bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway
Authors: Chen Lu , Wang Xiping , Tian Sha , Zhou Linxi , Wang Li , Liu Xiaohan , Yang Zihan , Fu Guiqiang , Liu Xingguang , Ding Chen , Zou Duohong 
Published: August 2024

Abstract
Human dental pulp stem cells (HDPSCs) showed an age-dependent decline in proliferation and differentiation capacity. Decline in proliferation and differentiation capacity affects the dental stromal tissue homeostasis and impairs the regenerative capability of HDPSCs. However, which age-correlated proteins regulate the senescence of HDPSCs remain unknown. Our study investigated the proteomic characteristics of HDPSCs isolated from subjects of different ages and explored the molecular mechanism of age-related changes in HDPSCs. Our study showed that the proliferation and osteogenic differentiation of HDPSCs were decreased, while the expression of aging-related genes (p21, p53) and proportion of senescence-associated β-galactosidase (SA-β-gal)-positive cells were increased with aging. The bioinformatic analysis identified that significant proteins positively correlated with age were enriched in response to the mammalian target of rapamycin (mTOR) signaling pathway (ILK, MAPK3, mTOR, STAT1, and STAT3). We demonstrated that OSU-T315, an inhibitor of integrin-linked kinase (ILK), rejuvenated aged HDPSCs, similar to rapamycin (an inhibitor of mTOR). Treatment with OSU-T315 decreased the expression of aging-related genes (p21, p53) and proportion of SA-β-gal-positive cells in HDPSCs isolated from old (O-HDPSCs). Additionally, OSU-T315 promoted the osteoblastic differentiation capacity of O-HDPSCs in vitro and bone regeneration of O-HDPSCs in rat calvarial bone defects model. Our study indicated that the proliferation and osteoblastic differentiation of HDPSCs were impaired with aging. Notably, the ILK/AKT/mTOR/STAT1 signaling pathway may be a major factor in the regulation of HDPSC senescence, which help to provide interventions for HDPSC senescence.
Oral probiotic administration attenuates postexercise inflammation in horses
Authors: Jacobs Robert D , Grum Daniel , Trible Benjamin , Ayala Diana I , Karnezos Theodore P , Gordon Mary E 
Published: August 2024

Abstract
Probiotics are commonly incorporated into equine diets to impart health and performance benefits; however, peer-reviewed evidence supporting their efficacy in horses is limited. Interestingly, bacteria from the Bacillus genus are gaining interest for their unique ability to impact metabolic, immune, and inflammatory pathways. The objective of this trial was to evaluate a selection of Bacilli for their role in altering the inflammatory response in horses to exercise. Eighteen horses were utilized in a randomized cross-over trial. Horses were randomly assigned to one of 6 starting treatments including a negative and positive control, and groups that received one of 4 probiotics (Bacillus coagulans GBI-30, 6086, Bacillus subtilis-1, Bacillus subtilis-2, or Bacillus amyloliquefaciens) top dressed to their daily ration at a rate of 8 billion CFU/d mixed into dried whey powder. All horses received a similar base diet of grass hay offered at 2.0% of bodyweight daily along with 4.54 kg of a commercially available textured horse feed. Each 3-wk phase of the trial consisted of a 2-wk dietary acclimation followed by a 1-wk exercise challenge and sample collection. Between phases, horses were offered only their base diet. On the day of exercise, horses were offered their 0700 ration and then subjected to a 2-h standardized exercise test. Blood samples were obtained prior to starting exercise and then again at 0, 2, 4, 6, 8, 24, 48, and 72-h postexercise. Horses in the positive control group were administered 0.23 mg/kg BW flunixin meglumine immediately following the 0-h sampling. Samples were analyzed for serum amyloid A (SAA), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) concentrations. Data were evaluated via ANOVA using the MIXED procedure in SAS 9.4. Exercise-induced inflammation as evidenced by SAA, IL-6, and PGE2 increases postexercise. Horses consuming B. coagulans GBI-30, 6086 had reduced production of SAA, IL-6, and PGE2 compared to all other probiotic-fed groups and the negative control (P &lt; 0.001). The positive control successfully ameliorated the postexercise inflammatory response. These data highlight the potential for B. coagulans GBI-30, 6086 to be incorporated into equine rations as a method to support optimal response to exercise or other inflammation-inducing challenges. Additional research is ongoing to elucidate the methodology by which these results occur.
Assessment of cytoprotective and genoprotective effects of Moringa oleifera and Tinospora cordifolia extracts in vitro
Authors: Bagri Preeti , Kumar Vinod , Batra Kanisht 
Published: August 2024

Abstract

Background
Moringa oleifera and Tinospora cordifolia is extensively used as an ingredient of food and in traditional medicine for the management of a variety of diseases.

Material and methods
The extracts of leaf of Moringa oleifera and stem of Tinospora cordifolia were assessed to examine their ability to inhibit the oxidative DNA damage (by DNA protection assay), cytoprotective and genoprotective potential (by Comet assay) in V79 cells individually and in combinations.

Result
It was found that these extracts could significantly inhibit the OH-dependent damage of pUC18 plasmid DNA. M. oleifera extract (160 and 320 μg/mL) and Tinospora cordifolia extract (640, 1,280 and 2,560 μg/mL) individually showed higher DNA protection activity. M. oleifera (1,280 μg/mL) combined with Tinospora cordifolia (640 μg/mL) showed best cytoprotective and genoprotective activities among different concentration combinations and various concentrations of individual plants in V79 cell line against hydrogen peroxide induced cytotoxicity and genotoxicity.

Conclusion
This study demonstrates the cytoprotective and genoprotective activity of M. oleifera and Tinospora cordifolia individually or in combination.
The Impact of Delayed Transition From Noninvasive to Invasive Mechanical Ventilation on Hospital Mortality in Immunocompromised Patients With Sepsis*
Authors: Xu Yang , Wang Yi-Fan , Liu Yi-Wei , Dong Run , Chen Yan , Wang Yi , Weng Li , Du Bin ,   for the China Critical Care Clinical Trials Group (CCCCTG) and China National Critical Care Quality Control Center Group
Published: August 2024

OBJECTIVE:
To determine whether mortality differed between initial invasive mechanical ventilation (IMV) or noninvasive ventilation (NIV) followed by delayed IMV in immunocompromised patients with sepsis.

DESIGN:
Retrospective analysis using the National Data Center for Medical Service claims data in China from 2017 to 2019.

SETTING:
A total of 3530 hospitals across China.

PATIENTS:
A total of 36,187 adult immunocompromised patients with sepsis requiring ventilation.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
The primary outcome was hospital mortality. Patients were categorized into NIV initiation or IMV initiation groups based on first ventilation. NIV patients were further divided by time to IMV transition: no transition, immediate (≤ 1 d), early (2–3 d), delayed (4–7 d), or late (≥ 8 d). Mortality was compared between groups using weighted Cox models. Over the median 9-day follow-up, mortality was similar for initial NIV versus IMV (adjusted hazard ratio [HR] 1.006; 95% CI, 0.959–1.055). However, among NIV patients, a longer time to IMV transition is associated with stepwise increases in mortality, from immediate transition (HR 1.65) to late transition (HR 2.51), compared with initial IMV. This dose-response relationship persisted across subgroups and sensitivity analyses.

CONCLUSIONS:
Prolonged NIV trial before delayed IMV transition is associated with higher mortality in immunocompromised sepsis patients ultimately intubated.
Speech Recognition and Subjective Hearing Abilities for Electric–Acoustic Stimulation Users With Unilateral Hearing Loss
Authors: Dillon Margaret T. , Buss Emily , Thompson Nicholas J. , Richter Margaret E. , Davis Amanda G. , Overton Andrea B. , Rooth Meredith A. , Canfarotta Michael W. , Selleck A. Morgan , Dedmon Matthew M. , Brown Kevin D. 
Published: August 2024

ObjectiveSome cochlear implant (CI) recipients with unilateral hearing loss (UHL) have functional acoustic hearing in the implanted ear, warranting the fitting of an ipsilateral electric–acoustic stimulation (EAS) device. The present study assessed speech recognition and subjective hearing abilities over time for EAS users with UHL.Study DesignProspective, repeated-measures.SettingTertiary referral center.PatientsAdult CI recipients with normal-to-moderate low-frequency acoustic thresholds in the implanted ear and a contralateral pure-tone average (0.5, 1, and 2 kHz) ≤25 dB HL.Main Outcome MeasuresParticipants were evaluated preoperatively and at 1, 3, and 6 months post-activation. Speech recognition for the affected ear was evaluated with CNC words in quiet. Masked speech recognition in the bilateral condition was evaluated with AzBio sentences in a 10-talker masker (0 dB SNR) for three spatial configurations: target from the front and masker either colocated with the target or presented 90 degrees toward the affected or contralateral ear. Responses to the Speech, Spatial, and Qualities of Hearing Scale subscales were used to assess subjective hearing abilities.ResultsParticipants experienced significant improvements in CNC scores (F(3,13)= 14.90,p< 0.001), and masked speech recognition in the colocated (F(3,11)= 3.79,p= 0.043) and masker toward the contralateral ear (F(3,11)= 4.75,p= 0.023) configurations. They also reported significantly better abilities on the Speech Hearing (F(3,13)= 5.19,p= 0.014) and Spatial Hearing (F(3,13)= 10.22,p= 0.001) subscales.ConclusionsAdults with UHL and functional acoustic hearing in the implanted ear experience significant improvements in speech recognition and subjective hearing abilities within the initial months of EAS use as compared with preoperative performance and perceptions.
Microneedle-Mediated Delivery of siRNA via Liposomal-Based Transfection for Inner Ear Gene Therapy
Authors: Feng Sharon J. , Voruz François , Leong Stephen , Hammer Daniella R. , Breil Eugénie , Aksit Aykut , Yu Michelle , Chiriboga Lauren , Olson Elizabeth S. , Kysar Jeffrey W. , Lalwani Anil K. 
Published: August 2024

Hypothesis
Microneedle-mediated intracochlear injection of siRNA-Lipofectamine through the round window membrane (RWM) can be used to transfect cells within the cochlea.

Background
Our laboratory has developed 100-μm diameter hollow microneedles for intracochlear injection through the guinea pig RWM. In this study, we test the feasibility of microneedle-mediated injection of siRNA and Lipofectamine, a commonly used reagent with known cellular toxicity, through the RWM for cochlear transfection.

Methods
Fluorescently labeled scramble siRNA was diluted into Lipofectamine RNAiMax and OptiMEM. One microliter of 5 μM siRNA was injected through the RWM of Hartley guinea pigs at a rate of 1 μl/min (n = 22). In a control group, 1.0 μl of Lipofectamine, with no siRNA, was diluted into OptiMEM and injected in a similar fashion (n = 5). Hearing tests were performed before and either at 24 hours, 48 hours, or 5 days after injection. Afterward, animals were euthanized, and cochleae were harvested for imaging. Control cochleae were processed in parallel to untreated guinea pigs.

Results
Fluorescence, indicating successful transfection, was observed within the basal and middle turns of the cochlea with limited distribution in the apex at 24 and 48 hours. Signal was most intense in the organ of Corti, spiral ligament, and spiral ganglion. Little to no fluorescence was observed at 5 days post-injection. No significant changes in auditory brainstem response (ABR) were noted post-perforation at 5 days, suggesting that siRNA-Lipofectamine at low doses does not cause cochlear toxicity.

Conclusions
Small volumes of siRNA and Lipofectamine can be effectively delivered to cochlear structures using microneedles, paving the way for atraumatic cochlear gene therapy.
A first-in-kind MAPK13 inhibitor that can correct stem cell reprogramming and post-injury disease
Authors: Zhang Yong , Wu Kangyun , Mao Dailing , Iberg Courtney A. , Yin-Declue Huiqing , Sun Kelly , Wikfors Hallie A. , Keeler Shamus P. , Li Ming , Young Deanna , Yantis Jennifer , Crouch Erika C. , Chartock Joshua R. , Han Zhenfu , Byers Derek E. , Brody Steven L. , Romero Arthur G. , Holtzman Michael J. 
Published: August 2024

AbstractThe stress kinase MAPK13 (aka p38δ-MAPK) is an attractive entry point for therapeutic intervention because it regulates the structural remodeling that can develop after epithelial barrier injury in the lung and likely other tissue sites. However, a selective, safe, and effective MAPK13 inhibitor is not yet available for experimental or clinical application. Here we identify a first-in-kind MAPK13 inhibitor using structure-based drug design combined with a screening funnel for cell safety and molecular specificity. This inhibitor (designated NuP-4) down-regulates basal-epithelial stem cell reprogramming, structural remodeling, and pathophysiology equivalently toMapk13gene-knockout in mouse and mouse organoid models of post-viral lung disease. This therapeutic benefit persists after stopping treatment as a sign of disease modification and attenuates key aspects of inflammation and remodeling as an indication of disease reversal. Similarly, NuP-4 treatment can directly control cytokine-stimulated growth, immune activation, and mucinous differentiation in human basal-cell organoids. The data thereby provide a new tool and potential fix for long-term stem cell reprogramming after viral injury and related conditions that require MAPK13 induction-activation.New and noteworthyThis study identifies a small-molecule inhibitor for MAPK13 with efficacy and safety in models of the long-term disease that features epithelial stem cell reprogramming towards inflammation and structural remodeling. The present model has direct implications for respiratory disease triggered by viral infection and other inhaled toxins, but the tissue distribution of MAPK13 implies related actions at other epithelial barrier sites. The findings also refine a hypothesis for therapeutic intervention based on proper adjustment of MAPK13 function with a selective kinase inhibitor.
Analysis of micro-defect-induced cracking in the IPyC layer of TRISO particle with the XFEM
Authors: Li Yunhao , Wei Qian , Li Luxian 
Published: August 2024

PurposeWe use the extended finite element method (XFEM) to model the whole process of initiation and propagation of cracks in the inner dense pyrolytic carbon (IPyC) layer of tri-structural isotropic (TRISO) particle induced by the microdefect in an irradiation-induced thermomechanical coupling environment and study the effect of microdefect sizes on the propagation path.Design/methodology/approachThe irradiation-induced thermal–mechanical coupling analysis is first conducted for the representative volume element (RVE) of the TRISO particle by using the conventional finite element method (CFEM) so that the stress distribution is obtained. The stress results are then restored for the enriched elements, and the simulation of crack initiation and propagation is eventually carried out by using the XFEM.Findings1. As a crack initiates in the IPyC layer, it will terminate at the free edge of the RVE TRISO particle in the end. 2. The size of the microdefect has a significant impact on the propagation path.Originality/valueThe ceramic dispersion microencapsulated (CDM) fuel is a good accident-resistant fuel whose safe operation is crucial to the safety and reliability of the whole nuclear reactor. It is of great scientific significance and practical value to study the irradiation-induced thermomechanical coupling stress distribution and cracking behavior in the IPyC layer of TRISO particles for the CDM fuel. Crack initiation and propagation analysis is challengeable for this complex multi-layer structure. This can help understand the failure mechanism of TRISO particles and evaluate the operation safety of the reactor.
Reinforcement learning for cooling rate control during quenching
Authors: Hachem Elie , Vishwasrao Abhijeet , Renault Maxime , Viquerat Jonathan , Meliga P. 
Published: August 2024

Purpose
The premise of this research is that the coupling of reinforcement learning algorithms and computational dynamics can be used to design efficient control strategies and to improve the cooling of hot components by quenching, a process that is classically carried out based on professional experience and trial-error methods. Feasibility and relevance are assessed on various 2-D numerical experiments involving boiling problems simulated by a phase change model. The purpose of this study is then to integrate reinforcement learning with boiling modeling involving phase change to optimize the cooling process during quenching.

Design/methodology/approach
The proposed approach couples two state-of-the-art in-house models: a single-step proximal policy optimization (PPO) deep reinforcement learning (DRL) algorithm (for data-driven selection of control parameters) and an in-house stabilized finite elements environment combining variational multi-scale (VMS) modeling of the governing equations, immerse volume method and multi-component anisotropic mesh adaptation (to compute the numerical reward used by the DRL agent to learn), that simulates boiling after a phase change model formulated after pseudo-compressible Navier–Stokes and heat equations.

Findings
Relevance of the proposed methodology is illustrated by controlling natural convection in a closed cavity with aspect ratio 4:1, for which DRL alleviates the flow-induced enhancement of heat transfer by approximately 20%. Regarding quenching applications, the DRL algorithm finds optimal insertion angles that adequately homogenize the temperature distribution in both simple and complex 2-D workpiece geometries, and improve over simpler trial-and-error strategies classically used in the quenching industry.

Originality/value
To the best of the authors’ knowledge, this constitutes the first attempt to achieve DRL-based control of complex heat and mass transfer processes involving boiling. The obtained results have important implications for the quenching cooling flows widely used to achieve the desired microstructure and material properties of steel, and for which differential cooling in various zones of the quenched component will yield irregular residual stresses that can affect the serviceability of critical machinery in sensitive industries.
Calendar anomalies’ adaptiveness in exchange rates: evidence from the concordance coefficient and AR-GARCH tests
Authors: Villarreal-Samaniego Dacio 
Published: August 2024

PurposeThis research aims to examine the time-varying behavior of the Weekend, Turn-of-the-Month, January, and Halloween effects in eight foreign exchange rates against the U.S. dollar from the Adaptive Market Hypothesis (AMH) perspective. It also explores whether these anomalies can generate excess returns compared to a buy-and-hold strategy.Design/methodology/approachUsing daily return data from January 2004 to December 2023 in a rolling-window framework, the study employs the Concordance Coefficient test and AR-GARCH models to assess the time-varying behavior of four calendar anomalies. It also assesses the statistical significance of the trading strategies implied by these anomalies using t-tests and applies F-tests for subperiod analysis.FindingsThe results reveal a generalized time-varying presence of calendar anomalies in emerging currencies and, to a lesser extent, developed currencies. However, the trading strategies implied by these anomalies generally did not show statistical significance, except for the Turn-of-the-Month effect, which exhibited statistically significant unprofitability.Originality/valueThe study pioneers an analysis of five calendar anomalies across various currencies from the standpoint of the AMH and proposes case-specific explanations for their occurrence. It also examines the potential for the anomalies’ implied trading strategies to generate excess returns compared to a straightforward buy-and-hold strategy. Additionally, the study introduces the recently developed Concordance Coefficient test as a valuable alternative to other non-parametric methods.
Effects of performance appraisal on employees’ extra-role behaviors and turnover intentions – A parallel mediation model
Authors: Ghani Bilqees , Malik Muhammad Abdur Rahman , Memon Khalid Rasheed 
Published: August 2024

PurposeResearch on the underlying mechanisms that transfer the effects of performance appraisal (PA) on employees’ behaviors and intentions remains scarce. The social exchange view of performance appraisal can be a source of deeper understanding about these underlying mechanisms. This study aims to investigate how psychological empowerment (PE) and organizational commitment (OC) explain the link between performance appraisal and three important distal outcomes: voice behavior (VB), organizational citizenship behavior (OCB), and turnover intentions (TOI).Design/methodology/approachThe current study utilizes two wave – two source data from a sample of 250 employees and their supervisors from private organizations in Pakistan and tested the mediation model using SMART-PLS.FindingsResults demonstrated that organizational commitment mediated the effects of performance appraisal on VB, OCB, and TOI, whereas psychological empowerment mediated the effects of performance appraisal on VB and OCB. These results have significant implications for theory and practice.Originality/valueThis study adopts the social exchange perspective to examine the mediation mechanisms linking PA with the three distal outcomes: VB, OCB and TOI. The paper identifies two novel mediators of PA – outcome relationship, i.e., psychological empowerment and organizational commitment.
The path to overcoming the liability of foreignness using the eclectic paradigm: evidence from China
Authors: Wang Na , Sun Huan 
Published: August 2024

Purpose
The purpose of this study is to examine different paths to overcoming the liability of foreignness. Based on the eclectic paradigm, the authors construct a theoretical framework comprising enterprise nature, location choice, entry mode and internationalization strategy.

Design/methodology/approach
The paper uses fuzzy-set qualitative comparative analysis (fsQCA) method to test the framework with data covering 120 multinational Chinese subsidiaries in 34 host in 2019.

Findings
The results show that liability of foreignness (LOF) is multiple concurrency, equifinality and asymmetry. When investing in Belt and Road (B&R) countries, non-SEOs can weaken LOF by applying the greenfield mode and resource-seeking strategy, other MNEs can implement a market- or resource-seeking strategy via cross-border M&A to reduce LOF. But when investing in non-B&R countries with a strategic asset-seeking strategy, the LOF is increased. The B&R initiative can reduce the LOF effectively.

Originality/value
The authors construct a general framework to explain the paths of overcoming LOF by bridging the OLI with LOF and introduce fsQCA method into the field of LOF to make up for the shortcoming of existing test method by explaining the influence of more than three factors on LOF.