bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRPF8 controls alternative splicing of PIRH2 to modulate the p53 pathway and survival of human ESCs
Authors: Sun Yiyang , Zhang Lingling , Fang Zhuoqing , Liu Dingyu , Shao Min , Liu Yujie , Liao Bing , Jin Ying 
Published: June 2023

AbstractHuman embryonic stem cells (hESCs) have great potential for developmental biology and regenerative medicine. However, extensive apoptosis often occurs when hESCs respond to various stresses or injuries. Understanding the molecular control and identifying new factors associated with hESC survival are fundamental to ensure the high quality of hESCs. In this study, we report that PRPF8, an RNA spliceosome component, is essential for hESC survival. PRPF8 knockdown (KD) induces p53 protein accumulation and activates the p53 pathway, leading to apoptosis in hESCs. Strikingly, silencing of p53 rescues PRPF8 KD‐induced apoptosis, indicating that PRPF8 KD triggers hESC apoptosis through activating the p53 pathway. In search for the mechanism by which p53 pathway is activated by PRPF8 KD, we find that PRPF8 KD alters alternative splicing of many genes, including PIRH2 which encodes an E3 ubiquitin ligase of p53. PIRH2 has several isoforms such as PIRH2A, PIRH2B, and PIRH2C. Intriguingly, PRPF8 KD specifically increases the transcript level of the PIRH2B isoform, which lacks a RING domain and E3 ligase activity. Functionally, PIRH2B KD partially rescues the reduction in cell numbers and upregulation of P21 caused by PRPF8 KD in hESCs. The finding suggests that PRPF8 controls alternative splicing of PIRH2 to maintain the balance of p53 pathway activity and survival of hESCs. The PRPF8/PIRH2/p53 axis identified here provides new insights into how p53 pathway and hESC survival are precisely regulated at multiple layers, highlighting an important role of posttranscriptional machinery in supporting hESC survival.
Counterfactual estimation of efficacy against placebo for novel PrEP agents using external trial data: example of injectable cabotegravir and oral PrEP in women
Authors: Donnell Deborah , Gao Fei , Hughes James P. , Hanscom Brett , Corey Lawrence , Cohen Myron S. , Edupuganti Srilatha , Mgodi Nyaradzo , Rees Helen , Baeten Jared M. , Gray Glenda , Bekker Linda‐Gail , Hosseinipour Mina , Delany‐Moretlwe Sinead 
Published: June 2023

AbstractIntroductionMultiple antiretroviral agents have demonstrated efficacy for human immunodeficiency virus (HIV) pre‐exposure prophylaxis (PrEP). As a result, clinical trials of novel agents have transitioned from placebo‐ to active‐controlled designs; however, active‐controlled trials do not provide an estimate of efficacy versus no use of PrEP. Counterfactual placebo comparisons using other data sources could be employed to provide this information.MethodsWe compared the active‐controlled study (HPTN 084) of injectable cabotegravir (CAB‐LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) among women from seven countries in Africa to three external, contemporaneous randomized HIV prevention trials from which we constructed counterfactual placebo estimates. We used direct standardization via analysis weights to achieve the same distribution of person‐years between the external study and HPTN 084, across strata predictive of HIV risk (country and selected risk covariates). We estimated prevention efficacy against a counterfactual placebo to provide information on the use of CAB‐LA and FTC/TDF compared to no intervention. We compared the counterfactual placebo findings for FTC/TDF to previous placebo‐controlled trials, adjusted for observed adherence to daily pills.ResultsDistribution of age and baseline prevalence of gonorrhoea and chlamydia were similar among matched counterfactual placebo and observed HPTN 084 arms after standardization. Counterfactual estimates of CAB‐LA versus placebo in all three settings showed a consistent risk reduction of 93%–94%, with lower bounds of the confidence intervals above 72%. Observed adherence (quantifiable tenofovir in plasma) in HPTN 084 was 54%–56%, and estimated efficacy of daily oral FTC/TDF against a counterfactual placebo was consistent with a predicted risk reduction of 39%–40% for this level of daily pill use.ConclusionsCounterfactual placebo rates of HIV acquisition derived from external trial data in similar locations and time can be used to support estimates of placebo‐based efficacy of a novel HIV prevention agent. External trial data must be standardized to be representative of the clinical trial cohort testing the novel HIV prevention agent, accounting for confounders.
One‐pot fabrication of magnetic adsorbent based on polymeric ionic liquid/aminated carbon nanotubes composite for efficient capture of synthetic auxins in complex samples prior to chromatographic analysis
Authors: Zhang YueYue , Huang Youfang , Huang Xiaojia 
Published: June 2023

Efficient enrichment is a challenging and indispensable step in the quantification of polar synthetic auxins in complex samples. In the current study, a new magnetic adsorbent based on polymeric ionic liquid/aminated carbon nanotube composite was fabricated with a one‐pot precipitation copolymerization strategy and employed as the extraction phase of magnetic solid phase extraction of synthetic auxins. Various characterization techniques were utilized to inspect the morphology, structure, magnetic property, and functional groups of the prepared adsorbent. Under the optimal conditions, the obtained adsorbent displayed satisfactory capture performance towards studied auxins through multiple interactions. Adsorption studies evidenced that the adsorption procedure of the developed method towards analytes was fit for the Freundlich adsorption model and pseudo‐second‐order kinetics. Combining with high‐performance liquid chromatography, sensitive and reliable method for the identification and quantification of trace synthetic auxins in environmental water and fruit juice samples was developed. The obtained limits of detection for water and fruit juice samples located in the ranges of 0.0059–0.013 and 0.018–0.031 μg/L, respectively. Recoveries in actual samples with different fortified contents varied from 82.2% to 117%, with satisfactory reproducibility. The results will evidence that the introduced extraction technique is a useful alternative for the entrapment of trace synthetic auxins from complex samples.
Behavior‐specific habitat selection by raccoons in the Prairie Pothole Region of Manitoba
Authors: Milling Charlotte R. , Gehrt Stanley D. 
Published: June 2023

AbstractPatterns of resource selection depend upon an animal's behavioral state. Because management strategies are often crafted from an understanding of animal space use, incorporating behavior explicitly into analyses of resource selection has the potential to improve outcomes. In the Prairie Pothole Region of Manitoba, Canada, raccoons (Procyon lotor) are a nest predator of waterfowl, but it is unclear how raccoons use this landscape during the waterfowl nesting season. Our objective was to use high‐resolution global positioning system (GPS) telemetry to differentiate among behaviors by raccoons and evaluate behavior‐specific habitat selection during the waterfowl nesting season. We collected approximately 32,000 locations from 33 animals during the 2018, 2019, and 2021 nesting seasons, amounting to 632 animal‐night's worth of movement data. We used hidden Markov models (HMM) to fit 4‐state models to the movement trajectories, classified observations into discrete behaviors, and fit behavior‐specific random forest resource selection models to evaluate the relative importance of habitat features on selection. Proximity to a wetland was the most important variable contributing to selection for the resting, foraging, and slow travel states. Probability of use was as high as 95% within or immediately adjacent to a wetland for animals engaged in those behaviors, and our best HMM predicted increasing probability of switching from resting or foraging to directed travel with increasing distance from a wetland edge. Human‐use sites were also important to foraging animals, suggesting raccoons subsidize their diet with anthropogenic food resources during spring and summer. These results illuminate the complexity of habitat selection by a waterfowl predator in this patchy landscape, allowing managers to develop effective conservation strategies (e.g., wetland prioritization and conservation, elimination of anthropogenic subsidies) where raccoons are having a disproportionate effect during the waterfowl nesting season.
Effect of continuous local dexamethasone on tissue biomechanics and histology after inhalational burn in a preclinical model
Authors: Malka Ronit , Gonzales Gabriela , Detar Will , Marinelli Lisa , Lee Christine M. , Isaac Alisa , Miar Solaleh , Cook Stacy , Guda Teja , Dion Gregory R. 
Published: June 2023

AbstractObjectiveInhalational burns frequently lead to dysphonia and airway stenosis. We hypothesize local dexamethasone delivery via a novel drug‐eluting electrospun polymer‐mesh endotracheal tube (ETT) reduces biomechanical and histologic changes in the vocal folds in inhalational burn.MethodsDexamethasone‐loaded polymer mesh was electrospun onto ETTs trimmed to transglottic endolaryngeal segments and secured in nine Yorkshire Crossbreed swine with directed 150°C inhalation burns. Uncoated ETTs were implanted in nine additional swine with identical burns. ETT segments were maintained for 3 and 7 days. Vocal fold (VF) structural stiffness was measured using automated‐indentation mapping and compared across groups and to four uninjured controls, and matched histologic assessment performed. Statistical analysis was conducted using two‐way ANOVA with Tukey's post hoc test and Wilcoxon rank‐sum test.ResultsVF stiffness after burn decreased with longer intubation, from 19.4 (7.6) mN/mm at 3 days to 11.3 (5.2) mN/mm at 7 days (p < .0001). Stiffness similarly decreased with local dexamethasone, from 25.9 (17.2) mN/mm at 3 days to 18.1 (13.0) mN/mm at 7 days (p < .0001). VF stiffness in the dexamethasone group was increased compared to tissues without local dexamethasone (p = .0002), and all groups with ETT placement had higher tissue stiffness at 3 days (p < .001). No significant change in histologic evidence of epithelial ulceration or fibrosis was noted, while an increased degree of inflammation was noted in the dexamethasone group (p = .04).ConclusionLocal dexamethasone delivery increases VF stiffness and degree of inflammation compared to uncoated ETTs in an acute laryngeal burn model, reflected in early biomechanical and histologic changes in an inhalational burn model.
Biocompatible Polymer‐Modified Nanoplatform for Ferroptosis‐Enhanced Combination Cancer Therapy
Authors: He Meng , Dan Yuxin , Chen Mingsheng , Dong Chang‐Ming 
Published: June 2023

AbstractFerroptosis is a novel type of iron‐dependent non‐apoptotic pathway that regulates cell death and shows unique mechanisms including causing lipid peroxide accumulation, sensitizing drug‐resistant cancers, priming immunity by immunogenic cell death, and cooperatively acting with other anticancer modalities for eradicating aggressive malignancies and tumor relapse. Recently, there has been a great deal of effort to design and develop anticancer biocompatible polymeric nanoplatforms including polypeptide and PEGylated ones to achieve effective ferroptosis therapy (FT) and synergistic combination therapies including chemotherapy (CT), photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), gas therapy (GT) including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), and immunotherapy (IT). To be noted, the combo therapies such as FT‐CT, FT‐PTT, FT‐GT, and FT‐IT are attracting much efforts to fight against intractable and metastatic tumors as they can generate synergistic antitumor effects and immunogenic cell death (ICD) effects or modulate immunosuppressive tumor microenvironments to initiate strong antitumor immunity and memory effects. The polymeric Fenton nano‐agents with good biosafety and high anticancer efficacy will provide a guarantee for their applications. In this review, various biocompatible polymer‐modified nanoplatforms designed for FT and combo treatments are summarized for anticancer therapies and discussed for potential clinical transitions.
Referral strategy of e‐commerce platform under different selling modes
Authors: Wang Xin , Yu Lin , Zhang Shuhua , Wu Shuping , Yu Baoqin , Ye Xiaofen 
Published: June 2023

AbstractThis study considers a market comprising two suppliers and one e‐commerce platform. The two competitive suppliers sell products to consumers through the platform. The platform can choose three selling modes: reseller, market, and mixed. Additionally, we consider two referral strategies—namely, exclusive and nonexclusive recommendations—and build a three‐party Stackelberg game model. Per the findings, the difference in the players' decision‐making results exhibits an essential relationship with the recommendation market's initial size. A counterintuitive result is that the product price is not affected by the commission rate in the market mode. This provides referential insights for platforms and suppliers.
Predicting Ambulatory Capacity in Parkinson's Disease to Analyze Progression, Biomarkers, and Trial Design
Authors: Venuto Charles S. , Smith Greta , Herbst Konnor , Zielinski Robert , Yung Norman C.W. , Grosset Donald G. , Dorsey E. Ray , Kieburtz Karl 
Published: June 2023

ABSTRACTBackgroundIn Parkinson's disease (PD), gait and balance is impaired, relatively resistant to available treatment and associated with falls and disability. Predictive models of ambulatory progression could enhance understanding of gait/balance disturbances and aid in trial design.ObjectivesTo predict trajectories of ambulatory abilities from baseline clinical data in early PD, relate trajectories to clinical milestones, compare biomarkers, and evaluate trajectories for enrichment of clinical trials.MethodsData from two multicenter, longitudinal, observational studies were used for model training (Tracking Parkinson's, n = 1598) and external testing (Parkinson's Progression Markers Initiative, n = 407). Models were trained and validated to predict individuals as having a “Progressive” or “Stable” trajectory based on changes of ambulatory capacity scores from the Movement Disorders Society Unified Parkinson's Disease Rating Scale parts II and III. Survival analyses compared time‐to‐clinical milestones and trial outcomes between predicted trajectories.ResultsOn external evaluation, a support vector machine model predicted Progressive trajectories using baseline clinical data with an accuracy, weighted‐F1 (proportionally weighted harmonic mean of precision and sensitivity), and sensitivity/specificity of 0.735, 0.799, and 0.688/0.739, respectively. Over 4 years, the predicted Progressive trajectory was more likely to experience impaired balance, loss of independence, impaired function and cognition. Baseline dopamine transporter imaging and select biomarkers of neurodegeneration were significantly different between predicted trajectory groups. For an 18‐month, randomized (1:1) clinical trial, sample size savings up to 30% were possible when enrollment was enriched for the Progressive trajectory versus no enrichment.ConclusionsIt is possible to predict ambulatory abilities from clinical data that are associated with meaningful outcomes in people with early PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Mental health status of children who use foreign languages at home in Japan
Authors: Takahashi Michio , Nishimura Tomoko , Osuka Yuko , Tsukui Nobuaki , Adachi Masaki , Katayama Taiichi , Wakuta Manabu 
Published: June 2023

AbstractAimLittle is known about the mental health status of children in Japan whose roots are in foreign countries. The differences in language that are used every day may be a factor that makes adaptation difficult for these children. The aim of the present study, therefore, was to examine the mental health status of children who use foreign languages at home via a cross‐sectional survey in a large cohort.MethodsThe survey was conducted among children who attended public elementary and junior high schools in a large city in Japan. Data were received from 20,596 elementary school‐aged (above 4th grade) and 19,464 junior high school‐aged children. We compared mental health status evaluated by the Patient Health Questionnaire‐4 in the group based on language usage at home (only Japanese, only foreign languages, and both languages).ResultsWe found that children who used foreign languages at home exhibited worse mental health status than children who used only Japanese at home. In addition, mental health status was slightly better among junior high school‐aged children who used only foreign languages at home than among elementary school‐aged children. This tendency was not observed in the group of children who used both languages at home.ConclusionOur results suggest that children in Japanese society who use foreign languages at home have worse mental health, therefore there is a need for support for these children living in Japan.
Novel Biocompatible Magnetoelectric MnFe2O4 Core@BCZT Shell Nano–Hetero‐Structures with Efficient Catalytic Performance
Authors: Chernozem Roman V. , Urakova Alina O. , Chernozem Polina V. , Koptsev Danila A. , Mukhortova Yulia R. , Grubova Irina Yu. , Wagner Dmitry V. , Gerasimov Evgeny Yu. , Surmeneva Maria A. , Kholkin Andrei L. , Surmenev Roman A. 
Published: June 2023

AbstractMagnetoelectric (ME) small‐scale robotic devices attract great interest from the scientific community due to their unique properties for biomedical applications. Here, novel ME nano hetero‐structures based on the biocompatible magnetostrictive MnFe2O4 (MFO) and ferroelectric Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT) are developed solely via the hydrothermal method for the first time. An increase in the temperature and duration of the hydrothermal synthesis results in increasing the size, improving the purity, and inducing morphology changes of MFO nanoparticles (NPs). A successful formation of a thin epitaxial BCZT‐shell with a 2–5 nm thickness is confirmed on the MFO NPs (77 ± 14 nm) preliminarily treated with oleic acid (OA) or polyvinylpyrrolidone (PVP), whereas no shell is revealed on the surface of pristine MFO NPs. High magnetization is revealed for the developed ME NPs based on PVP‐ and OA‐functionalized MFO NPs (18.68 ± 0.13 and 20.74 ± 0.22 emu g−1, respectively). Moreover, ME NPs demonstrate 95% degradation of a model pollutant Rhodamine B within 2.5 h under an external AC magnetic field (150 mT, 100 Hz). Thus, the developed biocompatible core–shell ME NPs of MFO and BCZT can be considered as a promising tool for non‐invasive biomedical applications, environmental remediation, and hydrogen generation for renewable energy sources.
Counteracting sociocultural barriers in global software engineering using group activities
Authors: Yasin Affan , Fatima Rubia , Ali Khan Javed , Liu Lin , Ali Raian , Wang Jianmin 
Published: June 2023

AbstractIn modern times, internationally organized teams face a number of coordination problems owing to their different physical operating locations. These challenges usually come in temporal, cultural, and linguistic forms. To resolve some of these issues, we need more coordination, teamwork, and shared understanding in the requirements engineering phase. Many approaches have been introduced to overcome these challenges associated with global software engineering (GSE). The objective of this research study is to introduce amateurs to GSE and improve their understanding of its associated challenges through an activity‐based learning approach. Our method is primarily targeted toward students who already have theoretical knowledge on the topic but require first‐hand experience with GSE. With the aforementioned motivation in mind, we propose, designe, and empirically evaluate two different activities that can help enhance awareness of GSE challenges. For each activity, we simulate an environment wherein participants are made to go through various constructed coordination challenges related to communication, time management, team mistrust, linguistic barriers, cultural barriers, and distribution of tasks. The effectiveness of our proposed activities, captured by the extent to which participants were able to deal with GSE challenges, was judged through various techniques including (i) observation, (ii) post activities survey questionnaire, and (iii) brainstorming and discussion. We show that the proposed activities were effective in helping students learn and further their understanding of GSE concepts. In particular, discussion sessions and survey questionnaire results reflect their ability to identify critical GSE challenges (specifically related to teams) in a simulated scenario.
Higher derivative couplings of hypermultiplets
Authors: Chang Hao-Yuan , Sezgin Ergin , Tanii Yoshiaki 
Published: June 2023

Abstract
We construct the four-derivative supersymmetric extension of (1, 0), 6D supergravity coupled to Yang-Mills and hypermultiplets. The hypermultiplet scalars are taken to parametrize the quaternionic projective space Hp(n) = Sp(n, 1)/Sp(n) × Sp(1)R. The hyperscalar kinetic term is not deformed, and the quaternionic Kähler structure and symmetries of Hp(n) are preserved. The result is a three parameter Lagrangian supersymmetric up to first order in these parameters. Considering the case of Hp(1) we compare our result with that obtained from the compactification of 10D heterotic supergravity on four-torus, consistently truncated to N = (1, 0), in which the hyperscalars parametrize SO(1, 4)/SO(4). We find that depending on how the Sp(1) is embedded in the SO(4), the results agree for a specific value of the parameter that governs the higher derivative hypermultiplet couplings.
PRECISE Scale: a quantitative classification for androgenetic alopecia and its application to hair transplantation
Authors: Pittella Felipe , Castro Carlo G. , Trivellini Roberto , Sethi Pradeep , La Padula Simone , Sanabria Baltazar , Paes Camila Q. , Palmieri Miguel G. S. , Pittella Frederico 
Published: June 2023

Abstract
Background
Androgenetic alopecia (AGA) is a prevalent genetic condition that can affect both male and female, and is considered the most frequent form of hair loss. Traditional scales and methods of classifying AGA are basically qualitative.

Objective
This work aims to propose a quantitative scale to classify AGA in order to assist hair transplantation surgery.

Methods
Based on whole hairless and thinning areas that needs to receive follicular units in a hair transplantation procedure, basic equations to support the scale are proposed. Additionally, the study involves simulations that apply the classification system and compare its results with those of qualitative methods.

Results
The PRECISE scale utilizes a range of 0–10, using 30 cm2 as the measured standard of a bald area. For hair transplantation, 1500 follicular units (FU) are recommended for each score in the PRECISE scale. Technological and manual methods to measure the hairless and thinning areas are presented and discussed. This new quantitative classification, combined with different and complementary methods of measurement of hairless and thinning areas endorse the understanding of the clinical condition by the patient and the planning of a surgery procedure.

Conclusion
The developed PRECISE scale brings a different way of classifying Androgenetic alopecia (AGA), through an essentially quantitative evaluation. It can be used to elaborate the best strategy for the hair transplantation surgery and to improve the outcomes.

Level of Evidence V
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