bluuebunny/crossref_metadata_2025_split huggingface dataset:
Notch‐Hes1 signaling activation in Caroli disease and polycystic liver disease
Authors: Takahashi Kenta , Sato Yasunori , Yamamura Minako , Nakada Satoko , Tamano Yuko , Sasaki Motoko , Harada Kenichi 
Published: June 2021

AbstractThe Notch signaling pathway plays a key role in the morphogenesis of the biliary tree, but its involvement in cystic biliary diseases, such as Caroli disease (CD) and polycystic liver disease (PLD), has yet to be determined. Immunostaining was performed using liver sections of CD and PLD, and the results were compared with those of congenital hepatic fibrosis (CHF) and von Meyenburg complex (VMC). The expression of Notch receptor 1 (Notch1) was increased in the nuclei of biliary epithelial cells in all cases of CD and PLD, whereas it remained at a low level in CHF and VMC. In addition, Notch2 and Notch3 were preferably expressed in the nuclei of biliary epithelial cells of PLD. Accordingly, the Notch effector Hes1 was highly expressed in biliary epithelial cells of CD and PLD, and the cell proliferative activity was significantly higher in CD and PLD. The expression of the Notch ligand Delta‐like 1 was significantly increased in biliary epithelial cells of CD and PLD, which may be causally associated with the nuclear overexpression of Notch1 and Hes1. These results indicate that aberrant activation of the Notch‐Hes1 signaling pathway may be responsible for the progression of biliary cystogenesis in CD and PLD.
Evaluation of high salinity tolerance in Pongamia pinnata (L.) Pierre by a systematic analysis of hormone‐metabolic network
Authors: Marriboina Sureshbabu , Sharma Kapil , Sengupta Debashree , Yadavalli Anurupa Devi , Sharma Rameshwar Prasad , Reddy Attipalli Ramachandra 
Published: June 2021

AbstractSalinity stress results in significant losses in plant productivity and loss of cultivable lands. Although Pongamia pinnata is reported to be a salt‐tolerant semiarid biofuel tree, the adaptive mechanisms to saline environments are elusive. Despite a reduction in carbon exchange rate (CER), the unchanged relative water content provides no visible salinity induced symptoms in leaves of hydroponic cultivated Pongamia seedlings for 8 days. Our Na+‐specific fluorescence results demonstrated that there was an effective apoplastic sodium sequestration in the roots. Salinity stress significantly increased zeatin (~5.5‐fold), and jasmonic acid (~3.8‐fold) levels in leaves while zeatin (~2.5‐fold) content increased in leaves as well as in roots of salt‐treated plants. Metabolite analysis suggested that osmolytes such as myo‐inositol and mannitol were enhanced by ~12‐fold in leaves and roots of salt‐treated plants. Additionally, leaves of Pongamia showed a significant enhancement in carbohydrate content, while fatty acids were accumulated in roots under salt stress condition. At the molecular level, salt stress enhanced the expression of genes related to transporters, including the Salt Overly Sensitive 2 gene (SOS2), SOS3, vacuolar‐cation/proton exchanger, and vacuolar‐proton/ATPase exclusively in leaves, whereas the Sodium Proton Exchanger1 (NHX1), Cation Calcium Exchanger (CCX), and Cyclic Nucleotide Gated Channel 5 (CNGC5) were up‐regulated in roots. Antioxidant gene expression analysis clearly demonstrated that peroxidase levels were significantly enhanced by ~10‐fold in leaves, while Catalase and Fe‐superoxide Dismutase (Fe‐SOD) genes were increased in roots under salt stress. The correlation interaction studies between phytohormones and metabolites revealed new insights into the molecular and metabolic adaptations that confer salinity tolerance to Pongamia.
Addition of zolpidem to combination therapy with atomoxetine‐oxybutynin increases sleep efficiency and the respiratory arousal threshold in obstructive sleep apnoea: A randomized trial
Authors: Messineo Ludovico , Carter Sophie G. , Taranto‐Montemurro Luigi , Chiang Alan , Vakulin Andrew , Adams Robert J. , Carberry Jayne C. , Eckert Danny J. 
Published: June 2021

AbstractBackground and objectiveAtomoxetine combined with oxybutynin (Ato‐Oxy) has recently been shown to reduce obstructive sleep apnoea (OSA) severity by >60%. However, Ato‐Oxy also modestly reduced the respiratory arousal threshold, which may decrease sleep quality/efficiency. We sought to investigate the additional effect of zolpidem with Ato‐Oxy on sleep efficiency (primary outcome), the arousal threshold, OSA severity, other standard polysomnography (PSG) parameters, next‐day sleepiness and alertness (secondary outcomes).MethodsTwelve participants with OSA received 10 mg zolpidem plus Ato‐Oxy (80‐5 mg, respectively) or Ato‐Oxy plus placebo prior to overnight in‐laboratory PSG according to a double‐blind, randomized, crossover design (1‐week washout). Participants were fitted with an epiglottic catheter, a nasal mask and pneumotachograph to quantify arousal threshold and airflow. Next‐day sleepiness and alertness were assessed via the Karolinska Sleepiness Scale and a driving simulation task.ResultsThe addition of zolpidem increased sleep efficiency by 9% ± 13% (80.9% ± 16.9% vs. 88.2% ± 8.2%, p = 0.037) and the respiratory arousal threshold by 17% ± 18% (−26.6 ± 14.5 vs. −33.8 ± 20.3 cm H2O, p = 0.004) versus Ato‐Oxy + placebo. Zolpidem did not systematically change OSA severity. Combination therapy was well tolerated, and zolpidem did not worsen next‐day sleepiness. However, median steering deviation during the driving simulator task increased following the zolpidem combination.ConclusionZolpidem improves sleep efficiency via an increase in the respiratory arousal threshold to counteract potential wake‐promoting properties of atomoxetine in OSA. These changes occur without altering the rate of respiratory events or overnight hypoxaemia. However, while the addition of zolpidem does not increase next‐day perceived sleepiness, caution is warranted given the potential impact on next‐morning objective alertness.
Quantitative Analysis of Safety Risks and Relationship with Delayed Project Completion Times
Authors: Alkaissy Maryam , Arashpour Mehrdad , Li Heng , Alaghmand Sina , Nezamian Abe 
Published: June 2021

AbstractDynamic work environments in construction and civil infrastructure sectors remain susceptible to safety risks. Although previous research has resulted in improvements, there is currently a gap in measuring temporal impacts of safety risks quantitatively. Precise modeling of potential delays caused by safety incidents is vital for efficient management of risks and making informed decisions on project contingency. Toward this aim, the current research adopts a nondeterministic modeling method to simulate and quantify safety incidents and find correlations with project delays. Using a deductive approach, three research questions were formulated, and investigations conducted on Australian data collected from 2016 onwards. Quantitative impacts of safety risks on project completion times were numerically measured. Furthermore, safety risks were ranked based on their significance of temporal impacts on project performance. This paper contributes to the theory of safety management by developing a nondeterministic method to model impacts of safety risks at both industry and project levels. Practical contributions and outcomes can facilitate using machine learning methods to plan proportionate time buffers to address safety risks.
Bivariate change point detection: Joint detection of changes in expectation and variance
Authors: Messer Michael 
Published: June 2021

AbstractA method for change point detection is proposed. We consider a univariate sequence of independent random variables with piecewise constant expectation and variance, apart from which the distribution may vary periodically. We aim to detect change points in both expectation and variance. For that, we propose a statistical test for the null hypothesis of no change points and an algorithm for change point detection. Both are based on a bivariate moving sum approach that jointly evaluates the mean and the empirical variance. The joint consideration helps improve inference compared with separate univariate approaches. We infer on the strength and the type of changes with confidence. Nonparametric methodology supports the analysis of diverse data. Additionally, a multiscale approach addresses complex patterns in change points and effects. We demonstrate the performance through theoretical results and simulation studies. A companion R‐package jcp (available on CRAN) is discussed.
Extending the Reach of Tooling Theory: A Neurocognitive and Phylogenetic Perspective
Authors: Colbourne Jennifer A. D. , Auersperg Alice M. I. , Lambert Megan L. , Huber Ludwig , Völter Christoph J. 
Published: June 2021

AbstractTool use research has suffered from a lack of consistent theoretical frameworks. There is a plethora of tool use definitions and the most widespread ones are so inclusive that the behaviors that fall under them arguably do not have much in common. The situation is aggravated by the prevalence of anecdotes, which have played an undue role in the literature. In order to provide a more rigorous foundation for research and to advance our understanding of the interrelation between tool use and cognition, we suggest the adoption of Fragaszy and Mangalam's (2018) tooling framework, which is characterized by the creation of a body‐plus‐object system that manages a mechanical interface between tool and surface. Tooling is limited to a narrower suite of behaviors than tool use, which might facilitate its neurocognitive investigation. Indeed, evidence in the literature indicates that tooling has distinct neurocognitive underpinnings not shared by other activities typically classified as tool use, at least in primates. In order to understand the extent of tooling incidences in previous research, we systematically surveyed the comprehensive tool use catalog by Shumaker et al. (2011). We identified 201 tool use submodes, of which only 81 could be classified as tooling, and the majority of the tool use examples across species were poorly supported by evidence. Furthermore, tooling appears to be phylogenetically less widespread than tool use, with the greatest variability found in the primate order. However, in order to confirm these findings and to understand the evolution and neurocognitive mechanisms of tooling, more systematic research will be required in the future, particularly with currently underrepresented taxa.
Acute Cardiometabolic and Perceptual Responses to Individual and Group-Based Body-Weight Resistance Exercise in Girls
Authors: Ricci Jeanette M. , Currie Katharine D. , Astorino Todd A. , Pfeiffer Karin A. 
Published: June 2021

Girls’ acute responses to group-based high-intensity interval exercise (HIIE) are not well characterized. Purpose: To compare acute responses to treadmill-based HIIE (TM) and body-weight resistance exercise circuit (CIRC) and to CIRC performed in a small-group setting (group CIRC). Method: Nineteen girls (9.1 [1.1] y) completed exercise testing on a TM to determine peak oxygen uptake, peak heart rate (HRpeak), and maximal aerobic speed. The TM involved eight 30-second sprints at 100% maximal aerobic speed. The CIRC consisted of 8 exercises of maximal repetitions performed for 30 seconds. Each exercise bout was followed by 30 seconds of active recovery. The blood lactate concentration was assessed preexercise and postexercise. The ratings of perceived exertion, affective valence, and enjoyment were recorded at preexercise, Intervals 3 and 6, and postexercise. Results: The mean heart rate was higher during group CIRC (92% [7%] HRpeak) than CIRC (86% [7%] HRpeak) and TM (85% [4%] HRpeak) ( = .49). The mean oxygen uptake equaled 76% (11%) of the peak oxygen uptake for CIRC and did not differ from TM (d = 0.02). The CIRC elicited a greater postexercise blood lactate concentration versus TM (5.8 [1.7] vs 1.4 [0.4] mM, d = 3.61). The perceptual responses were similar among conditions (P > .05), and only the rating of perceived exertion increased during exercise ( = .78). Conclusion: Whether performed individually or in a small group, CIRC represents HIIE and may be a feasible alternative to running-based HIIE.
Subduction initiation-induced rapid emplacement of garnet-bearing peridotites at a nascent forearc: Petrological and Os-Li isotopic evidence from the Purang ophiolite, Tibet
Authors: Gong Xiao-Han , Xu Ji-Feng , Shi Ren-Deng , Su Ben-Xun , Huang Qi-Shuai , Huang Xiao-Xiao 
Published: June 2021

Abstract
Garnet-bearing peridotites commonly occur in the deeper parts of mature or thickened oceanic lithosphere, and are rarely exhumed and emplaced onto the seafloor. The Purang ophiolitic peridotites in south Tibet contain rare symplectite pseudomorphs after garnet, offering a unique window into the still poorly understood evolution of the deep oceanic lithosphere. Here, integrated petrologic and Os-Li isotopic data are used to constrain the evolution and dynamics of emplacement for these garnet peridotite protoliths. The Purang peridotites show wide variations of chemical compositions (spinel Cr#: 0.2–0.8) and Os model ages (up to 2.0 Ga), thus representing a piece of heterogeneous oceanic mantle lithosphere. Dunite channels show two distinctive groups of Cr# of spinels and Os-isotope compositions, with the low- to medium-Cr# (0.2–0.6) and high-Cr# (0.7–0.8) dunites reflecting the reaction of host lherzolites/harzburgites with percolating mid-ocean ridge basalt–like and boninitic melts, respectively. This confirms recent subduction initiation-related melt percolation in the Purang peridotites. Coexisting olivines and pyroxenes in the peridotites show systematic Li elemental and isotopic disequilibrium, suggesting fast cooling of the peridotites to Li closure temperature shortly after the melt percolations, likely during exhumation of the peridotites onto the seafloor. This supports a close link between subduction initiation and tectonic emplacement of the Purang peridotites. Combined with other geological evidence, we suggest the Purang peridotites may originate from the deep part of old, thick oceanic lithosphere of the Neo-Tethys. This thick oceanic lithosphere was progressively weakened and thinned likely during widespread plume-lithosphere interaction, triggering the transformation of garnet peridotite protoliths to spinel peridotites. Subsequently, initiation of a new subduction zone along the lithospheric weakness caused rapid ascent and emplacement of the Purang peridotites at a nascent forearc.
Performance assessment of the county healthcare systems in Kenya: a mixed-methods analysis
Authors: Moses Mark W , Korir Julius , Zeng Wu , Musiega Anita , Oyasi Joyce , Lu Ruoyan , Chuma Jane , Di Giorgio Laura 
Published: June 2021

IntroductionA well performing public healthcare system is necessary for Kenya to continue progress towards universal health coverage (UHC). Identifying actionable measures to improve the performance of the public healthcare system is critical to progress towards UHC. We aimed to measure and compare the performance of Kenya’s public healthcare system at the county level and explore remediable drivers of poor healthcare system performance.MethodsUsing administrative data from fiscal year 2014/2015 through fiscal year 2017/2018, we measured the technical efficiency of 47 county-level public healthcare systems in Kenya using stochastic frontier analysis. We then regressed the technical efficiency measure against a set of explanatory variables to examine drivers of efficiency. Additionally, in selected counties, we analysed surveys and focus group discussions to qualitatively understand factors affecting performance.ResultsThe median technical efficiency of county public healthcare systems was 84% in fiscal year 2017/2018 (with an IQR of 79% to 90%). Across the four fiscal years of data, 27 out of the 47 Kenyan counties had a declining technical efficiency score. Our regression analysis indicated that impediments to the flow of funding—measured by the budget absorption rate which is the ratio between funds spent and funds released—were significantly related to poor healthcare system performance. Our analysis of interviews and surveys yielded a similar conclusion as nearly 50% of respondents indicated issues stemming from poor budget absorption were significant drivers of poor healthcare system performance.ConclusionPublic healthcare systems at the county-level in Kenya general performed well; however, addressing delays in the flow of funding is a concrete step to improve healthcare system performance. As Kenya—and other countries—provides additional funding to meet their UHC goals, establishing a strong and robust public financial management system is critical to ensure that the benefits of UHC are realised.
Safety and efficacy of lacosamide versus phenytoin for refractory seizures in neurosurgical patients
Authors: Schaidle Sarah , Greathouse Kasey , McConnell Deepika 
Published: June 2021

BackgroundPostoperative neurosurgical patients have increased risk of seizures. Traditional anti-epileptics, such as phenytoin, are not always effective and cause adverse effects. Levetiracetam is the first-line therapy due to its similar efficacy and more favourable side effect profile. However, many patients continue to seize despite adequate dosing. Lacosamide has been used for refractory seizures and may offer similar seizure control without the negative aspects of traditional agents. The purpose of this study is to evaluate if lacosamide is as safe and effective as phenytoin in terminating seizures in neurosurgical patients already on levetiracetam.MethodsThis retrospective, single-centre cohort study identified neurosurgical intensive care unit (ICU) patients ≥18 years old who had received levetiracetam plus either phenytoin or lacosamide at Northwestern Memorial Hospital between 1 January 2016 and 31 August 2017. The primary endpoint was treatment failure and the secondary endpoint was safety assessed by liver function tests, blood pressure, heart rate and ECG.Results70 patients were included in this study, 52 in the phenytoin group and 18 in the lacosamide group. Both phenytoin and lacosamide groups had similar treatment failure rates (25% vs 22% respectively, p=1). Phenytoin use resulted in a mean decrease in systolic blood pressure of 20.9 mm Hg compared with 9.8 mm Hg in the lacosamide group (p=0.019). There were no statistically significant differences in the rates of other adverse effects.ConclusionsThe use of lacosamide for refractory seizures in neurosurgical ICU patients was associated with similar failure rates, but fewer adverse effects when compared with phenytoin.
Predicting 90-day modified Rankin Scale score with discharge information in acute ischaemic stroke patients following treatment
Authors: ElHabr Andrew K , Katz Jeffrey M , Wang Jason , Bastani Mehrad , Martinez Gabriela , Gribko Michele , Hughes Danny R , Sanelli Pina 
Published: June 2021

ObjectivesTo understand variability in modified Rankin Scale scores from discharge to 90 days in acute ischaemic stroke patients following treatment, and examine prediction of 90-day modified Rankin Scale score by using discharge modified Rankin Scale and discharge disposition.Materials and methodsRetrospective analysis of acute ischaemic stroke patients following treatment was performed from January 2016 to March 2020. Data collection included demographic and clinical characteristics and outcomes data (modified Rankin Scale score at discharge, 30 days and 90 days and discharge disposition). Pearson’s χ2test assessed statistical differences in distribution of modified Rankin Scale scores at discharge, 30 days and 90 days. The predictive power of discharge modified Rankin Scale score and disposition quantified the association with 90-day outcome.ResultsA total of 280 acute ischaemic stroke patients (65.4% aged ≥65 years, 47.1% female, 60.7% white) were included in the analysis. The modified Rankin Scale score significantly changed between 30 and 90 days from discharge (p<0.001) after remaining stable from discharge to 30 days (p=0.665). The positive and negative predictive values of an unfavourable long-term outcome for discharge modified Rankin Scale scores of 3–5 were 67.7% (95% CI 60.4% to 75.0%) and 82.0% (95% CI 75.1% to 88.8%), and for non-home discharge disposition were 72.4% (95% CI 64.5% to 80.2%) and 74.5% (95% CI 67.8% to 81.3%), respectively.ConclusionsDischarge modified Rankin Scale score and non-home discharge disposition are good individual predictors of 90-day modified Rankin Scale score for ischaemic stroke patients following treatment.
Sources of work-related psychological distress experienced by UK-wide foundation and junior doctors: a qualitative study
Authors: Riley Ruth , Buszewicz Marta , Kokab Farina , Teoh Kevin , Gopfert Anya , Taylor Anna K , Van Hove Maria , Martin James , Appleby Louis , Chew-Graham Carolyn 
Published: June 2021

ObjectivesThis paper reports findings exploring work cultures, contexts and conditions associated with psychological distress in foundation and junior doctors.DesignQualitative study using in-depth interviews with 21 junior doctor participants. The interviews were audio-recorded, transcribed, anonymised and imported into NVivo V.11 to facilitate data management. Data were analysed using a thematic analysis employing the constant comparative method.SettingNHS in England.ParticipantsA purposive sample of 16 female and five male junior doctor junior doctor participants who self-identified as having stress, distress, anxiety, depression and suicidal thoughts, or having attempted to kill themselves.ResultsAnalysis reported four key themes: (1) workload and working conditions; (2) toxic work cultures—including abuse and bullying, sexism and racism, culture of blaming and shaming; (3) lack of support; (4) stigma and a perceived need to appear invulnerable.ConclusionThis study highlights the need for future solutions and interventions targeted at improving work cultures and conditions. There needs to be greater recognition of the components and cumulative effects of potentially toxic workplaces and stressors intrinsic to the work of junior doctors, such as the stress of managing high workloads and lack of access to clinical and emotional support. A cultural shift is needed within medicine to more supportive and compassionate leadership and work environments, and a zero-tolerance approach to bullying, harassment and discrimination.