bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct and Indirect Effects of Subsidized Dual Apprenticeships
Authors: Crépon Bruno , Premand Patrick 
Published: September 2024

Abstract
Public interventions in the apprenticeship market often aim to increase demand or returns. We set up a double-sided experiment with youth and firms to analyse a subsidized dual apprenticeship program. This intervention seeks to relax financial constraints for youth by offering a wage subsidy and to make apprenticeship more attractive by providing vocational training in technical skills that complements on-the-job training. We document a large increase in youth participation in apprenticeship, yet the inflow of apprentices induces little crowding out of traditional apprentices in firms. The intervention leads to an increase in youth demand for apprenticeship, enabling firms to fill open apprenticeship positions. The subsidy compensates apprentices for low wages but does not alleviate financial constraints. Consistent with the dual training component contributing to an increase in youth demand for apprenticeship, youth perform more complex tasks and have higher earnings 4 years after the start of the experiment.
Hybrid high and low molecular weight chains of hyaluronan for clitoral injection is an effective modality treatment for increasing female sexual satisfaction: an interventional, randomized-controlled parallel study
Authors: Atef Lina Mohammed , Mohammed Ghada Farouk , Al-Dhubaibi Mohammed Saleh , Soliman Mahmoud , Bahaj Saleh Salem , Saleh Yasser S N 
Published: October 2024

Abstract

Introduction
Hormonal, behavioral, psychological, surgical, and pharmacopsychological treatment approaches contribute to female sexual dysfunction (FSD).
Aim: The study is conducted to assess the effectiveness of hyaluronan high and low molecular weight hybrid cooperative complexes (hybrid H-HA/L-HA) in treating females with SD and to compare the female sexual function index (FSFI), dermatological life quality index (DLQI), and female genital self-image scale (FGSIS) before and after therapy.

Methods
We divided the 60 female participants into two groups. Hybrid H-HA/L-HA was administered to form pili of 0.25 cc around the clitoris in the direction of clock positions of 12, 3, 6, and 9. In Skene’s gland; 0.25 cc for each and 0.5 cc into the corpus/body of the clitoris. Two treatments were held 30 days apart.
The same procedure was repeated on the control group, but with saline as a placebo.

Outcomes
Women completed self-report questionnaires assessing sexual functioning using the FSFI, DLQI, and FGSIS before and after therapy.

Result
There was a significant (P = 634.152; P &lt; .05) increase in the study group’s weekly sexual interactions compared with the controls. The study group showed statistically significant amelioration in desire, arousal, lubrication, orgasm, satisfaction domains, overall score, and a decrease in pain following the first and second injection sessions (P = .014, .031, .003, .001, .011, .004, and .011, respectively). A comparison of the results between the two groups revealed significant improvement were found (P = .025).
There were significant improvements in the domains of the FGSIS compared with the controls (P = .026). The study group showed a substantial improvement in satisfaction with the way their genital area looked, comfort level when allowing a sexual partner to view their genital area, belief that their genitals smell perfectly fine without being self-conscious about them, and overall score (P = .022, .031, .003, .001, and .004, respectively) (P &lt; .05).
The hybrid H-HA/L-HA sessions resulted in significantly greater positive perceptions and feelings, leisure activities, interpersonal interactions, and general assessments (P = .021, .021, and .020, respectively) (P &lt; .05).

Clinical Implications
Female individuals with SD experience sexual improvements after hybrid H-HA/L-HA injection.

Strengths and Limitations
This is the first study focusing on female individuals with SD. We recommend conducting the study on a larger population and including their partners.

Conclusion
Hybrid H-HA/L-HA injection for rejuvenating the clitoral injection appears to be a reliable and safe method for enhancing female genital self-image, sexuality, and quality of life.
Jawbone periosteum‐derived cells with high osteogenic potential controlled by R‐spondin 3
Authors: Zhang Shu , Zhu Jingxian , Jin Siyu , Sun Wei , Ji Wei , Chen Zhi 
Published: September 2024

AbstractThe jawbone periosteum, the easily accessible tissue responding to bone repair, has been overlooked in the recent development of cell therapy for jawbone defect reconstruction. Therefore, this study aimed to elucidate the in vitro and in vivo biological characteristics of jawbone periosteum‐derived cells (jb‐PDCs). For this purpose, we harvested the jb‐PDCs from 8‐week‐old C57BL/6 mice. The in vitro cultured jb‐PDCs (passages 1 and 3) contained skeletal stem/progenitor cells and exhibited clonogenicity and tri‐lineage differentiation capacity. When implanted in vivo, the jb‐PDCs (passage 3) showed evident ectopic bone formation after 4‐week subcutaneous implantation, and active contribution to repair the critical‐size jawbone defects in mice. Molecular profiling suggested that R‐spondin 3 was strongly associated with the superior in vitro and in vivo osteogenic potentials of jb‐PDCs. Overall, our study highlights the significance of comprehending the biological characteristics of the jawbone periosteum, which could pave the way for innovative cell‐based therapies for the reconstruction of jawbone defects.
Understanding the relationship between inflammation, apoptosis, and diabetes osteoporosis: A bioinformatics approach and experimental verification
Authors: Li Jun Quan , Li Bo , Fei Zhang Qing , Lei Shan Shan 
Published: September 2024

AbstractDiabetes osteoporosis (DOP) is a chronic metabolic bone disease. This study aimed to identify potential biomarkers of DOP and explore their underlying mechanisms through bioinformatics methods and experimental verification. Bioinformatics methods were used to identify differentially expressed genes (DEGs) for DOP based on GEO data and the GeneCards database. GO and KEGG enrichment analyses were used to search the key pathways. The STRING website was used to construct a protein–protein interaction (PPI) network and identify key genes. Then, 50 mg/mL glucose was used to interveneosteoblasts (OBs).CCK‐8 and Alizarin Red staining were used to investigate the proliferation and differentiation changes in OBs. Flowcytometry was used to investigate apoptosis. The membrane protein chip, WB, and RT‐PCR were used to verify the expression of key targets or pathways about DOP. Forty‐two common genes were screened between DOP‐related targets and DEGs. GO and KEGG enrichment analysis showed that DOP was mainly associated with cytokine‐cytokine receptor interactions, and apoptosis. PPI network analysis showed that TNF, IL1A, IL6, IL1B, IL2RA, Fas ligand (FASLG), and Fas cell surface death receptor (FAS) were key up‐regulated genes in the occurrence of DOP. The experiment results show that 50 mg/mL glucose significantly inhibited OBs proliferation but presented an increase in apoptosis. Membrane protein chip, WB, and RT‐PCR‐verified a significantly active in the expression of TNF/FASLG/FAS pathway. High glucose activated the TNF‐α/FAS/FASLG pathway and induced the inflammatory microenvironment and apoptosis, then impaired osteogenic differentiation of OBs. These may be an important mechanism for the occurrence and development of DOP.
HSP70 Promotes Pancreatic Cancer Cell Epithelial-Mesenchymal Transformation and Growth Via the NF-κB Signaling Pathway
Authors: Xiong Liumei , Li Danming , Xiao Gui , Tan Sipin , Xu Linfang , Wang Guiliang 
Published: October 2024

Objective
To study the effects of HSP70 on proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT) of pancreatic cancer cells and explore its underlying mechanisms.

Methods
Pancreatic cancer cell models with reduced HSP70 or increased HSP70 expression were established. Reverse transcription quantitative polymerase chain reaction and Western blot assays were used to determine mRNA and protein levels of HSP70, IKK/IκBa/NF-κB signaling pathway-related genes, and EMT markers. CCK-8 and cell cloning assays were used to evaluate cell proliferation and cloning abilities. Transwell and wound healing assays were used to assess the invasive and migratory properties of cells. Electrophoresis mobility shift assay (EMSA) and luciferase reporter assays were conducted to analyze NF-κB's promoter binding and transcriptional activities.

Results
HSP70 knockdown inhibited p-p65 nuclear translocation, the expression of p-p65, p-IKKα/β, p-IκBα, N-cadherin, Vimentin and Twist, NF-κB's promoter binding and transcriptional activities, pancreatic cancer cell proliferation, cloning, migration and invasion, while increased E-cadherin levels. HSP70 overexpression took the opposite effects. NF-κB signaling pathway modulation reversed EMT changes induced by altered HSP70 expression levels. rhHSP70 increased p-IKKα/β and p-IκBα protein levels.

Conclusions
HSP70 promotes EMT and enhances pancreatic cancer cell proliferation, migration, and invasion by activating NF-κB pathway.
Association between mitochondrial DNA copy number and neurodevelopmental outcomes among black and white preterm infants up to two years of age
Authors: Zhao Tingting , Li Aolan , Reese Bo , Cong Qianzi , Corwin Elizabeth J. , Taylor Sarah N. , Matson Adam , Chen Ming-Hui , Alder Nathan N. , Cong Xiaomei 
Published: October 2024

Abstract

Objectives:
Mitochondrial DNA copy number (mtDNAcn) is associated with mitochondrial function, with abnormal copy numbers having been linked to various disease states. Our study aims to understand the association between infant mtDNAcn and infant neurodevelopment, as well as the association with racial disparities.

Methods:
A longitudinal study was conducted with 55 preterm infants from whom a single blood sample was collected during their Neonatal intensive care unit (NICU) stay and used to analyze mtDNAcn. In addition, the NICU Network Neurobehavioral Scale at 36–38 postmenstrual age (PMA) and the Bayley Scale of Infant and Toddler Development (Bayley) Edition III at 1 and 2 years of corrected age were both conducted. Linear regression models were performed to investigate the relationship between infant clinical characteristics, infant neurobehavioral outcomes, and mtDNAcn.

Results:
The majority of infants studied were white (72.73%), non-Hispanic (70.91%), males (54.55%), delivered through C-section (72.73%), and without preterm premature rupture of membrane (76.36%). Increased mtDNAcn was associated with younger birth gestational age (<30.57 wk, P < 0.001). In addition, the opposite associations between mtDNAcn and neurodevelopmental outcomes were observed between white and black infants up to 1 year of gestational age.

Conclusions:
Increased mtDNAcn in white infants, and decreased mtDNAcn in black infants may be considered significant predictors of poor early-life neurodevelopmental outcomes in infants. A better understanding of the underlying mechanisms contributing to infant disparity in mtDNAcn and how low or high copy number impacts infant outcomes is essential.
A Wearable Mindfulness Brain–Computer Interface for Alleviating Car Sickness
Authors: Zhu Jiawei , Bao Xiaoyu , Huang Qiyun , Wang Tao , Huang Li , Han Yupeng , Huang Haiyun , Zhu Junbiao , Qu Jun , Li Kendi , Chen Di , Jiang Ya , Xu Kailin , Wang Zijian , Wu Wei , Li Yuanqing 
Published: October 2024

AbstractCar sickness, an enormous vehicular travel challenge, affects a significant pro-portion of the population. Pharmacological interventions are limited by adverse side effects, and effective nonpharmacological alternatives remain to be identified. Here, we introduce a novel closed-loop, artificial intelligence (AI)-driven, wear-able mindfulness brain–computer interface (BCI) to alleviate car sickness. As the user performs mindfulness meditation with a wearable headband, the BCI col-lects and analyses electroencephalography (EEG) data via a convolutional neural network to assess the user’s mindfulness state and provide real-time audiovisual feedback. This approach might efficiently redirect the user’s attention from phys-iological discomfort towards BCI-based mindfulness practices, thereby mitigating car sickness symptoms. The efficacy of the mindfulness BCI was rigorously evalu-ated in two real-world experiments, namely, short and long car rides, with a large cohort of more than 100 participants susceptible to car sickness. Remarkably, over 84% of the participants rated the mindfulness BCI intervention as effective, with significant reductions in car sickness severity, particularly in individuals with severe symptoms. Furthermore, EEG data analysis revealed prefrontal beta relative power as a neurobiological signature of car sickness, which, in conjunc-tion with attention shift theory and sensory conflict theory, provided mechanistic insights into the efficacy of the mindfulness BCI for alleviating car sickness. This study proposed the first nonpharmacological, wearable and effective car sickness intervention method and system with the potential to transform the travel expe-riences of hundreds of millions of people suffering from car sickness, which also represents a new application of BCI technology.
Histology-guided MRI segmentation of brainstem nuclei critical to consciousness
Authors: Olchanyi Mark , Augustinack Jean , Haynes Robin L. , Lewis Laura D. , Cicero Nicholas , Li Jian , Destrieux Christophe , Folkerth Rebecca D. , Kinney Hannah C. , Fischl Bruce , Brown Emery N. , Iglesias Juan Eugenio , Edlow Brian L. 
Published: September 2024

AbstractWhile substantial progress has been made in mapping the connectivity of cortical networks responsible for conscious awareness, neuroimaging analysis of subcortical arousal networks that modulate arousal (i.e., wakefulness) has been limited by a lack of a robust segmentation procedures for brainstem arousal nuclei. Automated segmentation of brainstem arousal nuclei is an essential step toward elucidating the physiology of arousal in human consciousness and the pathophysiology of disorders of consciousness. We created a probabilistic atlas of brainstem arousal nuclei built on diffusion MRI scans of fiveex vivohuman brain specimens scanned at 750 µm isotropic resolution. Labels of arousal nuclei used to generate the probabilistic atlas were manually annotated with reference to nucleus-specific immunostaining in two of the five brain specimens. We then developed a Bayesian segmentation algorithm that utilizes the probabilistic atlas as a generative model and automatically identifies brainstem arousal nuclei in a resolution- and contrast-agnostic manner. The segmentation method displayed high accuracy in both healthy and lesionedin vivoT1 MRI scans and high test-retest reliability across both T1 and T2 MRI contrasts. Finally, we show that the segmentation algorithm can detect volumetric changes and differences in magnetic susceptibility within brainstem arousal nuclei in Alzheimer’s disease and traumatic coma, respectively. We release the probabilistic atlas and Bayesian segmentation tool in FreeSurfer to advance the study of human consciousness and its disorders.
Rare variant aggregation highlights rare disease genes associated with brain volume variation
Authors: Wightman Douglas P. , Maciel Bernardo A.P.C. , Brouwer Rachel M. , van den Heuvel Martijn P. , Posthuma Danielle 
Published: September 2024

AbstractVariation in brain volume is associated with common and rare disorders. Investigating the genetics of brain volume may highlight overlap between diseases and biological mechanisms that explain disease symptoms. Previous studies examining genetic variants associated with brain volume have largely focused on common variants, with rare variant studies not primarily focusing on brain volume phenotypes or focusing on large structural variants. In this study, we aggregated rare variants within genes and associated genes with 44 brain volume phenotypes in the UK Biobank (N=40,374). We found convergence between genes within the same biological pathway and convergence between common and rare variants within the same gene. Seven of the genes associated with total or regional brain volume measures were also linked with rare brain disorders in previous literature. We successfully showed that rare variants in genes linked to rare brain disorders were also associated with sub-clinical brain volume variation.
The JAK inhibitor, Tofacitinib, Corrects the Overexpression of CEACAM6 and Limits Susceptibility to AIEC Caused by Reduced Activity of the IBD Associated Gene,PTPN2
Authors: Chatterjee Pritha , Canale Vinicius , King Stephanie J. , Shawki Ali , Lei Hillmin , Haddad Michael , Gries Casey M. , McGovern Dermot P.B. , Borneman James , McCole Declan F. 
Published: September 2024

AbstractBackground and AimsA cohort of patients with inflammatory bowel disease (IBD) exhibit expansion of the gut pathobiont, adherent-invasiveE. coli(AIEC). Loss of activity of the IBD susceptibility gene, protein tyrosine phosphatase type 2 (PTPN2), results in dysbiosis of the gut microbiota both in human subjects and mice. Further, constitutivePtpn2knock-out (Ptpn2-KO) mice display expansion of AIEC compared to wildtype littermates. CEACAM6, a host cell surface glycoprotein, is exploited by AIEC to attach to and enter intestinal epithelial cells (IECs). Here, we investigate the role of IEC-specificPTPN2in restricting AIEC invasion.MethodsBiopsies from IBD patients heterozygous (CT) or homozygous (CC) for thePTPN2SNP (single nucleotide polymorphism)rs1893217were processed for immunohistochemistry. HT-29 intestinal epithelial cells (IEC) were transfected with control shRNA (PTPN2-CTL), or a shRNA targeted towardsPTPN2(PTPN2-KD). Thers1893217SNP was inserted (PTPN2-KI), or a complete knock-out ofPTPN2(PTPN2- KO) was generated, with CRISPR-Cas9 gene editing of Caco-2BBe IEC lines. Adherence and invasion assays were performed with either the human IBD AIEC isolate, LF82, or a novel fluorescent-tagged mouse adherent-invasiveE. coli(mAIECred) at multiplicity of infection (MOI) of 10. IL-6 and the pan-JAK inhibitor tofacitinib were administered to interrogate JAK-STAT signaling. Protein expression was determined by western blotting and densitometry.ResultsCEACAM6 expression was elevated (colon and ileum) in IBD patients carrying thePTPN2 rs1893217SNP (CT, CC) compared to wildtype (TT) IBD patients. HT-29 and Caco-2BBe cell lines deficient inPTPN2expressed significantly higher levels of CEACAM6. Further,PTPN2-KI andPTPN2-KO cell lines also displayed greater adherence and invasion by AIEC LF82 and highermAIECredinvasion. CEACAM6 expression was further elevated after administration of IL-6 inPTPN2–deficient cell lines compared to untreated controls. Silencing of STAT1 and 3 partially reduced CEACAM6 protein expression. Tofacitinib significantly reduced the elevated CEACAM6 protein expression and the higher AIEC adherence and invasion inPTPN2-KI and PTPN2-KO cell lines compared to DMSO controls.ConclusionOur findings highlight a crucial role forPTPN2in restricting pathobiont entry into host cells. Our study also describes a role for the FDA-approved drug, tofacitinib (Xeljanz) in correcting the JAK-STAT- mediated over-expression of CEACAM6, used by pathobionts as an entry portal into host cells. These findings suggest a role for JAK-inhibitors in mitigating AIEC colonization in IBD-susceptible hosts.
Tissue resident memory CD4+T cells are sustained by site-specific levels of self-renewal and replacement from precursors
Authors: Chandler Jodie , Bullock M. Elise , Swain Arpit , Williams Cayman , van Dorp Christiaan H. , Seddon Benedict , Yates Andrew J. 
Published: September 2024

AbstractTissue-resident memory T cells (TRM) protect from repeated infections within organs and barrier sites. The breadth and duration of such protection is defined at minimum by three quantities; the rate at which new TRMare generated from precursors, their rate of self-renewal, and their loss rate through death, egress, or differentiation. Quantifying these processes in isolation is challenging. Here we combine genetic fate mapping tools and mathematical models to untangle these basic homeostatic properties of CD4+TRMin skin and lamina propria (LP) of healthy adult mice. We show that CD69+CD4+TRMin skin reside for∼24 days and self-renew more slowly, such that clones halve in size approximately every 5 weeks; and approximately 2% of cells are replaced daily from precursors. CD69+CD4+TRMin LP have shorter residencies (∼ 14 days) and are maintained largely by immigration (4-6% per day). We also find evidence that the constitutive replacement of CD69+CD4+TRMat both sites derives from circulating effector-memory CD4+T cells, in skin possibly via a CD69−intermediate. Our integrated approach maps the ontogeny of CD4+TRMin skin and LP and exposes their dynamic and distinct behaviours, with continual seeding and erosion potentially impacting the duration of immunity at these sites.
Re-evaluation of some popular CRAC channel inhibitors – structurally similar but mechanistically different?
Authors: Gökçe Yasin , Mahzabeen Sinayat , Ghoorahoo Joshua , Harper Matthew Thomas , Yaras Nazmi , Rahman Taufiq 
Published: September 2024

AbstractCa2+-release activated Ca2+(CRAC) channels mediate the store-operated Ca2+entry (SOCE) that is used almost by all cells to replenish depleted intracellular Ca2+stores. Aberrant CRAC channel functions have been implicated in various diseases including autoimmune diseases and as such these channels and the resultant pathway (SOCE) have been intensively studied by academic and pharmaceutical scientists over decades. To date, several small molecule inhibitors and few antibodies have been developed against these ion channels. Some small molecule inhibitors of the CRAC channels, namely BTP2, Synta66, Pyr6 and GSK-7975A, are widely used as tool compounds in the field but their mode of action remains unclear. In this study, we used whole cell electrophysiology supported by in silico modelling to propose likely binding site and binding mode of these four popular CRAC channel inhibitors.