tbuckley/cabot-search huggingface dataset:
Of mice, men and microbes: the impact of the microbiome on immune responses
Authors: David S Pisetsky
Journal: Annals of the Rheumatic Diseases (2020)

Rheumatic diseases are a diverse group of conditions in which the host and the environment interact to drive inflammation and autoreactivity. In this dyadic model, the strongest environmental influence is infection, with bacteria and viruses likely to trigger disease in a host predisposed by genetics; infection can either non-specifically stimulate the immune system to heighten the propensity for autoreactivity or specifically stimulate B and T cell autoreactivity by molecular mimicry. For many years, this venerable model has powerfully influenced the design of experiments in both the human and animal systems as well as their interpretation.

While the ‘one organism, one disease’ mechanism may pertain to at least some rheumatic diseases (eg, rheumatic fever following Streptococcus infection), for most other conditions, pathogenesis is more complicated, at least in part because one of the major sources of foreign organisms—bacteria, viruses, fungi and others—resides in or around the host as the microbiome. The microbiome is a huge biomass, with the mammalian host containing as many prokaryotic as eukaryotic cells; the number is in the trillions. Many studies have therefore addressed whether the microbiome can influence the occurrence of not only rheumatic diseases but also metabolic, cardiovascular and neuropsychiatric conditions, among others.1 2 

As shown recently in a provocative study by Rosshart et al 3, the host and the environment are not truly distinct, with data presented suggesting that the microbiome and the host have coevolved to produce an optimal balance of positive and negative effects. In their drive to study disease in a more reductionist way, investigators have likely disrupted this balance by breeding genetically inbred mice in very clean environments. Although a clean environment would seemingly reduce potential ‘contaminating’ influences of infection, it is very much unnatural and leads to a microbiome that itself can alter host responses and skew …
A prospective cohort study of condensed low-dose total skin electron beam therapy for mycosis fungoides: Reduction of disease burden and improvement in quality of life
Authors: Andrew Song, Ashley Gochoco, Tingting Zhan, Joya Sahu, Onder Alpdogan, Pierluigi Porcu, Neda Nikbakht, Wenyin Shi
Journal: Journal of the American Academy of Dermatology (2020)
CircAST: Full-Length Assembly and Quantification of Alternatively Spliced Isoforms in Circular RNAs
Authors: Jing Wu, Yan Li, Cheng Wang, Yiqiang Cui, Tianyi Xu, Chang Wang, Xiao Wang, Jiahao Sha, Bin Jiang, Kai Wang, Zhibin Hu, Xuejiang Guo, Xiaofeng Song
Journal: Genomics Proteomics & Bioinformatics (2019)

Circular RNAs (circRNAs), covalently closed continuous RNA loops, are generated from cognate linear RNAs through back splicing events, and alternative splicing events may generate different circRNA isoforms at the same locus. However, the challenges of reconstruction and quantification of alternatively spliced full-length circRNAs remain unresolved. On the basis of the internal structural characteristics of circRNAs, we developed CircAST, a tool to assemble alternatively spliced circRNA transcripts and estimate their expression by using multiple splice graphs. Simulation studies showed that CircAST correctly assembled the full sequences of circRNAs with a sensitivity of 85.63%-94.32% and a precision of 81.96%-87.55%. By assigning reads to specific isoforms, CircAST quantified the expression of circRNA isoforms with correlation coefficients of 0.85-0.99 between theoretical and estimated values. We evaluated CircAST on an in-house mouse testis RNA-seq dataset with RNase R treatment for enriching circRNAs and identified 380 circRNAs with full-length sequences different from those of their corresponding cognate linear RNAs. RT-PCR and Sanger sequencing analyses validated 32 out of 37 randomly selected isoforms, thus further indicating the good performance of CircAST, especially for isoforms with low abundance. We also applied CircAST to published experimental data and observed substantial diversity in circular transcripts across samples, thus suggesting that circRNA expression is highly regulated. CircAST can be accessed freely at https://github.com/xiaofengsong/CircAST.
Mild iron deficiency does not ameliorate the phenotype of a murine erythropoietic protoporphyria model
Authors: Paul J. Schmidt, Monica L. Hollowell, Kevin Fitzgerald, James S. Butler, Mark D. Fleming
Journal: American Journal of Hematology (2020)

Reduced ferrochelatase activity in erythropoietic protoporphyria (EPP) causes the accumulation of protoporphyrin IX (PPIX) leading to acute cutaneous photosensitivity and liver injury. Many EPP patients also have a mild hypochromic, microcytic anemia and iron deficiency. Iron deficiency can lead to decreased PPIX accumulation in another erythropoietic porphyria, congenital erythropoietic porphyria (CEP). Expression of the iron regulatory peptide hepcidin is negatively regulated by the serine protease TMPRSS6. Hepcidin induction by siRNA-mediated inhibition of TMPRSS6 expression reduces iron availability and induces iron deficiency. To interrogate the therapeutic potential of iron deficiency to modify EPP, we treated an ethylnitrosourea-induced mouse model of EPP, Fech m1Pas , with a GalNAc-conjugated Tmprss6 siRNA and PPIX levels, anemia and iron parameters were monitored. The GalNAc-RNAi therapeutic reduces Tmprss6 expression and induces mild iron deficiency in Fech m1Pas animals. However, decreases in erythrocyte PPIX levels and liver PPIX accumulation were not seen. These results indicate short-term induction of iron deficiency, at least in a murine model of EPP, does not lead to decreased PPIX production.
Abstract 189: Time to Awakening in Women Compared to Men After Out-Of-Hospital Cardiac Arrest
Authors: Sarah M Perman, Shelby Shelton, Stacie L Daugherty, Edward Havranek
Journal: Circulation (2019)

Background: Previous studies have shown that comatose survivors of cardiac arrest awaken approximately 3 days after return of spontaneous circulation (ROSC) however, variability in time to awakening is frequently observed. Recent data has shown that women metabolize drugs (sedatives and paralytics) differently than men. It is unknown if there are sex based differences in time to awakening for comatose survivors of cardiac arrest, and if this phenomenon might be affected by differences in withdrawal of life sustaining therapy (WLST). Objective: To determine if comatose women have different times to awakening after resuscitation from cardiac arrest. Methods: We analyzed 327 consecutive charts from a single center registry of all out of hospital cardiac arrest patients who had return of spontaneous circulation but remained comatose, cared for at an urban academic tertiary care hospital. Patient demographic and arrest characteristics were abstracted. We identified day of awakening for comatose survivors by abstracting day when Glasgow coma motor score was 6 as documented in nursing flowsheets. Time to withdrawal of life sustaining therapy was also abstracted for the cohort that did not awaken. Patients were excluded from analysis if they did not awaken or if they died for reasons other than WLST. Results: Twenty-eight percent of patients woke prior to hospital discharge and 43.4% underwent withdrawal of life sustaining therapy. Women made up 39.5% of the total cohort, 40% of the awakened cohort and 41% of the WLST cohort. Women had earlier day of awakening in comparison to men (day 2 (2, 4) vs. day 4 (2,5), p=0.0036), and also earlier time to WLST after ROSC than men (59 hours (26, 131) vs. 64 hours (22, 135), p=NS). Conclusion: In this single center cohort, there was a difference in time to awakening between men and women. How time to awakening might differ between the sexes with guideline concordant time to WLST is unknown. Further research is necessary to explore the role of therapeutic interventions and differing physiology between men and women as it applies to time to awakening.
Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors
Authors: Charles Dolladille, Stephane Ederhy, Stéphane Allouche, Querntin Dupas, Radj Gervais, Jeannick Madelaine, Marion Sassier, Anne-Flore Plane, Francois Comoz, Ariel Aron Cohen, Franck Roland Thuny, Jennifer Cautela, Joachim Alexandre
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immune checkpoint inhibitor (ICI)-associated early cardiac adverse events (CAEs), mostly acute and fulminant myocarditis, have been well characterized and mainly occur during the first 90 days after ICI therapy initiation. ICI-associated late CAEs (occurring after the first 90 days of treatment) have not yet been described. Methods First, we compared characteristics of a cohort involving early (defined as a CAE time to onset (TTO) of &lt;90 days after ICI therapy initiation) and late (defined as a CAE TTO of ≥90 days after ICI therapy initiation) ICI-associated CAE consecutive cases who were referred to three French cardio-oncology units. Second, ICI-associated CAE cases were searched in VigiBase, the WHO global individual case safety report database, and early and late ICI-associated CAEs were compared. Results In the cohort study, compared with early CAE cases (n=19, median TTO of 14 days), late ICI-associated CAE cases (n=19, median TTO of 304 days) exhibited significantly more left ventricular systolic dysfunction (LVSD) and heart failure (HF) and less frequent supraventricular arrhythmias. In VigiBase, compared with early cases (n=437, 73.3%, median TTO 21 days), the late ICI-associated CAE reports (n=159, 26.7%, median TTO 178 days) had significantly more frequent HF (21.1% vs 31.4%, respectively, p=0.01). Early and late ICI-associated CAE cases had similarly high mortality rates (40.0% vs 44.4% in the cohort and 30.0% vs 27.0% in VigiBase, respectively). Conclusions Late CAEs could occur with ICI therapy and were mainly revealed to be HF with LVSD. Trial registration numbers NCT03678337 , NCT03882580 , and NCT03492528 .
意欲消失と表現力の欠乏による陰性症状現象学の解明:DSM-5と精神分裂症調査との関連 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: J W Messinger, F Tremeau, D Antonius, V Prudent, D Malaspina, E Mendelsohn, A D Stanford
Journal: Clinical Psychology Review (2011)
Adhesion to Clinical Practices Guidelines (CPG'S) and Role on Survival for Soft Tissue Sarcoma Patients. Analysis of a Population Based Cohort from Rhone-Alpes Region
Authors: O. Derbel, C. Cropet, P. Meeus, F.-N. Gilly, G. Vaz, P. Thiesse, D. Cellier, D. Vince-Ranchere, J.-Y. Blay, I. Ray-Coquard
Journal: Annals of Oncology (2012)
The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells
Authors: Zhiyuan Hu, Mara Artibani, Abdulkhaliq Alsaadi, Nina Wietek, Matteo Morotti, Tingyan Shi, Zhe Zhong, Laura Santana Gonzalez, Salma El-Sahhar, Eli M. Carrami, Garry Mallett, Yun Feng, Kenta Masuda, Yiyan Zheng, Kay Chong, Stephen Damato, Sunanda Dhar, Leticia Campo, Riccardo Garruto Campanile, Hooman Soleymani majd, Vikram Rai, David Maldonado-Perez, Stephanie Jones, Vincenzo Cerundolo, Tatjana Sauka-Spengler, Christopher Yau, Ahmed Ashour Ahmed
Journal: Cancer Cell (2020)
Conservative versus Interventional Treatment for Spontaneous Pneumothorax
Authors: Simon G.A. Brown, Emma L. Ball, Kyle Perrin, Stephen E. Asha, Irene Braithwaite, Diana Egerton-Warburton, Peter G. Jones, Gerben Keijzers, Frances B. Kinnear, Ben C.H. Kwan, K.V. Lam, Y.C. Gary Lee, Mike Nowitz, Catherine A. Read, Graham Simpson, Julian A. Smith, Quentin A. Summers, Mark Weatherall, Richard Beasley
Journal: New England Journal of Medicine (2020)

Whether conservative management is an acceptable alternative to interventional management for uncomplicated, moderate-to-large primary spontaneous pneumothorax is unknown.In this open-label, multicenter, noninferiority trial, we recruited patients 14 to 50 years of age with a first-known, unilateral, moderate-to-large primary spontaneous pneumothorax. Patients were randomly assigned to immediate interventional management of the pneumothorax (intervention group) or a conservative observational approach (conservative-management group) and were followed for 12 months. The primary outcome was lung reexpansion within 8 weeks.A total of 316 patients underwent randomization (154 patients to the intervention group and 162 to the conservative-management group). In the conservative-management group, 25 patients (15.4%) underwent interventions to manage the pneumothorax, for reasons prespecified in the protocol, and 137 (84.6%) did not undergo interventions. In a complete-case analysis in which data were not available for 23 patients in the intervention group and 37 in the conservative-management group, reexpansion within 8 weeks occurred in 129 of 131 patients (98.5%) with interventional management and in 118 of 125 (94.4%) with conservative management (risk difference, -4.1 percentage points; 95% confidence interval [CI], -8.6 to 0.5; P = 0.02 for noninferiority); the lower boundary of the 95% confidence interval was within the prespecified noninferiority margin of -9 percentage points. In a sensitivity analysis in which all missing data after 56 days were imputed as treatment failure (with reexpansion in 129 of 138 patients [93.5%] in the intervention group and in 118 of 143 [82.5%] in the conservative-management group), the risk difference of -11.0 percentage points (95% CI, -18.4 to -3.5) was outside the prespecified noninferiority margin. Conservative management resulted in a lower risk of serious adverse events or pneumothorax recurrence than interventional management.Although the primary outcome was not statistically robust to conservative assumptions about missing data, the trial provides modest evidence that conservative management of primary spontaneous pneumothorax was noninferior to interventional management, with a lower risk of serious adverse events. (Funded by the Emergency Medicine Foundation and others; PSP Australian New Zealand Clinical Trials Registry number, ACTRN12611000184976.).
HIV Testing Outcomes Among Blacks or African Americans — 50 Local U.S. Jurisdictions Accounting for the Majority of New HIV Diagnoses and Seven States with Disproportionate Occurrences of HIV in Rural Areas, 2017
Authors: Aba D. Essuon, Hui Zhao, Guoshen Wang, Nicoline Collins, Debra Karch, Shubha Rao
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Identifying persons with human immunodeficiency virus (HIV) infection who are unaware of their status and linking them to care are critical steps in achieving viral suppression and reducing the risk for transmitting HIV (1). In 2017, 43% of new diagnoses of HIV infection were among persons who self-identify as blacks or African Americans (blacks) (2), who represent 13% of the U.S. population (3). Fewer blacks, compared with whites, were linked to HIV medical care within 90 days of diagnosis, retained in care, or virally suppressed (4). Ending the HIV Epidemic (EHE) is an initiative intended to reduce new HIV infections by 90% from 2020 to 2030 (5). EHE's Phase 1 is focused on 50 jurisdictions* that accounted for >50% of new diagnoses during 2016-2017 and seven states† with disproportionate HIV prevalence in rural areas (5). The purpose of this analysis was to examine HIV testing outcomes among blacks in high prevalence EHE jurisdictions, using CDC's 2017 National HIV Prevention Program Monitoring and Evaluation data. Blacks accounted for 43.2% of CDC-funded tests and 49.1% of new diagnoses of HIV infection. Seventy-nine percent of blacks with newly diagnosed HIV infection were linked to HIV medical care within 90 days (below the 2010 National HIV/AIDS Strategy goal of 85%), 71.4% interviewed for partner services, and 81.8% referred to prevention services. To achieve the goals of EHE, HIV prevention programs should focus on locally tailored evidence-based§ testing strategies to enhance and overcome barriers for linkage to and retention in care and reduce onward HIV transmission and HIV-related disparities.
SYK is activated by mutated MYD88 and drives pro-survival signaling in MYD88 driven B-cell lymphomas
Authors: Manit Munshi, Xia Liu, Jiaji G. Chen, Lian Xu, Nickolas Tsakmaklis, Maria G. Demos, Amanda Kofides, Maria Luisa Guerrera, Cristina Jimenez, Gloria G. Chan, Zachary R. Hunter, M. Lia Palomba, Kimon V. Argyropoulos, Kirsten Meid, Andrew Keezer, Joshua Gustine, Toni Dubeau, Jorge J. Castillo, Christopher J. Patterson, Jinhua Wang, Sara J. Buhrlage, Nathanael S. Gray, Steven P. Treon, Guang Yang
Journal: Blood Cancer Journal (2020)

Abstract Activating MYD88 mutations promote pro-survival signaling through BTK and HCK, both targets of ibrutinib. Despite high response rates, complete responses to ibrutinib are lacking, and other MYD88 triggered pro-survival pathways may contribute to primary drug resistance. B-cell receptor (BCR) signaling has been observed in lymphomas driven by mutated MYD88, even without activating the BCR pathway mutations. We identified activated SYK (p-SYK), a component of BCR in complex with MYD88 in MYD88 -mutated WM and ABC DLBCL lymphoma cells. Confocal microscopy confirmed co-localization of MYD88 with SYK in MYD88 -mutated cells. Knockdown of MYD88 or use of a MYD88 signaling inhibitor abrogated SYK activation, while expression of mutated but not wild-type MYD88 amplified p-SYK in MYD88 -mutated and wild-type lymphoma cells. Knockdown of SYK or use of inhibitors targeting SYK blocked p-STAT3 and p-AKT signaling in MYD88 -mutated cells. Cell viability analysis showed that combining ibrutinib and SYK inhibitors triggered synthetic killing of MYD88 -mutated lymphoma cells. Our findings extend the spectrum of mutated MYD88 pro-survival signaling to include SYK directed BCR cross talk in MYD88 -mutated lymphomas. Targeting SYK in combination with ibrutinib produces synthetic lethality, providing a framework for the clinical investigation of ibrutinib with SYK inhibitors in MYD88 -mutated lymphomas.
Isothermal microcalorimetry minimal inhibitory concentration testing in extensively drug resistant Gram-negative bacilli: a multicentre study
Authors: C. Tellapragada, B. Hasan, A. Antonelli, A. Maruri, C. de Vogel, D. Gijón, M. Coppi, A. Verbon, W. van Wamel, G.M. Rossolini, R. Cantón, C.G. Giske
Journal: Clinical Microbiology and Infection (2020)

To evaluate the performance of an isothermal microcalorimetry (IMC) method for determining the MICs among extensively drug-resistant Gram-negative bacilli.A collection of 320 clinical isolates (n = 80 of each) of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii from Sweden, Spain, Italy and the Netherlands were tested. The MICs were determined using the IMC device calScreener (Symcel, Stockholm, Sweden) and ISO-broth microdilution as the reference method. Essential agreement, categorical agreement, very major errors (VME), major errors (ME) and minor (mE) errors for each antibiotic were determined.Data from 316 isolates were evaluated. Four errors (two ME, one VME, one mE) among 80 K. pneumoniae, six errors (four ME, one VME, one mE) among 79 E. coli, 15 errors (seven VME, three ME, five mE) among 77 P. aeruginosa and 18 errors (12 VME, two ME, four mE) among 80 A. baumannii were observed. Average essential agreement and categorical agreement of the IMC method were 96.6% (95% confidence interval, 94.2-99) and 97.1% (95% confidence interval, 95.4-98.5) respectively when the MICs were determined at the end of 18 hours. Categorical agreement of the IMC method for prediction of MIC by the end of 8 hours for colistin, meropenem, amikacin, ciprofloxacin and piperacillin/tazobactam were 95%, 91.4%, 94%, 95.2% and 93.7% respectively.The IMC method could accurately determine the MICs among extensively drug-resistant clinical isolates of E. coli, K. pneumoniae, P. aeruginosa and A. baumannii isolates.
Epidemiological Features of NAFLD From 1999 to 2018 in China
Authors: Jianghua Zhou, Feng Zhou, Wenxin Wang, Xiao‐Jing Zhang, Yan‐Xiao Ji, Peng Zhang, Zhi‐Gang She, Lihua Zhu, Jingjing Cai, Hongliang Li
Journal: Hepatology (2020)

With dramatic changes in lifestyles over the last 20 years, nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disorder in China but has not received sufficient attention. NAFLD‐related advanced liver disease and its mortality along with its overall disease burden are expected to increase substantially. There is thus an imperative need to clarify the epidemiological features of NAFLD to guide a holistic approach to management. We summarize eight epidemiological features of NAFLD in China over the past two decades using systematic review and meta‐analysis methodology. Our data reveal a rapid growth in the NAFLD population, especially among younger individuals. Importantly, there is a strong ethnic difference in body mass index (BMI) and genetic risk of NAFLD compared with the US population. The etiology of advanced liver disease and its complications (e.g., hepatocellular carcinoma) has been altered because of a Westernized lifestyle and the implementation of effective vaccination strategies against viral hepatitis. Regional epidemiological patterns of NAFLD indicate that economics, environment, and lifestyle are critical factors in disease progression. The analysis also indicates that a large number of patients remain undiagnosed and untreated because of the inadequacy of diagnostic tools and the absence of effective pharmacologic therapies. Given the burden of NAFLD, future policy and research efforts need to address knowledge gaps to mitigate the risk burden.
CD226 deletion improves post-infarction healing via modulating macrophage polarization in mice
Authors: Jun Li, Yun Song, Jing-Yi Jin, Guo-Hua Li, Yong-Zheng Guo, Hong-Yu Yi, Jin-Rui Zhang, Ya-Jie Lu, Jing-Long Zhang, Cong-Ye Li, Chao Gao, Lu Yang, Feng Fu, Fu-lin Chen, Shu-Miao Zhang, Min Jia, Guo-Xu Zheng, Jian-Ming Pei, Li-Hua Chen
Journal: Theranostics (2020)

Macrophages are essential for wound repair after myocardial infarction (MI).CD226, a member of immunoglobulin superfamily, is expressed on inflammatory monocytes, however, the role of CD226 in infarct healing and the effect of CD226 on macrophage remain unknown.Methods: Wild type and CD226 knockout (CD226 KO) mice were subjected to permanent coronary ligation.CD226 expression, cardiac function and ventricular remodeling were evaluated.Profile of macrophages, myofibroblasts, angiogenesis and monocytes mobilization were determined.Results: CD226 expression increased in the infarcted heart, with a peak on day 7 after MI.CD226 KO attenuated infarct expansion and improved infarct healing after MI.CD226 deletion resulted in increased F4/80 + CD206 + M2 macrophages and diminished Mac-3 + iNOS + M1 macrophages accumulation in the infarcted heart, as well as enrichment of α-smooth muscle actin positive myofibroblasts and Ki67 + CD31 + endothelial cells, leading to increased reparative collagen deposition and angiogenesis.Furthermore, CD226 deletion restrained inflammatory monocytes mobilization, as revealed by enhanced retention of Ly6C hi monocytes in the spleen associated with a decrease of Ly6C hi monocytes in the peripheral blood, whereas local proliferation of macrophage in the ischemic heart was not affected by CD226 deficiency.In vitro studies using bone marrow-derived macrophages showed that CD226 deletion potentiated M2 polarization and suppressed M1 polarization.Conclusion: CD226 expression is dramatically increased in the infarcted heart, and CD226 deletion improves post-infarction healing and cardiac function by favoring macrophage polarization towards reparative phenotype.Thus, inhibition of CD226 may represent a novel therapeutic approach to improve wound healing and cardiac function after MI.