bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise training reverses cardiac aging phenotypes associated with heart failure with preserved ejection fraction in male mice
Authors: Roh Jason D. , Houstis Nicholas , Yu Andy , Chang Bliss , Yeri Ashish , Li Haobo , Hobson Ryan , Lerchenmüller Carolin , Vujic Ana , Chaudhari Vinita , Damilano Federico , Platt Colin , Zlotoff Daniel , Lee Richard T. , Shah Ravi , Jerosch‐Herold Michael , Rosenzweig Anthony 
Published: May 2020

AbstractHeart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age‐related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Given the strong association between aging and HFpEF, we hypothesized that ExT might reverse cardiac aging phenotypes that contribute to HFpEF pathophysiology and additionally provide a platform for novel mechanistic and therapeutic discovery. Here, we show that aged (24–30 months) C57BL/6 male mice recapitulate many of the hallmark features of HFpEF, including preserved left ventricular ejection fraction, subclinical systolic dysfunction, diastolic dysfunction, impaired cardiac reserves, exercise intolerance, and pathologic cardiac hypertrophy. Similar to older humans, ExT in old mice improved exercise capacity, diastolic function, and contractile reserves, while reducing pulmonary congestion. Interestingly, RNAseq of explanted hearts showed that ExT did not significantly modulate biological pathways targeted by conventional HF medications. However, it reversed multiple age‐related pathways, including the global downregulation of cell cycle pathways seen in aged hearts, which was associated with increased capillary density, but no effects on cardiac mass or fibrosis. Taken together, these data demonstrate that the aged C57BL/6 male mouse is a valuable model for studying the role of aging biology in HFpEF pathophysiology, and provide a molecular framework for how ExT potentially reverses cardiac aging phenotypes in HFpEF.
Phosphatidylethanol Levels in Postpartum Women and Their Newborns in Uruguay and Brazil
Authors: Baldwin Aileen E. , Hayes Nicole , Ostrander Erika , Magri Raquel , Sass Nelson , dos Anjos Mesquita Maria , Martínez Monica , Juliani Monica Correa , Cabral Pablo , Fleming Michael 
Published: May 2020

BackgroundThere is increasing interest in the development of newborn screening tests to identify children at risk of fetal alcohol spectrum disorder (FASD) in order to provide these children with early intervention. Phosphatidylethanol (PEth) has emerged as a potential universal newborn screening candidate.MethodsThe aim of this report was to present the results of a study designed to compare PEth levels in 1,140 postpartum women and their newborn infants in Montevideo, Uruguay, and Sao Paulo, Brazil. Self‐report alcohol use during pregnancy data was collected, along with both maternal and newborn dried blood spot samples for PEth analysis.ResultsThe average age and parity of the women in the sample were 26 years of age and 2.3 pregnancies. For the Uruguay sample (n = 611), 45.8% of postpartum women had PEth levels ≥ 8 ng/ml with a mean positive PEth of 43.6 ng/ml. In contrast, 86.8% of the newborns had PEth levels ≥ 8 ng/ml, with a mean positive PEth of 77.4 ng/ml. For the Brazil sample (n = 529), 33.2% of women had PEth levels ≥ 8 ng/ml with a mean positive PEth of 31 ng/ml. In contrast, 76.9% of the Brazil newborns had PEth levels ≥ 8 ng/ml and 43.9% with a mean positive PEth of 61.1 ng/ml. PEth levels were significantly higher in newborns compared with their postpartum mothers in both the Uruguay and Brazil samples. Self‐reported third‐trimester alcohol was 6% in the Uruguay sample and 9.1% in the Brazil sample compared with positive maternal PEth levels in 45.8% and 33.2%, respectively.ConclusionsClinicians may want to consider newborn PEth screening in high‐risk populations where prenatal alcohol use is common. The mechanism underlying significantly higher PEth levels in newborns compared with their mothers is not known.
Behavioural portfolio theory revisited: lessons learned from the field
Authors: Oehler Andreas , Horn Matthias 
Published: May 2020

AbstractWe examine the relation between households’ wealth and relative risk aversion (RRA) in two different frameworks: the Behavioural Portfolio Theory (BPT) and Merton’s consumption and portfolio choice model (CPCM). We apply the BPT to field data for the first time and show that the BPT provides a better fit than the CPCM to explain the financial risk‐taking of the households in Deutsche Bundesbank’s Panel on Household Finances survey. However, both models indicate decreasing RRA. While households’ education and financial literacy hardly improve the fit of either model, households show different risk‐taking behaviour in accordance with their self‐assessed risk attitude.
Different epigenome regulation and transcriptome expression of CD4+ and CD8+ T cells from monozygotic twins discordant for psoriasis
Authors: Li Xiaofang , Zhao Xincheng , Xing Jianxiao , Li Junqin , He Fusheng , Hou Ruixia , Wang Qiang , Yin Guohua , Li Xinhua , Zhang Kaiming 
Published: May 2020

AbstractObjectivesPsoriasis is an immunodeficient skin disorder, and its exact pathogenesis is unclear. Monozygotic twins are presumed to be genetically identical, and their phenotypic differences may be due to transcriptional regulation or epigenome factors. To explain the inconsistency between twins, we have collected 3 pairs of monozygotic twins who are discordant for psoriasis.MethodsReduced representation of bisulfite sequencing and RNA sequencing was conducted using the peripheral blood of the twins to find the genes playing important roles in psoriasis pathogenesis.ResultsAs a result, we found methylation diversity in four genes (MAST3, MTOR, PM20D1 and ZNF99), and we also found 9 differentially expressed genes (PPAN‐P2RY11, PIGV, RPS18, TMEM121, KIF21A, KCNH2, WNT10B, PRX and CDH24) by RNA sequencing. According to the conjoint analysis of methylation and the mRNA results, PTPN6, CCL5, NFATC1 and PRF1 were found to be closely related to psoriasis. We then annotated the genes to explore the associations between these genes and psoriasis.ConclusionsThese findings provide a better understanding of psoriasis that can improve the diagnosis and treatment of the disease.
‘Snail factors in testicular germ cell tumours and their regulation by the BMP4 signalling pathway’
Authors: Micati Diana J. , Radhakrishnan Karthika , Young Julia C. , Rajpert‐De Meyts Ewa , Hime Gary R. , Abud Helen E. , Loveland Kate L. 
Published: May 2020

AbstractBackgroundSnail transcription factors mediate key cellular transitions in many developmental processes, including spermatogenesis, and their production can be regulated by TGF‐β superfamily signalling. SNAI1 and SNAI2 support many cancers of epithelial origin. Their functional relevance and potential regulation by TGF‐β superfamily ligands in germ cell neoplasia are unknown.MethodsSNAI1, SNAI2 and importin 5 (IPO5; nuclear transporter that selectively mediates BMP signalling) cellular localization was examined in fixed normal adult human and/or neoplastic testes using in situ hybridization and/or immunohistochemistry. SNAI1 and SNAI2 functions were assessed using the well‐characterized human seminoma cell line, TCam‐2. Cell migration, adhesion/proliferation and survival were measured by scratch assay, xCELLigence and flow cytometry following siRNA‐induced reduction of SNAI1 and SNAI2 in TCam‐2 cells. The potential regulation of SNAI1 and SNAI2 in TCam‐2 cells by TGF‐β signalling ligands, activin A and BMP4 was evaluated following 48 hours culture, including with siRNA regulation of IPO5 to selectively restrict BMP4 signalling.ResultsIn normal testes, SNAI1 transcript was identified in some spermatogonia and in spermatocytes, and SNAI2 protein localized to nuclei of spermatogonia, spermatocytes and round spermatids. In neoplastic testes, both SNAI1 and SNAI2 were detected in GCNIS and in seminoma cells. SNAI1 and SNAI2 reduction in TCam‐2 cells by siRNAs significantly inhibited migration and survival, respectively. Exposure to BMP4, but not activin A, significantly increased SNAI2 (~18‐fold). IPO5 inhibition by siRNAs decreased BMP4‐induced SNAI2 upregulation (~5‐fold). Additionally, SNAI2 reduction using siRNAs inhibited BMP4‐induced TCam‐2 cell survival.ConclusionsThis is the first evidence that SNAI1 and SNAI2 are involved in human spermatogenesis, with independent functions. These outcomes demonstrate that SNAI1 and SNAI2 inhibition leads to loss of migratory and viability capacities in seminoma cells. These findings show the potential for therapeutic treatments targeting SNAIL or BMP4 signalling for patients with metastatic testicular germ cell tumours.
Clinical course of coronavirus disease‐2019 in pregnancy
Authors: Pereira Augusto , Cruz‐Melguizo Sara , Adrien Maria , Fuentes Lucia , Marin Eugenia , Perez‐Medina Tirso 
Published: May 2020

AbstractIntroductionThe aim of this study is to report our clinical experience in the management of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) during the first 30 days of the coronavirus disease (COVID‐19) pandemic.Material and methodsWe reviewed clinical data from the first 60 pregnant women with COVID‐19 whose care was managed at Puerta de Hierro University Hospital, Madrid, Spain from 14 March to 14 April 2020. Demographic data, clinical findings, laboratory test results, imaging findings, treatment received, and outcomes were collected. An analysis of variance (Kruskal‐Wallis test) was performed to compare the medians of laboratory parameters. Fisher's exact test was used to evaluate categorical variables. A correspondence analysis was used to explore associations between variables.ResultsA total of 60 pregnant women were diagnosed with COVID‐19. The most common symptoms were fever and cough (75.5% each) followed by dyspnea (37.8%). Forty‐one women (68.6%) required hospital admission (18 because of disease worsening and 23 for delivery) of whom 21 women (35%) underwent pharmacological treatment, including hydroxychloroquine, antivirals, antibiotics, and tocilizumab. No renal or cardiac failures or maternal deaths were reported. Lymphopenia (50%), thrombocytopenia (25%), and elevated C‐reactive protein (CRP) (59%) were observed in the early stages of the disease. Median CRP, D‐dimer, and the neutrophil/lymphocyte ratio were elevated. High CRP and D‐dimer levels were the parameters most frequently associated with severe pneumonia. The neutrophil/lymphocyte ratio was found to be the most sensitive marker for disease improvement (relative risk 6.65; 95% CI 4.1‐5.9). During the study period, 18 of the women (78%) delivered vaginally. All newborns tested negative for SARS‐CoV‐2 and none of them were infected during breastfeeding. No SARS‐CoV‐2 was detected in placental tissue.ConclusionsMost of the pregnant women with COVID‐19 had a favorable clinical course. However, one‐third of them developed pneumonia, of whom 5% presented a critical clinical status. CRP and D‐dimer levels positively correlated with severe pneumonia and the neutrophil/lymphocyte ratio decreased as the patients improved clinically. Seventy‐eight percent of the women had a vaginal delivery. No vertical or horizontal transmissions were diagnosed in the neonates during labor or breastfeeding.
Controlled case series demonstrates how parents can be trained to treat paediatric feeding disorders at home
Authors: Taylor Tessa , Blampied Neville , Roglić Nikolas 
Published: May 2020

AbstractAimPaediatric feeding disorders are normally managed by specialist clinics. We examined whether treatment gains were maintained when trained parents continued the programme at home and during meals out.MethodsThis controlled consecutive case series recruited 26 children (22 boys) with avoidant/restrictive food intake disorder, from a private paediatric feeding disorders practice in New South Wales, Australia. Their mean age was six (2‐13) years. All had severe feeding problems and mealtime skill deficits, and most had autism and developmental delays or intellectual disabilities. The children received intensive, individualised, behaviour‐analytic treatment for 11 (6‐21.5) days, and the parents were trained to continue it at home. The primary treatment outcomes included the range and amount of food eaten and mealtime behaviour.ResultsThe children met all of the therapeutic goals agreed at the treatment outset. They ate a mean of 92 different foods and improved how they ate, drank and behaved during mealtimes. The mean differences before and after treatment were clinically and statistically significant, and the gains were maintained during follow‐up at a mean of 2.3 years. Parental satisfaction and treatment acceptability were high.ConclusionSpecially trained parents successfully continued paediatric eating disorder treatment at home and maintained treatment gains.
Tomorrow Is Another Day: How Motives of Entrepreneurship Relate to the Pursuit of Business Growth
Authors: Prasastyoga Bramesada , van Leeuwen Esther , Harinck Fieke 
Published: May 2020

Past research has suggested that small business growth plays an important role in economic growth. This paper presents three studies that examined the psychological process underlying the relationship between motives of entrepreneurship and business growth pursuit by focusing on the role of time perspective. The results from three studies (Study 1, N = 142, and Study 2, N = 181, mostly Western small‐business owners; Study 3,N = 254, Indonesian small‐business owners) demonstrated that opportunity‐based entrepreneurship was positively associated with business growth pursuit through increased future time perspective (Studies 1 to 3), whereas necessity‐based entrepreneurship was negatively associated with business growth pursuit through increased present time perspective and decreased future time perspective (Study 3). These findings help explain why some business owners avoid business growth by highlighting the vital role of time perspective in explaining why and how motives of entrepreneurship relate to the pursuit of business growth across social and cultural contexts.
English hepatitis C registry data show high response rates to directly acting anti‐virals, even if treatment is not completed
Authors: Drysdale Kathryn , Ntuli Yevedzo , Bestwick Jonathan , Gelson William , Agarwal Kosh , Forton Daniel , Mutimer David , Elsharkawy Ahmed M. , Townley Ceri , Mahomed Faizel , Foster Graham R. 
Published: May 2020

SummaryBackgroundIn England, choice of hepatitis C therapy is determined by national contracts that change with time, facilitating comparisons between different regimens. England has a diverse population with hepatitis C including large proportions of uncommon viral genotypes.AimTo evaluate efficacy of directly acting anti‐viral treatments for hepatitis C in England using real‐world data from the national treatment registry.MethodsSustained virological response (SVR) rates 12 weeks after treatment completion for patients treated between 2014 and August 2018 who attended for SVR tests were analysed in univariate subgroups using Chi‐squared tests. Multivariate models were constructed with clinically relevant variables to determine predictors of SVR and evaluate the impact of treatment regimens.ResultsSVR data were available on 14,603 treated patients. The overall SVR rate was 95.59% [95% CI 95.25%‐95.91%]. Multivariable regression modelling in patients with genotype 1 infection showed that the odds of SVR with elbasvir/grazoprevir were higher than for those treated with sofosbuvir/ledipasvir (OR 1.891, 95% CI 1.072‐3.336, P = 0.028). For genotype 3, we found no significant difference between any of the treatment regimens. Patients who completed at least one third of the planned treatment duration achieved SVR rates in excess of 80%.ConclusionsAll of the currently licensed hepatitis C direct‐acting anti‐viral regimens had similar efficacy (>95%) in an unselected population. Noncompletion of planned treatment duration still resulted in over 80% SVR rates provided that more than one third of treatment was completed.
Impact of persistence with tumour necrosis factor inhibitors on healthcare resource utilization and costs in chronic inflammatory joint diseases
Authors: Belhassen Manon , Tubach Florence , Hudry Christophe , Woronoff‐Lemsi Macha , Levy‐Bachelot Laurie , Van Ganse Eric , Fautrel Bruno 
Published: May 2020

AimTo assess persistence with subcutaneous (SC) tumour necrosis factor (TNF) inhibitors as well as the impact of persistence on healthcare resource utilization (HCRU) and costs in patients with chronic inflammatory joint diseases.MethodsIn this cohort study using population‐based French claims data (from 2011 to 2014), we measured persistence with SC TNF inhibitors within 12 months (M0‐12) following treatment initiation in treatment‐naïve and treatment‐experienced users (divided into three cohorts: rheumatoid arthritis [RA], ankylosing spondylitis [AS] and psoriatic arthritis [PsA]). Persistent patients were propensity score matched to nonpersistent patients at M12. The impact of persistence status on HCRU and costs was assessed during M12‐24.ResultsOf treatment‐naïve (n = 3,804) and treatment‐experienced (n = 2,279) users, only 56.1% and 46.8% were persistent at M12, respectively. Nonpersistent patients had more outpatient visits, computerized tomography scans, spine or joint magnetic resonance imaging procedures and disease‐related hospitalizations, while persistent patients had more rheumatologist visits. Nonpersistent patients had lower drug costs but higher nondrug‐related healthcare and hospitalization costs than persistent patients. In AS and PsA, overall healthcare costs were similar in persistent and nonpersistent patients. In RA, overall healthcare costs were lower in persistent patients (15,753€ vs 17,590€ in treatment‐naïve and 17,622€ vs 21,177€ in treatment‐experienced).ConclusionPersistence with SC TNF inhibitors within first 12 months following treatment initiation was low in both treatment‐naïve and treatment‐experienced patients. Differences were observed in distribution of costs between persistent and nonpersistent patients, showing that nonpersistence with SC TNF inhibitors can lead to increased HCRU and higher costs.
Normalization of serum B‐cell maturation antigen levels predicts overall survival among multiple myeloma patients starting treatment
Authors: Jew Scott , Chang Tiffany , Bujarski Sean , Soof Camilia , Chen Haiming , Safaie Tahmineh , Li Mingjie , Sanchez Eric , Wang Cathy , Spektor Tanya M. , Emamy‐Sadr Marsiye , Swift Regina , Rahbari Ashkon , Patil Saurabh , Souther Eric , Berenson James R. 
Published: May 2020

SummarySerum B‐cell maturation antigen (sBCMA) is a novel biomarker for B‐cell malignancies. A normal reference range (<82·59 ng/ml) has been recently established but the impact of achieving normal levels to outcomes for patients receiving treatment for B‐cell malignancies has not been studied. We first found that among multiple myeloma (MM) patients starting a new treatment, those who begin treatment within normal sBCMA limits (<82·59 ng/ml) have improved progression‐free survival (PFS; P = 0·0398) and overall survival (OS; P = 0·0217) than those who do not. Furthermore, among patients who begin treatment with elevated (≥82·59 ng/ml) sBCMA levels, we assessed the relationship of a decrease in sBCMA to the normal range to OS and found that those who normalize sBCMA demonstrated improved OS (P = 0·0078). Normalizing patients also experienced a markedly improved overall response rate (P < 0·0001). Moreover, all patients who achieved complete remission (CR) showed normalization of sBCMA, and time to normalization (median 0·9 months) was faster than time to CR (5·0 months; P = 0·0036) for these patients. These results suggest that normalization of sBCMA may be an accurate predictor of OS for MM patients during treatment and predict for a higher likelihood of response.
A rationale for targeting the P2X7 receptor in Coronavirus disease 19
Authors: Di Virgilio Francesco , Tang Yong , Sarti Alba Clara , Rossato Marco 
Published: May 2020

Severe pneumonia which shares several of the features of acute respiratory distress syndrome (ARDS) is the main cause of morbidity and mortality in Coronavirus disease 19 (Covid‐19) for which there is no effective treatment, so far. ARDS is caused and sustained by an uncontrolled inflammatory activation characterized by a massive release of cytokines (cytokine storm), diffuse lung oedema, inflammatory cell infiltration, and disseminated coagulation. Macrophage and T lymphocyte dysfunction plays a central role in this syndrome. In several experimental in vitro and in vivo models, many of these pathophysiological changes are triggered by stimulation of the P2X7 receptor. We hypothesize that this receptor might be an ideal candidate to target in Covid‐19‐associated severe pneumonia.Linked ArticlesThis article is part of a themed issue on The Pharmacology of COVID‐19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc
Dams and protected areas: Quantifying the spatial and temporal extent of global dam construction within protected areas
Authors: Thieme Michele L. , Khrystenko Dmytro , Qin Siyu , Golden Kroner Rachel E. , Lehner Bernhard , Pack Shalynn , Tockner Klement , Zarfl Christiane , Shahbol Natalie , Mascia Michael B. 
Published: May 2020

AbstractProtected areas (PAs) are an essential tool for freshwater biodiversity conservation. Given past and expected future global increases in dams and impacts of dams on freshwater ecosystems, we document the number of dams existing or planned within PAs, their history, and the extent of PA downgrading, downsizing, and degazettement (PADDD) proximally caused by dams. Globally, at least 1,249 large dams are located within PAs; two‐thirds (907) were built before PA establishment. Additionally, 14% of planned geolocated hydropower dams (509 dams) are located within PAs. PADDD events have also legalized dam construction within existing PAs. Environmental safeguards should preclude development of dams within or adjacent to PAs and prioritize dams within PAs for possible removal and restoration.
Impacts of a trophy hunting ban on private land conservation in South African biodiversity hotspots
Authors: Parker Kim , De Vos Alta , Clements Hayley S. , Biggs Duan , Biggs Reinette 
Published: May 2020

AbstractPrivate land conservation areas (PLCAs) have become critical for achieving global conservation goals, but we lack understanding of how and when these areas respond to global pressures and opportunities. In southern Africa, where many PLCAs rely on trophy hunting as an income‐generating strategy, a potential ban on trophy hunting locally or abroad holds unknown consequences for the future conservation of these lands. In this study, we investigate the consequences of a potential trophy hunting ban in PLCAs in two biodiversity hotspots in South Africa's Eastern and Western Cape provinces. We used semistructured interviews with PLCA managers and owners to elicit perceived impacts of an internationally imposed trophy hunting ban on conservation activities in PLCAs, and to probe alternative viable land uses. The majority of interviewees believed that both the economic viability of their PLCA and biodiversity would be lost following a hunting ban. Owners would primarily consider transitioning to ecotourism or livestock farming, but these options were constrained by the social‐ecological context of their PLCA (e.g., competition with other PLCAs, ecological viability of farming). Our results suggest that a trophy hunting ban may have many unintended consequences for biodiversity conservation, national economies, and the livelihoods of PLCA owners and employees. Along with similar social‐ecological studies in other areas and contexts, our work can inform policy decisions around global trophy hunting regulation.