bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies
Authors: Chalitsios Christos V , Shaw Dominick E , McKeever Tricia M 
Published: October 2020

BackgroundInhaled (ICS) and oral (OCS) corticosteroids are used widely in asthma; however, the risk of osteoporosis and fragility fracture (FF) due to corticosteroids in asthma is not well-established.MethodsWe conducted two nested case-control studies using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we separately identified patients with osteoporosis or FF and gender-, age- and practice-matched controls. Conditional logistic regression was used to determine the association between ICS and OCS exposure, and the risk of osteoporosis or FF. The prevalence of patients receiving at least one bisphosphonate was also calculated.ResultsThere was a dose–response relationship between both cumulative dose and number of OCS/ICS prescriptions within the previous year, and risk of osteoporosis or FF. After adjusting for confounders, people receiving more OCS prescriptions (≥9 vs 0) had a 4.50 (95% CI 3.21 to 6.11) and 2.16 (95% CI 1.56 to 3.32) increased risk of osteoporosis and FF, respectively. For ICS (≥11 vs 0) the ORs were 1.60 (95% CI 1.22 to 2.10) and 1.31 (95% CI 1.02 to 1.68). The cumulative dose had a similar impact, with those receiving more OCS or ICS being at greater risk. The prevalence of patients taking ≥9 OCS and at least one bisphosphonate prescription was just 50.6% and 48.4% for osteoporosis and FF, respectively.ConclusionsThe findings suggest that exposure to OCS or ICS is an independent risk factors for bone health in patients with asthma. Steroid administration at the lowest possible level to maintain asthma control is recommended.
Biochemical adaptations of the stout razor clam (Tagelus plebeius) to changes in oxygen availability: resilience in a changing world?
Authors: Yusseppone M.S. , Noya Abad T. , Risoli M.C. , Sabatini S.E. , Ríos de Molina M.C. , Lomovasky B.J. 
Published: October 2020

Climate change is producing sea level rise and deoxygenation of the ocean, altering estuaries and coastal areas. Changes in oxygen availability are expected to have consequences on the physiological fitness of intertidal species. In this work we analyze the coping response of the intertidal stout razor clam (Tagelus plebeius (Lightfoot, 1786)) to extreme environmental changes in oxygen concentration. Their biochemical responses to normoxia, hypoxia, and hyperoxia transition at different intertidal level (low–high) were measured through an in situ transplant experiment. The high intertidal level negatively affected the analyzed traits of the T. plebeius populations. The differences in reactive oxygen species production, total oxyradical scavenger capacities, and catalase activity also suggested more stressful conditions at the high level where long-term hypoxia periods occur. Both hypoxia and re-oxygenation provoked re-adjustments in the antioxidant responses and higher lipid oxidative damage (normoxia < hypoxia < re-oxygenation). The observed responses in transplanted clams at the opposite intertidal level suggested the potential acclimation of T. plebeius to cope with new environmental conditions. These findings are discussed within a global changing context where both increasing deoxygenation conditions and sea level rise are predicted to be exacerbated in the area driven by climate change.
Confining and compressing the atom
Authors: Connerade Jean-Patrick 
Published: October 2020

Abstract
A review of effects due to the confinement and compression of atoms is presented. It is argued that they provide new insights into the properties of atoms and, in particular, into their interactions with the microscopic environment. Studies of confined atoms allow one to understand better the changes of behaviour which occur under pressure. Some applications to practical situations are also suggested.

Graphical abstract
Altered Gemcitabine and Nab-paclitaxel Scheduling Improves Therapeutic Efficacy Compared with Standard Concurrent Treatment in Preclinical Models of Pancreatic Cancer
Authors: Wolfe Adam R. , Robb Ryan , Hegazi Ahmad , Abushahin Laith , Yang Linlin , Shyu Duan-Liang , Trevino Jose G. , Cruz-Monserrate Zobeida , Jacob John R. , Palanichamy Kamalakannan , Chakravarti Arnab , Williams Terence M. 
Published: October 2020

Abstract

Purpose:
Concurrent gemcitabine and nab-paclitaxel treatment is one of the preferred chemotherapy regimens for metastatic and locally advanced pancreatic ductal adenocarcinoma (PDAC). Previous studies demonstrate that caveolin-1 (Cav-1) expression is critical for nab-paclitaxel uptake into tumors and correlates with response. Gemcitabine increases nab-paclitaxel uptake by increasing Cav-1 expression. Thus, we hypothesized that pretreatment with gemcitabine would further enhance the sensitivity of PDAC to nab-paclitaxel by increasing Cav-1 expression and nab-paclitaxel uptake.

Experimental Design:
We investigated the sensitivity of different gemcitabine and nab-paclitaxel treatment regimens in a panel of PDAC cell lines and orthotopic xenograft models. The sensitivity of different treatment regimens was compared with the standard concurrent treatment.

Results:
Pretreatment with gemcitabine before nab-paclitaxel increased Cav-1 and albumin uptake and significantly decreased proliferation and clonogenicity compared with concurrent treatment, which correlated with increased levels of apoptosis. Cav-1 silencing reduced the uptake of albumin, and therapeutic advantage was observed when cells were pretreated with gemcitabine prior to nab-paclitaxel. In addition, we observed that pretreatment with gemcitabine resulted in partial synchronization of cells in the G2–M-phase at the time of nab-paclitaxel treatment, providing another mechanism for the benefit of altered scheduling. In heterotopic and orthotopic xenograft models, the altered schedule of gemcitabine prior to nab-paclitaxel significantly delayed tumor growth compared with concurrent delivery without added toxicity.

Conclusions:
Pretreatment with gemcitabine significantly increased nab-paclitaxel uptake and correlated with an increased treatment efficacy and survival benefit in preclinical models, compared with standard concurrent treatment. These results justify preclinical and clinical testing of this altered scheduling combination.
TACIMA-218: A Novel Pro-Oxidant Agent Exhibiting Selective Antitumoral Activity
Authors: Abusarah Jamilah , Cui Yun , El-Hachem Nehme , El-Kadiry Abed El-Hakim , Hammond-Martel Ian , Wurtele Hugo , Beaudry Annie , Raynal Noël J.-M. , Robert Francis , Pelletier Jerry , Jankovic Maja , Mercier Francois , Kamyabiazar Samaneh , Annabi Borhane , Rafei Moutih 
Published: October 2020

AbstractWe report the discovery, via a unique high-throughput screening strategy, of a novel bioactive anticancer compound: Thiol Alkylating Compound Inducing Massive Apoptosis (TACIMA)-218. We demonstrate that this molecule engenders apoptotic cell death in genetically diverse murine and human cancer cell lines, irrespective of their p53 status, while sparing normal cells. TACIMA-218 causes oxidative stress in the absence of protective antioxidants normally induced by Nuclear factor erythroid 2–related factor 2 activation. As such, TACIMA-218 represses RNA translation and triggers cell signaling cascade alterations in AKT, p38, and JNK pathways. In addition, TACIMA-218 manifests thiol-alkylating properties resulting in the disruption of redox homeostasis along with key metabolic pathways. When administered to immunocompetent animals as a monotherapy, TACIMA-218 has no apparent toxicity and induces complete regression of pre-established lymphoma and melanoma tumors. In sum, TACIMA-218 is a potent oxidative stress inducer capable of selective cancer cell targeting.
How Much Do Nurses Know About Residents?
Authors: Asija Richa , Fairbairn Kelly , Sachdeva Shireen , Kreider Michael , Diaz Graal , Rayhrer Constanze 
Published: October 2020

Nurses work closely with residents on a daily basis but may not understand the details about residency training and experience. We investigated our institution to understand misconceptions nurses may have about residents and provide education. Nurses (n = 26) participated in a lecture about residents and were given identical surveys before and after the lecture. Twenty-two nurses (85%) were medical/surgical, 1 (4%) was obstetrical, and 3 (11%) were critical care. In the pre-education survey, nurses were able to correctly identify the main purpose of residency as educational. Most nurses knew that residents arrived at the hospital between 5:00 and 7:00 am and that residents could perform bedside procedures. A marked increase was found between correct pre- and post-survey answers in 4 questions: interns are doctors (15% vs. 77%), residents’ work hours (23% vs. 65%), correct average salary (39% vs. 92%), and correct paid time off (PTO) days per year (8% vs. 85%). Salaries were overestimated, and work hours and PTO were underestimated. Most nurses did not know interns are in fact doctors. Our post-educational survey demonstrated improved knowledge of resident credentials, challenges, and work environment. The mean result for the post-educational survey was significantly higher than the pre-educational survey results, indicating that the educational intervention was effective in improving nurses’ knowledge regarding residents.
Decrease in Respiratory Related Hospitalizations in Tracheostomy-Dependent Children Who Tolerate Passy-Muir Valve Use
Authors: Li Lilun , Wikner Emily , Behzadpour Hengameh , Perez Geovanny , Mudd Pamela 
Published: October 2020

Objective: To assess the effect of Passy-Muir® Valve (PMV) tolerance on respiratory illness and respiratory related hospital admissions in tracheostomy-dependent children. Methods: Retrospective cohort study of 262 patients who underwent tracheostomy placement between 2012 and 2018 at a tertiary free-standing children’s hospital. Outcome measures studied were number of reported upper respiratory infections and respiratory related hospitalizations per year (RRH/year). Results: About 135 (51.5%) tracheostomy-dependent children underwent PMV trials, and 106 (78.5%) of these children were able to tolerate PMV for at least 1 hour daily. When comparing children who tolerated PMV versus those who did not, the latter group had significantly higher rates of subglottic stenosis but no significant differences in RRH/year or average age. In those children who tolerated PMV and achieved routine use of PMV > 1 hour/day, an average of 1.14 RRH/year occurred prior to PMV tolerance, as compared with 0.57 RRH/year after PMV tolerance ( P = .003). Multivariate analysis shows that in patients <2 years, there is a significant decrease in RRH/year after PMV tolerance is attained (1.53 vs 0.76, P = .001), independent of indication for tracheostomy. Conclusion: In tracheostomy-dependent children who tolerate PMV use routinely >1 hour/day there are decreased rates of respiratory related hospitalizations (RRH). Children <2 years of age have the most impact of RRH, with rates that are significantly lower with routine use of the PMV.
Efficacy and safety of nebivolol in hypertensive patients: a meta-analysis of randomized controlled trials
Authors: Liu Jun-Ying , Guo Li-Na , Peng Wan-Zhong , Jiang Yang , Wang Ai-Li , Guo Xue-Min , Xu Ze-Sheng 
Published: October 2020

Purpose Our meta-analysis was undertaken to evaluate the efficacy and safety of nebivolol compared with other second-generation β blockers for hypertensive patients. Methods We searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov databases for randomized controlled trials (RCTs). The efficacy endpoints included systolic blood pressure (SBP), diastolic blood pressure (DBP), reduction of SBP and DBP, heart rate (HR), and adverse events (AEs). Findings Eight RCTs with 1514 patients met the inclusion criteria. HR was significantly lower in patients receiving other second-generation β blockers compared with patients receiving nebivolol. There was no difference the reduction of blood pressure (SBP and DBP) or the reduction of SBP or DBP between the groups. The incidence of AEs was lower in patients taking nebivolol compared with patients taking other second-generation β blockers. Conclusions No significant difference was demonstrated between nebivolol and other second-generation β blockers in the reduction of blood pressure, SBP, and DBP. The tolerability of nebivolol was significantly better compared with other second-generation β blockers, and nebivolol was also associated with a stable HR and a lower risk of AEs compared with other second-generation β blockers.
Effect of baicalin on gestational hypertension-induced vascular endothelial cell damage
Authors: Liu Yang , Xiong Miao , Zhou Fangfang , Shi Nana , Jia Yunbin 
Published: October 2020

Objective Baicalin is a compound extracted from the dried root of Scutellaria baicalensis Georgi. Studies have shown that baicalin has a protective effect on vascular endothelial cells, but whether baicalin could alleviate ascular endothelial cell damage in pregnancy-induced hypertensive patients remains unknown. Materials and methods We established a hypertensive pregnant rat model to study vascular endothelial injury during pregnancy-induced hypertension. Plasma epoprostenol (PGI-2), thromboxane A2 (Txa-2), β-human chorionic gonadotropin (β-HCG), and estrogen levels in rats were detected using ELISA. Vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and C-reactive protein (CRP) expression were detected using western blotting and quantitative PCR (q-PCR). Results Results showed that baicalin alleviated symptoms of pregnancy-induced hypertension. CRP, Txa-2, and β-HCG expression were significantly upregulated, while VEGF, eNOS, PGI-2, and estrogen expression was decreased in plasma and placental tissues of hypertensive rats. However, the levels of these injury indicators were significantly decreased after baicalin therapy, while the expression of protective indicators was significantly increased. Conclusion Baicalin reversed vascular endothelial cell injury in pregnant hypertensive rats by promoting VEGF, eNOS, PGI-2, and estrogen expression.
Effect of neurological screening on early dementia detection in southern Italy
Authors: De Cola Maria Cristina , Triglia Giuseppe , Camera Martina , Corallo Francesco , Di Cara Marcella , Bramanti Placido , Lo Buono Viviana 
Published: October 2020

Objective Population screening can facilitate early diagnosis of dementia and improve disease management. This study examined the effects of a screening campaign for neurodegenerative disorders on the early diagnosis of dementia using 2-year follow-up data. Methods A 5-day screening campaign was conducted that comprised neurological, neuropsychological and other specialist examinations. Identification of alterations during the neurological examination was followed-up by further diagnostic examinations to confirm the neurological impairment. Results Neurological alterations were observed in 39% of the screened subjects, who were mostly diagnosed with mild cognitive impairment and referred to a dementia and cognitive disorders centre. Suspicion of neurological impairment was a risk factor for inclusion in a specific neurological ambulatory follow-up and a condition for exemption from payment for medical examinations. Conclusions Neurodegenerative screening initiatives should include subjects selected by general practitioners. It would be useful to create a network including primary care physicians and cognitive disorder centres. Telemedicine tools (e.g., teleconsulting) could also be used to facilitate early diagnosis.
Melatonin attenuates AFB1-induced cardiotoxicity via the NLRP3 signalling pathway
Authors: Yan Hui , Ge Junhua , Gao Hongrui , Pan Yang , Hao Yan , Li Jian 
Published: October 2020

Objective This study was conducted to investigate the protective effect of melatonin against aflatoxin B1 (AFB1) cardiotoxicity by evaluating NOD-like receptor family pyrin domain containing protein 3 (NLRP3) signalling. Methods Four groups of five rats each were assessed: control group (vehicle only), two AFB1 (0.15 and 0.3 mg/kg)-treated groups, and a combined AFB1 (0.3 mg/kg) plus melatonin (5 mg/kg)-treated group. After 6 weeks of once-daily intragastric treatment, cardiac pathologic changes were observed under optical microscopy, and oxidative/antioxidative parameters were measured in myocardial homogenate. Cardiac tissue expression of NLRP3 and other important inflammasome components was also analysed. Results Compared with controls, increasing concentrations of AFB1 were associated with increased oxidative stress and caused myocardial structure damage. In addition, AFB1 dose-dependently activated the NLRP3 signalling pathway. All these indices were significantly ameliorated by combined AFB1 plus melatonin treatment versus high-dose AFB1 alone. Conclusion Melatonin may reduce NLRP3 inflammasome activation by inhibiting oxidative stress and thus protect against injury from AFB1-induced myocardial toxicity.
The Association of Preoperative Hematocrit With Adverse Events Following Exploratory Laparotomy in Septic Patients: A Retrospective Analysis
Authors: Chaturvedi Rahul , Burton Brittany N. , Trivedi Suraj , Schmidt Ulrich H. , Gabriel Rodney A. 
Published: October 2020

Background: Sepsis continues to be the leading cause of death in intensive care units and surgical patients comprise almost one third of all sepsis patients. Anemia is a modifiable risk factor for worse postoperative outcomes in sepsis patients. Here we aim to evaluate the association of preoperative anemia and postoperative mortality in sepsis patients undergoing exploratory laparotomy. Methods: The National Surgical Quality Improvement Program registry was used to query for preoperative sepsis patients undergoing exploratory laparotomy between 2014 and 2016. Preoperative hematocrit was stratified into 4 categories: ≥30% to polycythemia, <21%, 21 and less than 30%, and polycythemia. The primary outcome was 30-day mortality. Multivariable logistic regression was used to evaluate the association of preoperative hematocrit with primary and secondary endpoints. The multivariable analysis included preoperative hematocrit, gender, age, BMI, smoking status, functional status, hypertension, steroid use, bleeding disorder, and sepsis. The odds ratio (OR) with associated 95% confidence interval (CI) is reported for all outcomes. A p-value of less than <0.05 was considered statistically significant. Results: The unadjusted 30-day death rate was the highest for patients with preoperative hematocrit <21% (p < 0.001) compared to the other hematocrit cohorts. The odds of 30-day death was significantly increased for patients with preoperative hematocrit <21% (OR 2.39 95% CI: 1.28-4.49, p = 0.006) and 21-30% (OR 1.35, 95% CI: 1.05 -1.72, p = 0.017) compared to patients with preoperative hematocrit of ≥30% and less than polycythemic ranges (reference cohort). Conclusion: Preoperative anemia in sepsis patients undergoing surgery can lead to increased mortality, postoperative complications, and length of hospital stay. Diagnosing sepsis early in the hospital course can allow physicians more time to titrate anticoagulation medications and treat preoperative anemia.
Impact of Thrombocytopenia on Postoperative Bleeding Incidence in Patients Receiving Aspirin Following Coronary Artery Bypass Grafting
Authors: Rodino Anne M. , Henderson James B. , Dobbins Kelsey F. , Rubin Deanna T. , Hollis Ian B. 
Published: October 2020

Background: Early postoperative aspirin following coronary artery bypass graft (CABG) surgery has been shown to maintain bypass graft patency, reduce mortality, and prevent adverse cardiovascular events. Despite this known benefit, aspirin may be delayed due to thrombocytopenia and perceived higher bleeding risk. The purpose of this study was to assess the impact of postoperative platelet count on bleeding in patients receiving aspirin after CABG. Methods: A retrospective analysis included all patients who underwent CABG surgery at our institution from April 2014 to June 2018 and received aspirin within 24 hours. The primary outcome was International Society on Thrombosis and Hemostasis (ISTH) major bleeding within 7 days (or up to discharge) following CABG surgery compared between patients with and without postoperative thrombocytopenia. Results: This study included 280 patients. Major bleeding occurred in 24.6% of the population, with no difference when stratified by the presence or absence of postoperative thrombocytopenia (27.3% versus 23.8%, p = 0.571). There was no significant difference in hemoglobin fall (13.6% versus 14%, p = 0.948), transfusion requirement (6.1% versus 4.2%, p = 0.531), or critical site bleeding (12.1% versus 7.9%, p = 0.298). Conclusion: In this single-center analysis of patients who received aspirin within 24 hours of CABG, postoperative thrombocytopenia was not associated with an increase in bleeding.
Immunogenetics and human papillomavirus (HPV) in male genital lichen sclerosus (MGLSc)
Authors: Shim Tang Ngee , Harwood Catherine A , Marsh Steven GE , Gotch Frances M , Quint Wim , de Koning Maurits N , Francis Nick , Jameson Charles , Freeman Alex , Minhas Suks , Dinneen Michael , Muneer Asif , Bunker Christopher B 
Published: October 2020

Background The pathogenesis of male genital lichen sclerosus (MGLSc) is controversial. Incriminated factors include infection with human papillomavirus (HPV) and autoimmunity (e.g. Human Leukocyte Antigen [HLA]). To address the roles of HLA and HPV in MGLSc we studied adult Caucasian males with a clinical and histological diagnosis of MGLSc. The men in the study attended two specialised Male Genital Dermatoses Clinics between July 2011 and September 2012 and were selected and phenotyped from the clinical records. DNA was extracted from blood and paraffin-embedded biopsy sections, for HLA and HPV typing, respectively. HLA allele frequencies were compared with those derived from the UK-based Caucasian population. Eighty-eight cases of MGLSc were identified. HPV DNA was detected in 33/88 (37.5%) cases of MGLSc. HPV16 was the most prevalent type found: 11/88 (12.5%) MGLSc. No statistically significant HLA associations were established but HLA-B*35, -B*51, -C*15, -DRB1*04, -DRB1*10 (predisposition) and -DQA1*01 (protection) were revealed as alleles of interest. HPV16-associated MGLSc cases showed no statistically significant association with HLA genotype. The relationship between HPV and MGLSc suggests a passenger effect rather than a pathogenic role. HLA is not associated with MGLSc nor co-existent HPV16.