tbuckley/cabot-search huggingface dataset:
Occupational exposure to inhaled pollutants and risk of airflow obstruction: a large UK population-based UK Biobank cohort
Authors: Steven S Sadhra, Nuredin Mohammed, Om P Kurmi, David Fishwick, Sara De Matteis, Sally Hutchings, Debbie Jarvis, Jon G Ayres, Lesley Rushton
Journal: Thorax (2020)

Background Although around 10% to 15% of COPD burden can be attributed to workplace exposures, little is known about the role of different airborne occupational pollutants (AOP). The main aim of the study was to assess the effect size of the relationship between various AOP, their level and duration of exposure with airflow obstruction (AFO). Methods A cross-sectional analysis was conducted in 228 614 participants from the UK Biobank study who were assigned occupational exposure using a job exposure matrix blinded to health outcome. Adjusted prevalence ratios (PRs) and 95% CI for the risk of AFO for ever and years of exposure to AOPs were estimated using robust Poisson model. Sensitivity analyses were conducted for never-smokers, non-asthmatic and bi-pollutant model. Results Of 228 614 participants, 77 027 (33.7%) were exposed to at least one AOP form. 35.5% of the AFO cases were exposed to vapours, gases, dusts or fumes (VGDF) and 28.3% to dusts. High exposure to vapours increased the risk of occupational AFO by 26%. Exposure to dusts (adjusted PR=1.05; 95% CI 1.01 to 1.08), biological dusts (1.05; 1.01 to 1.10) and VGDF (1.04; 1.01 to 1.07) showed a significantly increased risk of AFO, however, statistically not significant following multiple testing. There was no significant increase in risk of AFO by duration (years) of exposure in current job. The results were null when restricted to never-smokers and when a bi-pollutant model was used. However, when data was analysed based on the level of exposure (low, medium and high) compared with no exposure, directionally there was increase in risk for those with high exposure to vapours, gases, fumes, mists and VGDF but statistically significant only for vapours. Conclusion High exposure (in current job) to airborne occupational pollutants was suggestive of higher risk of AFO. Future studies should investigate the relationship between lifetime occupational exposures and COPD.
Recurrent upper gastrointestinal ulcer bleeding treated by coil embolization guided by endoscopic ultrasonography
Authors: Lucía Medina-Prado, Sandra Baile-Maxía, Maryana Bozhychko, Carolina Mangas-Sanjuan, Juan Martínez-Sempere, Juan Antonio Casellas, José Ramón Aparicio
Journal: Endoscopy (2020)

Clinical case 1. A 45-year-old man diagnosed with locally advanced pancreatic adenocarcinoma was admitted to hospital for acute upper gastrointestinal bleeding (UGIB). Urgent gastroscopy showed a duodenal ulcer of about 15 mm and a visible vessel. The first treatment option was to inject diluted adrenaline and place two hemoclips. Despite the treatment, progressive anemia persisted.
The Association of Energy and Macronutrient Intake at Dinner Versus Breakfast With Disease-Specific and All-Cause Mortality Among People With Diabetes: The U.S. National Health and Nutrition Examination Survey, 2003–2014
Authors: Tianshu Han, Jian Gao, Lihong Wang, Chao Li, Lu Qi, Changhao Sun, Ying Li
Journal: Diabetes Care (2020)

This study aims to evaluate the association of energy and macronutrient intake at dinner versus breakfast with disease-specific and all-cause mortality in people with diabetes.A total of 4,699 people with diabetes who enrolled in the National Health and Nutrition Examination Survey from 2003 to 2014 were recruited for this study. Energy and macronutrient intake was measured by a 24-h dietary recall. The differences (Δ) in energy and macronutrient intake between dinner and breakfast (Δ = dinner - breakfast) were categorized into quintiles. Death information was obtained from the National Death Index until 2015. Cox proportional hazards regression models were developed to evaluate the survival relationship between Δ and diabetes, cardiovascular disease (CVD), and all-cause mortality.Among the 4,699 participants, 913 deaths, including 269 deaths due to diabetes and 314 deaths due to CVD, were documented. After adjustment for potential confounders, compared with participants in the lowest quintile of Δ in terms of total energy and protein, participants in the highest quintile were more likely to die due to diabetes (hazard ratio [HR]Δenergy 1.92, 99% CI 1.08-3.42; HRΔprotein 1.92, 99% CI 1.06-3.49) and CVD (HRΔenergy 1.69, 99% CI 1.02-2.80; HRΔprotein 1.96, 99% CI 1.14-3.39). The highest quintile of Δtotal fat was related to CVD mortality (HR 1.67, 99% CI 1.01-2.76). Isocalorically replacing 5% of total energy at dinner with breakfast was associated with 4% and 5% lower risk of diabetes (HR 0.96, 95% CI 0.94-0.98) and CVD (HR 0.95, 95% CI 0.93-0.97) mortality, respectively.Higher intake of energy, total fat, and protein from dinner than breakfast was associated with greater diabetes, CVD, and all-cause mortality in people with diabetes.
Comparative Effectiveness of Antibiotic Treatment Duration in Children With Pyelonephritis
Authors: Miriam T. Fox, Joe Amoah, Alice J. Hsu, Carrie A. Herzke, Jeffrey S. Gerber, Pranita D. Tamma
Journal: JAMA Network Open (2020)

<h3>Importance</h3> National guidelines recommend treating children with pyelonephritis for 7 to 14 days of antibiotic therapy, yet data are lacking to suggest a more precise treatment duration. <h3>Objective</h3> To compare the clinical outcomes of children receiving a short-course vs a prolonged-course of antibiotic treatment for pyelonephritis. <h3>Design, Setting, and Participants</h3> Retrospective observational study using inverse probability of treatment weighted propensity score analysis of data from 5 hospitals in Maryland between July 1, 2016, and October 1, 2018. Participants were children aged 6 months to 18 years with a urine culture growing<i>Escherichia coli</i>,<i>Klebsiella</i>species, or<i>Proteus mirabilis</i>with laboratory and clinical criteria for pyelonephritis. <h3>Exposures</h3> Treatment of pyelonephritis with a short-course (6 to 9 days) vs a prolonged-course (10 or more days) of antibiotics. <h3>Main Outcomes and Measures</h3> Composite outcome of treatment failure within 30 days of completing antibiotic therapy: (a) unanticipated emergency department or outpatient visits related to urinary tract infection symptoms, (b) hospital readmission related to UTI symptoms, (c) prolongation of the planned, initial antibiotic treatment course, or (d) death. A subsequent urinary tract infection caused by a drug-resistant bacteria within 30 days was a secondary outcome. <h3>Results</h3> Of 791 children who met study eligibility criteria (mean [SD] age 9.2 [6.3] years; 672 [85.0%]) were girls, 297 patients (37.5%) were prescribed a short-course and 494 patients (62.5%) were prescribed a prolonged-course of antibiotics. The median duration of short-course therapy was 8 days (interquartile range, 7-8 days), and the median duration of prolonged-course therapy was 11 days (interquartile range, 11-12 days). Baseline characteristics were similar between the groups in the inverse probability of treatment weighted cohort. There were 79 children (10.1%) who experienced treatment failure. The odds of treatment failure were similar for patients prescribed a short-course vs a prolonged-course of antibiotics (11.2% vs 9.4%; odds ratio, 1.22; 95% CI, 0.75-1.98). There was no significant difference in the odds of a drug-resistant uropathogen for patients with a subsequent urinary tract infection within 30 days when prescribed a short-courses vs prolonged-course of antibiotics (40% vs 64%; odds ratio, 0.36; 95% CI, 0.09-1.43). <h3>Conclusions and Relevance</h3> The study findings suggest that short-course antibiotic therapy may be as effective as prolonged-courses for children with pyelonephritis, and may mitigate the risk of future drug-resistant urinary tract infections. Additional studies are needed to confirm these findings.
Highly sensitive and specific detection of hepatitis B virus DNA and drug resistance mutations utilizing the PCR-based CRISPR-Cas13a system
Authors: S. Wang, H. Li, Z. Kou, F. Ren, Y. Jin, L. Yang, X. Dong, M. Yang, J. Zhao, H. Liu, N. Dong, L. Jia, X. Chen, Y. Zhou, S. Qiu, R. Hao, H. Song
Journal: Clinical Microbiology and Infection (2020)
Abstract IA25: Tumors alter gut microbiota to suppress immunity and foster progression
Authors: Mireia Hribe-Herranz, Kyle Bittinger, Ceylan Tanes, Stavros Rafail, Stefano Pierini, Edgar Ben-Joseph, Janos Tanyi, Andrea Facciabene
Journal: Cancer Research (2020)

Abstract Immune dysfunction is commonly observed in patients with cancer contributing to tumor progression. While previous work established a connection between the gut microbiota and the immune system, the mechanisms by which microbiotas contribute to cancer-associated immune dysfunction are not well understood. Using multiple mouse cancer models, we demonstrated robust alterations of gut microbiota in tumor-bearing mice and a substantial change in antimicrobial peptides produced by the gut epithelium. We identified an overall reduction in IFN-γ T cells in tumor-bearing mice, which was rescued with antibiotics treatment or by co-housing tumor-bearing mice with healthy mice. Similar to mouse, we observed changes in gut microbiota and antimicrobial peptides levels of patients diagnosed with ovarian or lung cancer. We identify Firmicutes Ruminococcus members as key promoters of immune dysfunctions and tumor development. These findings identify a new mechanism of immune modulation utilized by tumors to undermine the immune responses and promote tumor progression. Citation Format: Mireia Hribe-Herranz, Kyle Bittinger, Ceylan Tanes, Stavros Rafail, Stefano Pierini, Edgar Ben-Joseph, Janos Tanyi, Andrea Facciabene. Tumors alter gut microbiota to suppress immunity and foster progression [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA25.
Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes
Authors: Lihua Zhu, Zhi-Gang She, Xu Cheng, Juan-Juan Qin, Xiao-Jing Zhang, Jingjing Cai, Fang Lei, Haitao Wang, Jing Xie, Wenxin Wang, Haomiao Li, Peng Zhang, Xiaohui Song, Xi Chen, Mei Xiang, Chaozheng Zhang, Liangjie Bai, Da Xiang, Ming-Ming Chen, Yanqiong Liu, Youqin Yan, Mingyu Liu, Weiming Mao, Jinjing Zou, Liming Liu, Guohua Chen, Pengcheng Luo, Bing Xiao, Changjiang Zhang, Zixiong Zhang, Zhigang Lu, Junhai Wang, Haofeng Lu, Xigang Xia, Daihong Wang, Xiaofeng Liao, Gang Peng, Ping Ye, Jun Yang, Yufeng Yuan, Xiaodong Huang, Jiao Guo, Bing-Hong Zhang, Hongliang Li
Journal: Cell Metabolism (2020)
<i>HER2</i> Mutations in Non–Small Cell Lung Cancer: A Herculean Effort to Hit the Target
Authors: Christian Rolfo, Alessandro Russo
Journal: Cancer Discovery (2020)

Abstract Summary: Over the last two decades HER2 aberrations have been thoroughly investigated as potential therapeutic targets in advanced non–small cell lung cancer, with relatively modest results. Two articles published in this issue of Cancer Discovery further expand the knowledge on therapeutic exploitation of HER2 in lung cancer, addressing a large unmet medical need. See related article by Li et al., p. 674. See related article by Tsurutani et al., p. 688.
Primer on etiology and treatment of progressive/severe periodontitis: A systemic health perspective
Authors: Jørgen Slots
Journal: Periodontology 2000 (2020)

Abstract Periodontology is an infectious disease‐based discipline. The etiopathology of progressive/severe periodontitis includes active herpesviruses, specific bacterial pathogens, and proinflammatory cytokines. Herpesviruses and periodontopathic bacteria may interact synergistically to produce periodontal breakdown, and periodontal herpesviruses may contribute to systemic diseases. The infectious agents of severe periodontitis reside in deep pockets, furcation lesions, and inflamed gingiva, sites inaccessible by conventional (purely mechanical) surgical or nonsurgical therapy but accessible by systemic antibiotic treatment. This brief overview presents an effective anti‐infective treatment of severe periodontitis, which includes systemic chemotherapy/antibiotics against herpesviruses (valacyclovir [acyclovir]) and bacterial pathogens (amoxicillin + metronidazole or ciprofloxacin + metronidazole) plus common antiseptics (povidone‐iodine and sodium hypochlorite) and select ultrasonic scaling. The proposed treatment can cause a marked reduction or elimination of major periodontal pathogens, is acceptably safe, and can be carried out in minimal time with minimal cost.
Venetoclax for the treatment of translocation (11;14) AL amyloidosis
Authors: M. Hasib Sidiqi, Abdullah S. Al Saleh, Nelson Leung, Dragan Jevremovic, Mohammed A. Aljama, Wilson I. Gonsalves, Francis K. Buadi, Taxiarchis V. Kourelis, Rahma Warsame, Eli Muchtar, Miriam A. Hobbs, Martha Q. Lacy, David Dingli, Ronald S. Go, Suzanne R. Hayman, S. Vincent Rajkumar, Angela Dispenzieri, Morie A. Gertz, Shaji K. Kumar, Rafael Fonseca, Prashant Kapoor
Journal: Blood Cancer Journal (2020)
A pH-responsive silica–metal–organic framework hybrid nanoparticle for the delivery of hydrophilic drugs, nucleic acids, and CRISPR-Cas9 genome-editing machineries
Authors: Yuyuan Wang, Pawan K. Shahi, Ruosen Xie, Huilong Zhang, Amr A. Abdeen, Nisakorn Yodsanit, Zhenqiang Ma, Krishanu Saha, Bikash R. Pattnaik, Shaoqin Gong
Journal: Journal of Controlled Release (2020)
Covid-19: the challenge of patient rehabilitation after intensive care
Authors: Jacqui Thornton
Journal: BMJ (2020)

Covid-19: the challenge of patient rehabilitation after intensive careAs the UK's coronavirus patients begin to leave ICUs, Jacqui Thornton examines how the NHS plans to meet a "tsunami of need" Jacqui Thornton LondonCovid-19 has shone a bright light on the impressive work of NHS intensive care units (ICUs) around the UK.Now, as the first patients who have had the new virus and spent days ventilated in ICUs are discharged, the Chartered Society of Physiotherapy predicts a "tsunami of rehabilitation needs."Already there are question marks about whether appropriate rehabilitation-physical, cognitive, and psychological-will be available for the huge numbers of people who will need to deal with the enormous impact of a stay in critical care.Rehabilitation after a heart attack, trauma, or stroke has well established pathways.But rehabilitation for many of the thousands of people who spend time in intensive care every year is not automatic-despite severe muscle wastage and deconditioning, sleep disorders and severe fatigue, memory problems, anxiety, depression, and post-traumatic stress disorder. 1These "general" ICU patients may be the sickest people in the country, but once they leave they may be getting the least support.
Environmental contamination of SARS-CoV-2 in healthcare premises
Authors: Guangming Ye, Hualiang Lin, Song Chen, Shichan Wang, Zhikun Zeng, Wei Wang, Shiyu Zhang, Terri Rebmann, Yirong Li, Zhenyu Pan, Zhonghua Yang, Ying Wang, Fubing Wang, Zhengmin Qian, Xinghuan Wang
Journal: Journal of Infection (2020)
A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer
Authors: Richard D. Kim, Vincent Chung, Olatunji B. Alese, Bassell F. El-Rayes, Daneng Li, Taymeyah E. Al-Toubah, Michael J. Schell, Jun-Min Zhou, Amit Mahipal, Baek Hui Kim, Dae Won Kim
Journal: JAMA Oncology (2020)

Currently, there is no established second-line systemic treatment for biliary tract cancer (BTC). Preclinical data have demonstrated that the presence of tumor-infiltrating CD8 T cells and programmed cell death 1 ligand 1-expressing tumor cells in the tumor microenvironment of BTC supports the rationale of using programmed cell death 1 protein blockade immunotherapy in BTC.To evaluate anticancer activity of nivolumab in patients with advanced refractory BTC.In this single-group, multicenter phase 2 study of nivolumab, 54 patients with histologically confirmed BTC whose disease progressed while undergoing treatment with at least 1 line but no more than 3 lines of systemic therapy were enrolled between October 5, 2016, and December 26, 2018. Analysis was performed on an intention-to-treat basis.Nivolumab, 240 mg, was delivered intravenously every 2 weeks for 16 weeks, and then 480 mg was delivered intravenously every 4 weeks until disease progression or unacceptable toxic effects occurred.The primary end point was investigator-assessed objective response rate, and the secondary end points were progression-free survival, overall survival, and incidence of adverse events.A total of 54 patients (27 men and 27 women; median age, 65 years [range, 28-86 years]) enrolled, and 46 (22 men and 24 women; median age, 65 years [range, 28-86 years]) were examined for objective response with radiologic imaging. The investigator-assessed objective response rate was 22% (10 of 46), including 1 unconfirmed partial response, with a disease control rate of 59% (27 of 46). Central independent review found an objective response rate of 11% (5 of 46), including 1 unconfirmed partial response, with a disease control rate of 50% (23 of 46). All patients who responded to treated (hereafter referred to as responders) had mismatch repair protein-proficient tumors. The median duration of investigator-assessed response was not reached, with a median follow-up of 12.4 months. Among the intention-to-treat population, median progression-free survival was 3.68 months (95% CI, 2.30-5.69 months) and median overall survival was 14.24 months (95% CI, 5.98 months to not reached). Programmed cell death 1 ligand 1 expression in tumors was associated with prolonged progression-free survival (hazard ratio, 0.23; 95% CI, 0.10-0.51; P < .001). The most common treatment-related grade 3 or 4 toxic effects were hyponatremia (3 of 54 [6%]) and increased alkaline phosphatase (2 of 54 [4%]).This study found that nivolumab was well tolerated and showed modest efficacy with durable response in patients with refractory BTC. Further studies are warranted to verify the findings and evaluate biomarkers for improved treatment selection for patients.ClinicalTrials.gov Identifier: NCT02829918.
Communicating emerging risks of SGLT2 inhibitors—timeliness and transparency of medicine regulators
Authors: Alice Bhasale, Barbara Mintzes, Ameet Sarpatwari
Journal: BMJ (2020)

As new risks of SGLT2 inhibitors have emerged, how have regulators responded? <b>Alice Bhasale and colleagues</b> compare the number, timing, strength, and transparency of public safety communications across leading medicines regulators
Association of Topical Corticosteroids With Reduced Vulvar Squamous Cell Carcinoma Recurrence in Patients With Vulvar Lichen Sclerosus
Authors: Simone Chin, James Scurry, Jennifer Bradford, Geoffrey Lee, Gayle Fischer
Journal: JAMA Dermatology (2020)

This cohort study uses data from a medical record review of a dermatogynecology practice to describe the association between reduced recurrence of vulvar squamous cell carcinoma and use of topical corticosteroids in the treatment of vulvar lichen sclerosus.
Abstract #2980: Isothiocyanates induce formation of aggresome-like structures and inhibit ubiquitin-proteasome system
Authors: Lixin Mi, Nanqin Gan, Fung-Lung Chung
Journal: Cancer Research (2009)

Cruciferous vegetable-derived isothiocyanates (ITCs) are versatile cancer chemopreventivecompounds showing activity that induces cell cycle arrestand apoptosis. However, the detailed mechanisms underlying these events are still not fully understood. Recently we showed that tubulin is one of the molecular targets of isothiocyanates (ITCs). The binding to tubulin by ITCs induces not only tubulin conformation changes and microtubule depolymerization, but also a selective degradation of \#945;- and \#946;- tubulins in a proteasome-dependent manner. Here, we report that ITCs can induce formation of aggresome-like structures (ALS) in cytoplasm. In addition to \#945;- and \#946;- tubulins, some key aggresome marker proteins, including small molecular chaperone hsp27, proteasome, and ubiquitinated proteins, were also enriched in the complexes. Different from aggresome induced by transfected misfolding proteins, there was no enrichment of \#947;-tubulin, vimentin, dynein, hsp70, and hsp90 in ITC-induced aggresome. Since \#945;- and \#946;- tubulins became substrates of degradation, the ITC-induced ALS is not microtubule-dependent, opposite to that shown in the aggresome induced by transfected misfolding proteins. The elevated proteasome activity and facile degradation of tubulin within the ALS suggest that the ALS are micro-disposers of modified and misfolding tubulins. In contrast, the cytoplasmic ubiquitin-proteasome system (UPS) was significantly inhibited by ITC treatment in a dose- and time- dependent manner. Our results indicate that both the formation of ALS and the inhibition of UPS are unrelated to oxidative stress. The ALS formation and the UPS inhibition were substantially alleviated by pretreating cells with tubulin binding agents, such as colchicine, vinblastine, and taxol. Since these agents block ITC binding to tubulin, the alleviation indicates that the ITC binding to tubulin plays an essential role in the ALS formation and UPS inhibition. Also the potency of inducing ALS formation and UPS inhibition: BITC>PEITC>SFN, is the same as that of binding affinity to tubulin by these ITCs. Our data also show that proapoptotic proteins such as I\#954;B and cell cycle inhibitors such as p27 were accumulated due to the inhibited UPS. These results confirm that tubulin is a molecular target of ITCs and ITC binding to tubulin may underlie an important mechanism of the ITC-induced cell cycle arrest and apoptosis. (NCI grant CA 100853)  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2980.
The natural history of nonalcoholic fatty liver: A follow-up study
Authors: M TELI
Journal: Hepatology (1995)

Nonalcohol-induced fatty liver is widely believed to be a benign condition with little or no risk of disease progression. There have been occasional reports of progression to cirrhosis but none in the absence of preexisting fibrosis on the index biopsy specimen even when co-existing hepatitis was present (steatohepatitis). From our histological database (1978 to 1985), we identified 161 patients with fatty liver seen at our institution and traced the case notes of 156. One hundred five patients were initially excluded as having an alcohol-induced cause, and the remaining 51 either were seen in the clinic (37) or had died, in which cases copies of their death certificates were obtained (14). A further 7 patients were excluded after clinic attendance gave evidence of alcohol excess and another 4 after review of their initial biopsy showed the presence of fibrosis or steatohepatitis. The apparent cause of the steatosis in the 40 included patients with strictly nonalcohol-induced pure fatty liver was obesity in 12, diabetes in 4 (1 obese patient), and cachexia associated with extrahepatic malignancy in 6. Four of the remaining 19 had serological evidence of an autoimmune disorder, but none of these had any clinical or histological features of autoimmune liver disease. Nine patients had evidence of hyperlipidemia, 3 of whom were also obese. At a median follow-up of 11 years (7 to 16), 12 of 26 living patients had abnormal results of liver blood tests and had repeat liver biopsies performed. None had progressed to steatohepatitis or cirrhosis; 1 obese patient had developed mild fibrosis 9.8 years after her index biopsy. The remaining 14 living patients had normal blood tests and liver ultrasound and isotope scans. None of the 14 deceased patients died of a liver-related cause, and none had clinical evidence of liver disease before death. In the absence of preexisting fibrosis or steatohepatitis, fatty liver of nonalcohol-induced origin is an extremely benign condition. (Hepatology 1995; 22:1714-1719).