tbuckley/cabot-search huggingface dataset:
Multi-targeted properties of the probiotic <i>saccharomyces cerevisiae</i> CNCM I-3856 against enterotoxigenic <i>escherichia coli</i> (ETEC) H10407 pathogenesis across human gut models
Authors: Charlène Roussel, Kim De Paepe, Wessam Galia, Jana de Bodt, Sandrine Chalancon, Sylvain Denis, Françoise Leriche, Pascal Vandekerkove, Nathalie Ballet, Stéphanie Blanquet-Diot, Tom Van de Wiele
Journal: Gut Microbes (2021)

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of acute traveler's diarrhea. Adhesins and enterotoxins constitute the major ETEC virulence traits. With the dramatic increase in antibiotic resistance, probiotics are considered a wholesome alternative to prevent or treat ETEC infections. Here, we examined the antimicrobial properties of the probiotic Saccharomyces cerevisiae CNCM I-3856 against ETEC H10407 pathogenesis upon co-administration in the TNO gastrointestinal Model (TIM-1), simulating the physicochemical and enzymatic conditions of the human upper digestive tract and preventive treatment in the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME), integrating microbial populations of the ileum and ascending colon. Interindividual variability was assessed by separate M-SHIME experiments with microbiota from six human individuals. The probiotic did not affect ETEC survival along the digestive tract. However, ETEC pathogenicity was significantly reduced: enterotoxin encoding virulence genes were repressed, especially in the TIM-1 system, and a lower enterotoxin production was noted. M-SHIME experiments revealed that 18-days probiotic treatment stimulate the growth of Bifidobacterium and Lactobacillus in different gut regions (mucosal and luminal, ileum and ascending colon) while a stronger metabolic activity was noted in terms of short-chain fatty acids (acetate, propionate, and butyrate) and ethanol production. Moreover, the probiotic pre-treated microbiota displayed a higher robustness in composition following ETEC challenge compared to the control condition. We thus demonstrated the multi-inhibitory properties of the probiotic S. cerevisiae CNCM I-3856 against ETEC in the overall simulated human digestive tract, regardless of the inherent variability across individuals in the M-SHIME.
Antibacterial Dual Network Hydrogels for Sensing and Human Health Monitoring
Authors: Huan Lei, Jing Zhao, Xiaoxuan Ma, Hang Li, Daidi Fan
Journal: Advanced Healthcare Materials (2021)

Polymer-based conductive hydrogels have the synergistic advantages of high conductivity and tissue-like properties, making them promising candidates for the construction of flexible electronic devices. However, conductive hydrogel materials can easily absorb microorganisms due to their high water content. To address the problem that conductive hydrogels are susceptible to infection by external pathogens when monitoring wounds and when used in implanted organs, tannic acid-borax (TA-B) complexes are introduced into classical dual network polyacrylamide/agarose (PAM/Agar) hydrogels to form PAM/Agar/TA-B hydrogel conductors. These hydrogels are antibacterial and have good mechanical properties, light transmission, electrical conductivity, and adhesion. TA-B increases the compressive stress of the PAM/Agar/TA-B hydrogel by 58.14% compared to a PAM/Agar hydrogel. The PAM/Agar/TA-B hydrogel can be used as an electronic conductor for electronic skin and wearable sensors. Outstanding biocompatibility allows the hydrogel to be used as a monitoring device at wounds to monitor heartbeat, skin wounds, and internal tissue status in real time. In summary, an antibacterial strain sensing matrix that is safe for human health monitoring is developed.
Profiling receptor tyrosine kinase fusions in Chinese breast cancers.
Authors: Zhonghua Tao, Xichun Hu, Wen-Ming Cao, Jianxia Liu, Ting Li, Hong Xu, Kai Chen, Jian Zhang, Hao Zhou, Jie Sun, Jinming Han, Hua Yang, Lin Shao, Jianxing Xiang, Xiaoqian Guan, Min Li
Journal: Journal of Clinical Oncology (2021)

e15092 Background: Receptor tyrosine kinases (RTKs) are a class of tyrosine kinases that regulate cell-to-cell communication and control a variety of complex biological functions. Dysregulation of RTK signaling partly due to chromosomal rearrangements leads to novel tyrosine kinase fusion oncoproteins which are possibly driver alterations to cancers. Targeting some RTK fusions with specific tyrosine kinases inhibitors (TKIs) is an effective therapeutic strategy across a spectrum of RTK fusion-related cancers. However, there is still a paucity of extensive RTK fusion investigations in breast cancer. We aimed to characterize RTK fusions in Chinese breast cancer patients. Methods: An in-house sequencing database of 1440 Chinese breast cancer patients using a 520-gene NGS sequencing panel was thoroughly reviewed. RTK fusion was defined as an in-frame fusion with the tyrosine kinase domain of the RTK completely retained with the only exception of ERBB2 fusion which was not counted due to its unclear significance. Concomitant mutations and TMB were also analyzed and calculated. Patients’ clinical characteristics were retrieved from case records. Results: 27 RTK fusion-positive breast cancers (12 tissues + 15 plasmas) were identified, patients had a median age of 52 years. Triple-negative breast cancer subtype comprised 37% with luminal and HER2 positive subtypes being 40.8% and 22.2%, respectively. 77.8% of patients were at stage IV and 22.2% at stage I-III. Ten were treatment naïve. RTK fusions occurred in 2% of breast cancers in our database, compared with the prevalence of 0.6% and 1.3% in MSKCC and TCGA, respectively. In the subset of stage IV patients, our database showed a significantly higher RTK fusion frequency than that in MSKCC (3.2% vs. 0.6%, p = 0.013). FGFR2 fusions were seen most commonly (n = 7), followed by RET (n = 4), ROS1 (n = 3), NTRK3 (n = 3), BRAF (n = 2), and NTRK1 (n = 2). Other RTK fusions including ALK, EGFR, FGFR1, FGFR3, MET, and NTRK2 were identified in one patient each. Of note, the normalized abundance of RTK fusion (fusion AF/max AF) correlated negatively with TMB (r = -0.48, p = 0.017). Patients with TMB &lt; 4 (Muts/Mb) displayed a higher fusion abundance than those with TMB ≥ 4 (Muts/Mb) (p = 0.018), suggesting a higher likelihood of subclonal nature for RTK fusions in TMB-high patients. Moreover, CREBBP mutation only co-occurred with FGFR2 fusion (p = 0.012), while NTRK3 fusion and TP53 mutation were mutually exclusive (p = 0.019). Conclusions: This is the first study comprehensively delineating the prevalence and spectrum of RTK fusions in Chinese breast cancers. Further study is ongoing to identify the enriched subpopulation which may benefit from RTK fusion inhibitors.
Improving Community Engagement and Social Justice in Public Health Policymaking during the COVID Pandemics: Insights from Participatory Action-Research in Western Switzerland
Authors: Gaia Barazzetti, Francesca Bosisio
Journal: The American Journal of Bioethics (2021)

In his target article, Ismaili M’hamdi (2021) advocates for perfectionist public health policymaking, which entails fostering relevant and objectively valuable public health-related capabilities wh...
Use of Antimicrobials in a Cohort of US Nursing Homes—Reply
Authors: Nicola D. Thompson, Nimalie D. Stone, Shelley S. Magill
Journal: JAMA (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 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
BCG re-vaccination in Malawi: 30-year follow-up of a large, randomised, double-blind, placebo-controlled trial
Authors: Judith R Glynn, Katherine Fielding, Themba Mzembe, Lifted Sichali, Louis Banda, Estelle McLean, Chifundo Kanjala, Amelia C Crampin, Jorg M Ponnighaus, David K Warndorff, Paul E M Fine
Journal: The Lancet Global Health (2021)

BackgroundA large, double-blind, randomised, placebo-controlled trial of repeat BCG found 49% efficacy against leprosy but no protection against tuberculosis after 6–9 years' follow-up in 1995. We report here additional follow-up, which resulted in greatly increased tuberculosis case numbers, and allowed subgroup analysis.MethodsNearly 47 000 individuals of all ages living in northern Malawi with a BCG vaccine scar were randomly assigned (1:1) between 1986 and 1989 to receive a second BCG or placebo. The investigators and project staff remained masked to all interventions. Enhanced passive surveillance ensured ascertainment of tuberculosis and leprosy to the end of 2018. Tuberculosis case definitions included rigorous microbiological or histological confirmation. Prespecified subgroup analyses were by tuberculosis type, age at vaccination, time since vaccination, previous tuberculin reactivity, HIV status and Mycobacterium tuberculosis lineage. The original trial is registered with ISRCTN registry, ISRCTN11311670.FindingsIn follow-up until Dec 31, 2018, 824 participants had developed tuberculosis, including 786 with pulmonary disease, of whom 383 (63%) of 607 with known HIV status were HIV positive. There was no effect of a second BCG overall (odds ratio [OR] 0·92; 95% CI 0·80–1·05), or for pulmonary (0·93; 0·81–1·07), or lymph node tuberculosis (0·60; 0·31–1·17). The OR was lower for those with known HIV-negative tuberculosis (0·77; 0·59–1·00), for those vaccinated as children (aged <5 years, 0·74; 0·41–1·35; aged 5–14 years, 0·77; 0·60–0·99), and for cases arising at least 20 years after vaccination (0·79; 0·63–1·01). There were no differences by tuberculin status at vaccination, or lineage. There was no evidence of protection against leprosy beyond 10 years after vaccination (although there have been only nine diagnostically certain cases since 1995).InterpretationThere was no evidence that repeat BCG vaccination provides appreciable protection against overall tuberculosis in this rural African population with a high prevalence of HIV. Subgroup effects should not be overinterpreted given the multiple analyses done. However, the evidence for modest protection against HIV-negative tuberculosis, and for a delayed benefit in those vaccinated as children, is consistent with other observations in the literature.FundingLEPRA, Wellcome Trust, Bill & Melinda Gates Foundation.
Structurally defined tandem-responsive nanoassemblies composed of dipeptide-based photosensitive derivatives and hypoxia-activated camptothecin prodrugs against primary and metastatic breast tumors
Authors: Mengchi Sun, Hailun Jiang, Tian Liu, Xiao Tan, Qikun Jiang, Bingjun Sun, Yulong Zheng, Gang Wang, Yang Wang, Maosheng Cheng, Zhonggui He, Jin Sun
Journal: Acta Pharmaceutica Sinica B (2021)

Substantial progress in the use of chemo-photodynamic nano-drug delivery systems (nano-DDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise nanostructures, however, has limited the therapeutic efficacy of the prepared nano-DDS to date. Here, we report a structurally defined tandem-responsive chemo-photosensitive co-nanoassembly to eliminate primary breast tumor and prevent lung metastasis. This both-in-one co-nanoassembly is prepared by assembling a biocompatible photosensitive derivative (pheophorbide-diphenylalanine peptide, PPA-DA) with a hypoxia-activated camptothecin (CPT) prodrug [(4-nitrophenyl) formate camptothecin, N-CPT]. According to computational simulations, the co-assembly nanostructure is not the classical core-shell type, but consists of many small microphase regions. Upon exposure to a 660 nm laser, PPA-DA induce high levels of ROS production to effectively achieve the apoptosis of normoxic cancer cells. Subsequently, the hypoxia-activated N-CPT and CPT spatially penetrate deep into the hypoxic region of the tumor and suppress hypoxia-induced tumor metastasis. Benefiting from the rational design of the chemo-photodynamic both-in-one nano-DDS, these nanomedicines exhibit a promising potential in the inhibition of difficult-to-treat breast tumor metastasis in patients with breast cancer.
Abstract 13908: A Novel Low-Cost Cellular Functional Assay Reveals a Potential Role for Piezo1 in Hyperglycemia Induced Microcirculatory Disorders
Authors: Wandi Zhu, Manu Beerens, Tuomas O Kiviniemi, Evan Wilson, Rahul C Deo, Calum A Macrae
Journal: Circulation (2019)

Introduction: Peripheral blood testing is the most commonly used diagnostic tool, but focuses on plasma constituents and cell numbers or morphology, while providing little to no information on cell...
Abstract P102: Menthol Cigarette Use and Subclinical Cardiovascular Disease in African Americans in the Jackson Heart Study
Authors: Wendy B White
Journal: Circulation (2018)

Background: African Americans smoke menthol cigarettes at higher rates than other races and have a disproportionate burden of cardiovascular disease (CVD). Whereas smoking is a well described risk factor for CVD, it is unclear if menthol cigarettes are associated with more or less risk. Therefore, our aim was to evaluate the association between menthol cigarette use and subclinical atherosclerosis in the Jackson Heart Study (JHS). Methods: JHS participants (n=5,301) were classified by self-reported smoking status as current, past (smoked ≥400 cigarettes/life), or never smokers at Visit 1 (V1, 2000-2004). Menthol cigarette use data were captured at Visit 3 (V3, 2009-2013). We used multivariable logistic and robust linear regression models to examine the associations between cigarette type and measures of subclinical atherosclerosis [carotid intimal medial thickness (CIMT, Visit 1) and coronary artery calcium (CAC) or aorto-iliac calcium (AIC) by computed tomography (Visit 2, V2, 2005-2008)] to estimate β-coefficients (adjusted differences) comparing menthol to non-menthol (reference group) smoking. Results: There were 401 current smokers with available data on cigarette preference including 326 menthol (81%) and 75 non-menthol (19%) smokers at V3. Menthol cigarette preference in current smokers was not associated with significant differences in measures of subclinical atherosclerosis: CIMT (β -0.003, 95% CI -0.053, 0.046, p=0.90); CAC (β -0.20, 95% CI -1.09, 0.69, p=0.66) or AIC (β -0.32, 95% CI -1.23, 0.59, p=0.48). Conclusion: Our study provides no evidence for an association of menthol cigarette use with subclinical atherosclerosis in African Americans. These findings warrant replication by studies that address the limitations of this study, including the assumption that menthol smokers in V3 were long-term menthol smokers before V1 and V2, potential selection by exclusions of deaths related to smoking and CVD among participants at V3 and lack of longitudinal data on outcomes after the collection of menthol use data at V3.
Rate and severity of suspected SARS-Cov-2 reinfection in a cohort of PCR-positive COVID-19 patients
Authors: Jeff Slezak, Katia Bruxvoort, Heidi Fischer, Benjamin Broder, Bradley Ackerson, Sara Tartof
Journal: Clinical Microbiology and Infection (2021)

To estimate the burden and severity of suspected reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).A retrospective cohort of members of Kaiser Permanente Southern California with PCR-positive SARS-CoV-2 infection between 1st March 2020 and 31st October 2020 was followed through electronic health records for subsequent positive SARS-CoV-2 tests (suspected reinfection) ≥90 days after initial infection, through 31st January 2021. Incidence of suspected reinfection was estimated using the Kaplan-Meier method. Cox proportional hazards models estimated the association of suspected reinfection with demographic and clinical characteristics, hospitalization, and date of initial infection.The cohort of 75 149 was predominantly Hispanic (49 648/75 149, 66.1%) and included slightly more females than males (39 736, 52.9%), with few immunocompromised patients (953, 1.3%); 315 suspected reinfections were identified, with a cumulative incidence at 270 days of 0.8% (95% confidence interval (CI) 0.7-1.0%). Hospitalization was more common at suspected reinfection (36/315, 11.4%) than initial infection (4094/75 149, 5.4%). Suspected reinfection rates were higher in females (1.0%, CI 0.8-1.2% versus 0.7%, CI 0.5-0.9%, p 0.002) and immunocompromised patients (2.1%, CI 1.0-4.2% versus 0.8%, CI 0.7-1.0%, p 0.004), and lower in children than adults (0.2%, CI 0.1-0.4% versus 0.9%, CI 0.7-1.0%, p 0.023). Patients hospitalized at initial infection were more likely to have suspected reinfection (1.2%, CI 0.6-1.7% versus 0.8%, CI 0.7-1.0%, p 0.030), as were those with initial infections later in 2020 (150-day incidence 0.4%, CI 0.2-0.5% September-October versus 0.2%, CI 0.1-0.3% March-May and 0.3%, CI 0.2-0.3% June-August, p 0.008). In an adjusted Cox proportional hazards model, being female (hazard ratio (HR) 1.44, CI 1.14-1.81), adult (age 18-39, HR 2.71, CI 1.38-5.31, age 40-59 HR 2.22, CI 1.12-4.41, age ≥60 HR 2.52, CI 1.23-5.17 versus <18 years), immunocompromised (HR 2.48, CI 1.31-4.68), hospitalized (HR 1.60, CI 1.07-2.38), and initially infected later in 2020 (HR 2.26, CI 1.38-3.71 September-October versus March-May) were significant independent predictors of suspected reinfection.Reinfection with SARS-CoV-2 is uncommon, with suspected reinfections more likely in women, adults, immunocompromised subjects, and those previously hospitalized for coronavirus 2019 (COVID-19). This suggests a need for continued precautions and vaccination in patients with COVID-19 to prevent reinfection.
Health Impact and Cost-Effectiveness of Achieving the National Salt and Sugar Reduction Initiative Voluntary Sugar Reduction Targets in the United States: A Microsimulation Study
Authors: Siyi Shangguan, Dariush Mozaffarian, Stephen Sy, Yujin Lee, Junxiu Liu, Parke E. Wilde, Andrea L. Sharkey, Erin A. Dowling, Matti Marklund, Shafika Abrahams-Gessel, Thomas A. Gaziano, Renata Micha
Journal: Circulation (2021)

High intake of added sugar is linked to weight gain and cardiometabolic risk. In 2018, the US National Salt and Sugar Reduction Initiative proposed government-supported voluntary national sugar reduction targets. This intervention's potential effects and cost-effectiveness are unclear.
Childhood interstitial lung disease: short lessons from telomeres
Authors: Sormeh Salehian, Tom Semple, Rishi Pabary
Journal: Thorax (2021)

### Learning points

A 16-year-old boy with persisting fixed obstructive spirometry is approaching transition to adult services. He has been under long-term follow-up, initially referred aged 2 months by his local team for tachypnoea and mild respiratory distress since birth. He was born at term by vaginal delivery with meconium suctioned from his oropharynx and admitted to a special care baby unit for observation and intravenous antibiotics. Chest X-ray (CXR) at birth was reportedly consistent with possible meconium aspiration, although there was no neonatal resuscitation or ventilation required and he was discharged home after 4 days without an oxygen requirement.

Flexible bronchoscopy was arranged that was unremarkable, there was no evidence of aspiration or infection, he had a negative congenital infection screen and normal echocardiogram. CT chest showed linear atelectasis, occasional thickened interlobular septa and areas of secondary pulmonary lobular hyperinflation. Neither bronchopulmonary dysplasia (BPD) nor meconium aspiration syndrome really fits his neonatal history or imaging appearance. He was well in himself and so was discharged with a plan for regular outpatient review. Follow-up CT chest age 3 years (figure 1A) demonstrated persistent abnormality with an …
Indurated Plaques With Telangiectasias on the Lower Limbs
Authors: Claudia Sarró-Fuente, Javier Martín-Alcalde, José Luis López-Estebaranz
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
The HIV protease inhibitor, ritonavir, corrects diverse brain phenotypes across development in mouse model of DYT-TOR1A dystonia
Authors: Zachary F. Caffall, Bradley J. Wilkes, Ricardo Hernández-Martinez, Joseph E. Rittiner, Jennifer T. Fox, Kanny K. Wan, Miranda K. Shipman, Steven A. Titus, Ya-Qin Zhang, Samarjit Patnaik, Matthew D. Hall, Matthew B. Boxer, Min Shen, Zhuyin Li, David E. Vaillancourt, Nicole Calakos
Journal: Science Translational Medicine (2021)

Ritonavir, identified by a DYT1 dystonia in vitro drug screen, corrects neuronal firing response and white matter deficits in the DYT1 mouse brain.
ナノ製剤化α-マンゴスチンとトリプトリドの連続送達は,膵臓癌における透過障害を克服し,治療効果を改善する【JST・京大機械翻訳】
Authors: Feng Jingxian, Xu Minjun, Wang Jiahao, Zhou Songlei, Liu Yipu, Liu Shanshan, Huang Yukun, Chen Yu, Chen Liang, Song Qingxiang, Gong Jingru, Lu Huiping, Gao Xiaoling, Chen Jun
Journal: Biomaterials (2020)
CoCoA-diff: counterfactual inference for single-cell gene expression analysis
Authors: Yongjin P. Park, Manolis Kellis
Journal: Genome biology (2021)

Finding a causal gene is a fundamental problem in genomic medicine. We present a causal inference framework, CoCoA-diff, that prioritizes disease genes by adjusting confounders without prior knowledge of control variables in single-cell RNA-seq data. We demonstrate that our method substantially improves statistical power in simulations and real-world data analysis of 70k brain cells collected for dissecting Alzheimer's disease. We identify 215 differentially regulated causal genes in various cell types, including highly relevant genes with a proper cell type context. Genes found in different types enrich distinctive pathways, implicating the importance of cell types in understanding multifaceted disease mechanisms.
26548 DaxibotulinumtoxinA for injection (DAXI) demonstrates consistent efficacy, duration, and safety in females independent of age: Subgroup analysis from a large, phase 3 program
Authors: Glynis Ablon, Ava Shamban, Susan Weinkle, Susan H. Weinkle, Jessica Brown, Yan Liu
Journal: Journal of the American Academy of Dermatology (2021)