school faculty recipients of recent National Institutes of Health (NIH) RO1, RO1-equivalent, and K awards were invited to apply to the institute. The 99 applicants who met inclusion criteria were stratified by degree (MD or MD/PhD vs PhD), gender, and race/ethnicity. Enrollment was offered to applicants randomly selected for 40 spots, demographically balanced by sex, underrepresented in medicine minority (URMM) status, and degree. In April 2020, an inquiry was emailed to faculty enrolled in the institute requesting responses to questions about meaning in work, career choice, and values. A qualitative analysis of narrative data responses, using grounded theory, was undertaken to determine key themes. This study is part of a NIH-funded randomized trial to test the efficacy of a group peer mentoring course for midcareer faculty and study the course's mechanisms of action.Key themes in data.Of 40 enrolled participants, 39 responded to the inquiry, for a response rate of 97%. The analytic sample included 39 faculty members; 19 (47%) were women, 20 (53%) identified as URMM, and 20 (53%) had an MD or MD with PhD vs 19 (47%) with PhD degrees. Key themes in the data that emerged describing faculty lived experience of the pandemic included increased meaningfulness of work; professionalism and moral responsibility; enhanced relationships with colleagues; reassertion of career choice; disrupted research; impact on clinical work; attention to health disparities, social justice and advocacy; increased family responsibilities; psychological stress; and focus on leadership.During the pandemic, diverse PhD and physician investigators reported increased meaningfulness in work and professionalism and enhanced relationships, all intrinsic motivators associated with vitality. Working during the pandemic appears to have produced intrinsic rewards positively associated with vitality, in addition to adverse mental health effects. These findings have implications for combatting burnout and retaining investigators in the future.
The neurobiology of non-coding RNAs and Alzheimer’s disease pathogenesis: Pathways, mechanisms and translational opportunities
Authors: Elisabetta Lauretti, Konrad Dabrowski, Domenico Praticò
Journal: Ageing Research Reviews (2021)

In the past two decades, advances in sequencing technology and analysis of the human and mouse genome have led to the discovery of many non-protein-coding RNAs (ncRNAs) including: microRNA, small-interfering RNAs, piwi-associated small RNAs, transfer RNA-derived small RNAs, long-non-coding RNAs and circular RNAs. Compared with healthy controls, levels of some ncRNAs are significantly altered in the central nervous system and blood of patients affected by neurodegenerative disorders like Alzheimer's disease (AD). Although the mechanisms are still not fully elucidated, studies have revealed that these highly conserved ncRNAs are important modulators of gene expression, amyloid-β production, tau phosphorylation, inflammation, synaptic plasticity and neuronal survival, all features considered central to AD pathogenesis. Despite considerable difficulties due to their large heterogeneity, and the complexity of their regulatory pathways, research in this rapidly growing field suggests that ncRNAs hold great potential as biomarkers and therapeutic targets against AD. Herein, we summarize the current knowledge regarding the neurobiology of ncRNA in the context of AD pathophysiology.
Infection courses, virological features and IFN-α responses of HBV genotypes in cell culture and animal models
Authors: Min Zhang, Zhensheng Zhang, Michio Imamura, Mitsutaka Osawa, Yuji Teraoka, Jason Piotrowski, Yuji Ishida, Vitina Sozzi, Peter A. Revill, Takeshi Saito, Kazuaki Chayama, T Jake Liang
Journal: Journal of Hepatology (2021)
Human leukocyte antigen class II-based immune risk model for recurrence evaluation in stage I–III small cell lung cancer
Authors: Peixin Chen, Lishu Zhao, Hao Wang, Liping Zhang, Wei Zhang, Jun Zhu, Jia Yu, Sha Zhao, Wei Li, Chenglong Sun, Chunyan Wu, Yayi He, Caicun Zhou
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immunotherapy has revolutionized therapeutic patterns of small cell lung cancer (SCLC). Human leukocyte antigen class II (HLA class II) is related to antitumor immunity. However, the implications of HLA class II in SCLC remain incompletely understood. Materials and methods We investigated the expression patterns of HLA class II on tumor cells and tumor-infiltrating lymphocytes (TILs) by immunohistochemistry staining and its association with clinical parameters, immune markers, and recurrence-free survival (RFS) in 102 patients with stage I–III SCLC with radical surgery. Additionally, an HLA class II-based immune risk model was established by least absolute shrinkage and selection operator regression. With bioinformatics methods, we investigated HLA class II-related enrichment pathways and immune infiltration landscape in SCLC. Results HLA class II on tumor cells and TILs was positively expressed in 9 (8.8%) and 45 (44.1%) patients with SCLC, respectively. HLA class II on TILs was negatively associated with lymph node metastasis and positively correlated with programmed death-ligand 1 (PD-L1) on TILs (p&lt;0.001) and multiple immune markers (CD3, CD4, CD8, FOXP3; p&lt;0.001). Lymph node metastasis (OR 0.314, 95% CI 0.118 to 0.838, p=0.021) and PD-L1 on TILs (OR 3.233, 95% CI 1.051 to 9.95, p=0.041) were independent predictive factors of HLA class II on TILs. HLA class II positivity on TILs prompted a longer RFS (40.2 months, 95% CI 31.7 to 48.7 vs 28.8 months, 95% CI 21.4 to 36.3, p=0.014). HLA class II on TILs, PD-L1 on TILs, CD4, and FOXP3 were enrolled in the immune risk model, which categorized patients into high-risk and low-risk groups and had better power for predicting the recurrence than tumor stage. Pathway enrichment analyses showed that patients with high HLA class II expression demonstrated signatures of transmembrane transportation, channel activity, and neuroactive ligand–receptor interaction. High-risk SCLC patients had a higher proportion of T follicular helper cells (p=0.034) and a lower proportion of activated memory CD4-positive T cells (p=0.040) and resting dendritic cells (p=0.045) versus low-risk patients. Conclusions HLA class II plays a crucial role in tumor immune microenvironment and recurrence prediction. This work demonstrates the prognostic and clinical values of HLA class II in patients with SCLC.
Lipocalin allergens
Authors: Tuomas Virtanen
Journal: Allergy (2001)

Most animal‐derived major allergens causing respiratory sensitization belong to the family of proteins called lipocalins. Their sequential identity varies but the three‐dimensional structure is conserved. They are present in body fluids and secretions. Several lipocalins are able to bind and transport small hydrophobic ligands like retinol. The immunological characteristics of lipocalin allergens are poorly known. Cow dust‐derived allergen, Bos d2, which is a potent inducer of IgE production, was observed to induce the weak proliferative responses of peripheral blood mononuclear cells of asthmatic patients upon stimulation in vitro . The responses were Th2‐deviated and directed to a few epitopes in Bos d2. One of the epitopes, situated adjacent to a structurally conserved region of lipocalins, was recognized by the T cells of all patients. Computer predictions suggested that human endogenous lipocalins may contain epitopes in the corresponding region. We have proposed that the allergenicity of lipocalins may be associated with the adaptation of the immune system to the presence of endogenous lipocalins.
Poor T-cell receptor β repertoire diversity early posttransplant for severe combined immunodeficiency predicts failure of immune reconstitution
Authors: Ottavia M. Delmonte, Riccardo Castagnoli, Jason Yu, Christopher C. Dvorak, Morton J. Cowan, Blachy J. Dávila Saldaña, Suk See De Ravin, Ewelina Mamcarz, Catherine K. Chang, Stephen R. Daley, Linda M. Griffith, Luigi D. Notarangelo, Jennifer M. Puck
Journal: Journal of Allergy and Clinical Immunology (2021)

Development of a diverse T-cell receptor β (TRB) repertoire is associated with immune recovery following hematopoietic cell transplantation (HCT) for severe combined immunodeficiency (SCID). High-throughput sequencing of the TRB repertoire allows evaluation of clonotype dynamics during immune reconstitution.