tbuckley/cabot-search huggingface dataset:
Erythrocyte n-6 Polyunsaturated Fatty Acids, Gut Microbiota, and Incident Type 2 Diabetes: A Prospective Cohort Study
Authors: Zelei Miao, Jie-sheng Lin, Yingying Mao, Geng-dong Chen, Fang-fang Zeng, Hong-li Dong, Zengliang Jiang, Jiali Wang, Congmei Xiao, Menglei Shuai, Wanglong Gou, Yuanqing Fu, Fumiaki Imamura, Yu-ming Chen, Ju-Sheng Zheng
Journal: Diabetes Care (2020)

OBJECTIVE To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association. RESEARCH DESIGN AND METHODS We evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (n = 1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes and diversity and composition of gut microbiota. RESULTS Over 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both P &amp;lt; 0.05) during follow-up and significantly associated with microbiota β-diversity (P = 0.002). α-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes (P &amp;lt; 0.05). Seven genera (Butyrivibrio, Blautia, Oscillospira, Odoribacter, S24-7 other, Rikenellaceae other, and Clostridiales other) were enriched in quartile 1 of GLA and in participants without type 2 diabetes. CONCLUSIONS Relative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology.
A Single-Cell Atlas of the Human Healthy Airways
Authors: Marie Deprez, Laure-Emmanuelle Zaragosi, Marin Truchi, Christophe Becavin, Sandra Ruiz García, Marie-Jeanne Arguel, Magali Plaisant, Virginie Magnone, Kevin Lebrigand, Sophie Abelanet, Frédéric Brau, Agnès Paquet, Dana Pe’er, Charles-Hugo Marquette, Sylvie Leroy, Pascal Barbry
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: The respiratory tract constitutes an elaborate line of defense that is based on a unique cellular ecosystem.Objectives: We aimed to investigate cell population distributions and transcriptional changes along the airways by using single-cell RNA profiling.Methods: We have explored the cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling. A total of 77,969 cells were collected at 35 distinct locations, from the nose to the 12th division of the airway tree.Measurements and Main Results: The resulting atlas is composed of a high percentage of epithelial cells (89.1%) but also immune (6.2%) and stromal (4.7%) cells with distinct cellular proportions in different regions of the airways. It reveals differential gene expression between identical cell types (suprabasal, secretory, and multiciliated cells) from the nose (MUC4, PI3, SIX3) and tracheobronchial (SCGB1A1, TFF3) airways. By contrast, cell-type-specific gene expression is stable across all tracheobronchial samples. Our atlas improves the description of ionocytes, pulmonary neuroendocrine cells, and brush cells and identifies a related population of NREP-positive cells. We also report the association of KRT13 with dividing cells that are reminiscent of previously described mouse "hillock" cells and with squamous cells expressing SCEL and SPRR1A/B.Conclusions: Robust characterization of a single-cell cohort in healthy airways establishes a valuable resource for future investigations. The precise description of the continuum existing from the nasal epithelium to successive divisions of the airways and the stable gene expression profile of these regions better defines conditions under which relevant tracheobronchial proxies of human respiratory diseases can be developed.
Cardiovascular Disease Predicts Structural and Functional Progression in Early Glaucoma
Authors: Henry Marshall, Sean Mullany, Ayub Qassim, Owen Siggs, Mark Hassall, Bronwyn Ridge, Thi Nguyen, Mona Awadalla, Nicholas H. Andrew, Paul R. Healey, Ashish Agar, Anna Galanopoulos, Alex W. Hewitt, Stuart MacGregor, Stuart L. Graham, Richard Mills, Angela Shulz, John Landers, Robert J. Casson, Jamie E. Craig
Journal: Ophthalmology (2020)
Soft Microenvironments Induce Chemoresistance by Increasing Autophagy Downstream of Integrin-Linked Kinase
Authors: Alişya A. Anlaş, Celeste M. Nelson
Journal: Cancer Research (2020)

Breast cancer relapse can develop over the course of years as a result of dormant cancer cells that disseminate to secondary sites. These dormant cells are often resistant to conventional hormone and chemotherapy. Although recurrence is the main cause of death from cancer, microenvironmental factors that may influence resistance to therapy and duration of dormancy are largely unknown. Breast cancer relapse is often detected in tissues that are softer than the normal mammary gland or the primary breast tumor, such as bone marrow, brain, and lung. We therefore explored how stiffness of the microenvironment at secondary sites regulates tumor dormancy and the response of breast cancer cells to hormone and chemotherapy. In soft microenvironments reminiscent of metastatic sites, breast cancer cells were more resistant to the estrogen receptor modulator tamoxifen as a result of increased autophagy and decreased expression of estrogen receptor-α. Consistently, pharmacologic inhibition or genetic downregulation of autophagy increased the response of breast cancer cells to tamoxifen on soft substrata. In addition, autophagy was decreased downstream of integrin-linked kinase on stiff substrata. Altogether, our data show that tissue mechanics regulates therapeutic outcome and long-term survival of breast cancer cells by influencing autophagy. SIGNIFICANCE: These findings characterize the persistence of dormant cells at metastatic sites, where soft microenvironments downregulate estrogen receptor expression and upregulate autophagy, thereby promoting therapy resistance in breast cancer cells. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/19/4103/F1.large.jpg.
Strain Analysis Using Feature-Tracking CMR to Detect LV Systolic Dysfunction in Myocardial Iron Overload Disease
Authors: Enver Tahir, Roland Fischer, Regine Grosse, Philipp Tavrovski, Jin Yamamura, Jitka Starekova, Gunnar K. Lund, Peter Bannas, Joachim Graessner, Ulf K. Radunski, Kai Muellerleile, Gerhard Adam, Bjoern P. Schoennagel
Journal: JACC. Cardiovascular imaging (2020)
Determining factors in relation to lymphovascular characteristics and anastomotic configuration in supermicrosurgical lymphaticovenous anastomosis – A retrospective cohort study
Authors: Po-Lun Tsai, Shao-Chun Wu, Wei-Che Lin, Daisuke Mito, Min-Hsien Chiang, Ching-Hua Hsieh, Johnson Chia-Shen Yang
Journal: International Journal of Surgery (2020)

Supermicrosurgical lymphaticovenous anastomosis (LVA) can be performed in different configuration such as end-to-end (LVEEA), end-to-side (LVESA), and side-to-end (LVSEA). Each configuration has its own advantages and disadvantages. However, it has remained ambiguous as to which anastomotic o configuration to choose. The aim of this study is to analyze and compare the relative sizes of lymphatic vessel (LV) and recipient vein (RV), in attempts to provide the basis for proper selections of the anastomotic configuration.From March 2016 to October 2018, 100 lymphedema patients with 103 lymphedematous lower limbs (stage I-III) were included. All patients underwent supermicrosurgical LVA. Demographic data and intraoperative findings, including the number and size of the LV/RV, the size discrepancies, and the numbers of LVA performed were recorded. The severity of LVs were classified based on the lymphosclerosis classification (s0, s1, s2, and s3). One-way ANOVA test and post hoc analysis with Bonferroni's correction were performed for size discrepancy analysis.A total 730 LVA were performed with 621 LVs and 468 RVs, averaging 7.1 LVA per limb. Of these, 367 (50.3%) were LVEEA, 333 (45.6%) were LVESA, and 30 (4.1%) were LVSEA. The average LV and RV size was 0.61 ± 0.35 mm and 0.87 ± 0.43 mm, respectively (p < 0.001). The average LV size in different configuration: LVEEA = LVESA < LVSEA (p < 0.001); The average RV size: LVEEA = LVSEA < LVESA (p < 0.001); The size discrepancy: LVESA > LVSEA > LVEEA (p < 0.001).The LVSEA group has more s1 lymphatic vessels as opposed to LVEEA and LVESA (p = 0.004).The size and the comparative discrepancy between the LVs and RVs are the determining factors for proper anastomotic configuration selection during LVA. LVESA was more frequently performed when vessel size discrepancy was larger. The efficacy of each anastomotic configuration has yet to be determined.
COVID-19 Infections and Clinical Outcomes in Patients with Multiple Myeloma in New York City: A Cohort Study from Five Academic Centers
Authors: Malin Hultcrantz, Joshua Richter, Cara A. Rosenbaum, Dhwani Patel, Eric L. Smith, Neha Korde, Sydney X. Lu, Sham Mailankody, Urvi A. Shah, Alexander M. Lesokhin, Hani Hassoun, Carlyn Tan, Francesco Maura, Andriy Derkach, Benjamin Diamond, Adriana Rossi, Roger N. Pearse, Deepu Madduri, Ajai Chari, David Kaminetzky, Marc J. Braunstein, Christian Gordillo, Ran Reshef, Ying Taur, Faith E. Davies, Sundar Jagannath, Ruben Niesvizky, Suzanne Lentzsch, Gareth J. Morgan, Ola Landgren
Journal: Blood Cancer Discovery (2020)

Patients with multiple myeloma have a compromised immune system, due to both the disease and antimyeloma therapies, and may therefore be particularly susceptible to COVID-19. Here, we report outcomes and risk factors for serious disease in patients with multiple myeloma treated at five large academic centers in New York City in the spring of 2020, during which it was a global epicenter of the SARS-CoV-2 pandemic. Of 100 patients with multiple myeloma (male 58%; median age 68) diagnosed with COVID-19, 75 were admitted; of these, 13 patients (17%) were placed on invasive mechanical ventilation, and 22 patients (29%) expired. Of the 25 nonadmitted patients, 4 were asymptomatic. There was a higher risk of adverse outcome (intensive care unit admission, mechanical ventilation, or death) in Hispanics/Latinos (n = 21), OR = 4.7 (95% confidence interval, 1.3-16.7), and African American Blacks (n = 33), OR = 3.5 (1.1-11.5), as compared with White patients (n = 36). Patients who met the adverse combined endpoint had overall higher levels of inflammatory markers and cytokine activation. None of the other studied risk factors were significantly associated (P > 0.05) with adverse outcome: hypertension (n = 56), OR = 2.2 (0.9-5.4); diabetes (n = 18), OR = 0.9 (0.3-2.9); age >65 years (n = 63), OR = 1.8 (0.7-4.6); high-dose melphalan with autologous stem cell transplant <12 months (n = 7), OR = 0.9 (0.2-5.4); and immunoglobulin G <650 mg/dL (n = 42), OR = 0.9 (0.3-2.2). In this largest cohort to date of patients with multiple myeloma and COVID-19, we found the case fatality rate to be 29% among hospitalized patients and that race/ethnicity was the most significant risk factor for adverse outcome.Patients with multiple myeloma are immunocompromised, raising the question whether they are at higher risk of severe COVID-19 disease. In this large case series on COVID-19 in patients with multiple myeloma, we report 29% mortality rates among hospitalized patients and identify race/ethnicity as the most significant risk factor for severe outcome.See related commentary by Munshi and Anderson, p. 218. This article is highlighted in the In This Issue feature, p. 215.
Reply to Zhai and Bi
Authors: Hui Luo, Shanshan Shen, Qiang Cai
Journal: Endoscopy (2020)

See also:Gastric peroral endoscopic pyloromyotomy versus gastric electrical stimulation in the treatment of refractory gastroparesis: methodologic issuesEndoscopy 2020; 52(08): 711-711DOI: 10.1055/a-1176-1399
LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/β-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes
Authors: Cefan Zhou, Changhua Yi, Yongxiang Yi, Wenying Qin, Yanan Yan, Xueying Dong, Xuewen Zhang, Yuan Huang, Rui Zhang, Jie Wei, Declan William Ali, Marek Michalak, Xing-Zhen Chen, Jingfeng Tang
Journal: Molecular Cancer (2020)

Abstract Background Pancreatic cancer is one of the most lethal malignancies and has an extremely poor diagnosis and prognosis. The development of resistance to gemcitabine is still a major challenge. The long noncoding RNA PVT1 was reported to be involved in carcinogenesis and chemoresistance; however, the mechanism by which PVT1 regulates the sensitivity of pancreatic cancer to gemcitabine remains poorly understood. Methods The viability of pancreatic cancer cells was assessed by MTT assay in vitro and xenograft tumor formation assay in vivo. The expression levels of PVT1 and miR-619-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting analysis and qRT-PCR were performed to assess the protein and mRNA levels of Pygo2 and ATG14, respectively. Autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of PVT1 were further investigated by gain- and loss-of-function assays in vitro. Results In the present study, we demonstrated that PVT1 was up-regulated in gemcitabine-resistant pancreatic cancer cell lines. Gain- and loss-of-function assays revealed that PVT1 impaired sensitivity to gemcitabine in vitro and in vivo. We further found that PVT1 up-regulated the expression of both Pygo2 and ATG14 and thus regulated Wnt/β-catenin signaling and autophagic activity to overcome gemcitabine resistance through sponging miR-619-5p. Moreover, we discovered three TCF/LEF binding elements (TBEs) in the promoter region of PVT1, and activation of Wnt/β-catenin signaling mediated by the up-regulation of Pygo2 increased PVT1 expression by direct binding to the TBE region. Furthermore, PVT1 was discovered to interact with ATG14, thus promoting assembly of the autophagy specific complex I (PtdIns3K-C1) and ATG14-dependent class III PtdIns3K activity. Conclusions These data indicate that PVT1 plays a critical role in the sensitivity of pancreatic cancer to gemcitabine and highlight its potential as a valuable target for pancreatic cancer therapy.
“Star” miR-34a and CXCR4 antagonist based nanoplex for binary cooperative migration treatment against metastatic breast cancer
Authors: Xue Yang, Fang Gao, Wenan Zhang, Huipeng Li, Xinzhi Huang, Jiajia Wei, Jiayi Bian, Ying Yang, Chenggen Qian, Minjie Sun
Journal: Journal of Controlled Release (2020)
Reply to Dr. Lo
Authors: Carlos Robles-Medranda, Roberto Oleas, Manuel Valero, Miguel Puga-Tejada, Jorge Baquerizo-Burgos, Jesenia Ospina, Hannah Pitanga-Lukashok
Journal: Endoscopy (2020)

See also:Should we pursue high obliteration rate or high hemostatic rate in the therapy of gastric varices?Endoscopy 2020; 52(08): 709-709DOI: 10.1055/a-1167-8274
Response to: ‘Can telerheumatology improve rheumatic and musculoskeletal disease service delivery in sub-Saharan Africa?’ by Akpabio<i>et al</i>
Authors: Francesco Caso, Antonio del Puente, Nicolò Girolimetto, Marco Tasso, Corrado Caso, Raffaele Scarpa, Luisa Costa
Journal: Annals of the Rheumatic Diseases (2020)

The letter by Akpabio and colleagues1 raises an important question and describes an interesting scenario related to their geographical area. However, this scenario can easily be applied to several other experiences. In fact, the situation described by Akpabio and colleagues1 with regard to rheumatological centres being located in great urban areas as compared with the shortage of these specialists within their periphery is quite frequent.

The impact of the COVID-19 pandemic on everyday practice gives us an opportunity to speed up the development of the process already known as telemedicine, which may be an attempt to correct some of these disparities.

The authors of the letter indicate many and relevant suggestions which we find very adequate and deserve immediate consideration. In particular, during this phase, we feel that it is necessary to manage this development. What can this mean? First of all, it should be outlined that telemedicine does not mean reduced need for specialists. Each one of us has experienced the burden of this approach. Telemedicine, as compared with the traditional inperson medical consultation, means greater effort in terms of more complex visit planning, of time spent, of organisation (detailed patient charts …
The Cost of Technology
Authors: Elizabeth Toll
Journal: JAMA (2012)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Comparative epidemiology and factors associated with major healthcare-associated methicillin-resistant Staphylococcus aureus clones among interconnected acute-, intermediate- and long-term healthcare facilities in Singapore
Authors: Angela Chow, Htet Lin Htun, Pei-Yun Hon, Brenda Ang, Kala Kanagasabai, Jocelyn Koh, Matthew T.G. Holden, Li-Yang Hsu
Journal: Clinical Microbiology and Infection (2020)
Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities
Authors: Marcus R. Kelly, Kaja Kostyrko, Kyuho Han, Nancie A. Mooney, Edwin E. Jeng, Kaitlyn Spees, Phuong T. Dinh, Keene L. Abbott, Dana M. Gwinn, E. Alejandro Sweet-Cordero, Michael C. Bassik, Peter K. Jackson
Journal: Cancer Discovery (2020)

Abstract Activating mutations in RAS GTPases drive many cancers, but limited understanding of less-studied RAS interactors, and of the specific roles of different RAS interactor paralogs, continues to limit target discovery. We developed a multistage discovery and screening process to systematically identify genes conferring RAS-related susceptibilities in lung adenocarcinoma. Using affinity purification mass spectrometry, we generated a protein–protein interaction map of RAS interactors and pathway components containing hundreds of interactions. From this network, we constructed a CRISPR dual knockout library targeting 119 RAS-related genes that we screened for KRAS-dependent genetic interactions (GI). This approach identified new RAS effectors, including the adhesion controller RADIL and the endocytosis regulator RIN1, and &amp;gt;250 synthetic lethal GIs, including a potent KRAS-dependent interaction between RAP1GDS1 and RHOA. Many GIs link specific paralogs within and between gene families. These findings illustrate the power of multiomic approaches to uncover synthetic lethal combinations specific for hitherto untreatable cancer genotypes. Significance: We establish a deep network of protein–protein and genetic interactions in the RAS pathway. Many interactions validated here demonstrate important specificities and redundancies among paralogous RAS regulators and effectors. By comparing synthetic lethal interactions across KRAS-dependent and KRAS-independent cell lines, we identify several new combination therapy targets for RAS-driven cancers. This article is highlighted in the In This Issue feature, p. 1775
AB0729 ASSOCIATIONS BETWEEN CARDIAC CONDUCTION AND DISEASE CHARACTERISTICS IN AXIAL SPONDYLOARTHRITIS
Authors: S. S. Zhao, N. L. Harrison, J. Ang, N. Goodson
Journal: Annals of the Rheumatic Diseases (2020)

Background: Cardiac conduction defects are well-documented in axial spondyloarthritis. However, historical literature (many from an era when axSpA was less well managed compared to modern day) include patients with advanced disease that may explain their high prevalence. Many recent studies reply on administrative codes that may under-report conduction defects. Thorough examination of ECG measurements and axSpA characteristics are scarce. Objectives: To describe a range of cardiac conduction measurements in axSpA and their association with disease characteristics. Methods: We conducted a single-centre cross-sectional study of consecutive patients meeting the ASAS axial SpA criteria in Liverpool, UK. Patients were excluded if they had a known/symptomatic conduction defect. Disease assessment included BASDAI, spinal pain, BASFI, CRP, ESR, HLA-B27, BMI, the presence of extra-articular manifestations (uveitis, psoriasis, IBD) and use of NSAIDs and TNFi. Each patient underwent a 12-lead ECG (GE healthcare; MAC2000) to obtain: PR (atrio-ventricular conduction), QRS (ventricular depolarization) and QTc (ventricular de- and repolarization) intervals in milliseconds (ms). QTc was corrected for heart rate using Bazett’s formula. Prolonged PR interval was defined as &gt;200ms, prolonged QRS as &gt;100ms and prolonged QTc as &gt;440ms in men and &gt;460ms in women. QT dispersion has been shown to predict a range of cardiac outcomes; we measured this as the difference between the longest and shortest QT in two consecutive cardiac cycles. Associations between patient characteristics and ECG measurements were assessed using univariable linear or logistic regression. Bonferroni correction was applied for multiple comparisons. Results: 163 patients underwent ECG testing: mean age 52 (SD14) years, mean symptom duration 10 years (SD 9.6), 79% male and 74% HLA-B27 positive (among 78 tested). 1 patient had Wolf-Parkinson-White (accessory pathway). Summary of the 4 measurements are shown in Table 1. None of these 4 ECG measures were associated with age, symptom duration, gender, BMI, disease severity (BASDAI, spinal pain, BASFI and log transformed CRP/ESR), HLA-B27, EAMs or NSAIDs/TNFi. Conclusion: Conduction defects were rare in this group of axSpA patients. Only 3% had prolonged AV conduction, which is no higher than general population estimates [1]. The prognostic value of these conduction defects and QT dispersion requires further study. References: [1]van der Ende et al. Population-based values and abnormalities of the electrocardiogram in the general Dutch population: The LifeLines Cohort Study. Clin Cardiol. 2017; 40(10): 865–872 Table 1. ECG measurements in 163 axSpA patients. Mean (SD) n (%) PR, ms 149 (24) PR&gt;200ms 5 (3%) QRS, ms 91 (15) QRS&gt;100ms 25 (16%) QTc, ms 385 (32) QTc prolonged 6 (4%) QT dispersion, ms 43 (21) QT dispersion &gt;50ms 41 (26%) Disclosure of Interests: None declared