bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rare cause of postmenopausal hyperandrogenism
Authors: De Vis Maarten , Brock Stefanie , Cosyns Stefan , Velkeniers Brigitte 
Published: January 2021

We present an unusual case of mucinous cystadenoma presenting with severe virilisation in a postmenopausal woman. A 71-year-old woman was referred to our outpatient endocrinology clinic because of rapidly progressive androgenic alopecia, clitoromegaly and male pattern pubic hair growth for 1 year. Her medical history was unremarkable. The serum testosterone level was 3.35 µg/L (normal range, <0.4 µg/L), and the dehydroepiandrosterone sulfate level was 267 µg/L (normal range, 100–800 µg/L). MRI of the abdomen revealed a 4×4 cm cystic ovarian mass. A bilateral salpingo-oophorectomy was performed, and histopathology showed a unilocular cystic structure with a yellowish content, compatible with mucinous cystadenoma. Postoperative testosterone levels quickly normalised (<0.4 µg/L).Rapidly developing postmenopausal hyperandrogenism easily turns into a diagnostic challenge for the clinician. Hormone-secreting neoplasms of the ovary are most commonly of sex cord stromal derivation, but atypical causes must be recognised as well. Cystadenomas are among the most common benign ovarian neoplasms and are classically considered ‘non-functional’ tumours. Most of these tumours are asymptomatic and found incidentally on pelvic examination or with ultrasound. To date and to the best of our knowledge, there are only five cases of mucinous adenoma causing virilisation in postmenopausal women identified in the literature. This sixth case adds strength to the link between ovarian mucinous cystadenoma and severe, rapidly progressive hyperandrogenism during menopause. In this case, surgical resection is the treatment of choice.
Peripheral artery disease, lower limb revascularization, and amputation in diabetes patients with and without coronary artery disease: a cohort study from the Western Denmark Heart Registry
Authors: Olesen Kevin Kris Warnakula , Gyldenkerne Christine , Thim Troels , Thomsen Reimar Wernich , Maeng Michael 
Published: January 2021

IntroductionPatients with diabetes have increased risk of lower limb revascularization and amputation due to higher risk of peripheral artery disease (PAD) and peripheral neuropathy. The additive effect of coronary artery disease (CAD) is less clear. We examined the risk of PAD, lower limb revascularization, and amputation in diabetes and non-diabetes patients with and without CAD in patients examined by coronary angiography (CAG).Research design and methodsWe included all patients undergoing CAG between 2003 and 2016 in Western Denmark. Patients with previous CAD, PAD, lower limb revascularization, or amputation were excluded. Patients were stratified by diabetes and CAD status and followed for a maximum of 10 years. Outcomes were PAD, lower limb revascularization, and amputation. We estimated 10-year cumulative incidences and adjusted HRs (aHRs) using patients neither diabetes nor CAD as reference.ResultsA total of 118 787 patients were included, of whom 41 878 (35%) had neither diabetes nor CAD, 5735 (5%) had diabetes alone, 59 427 (50%) had CAD alone, and 11 747 (10%) had both diabetes and CAD. Median follow-up was 6.9 years. Diabetes patients without CAD had higher risk of PAD (3.5%, aHR 1.73, 95% CI 1.51 to 1.97), lower limb revascularization (1.6%, aHR 1.55, 95% CI 1.16 to 2.05), and lower limb amputation (2.4%, aHR 5.51, 95% CI 4.09 to 7.43) compared with patients with neither diabetes nor CAD. CAD was associated with 2.5-fold and 1.8-fold higher risk of PAD and amputation, respectively, among patients without diabetes, and associated with 3.9-fold and 9.5-fold higher risk of PAD and lower limb amputation among patients with diabetes.ConclusionsDespite absence of obstructive CAD, patients with diabetes remained at higher risk of PAD, lower limb revascularization, and lower limb amputation. Diabetes was more strongly associated with amputation than CAD, but CAD exacerbated the risks of PAD, revascularization, and amputation in patients with diabetes.
Capability building for large-scale transformational change: learning from an evaluation of a national programme
Authors: Smith Iain M , Bayliss Elaine , Mukoro Felix 
Published: January 2021

BackgroundThe Long Term Plan presents an ambitious vision for England’s National Health Service which will require a sustained programme of transformational change. The Virtual Academy of Large-Scale Change (VALSC) was developed to build capability in health and care system teams involved in transformation or redesign programmes.MethodsTo evaluate the VALSC, quantitative and qualitative data were collected and reviewed against the Kirkpatrick model. Quantitative data were collected via end-of-session surveys to assess individual knowledge before and after participating in capability-building interventions. Qualitative data were also collected and included post-intervention surveys and interviews. Interviews were transcribed and analysed using an inductive approach to identify themes that were subsequently assessed against the Kirkpatrick model.ResultsResults suggest that the VALSC programme has helped build capability for large-scale change in terms of learning, behaviour change and impact. Participants’ ipsative self-assessment of knowledge demonstrated a significant change (p<0.001) and qualitative data suggested three broad themes in which the VALSC made an impact. First, participants were empowered with transformation and change skills which they applied to local health and care challenges. Second, VALSC helped strengthen connections within and between transformational change teams. Third, VALSC helped transformational change teams to engage more effectively with their stakeholders.ConclusionsThe VALSC developed knowledge, skills, behavioural change and application impact that built capability in individuals and teams. Therefore, continuing to develop capability-building offers that empower and build agency in front-line staff working on service transformation and equip them with approaches, methods and tools to increase their chances of success, is recommended.
Specialty COPD care during COVID-19: patient and clinician perspectives on remote delivery
Authors: Wu Frances , Burt Jenni , Chowdhury Teena , Fitzpatrick Raymond , Martin Graham , van der Scheer Jan W , Hurst John R 
Published: January 2021

IntroductionThe COVID-19 pandemic has impacted specialty chronic obstructive pulmonary disease (COPD) care. We examined the degree to which care has moved to remote approaches, eliciting clinician and patient perspectives on what is appropriate for ongoing remote delivery.MethodsUsing an online research platform, we conducted a survey and consensus-building process involving clinicians and patients with COPD.ResultsFifty-five clinicians and 19 patients responded. The majority of clinicians felt able to assess symptom severity (n=52, 95%), reinforce smoking cessation (n=46, 84%) and signpost to other healthcare resources (n=44, 80%). Patients reported that assessing COPD severity and starting new medications were being addressed through remote care. Forty-three and 31 respondents participated in the first and second consensus-building rounds, respectively. When asked to rate the appropriateness of using remote delivery for specific care activities, respondents reached consensus on 5 of 14 items: collecting information about COPD and overall health status (77%), providing COPD education and developing a self-management plan (74%), reinforcing smoking cessation (81%), deciding whether patients should seek in-person care (72%) and initiating a rescue pack (76%).ConclusionAdoption of remote care delivery appears high, with many care activities partially or completely delivered remotely. Our work identifies strengths and limitations of remote care delivery.
Effect of losartan on performance and physiological responses to exercise at high altitude (5035 m)
Authors: Lucas Samuel J E , Malein William L , Thomas Owen D , Ashdown Kimberly M , Rue Carla A , Joyce Kelsey E , Newman Charles , Cadigan Patrick , Johnson Brian , Myers Stephen D , Myers Fiona A , Wright Alexander D , Delamere John , Imray Chris H E , Bradwell Arthur R , Edsell Mark 
Published: January 2021

ObjectiveAltitude-related and exercise-related elevations in blood pressure (BP) increase the likelihood of developing pulmonary hypertension and high-altitude illness during high-altitude sojourn. This study examined the antihypertensive effect and potential exercise benefit of the angiotensin II receptor antagonist losartan when taken at altitude.MethodsTwenty participants, paired for age and ACE genotype status, completed a double-blinded, randomised study, where participants took either losartan (100 mg/day) or placebo for 21 days prior to arrival at 5035 m (Whymper Hut, Mt Chimborazo, Ecuador). Participants completed a maximal exercise test on a supine cycle ergometer at sea level (4 weeks prior) and within 48 hours of arrival to 5035 m (10-day ascent). Power output, beat-to-beat BP, oxygen saturation (SpO2) and heart rate (HR) were recorded during exercise, with resting BP collected from daily medicals during ascent. Before and immediately following exercise at 5035 m, extravascular lung water prevalence was assessed with ultrasound (quantified via B-line count).ResultsAt altitude, peak power was reduced relative to sea level (p<0.01) in both groups (losartan vs placebo: down 100±29 vs 91±28 W, p=0.55), while SpO2(70±6 vs 70±5%, p=0.96) and HR (146±21 vs 149±24 bpm, p=0.78) were similar between groups at peak power, as was the increase in systolic BP from rest to peak power (up 80±37 vs 69±33 mm Hg, p=0.56). Exercise increased B-line count (p<0.05), but not differently between groups (up 5±5 vs 8±10, p=0.44).ConclusionLosartan had no observable effect on resting or exercising BP, exercise-induced symptomology of pulmonary hypertension or performance at 5035 m.
Impact of pregnancy and risk factors for ventricular arrhythmias in women with tetralogy of Fallot
Authors: Quattrone Alessia , Lie Oyvind H , Nestaas Eirik , de Lange Charlotte , Try Kirsti , Lindberg Harald L , Skulstad Helge , Erikssen Gunnar , Edvardsen Thor , Haugaa Kristina , Estensen Mette E 
Published: January 2021

ObjectivePatients with tetralogy of Fallot (TOF) have high survival rates 30 years after surgical repair. Many patients experience pregnancy; however, the effects of pregnancy on the long-term cardiovascular outcome are not well known. We investigated the association of pregnancy and cardiac function with occurrence of ventricular arrhythmia (VA) in women with TOF.MethodsWe recruited 80 women with repaired TOF from the national database. Holter monitoring or implanted devices detected VA, defined as non-sustained or sustained ventricular tachycardia or aborted cardiac arrest. All patients underwent echocardiography. Blood tests included NT-proBNP (N-terminal pro-brain natriuretic peptide).Results55 (69%) women had experienced pregnancy. Mean age was lower in nulliparous compared with those with children (30±9 vs 40±9, p<0.01).VA had occurred in 17 (21%) women. Prevalence of VA was higher in women who had experienced pregnancy (n=16, 94%) compared with nulliparous (n=1, 6%) (p=0.02), also when adjusted for age (OR 12.9 (95% CI 1.5 to 113.2), p=0.02).Right ventricular mechanical dispersion was more pronounced in patients with VA (50±8 ms vs 39±14 ms, p=0.01, age-adjusted OR 2.1 (95% CI 1.3 to 7.5), p=0.01). NT-proBNP was also a marker of VA (211 ng/L (127 to 836) vs 139 ng/L (30 to 465), p=0.007). NT-proBNP >321 ng/L (normal values <170 ng/L) detected women with VA (p=0.019), also independent of age (OR 7.2 (95% CI 1.7 to 30.1), p=0.007).ConclusionPregnancy was associated with higher prevalence of VA among women with TOF. Right ventricular mechanical dispersion and NT-proBNP were age-independent markers of VA. These may have importance for pregnancy counselling and risk stratification.
Effects of alcohol consumption and smoking on risk for RA: results from a Swedish prospective cohort study
Authors: Hedenstierna Louise , Bellocco Rino , Ye Weimin , Adami Hans-Olov , Åkerstedt Torbjörn , Trolle Lagerros Ylva , Hedström Anna Karin 
Published: January 2021

ObjectiveSeveral, but not all studies, have shown a dose-dependent inverse association with alcohol consumption and rheumatoid arthritis (RA), whereas smoking is an established risk factor for RA. We aimed to study the association between alcohol consumption and RA incidence and investigate a potential interaction between alcohol and smoking habits, regarding RA incidence.MethodsWe used a prospective cohort study, based on 41 068 participants with detailed assessment of alcohol intake, smoking and potential confounders at baseline in 1997. We ascertained a total of 577 incident cases of RA during a mean of 17.7 years of follow-up through linkage to nationwide and essentially complete databases. Multivariate Cox proportional hazards models were used to estimate HR with 95% CI. Interaction on the additive scale between alcohol and smoking was estimated by calculating the attributable proportion due to interaction (AP).ResultsOverall, alcohol consumption was associated with a 30% reduced incidence of RA (HR 0.69, 95% CI 0.55 to 0.86) with a dose–response relationship (p value for trend <0.001) which remained significant after stratification by age and smoking habits. The positive association between smoking and RA incidence was reduced with increasing alcohol consumption (p value for trend <0.001). A synergistic effect was observed between alcohol and smoking (AP 0.40, 95% CI 0.15 to 0.64), indicating that 40% of the cases among the double exposed are due to the interaction per se.ConclusionsOur findings suggest an inverse association between alcohol consumption and RA incidence, and a synergistic effect between alcohol and smoking.
Preparation of Stable Hydrophilic Polyethyleneimine Cross-Linked Graphene Oxide/Titanium Dioxide Membranes for Dye Separation
Authors: Liu Hongwei , Liu Jinhua , Li Jun , Liu Zhanchao , Wu Weifu , Song Yunfeng , Liu Yan 
Published: January 2021

An excellent novel laminar and hierarchical polyethyleneimine cross-linked graphene oxide/titanium dioxide (GO–TiO2–PEI) membrane was successfully prepared by vacuum filtration technology using polyethyleneimine (PEI) as the cross-linking agent and a GO–TiO2 nanocomposite as the substrate. The resultant membrane (GO–TiO2–PEI) displayed a favorable antifouling performance with bovine serum albumin (BSA) and showed good hydrophilicity and wettability, with a static water contact angle of 13.2∘. The stability of the GO–TiO2–PEI membrane in aqueous solution obviously improved with the cross-linking of PEI compared with that of the GO and GO–TiO2 membranes. The GO–TiO2–PEI membrane also exhibited a satisfactory water flux of 48.6[Formula: see text]L m[Formula: see text] h[Formula: see text] bar[Formula: see text]. The GO–TiO2–PEI membrane exhibited a good performance for effectively separating different dyes including methylene blue (MB), rhodamine B (RB), methyl orange (MO), sunset yellow (SY), new coccine (NC) and amaranth. All the above results suggested that the GO–TiO2–PEI membrane could be used as an excellent stable hydrophilic membrane for efficiently separating dyes from aqueous solution.
Current situation of early warning and emergency countermeasures of volcanic eruptions in China
Authors: Wang Xinru , Pan Bo , Pan Mao , Liang Yiqiang 
Published: January 2021

Abstract
Volcanic eruptions, as major natural disasters, often cause considerable numbers of casualties and economic losses. Given the substantial potential hazards posed to society, volcanic eruptions have become a central concern for national public safety systems. This paper introduces the risk degrees and classification of activity of major active volcanoes in China, reviews early warning policies in the government response to volcanic eruptions, compares the early warning levels of China and the USA, and proposes an early warning theme adapted to the characteristics of volcanic activity in mainland China. The current volcanic warning system of China still has considerable room for improvement; therefore, improvements in monitoring volcanic activities and the antihazard capacity of volcanic eruption in the future are urgently needed.
Combining Neratinib with CDK4/6, mTOR, and MEK Inhibitors in Models of HER2-positive Cancer
Authors: Zhao Ming , Scott Stephen , Evans Kurt W. , Yuca Erkan , Saridogan Turcin , Zheng Xiaofeng , Wang Heping , Korkut Anil , Cruz Pico Christian X. , Demirhan Mehmet , Kirby Bryce , Kopetz Scott , Diala Irmina , Lalani Alshad S. , Piha-Paul Sarina , Meric-Bernstam Funda 
Published: January 2021

Abstract

Purpose:
Neratinib is an irreversible, pan-HER tyrosine kinase inhibitor that is FDA approved for HER2-overexpressing/amplified (HER2+) breast cancer. In this preclinical study, we explored the efficacy of neratinib in combination with inhibitors of downstream signaling in HER2+ cancers in vitro and in vivo.

Experimental Design:
Cell viability, colony formation assays, and Western blotting were used to determine the effect of neratinib in vitro. In vivo efficacy was assessed with patient-derived xenografts (PDX): two breast, two colorectal, and one esophageal cancer (with HER2 mutations). Four PDXs were derived from patients who received previous HER2-targeted therapy. Proteomics were assessed through reverse phase protein arrays and network-level adaptive responses were assessed through Target Score algorithm.

Results:
In HER2+ breast cancer cells, neratinib was synergistic with multiple agents, including mTOR inhibitors everolimus and sapanisertib, MEK inhibitor trametinib, CDK4/6 inhibitor palbociclib, and PI3Kα inhibitor alpelisib. We tested efficacy of neratinib with everolimus, trametinib, or palbociclib in five HER2+ PDXs. Neratinib combined with everolimus or trametinib led to a 100% increase in median event-free survival (EFS; tumor doubling time) in 25% (1/4) and 60% (3/5) of models, respectively, while neratinib with palbociclib increased EFS in all five models. Network analysis of adaptive responses demonstrated upregulation of EGFR and HER2 signaling in response to CDK4/6, mTOR, and MEK inhibition, possibly providing an explanation for the observed synergies with neratinib.

Conclusions:
Taken together, our results provide strong preclinical evidence for combining neratinib with CDK4/6, mTOR, and MEK inhibitors for the treatment of HER2+ cancer.
CD4
+
T Cell‐Specific Proteomic Pathways Identified in Progression of Hypertension Across Postmenopausal Transition
Authors: Uhlorn Joshua A. , Husband Nathaniel A. , Romero‐Aleshire Melissa J. , Moffett Caitlin , Lindsey Merry L. , Langlais Paul R. , Brooks Heddwen L. 
Published: January 2021

Background

Menopause is associated with an increase in the prevalence and severity of hypertension in women. Although premenopausal females are protected against T cell‐dependent immune activation and development of angiotensin II (Ang II) hypertension, this protection is lost in postmenopausal females. Therefore, the current study hypothesized that specific CD4
+
T cell pathways are regulated by sex hormones and Ang II to mediate progression from premenopausal protection to postmenopausal hypertension.

Methods and Results

Menopause was induced in C57BL/6 mice via repeated 4‐vinylcyclohexene diepoxide injections, while premenopausal females received sesame oil vehicle. A subset of premenopausal mice and all menopausal mice were infused with Ang II for 14 days (Control, Ang II, Meno/Ang II). Proteomic and phosphoproteomic profiles of CD4
+
T cells isolated from spleens were examined. Ang II markedly increased CD4
+
T cell protein abundance and phosphorylation associated with DNA and histone methylation in both premenopausal and postmenopausal females. Compared with premenopausal T cells, Ang II infusion in menopausal mice increased T cell phosphorylation of MP2K2, an upstream regulator of ERK, and was associated with upregulated phosphorylation at ERK targeted sites. Additionally, Ang II infusion in menopausal mice decreased T cell phosphorylation of TLN1, a key regulator of IL‐2Rα and FOXP3 expression.

Conclusions
These findings identify novel, distinct T cell pathways that influence T cell‐mediated inflammation during postmenopausal hypertension.
Early Aspirin Discontinuation After Coronary Stenting: A Systematic Review and Meta‐Analysis
Authors: Wiebe Jens , Ndrepepa Gjin , Kufner Sebastian , Lahmann Anna L. , Xhepa Erion , Kuna Constantin , Voll Felix , Gosetti Rosanna , Laugwitz Karl‐Ludwig , Joner Michael , Kastrati Adnan , Cassese Salvatore 
Published: January 2021

Background
The clinical impact of early aspirin discontinuation compared with dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention with stenting remains poorly studied. We investigated the clinical outcomes of patients assigned to either early aspirin discontinuation or DAPT after percutaneous coronary intervention with stenting.

Methods and Results

We performed a meta‐analysis of aggregate data from randomized clinical trials enrolling participants receiving a percutaneous coronary intervention with stenting and assigned to either early aspirin discontinuation or DAPT. Scientific databases were searched from inception through March 30, 2020. Trial‐level hazard ratios (HRs) and 95% CIs were pooled using a random effects model with inverse variance weighting. The primary outcome was all‐cause death. Secondary outcomes were myocardial infarction, stent thrombosis, stroke, and major bleeding. Overall, 36 206 participants were allocated to either early aspirin discontinuation (experimental therapy, n=18 088) or DAPT (control therapy, n=18 118) in 7 trials. Median follow‐up was 12 months. All‐cause death occurred in 2.5% of patients assigned to experimental and 2.9% of patients assigned control therapy (hazard ratio [HR], 0.91, 95% CI, 0.75–1.11;
P
=0.37). Overall, patients treated with experimental versus control therapy showed no significant difference in terms of myocardial infarction (HR, 1.02 [0.85–1.22],
P
=0.81), stent thrombosis (HR, 1.02 [0.87–1.20],
P
=0.83), or stroke (HR, 1.01 [0.68–1.49],
P
=0.96). However, the risk for major bleeding (HR, 0.58 [0.43–0.77],
P
<0.01) was significantly reduced by experimental as compared with control therapy.

Conclusions
In patients treated with percutaneous coronary intervention and stenting, assigned to a strategy of early aspirin discontinuation versus DAPT, the risk of death and ischemic events is not significantly different but the risk of bleeding is lower.