tbuckley/cabot-search huggingface dataset:
International travel as risk factor for Chlamydia trachomatis infections among young heterosexuals attending a sexual health clinic in Melbourne, Australia, 2007 to 2017
Authors: Ei T Aung, Eric PF Chow, Christopher K Fairley, Jane S Hocking, Catriona S Bradshaw, Deborah A Williamson, Marcus Y Chen
Journal: Eurosurveillance (2019)

BackgroundInternational travel is considered a risk factor for acquiring Chlamydia trachomatis; however, there are little empirical data to support this.AimTo examine the prevalence and risk factors for Chlamydia trachomatis infections among heterosexual international travellers (n = 28,786) attending the Melbourne Sexual Health Centre (MSHC), Australia, compared to Australian residents (n = 20,614).MethodsWe conducted a repeated cross-sectional study and analysed sexual behaviours and chlamydia positivity among heterosexual males and females aged ≤ 30 attending MSHC for the first time between January 2007 and February 2017. 'Travellers' were defined as individuals born outside of Australia who had resided in the country < 2 years. Associations between patient characteristics and chlamydia positivity were examined.ResultsChlamydia positivity was higher among travellers (11.2%) compared with Australian residents (8.5%; p < 0.001). Male travellers had higher chlamydia positivity (12.1%) than Australian males (9.3%; p < 0.001), as did female travellers (10.4%) compared with Australian females (7.7%; p < 0.001). Travellers had a higher mean number of sexual partners than Australian residents among males (5.7 vs 4.7; p < 0.001) and females (3.6 vs 3.2; p < 0.001). Travellers from the United Kingdom, Europe, Ireland and New Zealand accounted for 29.6%, 21%, 8.5% and 5.8% of C.trachomatis infections, respectively. Chlamydia in males and females was associated with younger age (≤ 25), inconsistent condom use, a higher number of sexual partners (≥ 4 partners) and being a traveller (p < 0.001).ConclusionsWe found that international travel is an independent risk factor for chlamydia among young heterosexual travellers in Australia, who should therefore be a target group for chlamydia prevention.
Abstract 17004: Right Bundle Branch Block (RBBB) is Associated With Poor Prognosis in Patients With Anterior Wall ST Elevation Myocardial Infarction (AWMI): A Nationwide Study Using the National Inpatient Sample (NIS)
Authors: Rishi Shrivastav, Prateeth Pati, Stuthi Perimbeti, Jacqueline Tamis-holland
Journal: Circulation (2018)

Introduction: Blood supply to the right bundle comes from the left coronary circulation, which also supplies other major dominant areas of the myocardium. Intuitively, RBBB in the setting of AWMI would indicate more extensive myocardial involvement and thus portend a worse prognosis. Limited previous studies on RBBB in AWMI have demonstrated adverse outcomes, however large scale observational studies are still lacking. We hypothesized that as compared to patients without RBBB, the presence of RBBB in patients with AWMI would be associated with increased morbidity and mortality. Methods: The NIS was analyzed to identify adult admissions (&gt;18 years of age) with a primary diagnosis of AWMI (ICD-9 codes 410.0 and 410.1) between 1999 and 2014 (N=219,302 weighted N=1,075,874). Using ICD-9 code 426.4, these admissions were further stratified for RBBB. Using Chi-Square test, we performed bivariate analysis to determine in-hospital mortality across various categorical variables. Multivariate analysis using Cox Proportional Hazard regression was then performed to control for confounders and determine the hazard of acute heart failure (428.21 and 428.23), complete heart block (426.0), implantation of a permanent pacemaker (37.71, 37.81,37.82, 37.83 and 00.51) and in-hospital mortality for patients with AWMI and RBBB as compared to patients with AWMI and no RBBB. Results: Out of the 1,075,874 admissions with primary diagnosis of AWMI, about 1.78% (19,153) had RBBB. The mean age of patients with and without RBBB was 69.49 years and 68.46 years (p&lt;0.001) respectively. As compared to patients with AWMI and no RBBB, mortality was significant higher for patients with AWMI and RBBB [9.19% (97,138) vs 15.30% (2930); p&lt;0.0001]. After adjustment, RBBB in the setting of AWMI was associated with a 60% percent increase in the risk of in-hospital mortality (Hazard Ratio 1.60, 95% CI 1.54-1.66; p&lt;0.001) and a higher likelihood for other complications (Table 1). Conclusions: The presence of RBBB in the setting of an AWMI is a significant independent predictor of poor prognosis, including a higher rate of acute heart failure, complete heart block and the need for a permanent pacer, as well as a higher in-hospital mortality
“To measure is to know” certainly applies to ERCP training
Authors: Arjun D. Koch
Journal: Endoscopy (2019)

Awareness of the quality of endoscopic procedures has increased over recent decades. This has led to the development of numerous quality programs and performance measures being defined to monitor and improve outcomes. Endoscopic retrograde cholangiopancreatography (ERCP) is considered to be one of the most complex and challenging procedures in gastrointestinal endoscopy. It carries a high risk of complications, and therefore, high quality performance is crucial. In order to attain competence in performing this procedure, it is obvious that extensive training is necessary. Questions that then immediately arise are: How much training is necessary? And, What level of performance is acceptable for subsequent unsupervised independent practice? To answer these questions, the performance of trainees has to be monitored and assessed. This not only generates an impression of progress and the extent to which certain end points have been met, but it also creates awareness of things that need improvement. This opens up the feedback loop that can be used to intervene in the learning curves of individual trainees, and is a good example of a Plan-Do-Check-Act (PDCA) cycle. In other words, it is hard to improve when one does not reflect on performance or, as the old adage says, “to measure is to know.”
TBCRC023: A Randomized Phase II Neoadjuvant Trial of Lapatinib Plus Trastuzumab Without Chemotherapy for 12 versus 24 Weeks in Patients with HER2-Positive Breast Cancer
Authors: Mothaffar F. Rimawi, Polly Niravath, Tao Wang, Brent N. Rexer, Andres Forero, Antonio C. Wolff, Rita Nanda, Anna M. Storniolo, Ian Krop, Matthew P. Goetz, Julie R. Nangia, Sao Jiralerspong, Anne Pavlick, Jamunarani Veeraraghavan, Carmine De Angelis, Carolina Gutierrez, Rachel Schiff, Susan G. Hilsenbeck, C. Kent Osborne
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Prior neoadjuvant trials with 12 weeks of dual anti-HER2 therapy without chemotherapy demonstrated a meaningful pathologic complete response (pCR) in patients with HER2-positive breast cancer. In this trial, we sought to determine whether longer treatment would increase the rate of pCR. Patients and Methods: TBCRC023 (NCT00999804) is a randomized phase II trial combining a Simon phase II design in the experimental arm with a pick-the-winner design, not powered for direct comparison. Women with HER2-positive breast tumors measuring ≥2 cm (median = 5 cm) were randomized in a 1:2 ratio to 12 versus 24 weeks of lapatinib and trastuzumab. Letrozole (along with ovarian suppression if premenopausal) was administered in patients whose tumors were also estrogen receptor (ER) positive. All evaluable patients were assessed for in-breast pCR. Results: Ninety-seven patients were enrolled (33 in 12-week arm and 64 in 24-week arm), of whom 94 were evaluable. Median age was 51 years, and 55% were postmenopausal. Median tumor size was 5 cm, and 65% were ER-positive. The rate of pCR in the 24-week arm was 28% and numerically superior to the 12-week arm (12%). This was driven by increased pCR in the ER-positive subgroup (33% vs. 9%). Study treatment was well tolerated, with grade 1–2 diarrhea and acneiform rash being the most common toxicities. Conclusions: Treatment with dual anti-HER2 therapy for 24 weeks led to a numeric increase in pCR rate in women with HER2-positive breast cancer, without using chemotherapy. If validated, this approach may help identify patients who may benefit from deescalation of therapy.
The gut microbiota-inflammation-brain axis in end-stage renal disease: perspectives from default mode network
Authors: Yun Fei Wang, Li Juan Zheng, Ya Liu, Yu Bing Ye, Song Luo, Guang Ming Lu, Dehua Gong, Long Jiang Zhang
Journal: Theranostics (2019)

The gut-brain axis in end-stage renal disease (ESRD) is attracting more and more attention.However, the mechanism of gut-brain axis based cognitive disorders in ESRD patients remains unclear.The purpose of this study was to investigate the linkages between the gut microbiota, inflammatory cytokines, brain default mode network (DMN) and cognitive function in ESRD patients.Methods: This prospective study enrolled 28 ESRD patients (13 males and 15 females, mean age of 44 ± 14 years) and 19 healthy controls (HCs) (12 males and 7 females, mean age of 44 ± 10 years).All subjects underwent stool microbiota analysis, blood inflammatory cytokines examination, brain MRI scans and cognitive assessments.Resting state functional MRI (rs-fMRI) data were used to construct DMN and graph theory was applied to characterize network topological properties.Two samples t-test was applied for the comparisons between ESRD and HCs.Correlation analysis and mediation analysis were conducted among factors with significant group differences.Results: ESRD patients displayed gut microbiota alterations, increased systemic inflammation and worse cognitive performance compared to HCs (all p < 0.05).Graph analysis revealed disrupted DMN topological organization, aberrant nodal centralities and functional connectivities (FCs) in ESRD patients relative to HCs (all p < 0.05, FDR corrected).Significant correlations were found between gut microbiota, inflammatory cytokines, DMN network measures and cognitive assessments.Mediation analysis found that gut microbiota alteration impaired DMN connectivity by increasing systemic inflammation. Conclusion:The present study first revealed gut microbiota alterations, systemic inflammation, DMN dissociation and cognitive dysfunction in ESRD patients simultaneously and further illuminated their inner relationship.
In-vitro bioactivity evaluation and physical properties of an epoxy-based dental sealer reinforced with synthesized fluorine-substituted hydroxyapatite, hydroxyapatite and bioactive glass nanofillers
Authors: Bahaa Abdulrazzaq Jerri Al-Bakhsh, Farhad Shafiei, Atieh Hashemian, Kiana Shekofteh, Behnam Bolhari, Marjan Behroozibakhsh
Journal: Bioactive Materials (2019)

The purpose of this study was to evaluate the physical properties and bioactivity potential of epoxy-based dental sealers modified with synthesized bioactive glass (BAG), hydroxyapatite (HA) and fluorine substituted hydroxyapatite (FHA) nanoparticles. The synthesized powders were incorporated at 10% and 20% into the epoxy-based dental sealer. The setting time, flow and solubility and microhardness of the modified and unmodified samples were examined. The bioactivity was evaluated using FESEM-EDX and elemental mapping, ATR-FTIR and XRD. The flow value of all of the experimental groups except the FHA modified samples, was greater than 20 mm. Concerning solubility, no specimens exhibited more than 1% weight loss. The solubility value of the FHA groups was statistically significant lower than other groups (p ≤ 0.001). The mean hardness values of all of the modified samples were significantly higher than the unmodified group (p ≤ 0.001). Regarding bioactivity, in vitro study revealed that after 3 days immersion in SBF a compact and continuous calcium phosphate layer formed on the surface of epoxy sealers containing BAG and HA nanoparticles. Based on these results, the addition of BAG and HA nanoparticles did not adversely alter the physical properties of epoxy sealers. Additionally, they improved the in vitro bioactivity of the epoxy sealer.
Decarbonise the electricity grid for a sustainable NHS
Authors: Jeremy Wight
Journal: BMJ (2019)

Van Hove and Leng, of the National Institute for Health and Care Excellence (NICE), are right to call for a more sustainable NHS, but wrong about a system-wide approach being needed to move us towards a carbon neutral healthcare system.1 We need more than that.

Achieving a carbon neutral system will be impossible until the wider …
<i>Pten</i> loss in Lgr5<sup>+</sup> hair follicle stem cells promotes SCC development
Authors: Haiyan Chen, Xusheng Wang, Yu Chen, Jimin Han, Deqiang Kong, Meishu Zhu, Xiaobing Fu, Yaojiong Wu
Journal: Theranostics (2019)

Accumulating data support that tissue stem cells give rise to cancer cells.Hair follicle stem cells (HFSCs) undergo cyclic quiescence and activation and may sever as the origin of cutaneous squamous cell carcinoma (SCC).Pten is a tumor suppressor gene that is frequently mutated in hereditary cancer syndromes such as Cowden disease, which is featured with papillomatosis in cutaneous tissues and hyperkeratosis in the acral region of the skin.Additionally, mice with keratinocyte-specific Pten deficiency (k5-Pten -/-mice) show epidermal hyperplasia and spontaneous tumor formation.However, the impact of Pten mutation in HFSCs, such as in Lgr5 + HFSCs, on SCC formation is unclear.Methods: We established experiments with wildtype and Lgr5-CreER; Pten flox/flox mice, and used DMBA/TPA two-stage skin carcinogenesis model to explore the effect of Pten loss in Lgr5 + HFSCs of 3 weeks old mice in skin carcinogenesis.In vitro experiments (cell culture and protein expression analysis) are employed to investigate molecular mechanisms involved.Results: Pten loss in Lgr5 + HFSCs promoted SCC formation, which was attenuated in TNF -/-mice.Notably, β-catenin loss in Lgr5 + HFSCs decreased the formation of SCC.In addition, Pten loss in cultured epidermal stem cells upregulated the levels of both phospho-Akt and β-catenin.Conclusion: Pten loss in Lgr5 + cells induced Akt/β-catenin signaling, and SCCs can subsequently be raised as progeny from these primed Lgr5 + stem cells.
miR-302a Inhibits Metastasis and Cetuximab Resistance in Colorectal Cancer by Targeting NFIB and CD44
Authors: Lina Sun, Ying Fang, Xin Wang, Yanan Han, Feng Du, Cunxi Li, Huaying Hu, Hao Liu, Qi Liu, Jing Wang, Junrong Liang, Ping Chen, Hongbin Yang, Yongzhan Nie, Kaichun Wu, Daiming Fan, Robert J. Coffey, Yuanyuan Lu, Xiaodi Zhao, Xin Wang
Journal: Theranostics (2019)

Introduction: Metastasis and drug resistance contribute substantially to the poor prognosis of colorectal cancer (CRC) patients. However, the epigenetic regulatory mechanisms by which CRC develops metastatic and drug-resistant characteristics remain unclear. This study aimed to investigate the role of miR-302a in the metastasis and molecular-targeted drug resistance of CRC and elucidate the underlying molecular mechanisms. Methods: miR-302a expression in CRC cell lines and patient tissue microarrays was analyzed by qPCR and fluorescence in situ hybridization. The roles of miR-302a in metastasis and cetuximab (CTX) resistance were evaluated both in vitro and in vivo. Bioinformatic prediction algorithms and luciferase reporter assays were performed to identify the miR-302a binding regions in the NFIB and CD44 3'-UTRs. A chromatin immunoprecipitation assay was performed to examine NFIB occupancy in the ITGA6 promoter region. Immunoblotting was performed to identify the EGFR-mediated pathways altered by miR-302a. Results: miR-302a expression was frequently reduced in CRC cells and tissues, especially in CTX-resistant cells and patient-derived xenografts. The decreased miR-302a levels correlated with poor overall CRC patient survival. miR-302a overexpression inhibited metastasis and restored CTX responsiveness in CRC cells, whereas miR-302a silencing exerted the opposite effects. NFIB and CD44 were identified as novel targets of miR-302a. miR-302a inhibited the metastasis-promoting effect of NFIB that physiologically activates ITGA6 transcription. miR-302a restored CTX responsiveness by suppressing CD44-induced cancer stem cell-like properties and EGFR-mediated MAPK and AKT signaling. These results are consistent with clinical observations indicating that miR-302a expression is inversely correlated with the expression of its targets in CRC specimens. Conclusions: Our findings show that miR-302a acts as a multifaceted regulator of CRC metastasis and CTX resistance by targeting NFIB and CD44, respectively. Our study implicates miR-302a as a candidate prognostic predictor and a therapeutic agent in CRC.
Long-Term Exposure to Particulate Air Pollution, Black Carbon, and Their Source Components in Relation to Ischemic Heart Disease and Stroke
Authors: Petter L. S. Ljungman, Niklas Andersson, Leo Stockfelt, Eva M. Andersson, Johan Nilsson Sommar, Kristina Eneroth, Lars Gidhagen, Christer Johansson, Anton Lager, Karin Leander, Peter Molnar, Nancy L. Pedersen, Debora Rizzuto, Annika Rosengren, David Segersson, Patrik Wennberg, Lars Barregard, Bertil Forsberg, Gerd Sallsten, Tom Bellander, Göran Pershagen
Journal: Environmental Health Perspectives (2019)

BACKGROUND: Long-term exposure to particulate matter (PM) in ambient air has been associated with cardiovascular mortality, but few studies have considered incident disease in relation to PM from different sources. OBJECTIVES:We aimed to study associations between long-term exposure to different types of PM and sources, and incident ischemic heart disease (IHD) and stroke in three Swedish cities. METHODS: Based on detailed emission databases, monitoring data, and high-resolution dispersion models, we calculated source contributions to PM with aerodynamic diameter ≤10 lm (PM 10 ), PM with aerodynamic diameter ≤2:5 lm (PM 2:5 ), and black carbon (BC) from road wear, traffic exhaust, residential heating, and other sources in Gothenburg, Stockholm, and Umeå.Registry data for participants from four cohorts were used to obtain incidence of IHD and stroke for first hospitalization or death.We constructed time windows of exposure for same-year, 1-to 5-y, and 6-to 10y averages preceding incidence from annual averages at residential addresses.Risk estimates were based on random effects meta-analyses of cohortspecific Cox proportional hazard models.RESULTS: We observed 5,166 and 3,119 incident IHD and stroke cases, respectively, in 114,758 participants.Overall, few consistent associations were observed between the different air pollution measures and IHD or stroke incidence.However, same-year levels of ambient locally emitted BC (range: 0:01 -4:6 lg=m 3 ) were associated with a 4.0% higher risk of incident stroke per interquartile range (IQR), 0:30 lg=m 3 [95% confidence interval (CI): 0.04, 7.8].This association was primarily related to BC from traffic exhaust.PM 10 (range: 4:4 -52 lg=m 3 ) and PM 2:5 (range: 2:9 -22 lg=m 3 ) were not associated with stroke.Associations with incident IHD were observed only for PM 2:5 exposure from residential heating.DISCUSSION: Few consistent associations were observed between different particulate components and IHD or stroke.However, long-term residential exposure to locally emitted BC from traffic exhaust was associated with stroke incidence.The comparatively low exposure levels may have contributed to the paucity of associations.
Microglia exacerbate white matter injury via complement C3/C3aR pathway after hypoperfusion
Authors: Lin-Yuan Zhang, Jiaji Pan, Muyassar Mamtilahun, Yuan Zhu, Liping Wang, Ashwin Venkatesh, Rubing Shi, Xuanqiang Tu, Kunlin Jin, Yongting Wang, Zhijun Zhang, Guo-Yuan Yang
Journal: Theranostics (2019)

Microglial activation participates in white matter injury after cerebral hypoperfusion. However, the underlying mechanism is unclear. Here, we explore whether activated microglia aggravate white matter injury via complement C3-C3aR pathway after chronic cerebral hypoperfusion. Methods: Adult male Sprague-Dawley rats (n = 80) underwent bilateral common carotid artery occlusion for 7, 14, and 28 days. Cerebral vessel density and blood flow were examined by synchrotron radiation angiography and three-dimensional arterial spin labeling. Neurobehavioral assessments, CLARITY imaging, and immunohistochemistry were performed to evaluate activation of microglia and C3-C3aR pathway. Furthermore, C3aR knockout mice were used to establish the causal relationship of C3-C3aR signaling on microglia activation and white matter injury after hypoperfusion. Results: Cerebral vessel density and blood flow were reduced after hypoperfusion (p<0.05). Spatial learning and memory deficits and white matter injury were shown (p<0.05). These impairments were correlated with aberrant microglia activation and an increase in the number of reactive microglia adhering to and phagocytosed myelin in the hypoperfusion group (p<0.05), which were accompanied by the up-regulation of complement C3 and its receptors C3aR (p<0.05). Genetic deletion of C3ar1 significantly inhibited aberrant microglial activation and reversed white matter injury after hypoperfusion (p<0.05). Furthermore, the C3aR antagonist SB290157 decreased the number of microglia adhering to myelin (p<0.05), attenuated white matter injury and cognitive deficits in chronic hypoperfusion rats (p<0.05). Conclusions: Our results demonstrated that aberrant activated microglia aggravate white matter injury via C3-C3aR pathway during chronic hypoperfusion. These findings indicate C3aR plays a critical role in mediating neuroinflammation and white matter injury through aberrant microglia activation, which provides a novel therapeutic target for the small vessel disease and vascular dementia.