bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graduate rural work outcomes of the first 8 years of a medical school: What can we learn about student selection and clinical school training pathways?
Authors: Fuller Lara , Beattie Jessica , Versace Vincent 
Published: May 2021

AbstractObjectiveTo determine the student characteristics and clinical school training pathways that are associated with postgraduate rural practice.DesignA cross‐sectional observational study.SettingDeakin University's School of Medicine, encompassing 3 rural and 2 metropolitan clinical schools, including a rural longitudinal integrated clerkship (LIC) year.ParticipantsA total of 948 School of Medicine medical graduates (2011‐2018) who had an Australian Health Practitioners Regulation Agency registered work location in Australia (September 2019).Main outcome measure(s)Graduates' work locations were linked with admission and clinical school training data and analysed for significant associations.ResultsGraduates completing a rural LIC year and a regional rural clinical school year were 7 times more likely to be working rurally than metropolitan trainees. A small number of rural background (RB) students completed a rural LIC and rural clinical school year, 66.7% of whom were practising rurally. Further associations with rural practice were attending a rural clinical school for 2 years or a rural LIC for 1 year, student having a RB, rurally bonded course placement and being an international student.ConclusionThe significant influence of a rural LIC year on graduate rural work location is noteworthy, especially when undertaken by students from a RB in combination with a second regional rural clinical school year. These findings support the strategic alignment of rural student selection with rural clinical school training pathways to achieve the greatest impact on rural graduate workforce outcomes.
Micro‐credit NGOs and strategic trust: An odd couple?
Authors: Huda Kazi A. S. M. Nurul 
Published: May 2021

AbstractThis study contributes to the micro‐credit literature by addressing the lack of philosophical dialogue concerning the issue of trust between micro‐credit NGOs and rural poor women. The study demonstrates that one of the root causes of NGOs’ contested roles in Bangladesh is the norm that they use (i.e., trust) to rationalize their micro‐credit activities. I argue that Bangladeshi micro‐credit NGOs’ trust in poor village women is not genuine because they resort to group responsibility sustained through aggressive surveillance. I maintain so by drawing on a trust‐based theoretical framework that uses various philosophical insights. Drawing on the same conceptual framework, I also contend, somewhat softening the previous claim, that if micro‐credit trust is trust at all, it is at most strategic, not generalized. For being strategic, it has many undermining effects on local social solidarity norms, rendering Bangladeshi micro‐credit NGOs and strategic trust an odd couple with no moral compass. To bring forth the moral impetus in micro‐credit activities, I lay out some recommendations intended for organizations, managers, and policymakers, consistent with normative corporate social responsibility initiatives. However, further studies can be initiated based on this paper, suggesting its importance for future research.
Inactivation of the CB2 receptor accelerated the neuropathological deterioration in TDP‐43 transgenic mice, a model of amyotrophic lateral sclerosis
Authors: Rodríguez‐Cueto Carmen , Gómez‐Almería Marta , García Toscano Laura , Romero Julián , Hillard Cecilia J. , de Lago Eva , Fernández‐Ruiz Javier 
Published: May 2021

AbstractThe activation of the cannabinoid receptor type‐2 (CB2) afforded neuroprotection in amyotrophic lateral sclerosis (ALS) models. The objective of this study was to further investigate the relevance of the CB2 receptor through investigating the consequences of its inactivation. TDP‐43(A315T) transgenic mice were crossed with CB2 receptor knock‐out mice to generate double mutants. Temporal and qualitative aspects of the pathological phenotype of the double mutants were compared to TDP‐43 transgenic mice expressing the CB2 receptor. The double mutants exhibited significantly accelerated neurological decline, such that deteriorated rotarod performance was visible at 7 weeks, whereas rotarod performance was normal up to 11 weeks in transgenic mice with intact expression of the CB2 receptor. A morphological analysis of spinal cords confirmed an earlier death (visible at 65 days) of motor neurons labelled with Nissl staining and ChAT immunofluorescence in double mutants compared to TDP‐43 transgenic mice expressing the CB2 receptor. Evidence of glial reactivity, measured using GFAP and Iba‐1 immunostaining, was seen in double mutants at 65 days, but not in TDP‐43 transgenic mice expressing the CB2 receptor. However, at 90 days, both genotypes exhibited similar changes for all these markers, although surviving motor neurons of transgenic mice presented some morphological abnormalities in absence of the CB2 receptor that were not as evident in the presence of this receptor. This faster deterioration seen in double mutants led to premature mortality compared with TDP‐43 transgenic mice expressing the CB2 receptor. We also investigated the consequences of a pharmacological inactivation of the CB2 receptor using the selective antagonist AM630 in TDP‐43 transgenic mice, but results showed only subtle trends towards a greater deterioration. In summary, our results confirmed the potential of the CB2 receptor agonists as a neuroprotective therapy in ALS and strongly support the need to progress towards an evaluation of this potential in patients.
Open globe injuries: Epidemiology, visual and surgical predictive variables, prognostic models, and economic cost analysis
Authors: Lee Brendon W. H. , Hunter Damien , Robaei Dana S. , Samarawickrama Chameen 
Published: May 2021

AbstractBackgroundOpen globe injuries (OGI) represent a visually and economically devastating cause of vision loss. We examined the epidemiology, predictive variables, prognostic models, and economic cost of surgically managed OGI.MethodsA retrospective tertiary centre study from 2008 to 2018 of 155 consecutive OGI in individuals aged 16 and older was performed. Medical records review, application of Ocular Trauma Score (OTS) and Classification and Regression Tree Analysis (CART) and cost analysis were undertaken. Key outcomes measured were visual acuity, number of operating theatre visits, prognostication using OTS and CART and estimated costs.ResultsYounger males at work with inadequate protective eyewear (89.1%) and falls in the elderly were overrepresented. Inferior visual outcomes were associated with a more severe OTS score, a larger injury zone, increasing age, the presence of retinal detachment, extraocular muscle involvement, intraocular foreign body, and globe rupture (R2 = 0.723, p < 0.001). Multiple operating theatre visits were required in the presence of retinal detachment, lens or orbit involvement, work‐related injury, globe rupture, and a history of previous intraocular surgery (R2 = 0.0423, p < 0.001). Both OTS and CART prognosticated outcomes (p < 0.001). The OTS predicted for no vision (no light perception/enucleation/evisceration) and profound visual loss (worse than 6/120; specificity: both 100%, sensitivity: 88.2% and 88%) whereas the CART predicted for visual survival (light perception or better) and minimal‐to‐severe visual loss (6/120 or better; specificity: 88.5% and 81.7% , sensitivity: 97.7% and 100%). Estimated annual OGI cost for Australia was AUD48.1–60.5 million (USD37.3–47.0 million).ConclusionsThe total cost of OGI is immense with young males and the elderly being disproportionately affected. Implementation of targeted government legislation and public health preventative measures may be cost‐effective in ameliorating the significant burden.
Safety and pharmacokinetics of docetaxel in combination with pegvorhyaluronidase alfa in patients with non‐small cell lung cancer
Authors: Heineman Thomas , Baumgart Megan , Nanavati Charvi , Gabrail Nash , Van Wart Scott A. , Mager Donald E. , Maneval Daniel C. , Fathallah Anas M. , Sekulovich Rose E. 
Published: May 2021

AbstractThis open‐label, phase Ib study (NCT02346370) assessed the effect of pegvorhyaluronidase alfa (PVHA; PEGPH20) on the plasma pharmacokinetics (PKs) and safety of docetaxel in 15 patients with stage IIIB/IV non‐small cell lung cancer (NSCLC). The docetaxel PK profile from this study was consistent with simulations from a published docetaxel population PK model, and did not demonstrate an effect of PVHA on docetaxel PK. A maximum a posteriori Bayesian fit of the literature PK model to the docetaxel PK appeared unbiased. Adverse events (AEs) were generally consistent with previous reports for docetaxel monotherapy in NSCLC, except for higher incidence of musculoskeletal events, including myalgias, with PVHA plus docetaxel. The most common AEs were fatigue (87%), muscle spasms (60%), and myalgia (53%). Four patients experienced thromboembolic events (27%), three leading to treatment discontinuation. PVHA appeared to demonstrate an acceptable safety profile when given with docetaxel without significantly changing the plasma PK of docetaxel in patients with stage IIIB/IV NSCLC.
Opportunities and challenges in translational science
Authors: Austin Christopher P. 
Published: May 2021

AbstractThe mission of translational science is to bring predictivity and efficiency to the development and dissemination of interventions that improve human health. Ten years ago this year, the National Center for Advancing Translational Sciences was founded to embody, conduct, and support this new discipline. The Center’s first decade has brought substantial progress across a broad range of translational areas, from diagnostic and drug development to clinical trials to implementation science to education. The origins of the translational science and advances to this point are reviewed here and allow the establishment of an ambitious future research agenda for the field.
Modeling and simulation to predict the degree of disability over time in acute ischemic stroke patients
Authors: Park Sang‐In , Kang Dong‐Wha , Lim Hyeong‐Seok 
Published: May 2021

AbstractDisability in patients with acute stroke varies over time, with the prediction of outcomes being critical for proper management. This study aimed to develop a model to predict the cumulative probability of each modified Rankin Scale (mRS) score over time with inclusion of significant covariates. Longitudinal data obtained from 193 patients, 1–24 months after onset of acute ischemic stroke, were included for a modeling analysis using nonlinear mixed‐effect modeling (NONMEM). After selecting a model that best described the time course of the probability of different mRS scores, potential covariates were tested. Visual predicted check plots, parameter estimates, and decreases in minimum objective function values were used for model evaluation. The inclusion of disease progression (DP) in the baseline proportional odds cumulative logit model significantly improved the model compared to the baseline model without DP. An inhibitory maximum effect (Emax) model was determined to be the best DP model for describing the probability of specific mRS scores over time. In the final model, DP was multiplied with the baseline cumulative logit probability with a baseline adjustment. In addition to differences in lesion volume (DLV), the final model included comorbid diabetes mellitus (DM) and baseline National Institutes of Health Stroke Scale (NIHSS) scores on Emax as statistically significant covariates. This study developed a model including DLV, NIHSS score, and comorbid DM for predicting the disability time course in patients with acute ischemic stroke. This model may help to predict disease outcomes and to develop more appropriate management plans for patients with acute stroke.
Echocardiographic parameters associated with in‐hospital adverse outcomes in patients with Takotsubo syndrome
Authors: Farina Lauren A. , Tibrewala Anjan , Voit Jay M. , Raissi Sasan R. , Chen Liqi , Welty Leah J. , Khan Sadiya S. , Freed Benjamin H. , Akhter Nausheen 
Published: May 2021

AbstractIntroductionTakotsubo syndrome (TTS) is an acute heart failure syndrome that leads to significant morbidity and mortality. We sought to evaluate the association of cardiac mechanics on presentation with in‐hospital adverse outcomes in patients with apical TTS.MethodsWe retrospectively identified 468 patients with TTS based on ICD‐9/10 codes between 2006 and 2017. The association of echocardiographic parameters with a composite outcome of heart failure and all‐cause mortality during the index hospitalization was analyzed.ResultsOne hundred and forty one patients with the apical subtype and adequate imaging were included. 113 (80.1%) were female, left ventricular ejection fraction (LVEF) was 41.7% ± 12.4%, and global longitudinal strain was −10.1% ± 3.2%. The composite outcome occurred in 58 patients (41%), with heart failure occurring in 55 patients and death occurring in nine patients. Global longitudinal strain, global circumferential strain, global radial strain, right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular free wall strain were significantly worse in patients who experienced the composite outcome in univariate analyses. However, only LVEF was independently associated with the composite outcome in multivariable‐adjusted analysis.ConclusionsIn patients with apical TTS, the strain has limited prognostic utility in the acute setting compared to LVEF, which was the only echocardiographic parameter associated with in‐hospital heart failure and all‐cause mortality.
Regional spillover into third‐order European elections
Authors: Schakel Arjan H. 
Published: May 2021

AbstractSecond‐order election research clearly reveals that national incumbency impacts on European election outcomes but despite the increasing importance of regions few studies explore the impact of regional politics. I theorize that governmental status at the regional level, regional authority, and the relative timing of the regional election affects vote share swings between European and previously held national elections. Based on an analysis including 12,545 vote share swings for 468 parties that compete elections held in 209 regions in 11 European Union member states since 1979, I find strong evidence for prospective regional voting, that is, voters rewarding parties in government at the regional level. First, parties that are in national opposition and in regional government incur larger vote share gains than parties that are in opposition at both levels. Second, these vote share gains become larger when regional authority increases and, third, when a regional election has preceded a European election.
Aberrant expression of LncRNA CASC2 mediated the cell viability, apoptosis and autophagy of colon cancer cells by sponging miR‐19a via NF‐κB signaling pathway
Authors: Zhang Peng , Pan Yan , Sun Jujun , Pan Gaiyan 
Published: May 2021

AbstractAbnormal and rapid proliferation of colon cancer cells is a severe problem that can be regulated by non‐coding RNAs. Thus, our study focused on effects of lncRNA CASC2 and miR‐19a on colon cancer cells. Expressions of lncRNA CASC2, miR‐19a, Bcl‐2, Bax and NF‐κB/p65 were examined by RT‐qPCR. Cell viabilities were detected by CCK‐8. A luciferase report assay was used for measuring binding conditions between lncRNA CASC2 and miR‐19a. Western blotting was used to evaluate expression of LC3‐I, LC3‐II and p62 related to autophagy. Expression of lncRNA CASC2 lower in cancer cell lines and the overexpression reduced the cell viability of HT29 and SW480. Furthermore, Bcl‐2 was suppressed by overexpressed lncRNA CASC2, while Bax was upregulated. LC3‐Ⅰ and p62 were both inhibited, but LC3‐Ⅱ was promoted. MiR‐19a was predicted to bind lncRNA CASC2 and expressed higher in cancer cell lines. Overexpressed miR‐19a reduced expression of lncRNA CASC2 and increased cell viability. This was repressed by upregulated lncRNA CASC2. Bcl‐2 and Bax expression and proteins implicated in autophagy that are regulated by lncRNA CASC2 upregulation were reversed by miR‐19a overexpression. NF‐κB was upregulated in colon cancer cell lines, while inhibition of NF‐κB reversed functions of lncRNA CASC2 and magnified roles of miR‐19a. Our findings showed that lncRNA CASC2 inhibited cell viability in colon cancer cell lines and miR‐19a reversed its functions through the NF‐κB signalling pathway, suggesting that these could be factors in treating colon cancer in the future.
Identification of growth differentiation factor 15 as a pro‐fibrotic factor in mouse liver fibrosis progression
Authors: Qi Peng , Ma Ming‐Ze , Kuai Jing‐Hua 
Published: May 2021

AbstractThe aim of this study was elucidate the inhibitory role of growth differentiation factor 15 (GDF15) in liver fibrosis and its possible activation mechanism in hepatic stellate cells (HSCs) of mice. We generated a GDF15‐neutralizing antibody that can inhibit TGF‐β1–induced activation of the TGF‐β/Smad2/3 pathway in LX‐2 cells. All the mice in this study were induced by carbon tetrachloride and thioacetamide. In addition, primary HSCs from mice were isolated from fresh livers using Nycodenz density gradient separation. The severity and extent of liver fibrosis were evaluated by Sirius Red and Masson staining. The effect of GDF15 on the activation of the TGF‐β pathway was detected using dual‐luciferase reporter and Western blotting assays. The expression of GDF15 in cirrhotic liver tissue was higher than that in normal liver tissue. Blocking GDF15 with a neutralizing antibody resulted in a delay in primary hepatic stellate cell activation and remission of liver fibrosis induced by carbon tetrachloride or thioacetamide. Meanwhile, TGF‐β pathway activation was partly inhibited by a GDF15‐neutralizing antibody in primary HSCs. These results indicated that GDF15 plays an important role in regulating HSC activation and liver fibrosis progression. The inhibition of GDF15 attenuates chemical‐inducible liver fibrosis and delays hepatic stellate cell activation, and this effect is probably mainly attributed to its regulatory role in TGF‐β signalling.
The bright side of third‐party marketplaces in retailing
Authors: Zheng Shengming , Yu Yugang , Ma Buqing 
Published: May 2021

AbstractA prevalent practice for retailers is to provide a marketplace for third‐party sellers (3P sellers) to sell products directly to consumers, charging the sellers a commission fee. This study investigates the downstream retailer's optimal strategy to introduce a 3P seller who sells a substitutable product. We develop a game‐theoretic model, through which our first result shows that the retailer introduces a 3P seller only when the marginal costs of the products are in a medium range. Second, the retailer's strategy of introducing a 3P seller may benefit the manufacturer, even though the introduction creates downstream competition that may reduce the sales of the manufacturer's product. This happens because the strategy of introducing a 3P seller can mitigate the double marginalization between the manufacturer and retailer. In contrast to the conventional wisdom that introducing a 3P seller always results in a “win–lose” outcome for the retailer and manufacturer, we derive evidence that introducing a 3P seller can lead to a “win‐win” outcome for the retailer and manufacturer and thus improve the channel performance. Lastly, we find that the retailer's 3P seller introduction strategy can also improve the consumer surplus because this strategy increases competition.
Water sensitivity of cement‐based materials
Authors: Zhou Chunsheng , Zhang Xiaoyu , Wang Zhendi , Yang Zhenli 
Published: May 2021

AbstractCement‐based materials are the most widely used construction materials on the planet. Cement‐based materials play a fundamental role in modern civilization and will for the foreseeable future. Although great efforts have been devoted to discovering the behaviors and optimizing their performances, several long‐standing controversies persist for the fundamental water‐related properties of cement‐based materials, which hinder theoretical researches and mislead technological developments. Inspired by the decreasing water permeability of clay‐bearing rocks, the term “water sensitivity” in geophysics is borrowed and proposed for cement‐based materials. The lamellar structure of negatively charged nanoparticles is responsible for swelling in clay‐based reservoir rocks. Amorphous calcium silicate hydrate gels in cement‐based materials have similar micro‐structural characteristics. They probably swell upon wetting and contract upon drying, making the pore structure of cement‐based materials dependent on water content. More importantly, several unexplained behaviors of cement‐based materials can be rationalized using water sensitivity. Thorough exploration of both the micro‐structural characteristics and performances validate the use of water sensitivity for cement‐based materials. Because water participates in or regulates almost all physical and chemical processes of cement‐based materials, water sensitivity can be a part of the interpretations of almost all of their properties and performances.
Historical biogeography of New World passalid beetles (Coleoptera, Passalidae) reveals Mesoamerican tropical forests as a centre of origin and taxonomic diversification
Authors: Beza‐Beza Cristian F. , Jiménez‐Ferbans Larry , McKenna Duane D. 
Published: May 2021

AbstractAimThe fauna of Mesoamerica is extraordinarily species rich and exhibits a high degree of local, regional and high‐elevation endemism. Traditionally, this area has been seen as a transition zone between the Nearctic and Neotropical regions; in contrast, new data suggest that Mesoamerica is a centre of origin and taxonomic diversification. For example, the diversity of species and genera of Passalidae in Mesoamerica is concentrated in montane environments and there are many locally endemic taxa; thus, Mesoamerica has been suggested as a centre of origin and taxonomic diversification for the group. However, this hypothesis has not been formally tested.LocationNew World tropics, with an emphasis on Mesoamerica.TaxonColeoptera, Passalidae (tribes Passalini and Proculini)MethodsWe studied timing and geographic patterns in the taxonomic diversification of Neotropical Passalidae. We used DNA sequence data from 3 genes (CAD, Wingless, 28S) for 93 species of Passalidae, along with information from the fossil record, to generate a time‐calibrated phylogeny for the group. Additionally, we performed Ancestral Area Estimation and Ancestral State Reconstruction of the altitudinal distribution niche.ResultsThe divergence time analyses recovered a much older estimated timing of origin and diversification events in Passalidae than previously proposed. We recovered the origins of the New World Passalidae in the late Jurassic and the split between Passalini and Proculini during the mid‐Cretaceous. Moreover, we observed congruence between timing and patterns of clade diversification and major paleogeographical events; for example, the origin and crown diversification of montane genera during the uplift and emergence of Mesoamerica from the sea.Main conclusionsOrogenic events throughout the Paleogene and Neogene played a major role in the diversification of New World Passalidae. Moreover, Nuclear and Southern Mesoamerica are centres of origin and taxonomic diversification for Proculini.