bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral immune cell dysregulation following diffuse traumatic brain injury in pigs
Authors: Wofford Kathryn L. , Browne Kevin D. , Loane David J. , Meaney David F. , Cullen D. Kacy 
Published: December 2024

AbstractTraumatic brain injury (TBI) is a global health problem affecting millions of individuals annually, potentially resulting in persistent neuropathology, chronic neurological deficits, and death. However, TBI not only affects neural tissue, but also affects the peripheral immune system’s homeostasis and physiology. TBI disrupts the balanced signaling between the brain and the peripheral organs, resulting in immunodysregulation and increasing infection susceptibility. Indeed, secondary infections following TBI worsen neurological outcomes and are a major source of mortality and morbidity. Despite the compelling link between the damaged brain and peripheral immune functionality, little is known about how injury severity affects the peripheral immune system in closed-head diffuse TBI, the most common clinical presentation including all concussions. Therefore, we characterized peripheral blood mononuclear cells (PBMCs) and plasma changes over time and across injury severity using an established large-animal TBI model of closed-head, non-impact diffuse rotational acceleration in pigs. Across all timepoints and injury levels, we did not detect any changes to plasma cytokine concentrations. However, changes to the PBMCs were detectable and much more robust. We observed the concentration and physiology of circulating PBMCs changed in an injury severity-dependent manner, with most cellular changes occurring within the first 10 days following a high rotational velocity injury. Here, we report changes in the concentrations of myeloid and T cells, changes in PBMC composition, and changes in phagocytic clearance over time. Together, these data suggest that following a diffuse brain injury in a clinically relevant large-animal TBI model, the immune system exhibits perturbations that are detectable into the subacute timeframe. These findings invite future investigations into therapeutic interventions targeting peripheral immunity and the potential for peripheral blood cellular characterization as a diagnostic tool.
Emergency contraceptive pill awareness in Bangladesh: missed opportunities in antenatal care and family welfare assistant visits
Authors: Ara Tasnim , Sathi Shahnaj Sultana , Shiblee Shafayatul Islam , Esha Sumaiya Nusrat , Amin Md Tazvir , Rahman Md Mahabubur 
Published: December 2024

Abstract
Background
Despite high coverage of antenatal care (ANC) and family welfare assistant (FWA) visits, emergency contraceptive pill (ECP) awareness is critically low in Bangladesh. We aim to investigate the missed opportunities in generating ECP awareness through ANC and FWA visit programs; and assess the missed opportunities and sociodemographic discrimination in receiving family planning (FP) counseling during ANC.

Methods
We used data from the nationwide Bangladesh Demographic and Health Survey 2017–18. Sample includes 5012 reproductive-aged women who gave live birth in the last 3 years preceding the survey. We used mixed-effect multiple logistic regression considering women nested within clusters to conclude.

Results
Nationally, 79% of women who gave live birth in the last 3 years preceding the survey were unaware of ECP. The estimated missed opportunities in generating ECP awareness was 59.5% in ANC, 0.9% in FWA visits, and 12.3% in both ANC and FWA visits. While FWA visit was not associated with ECP awareness, receiving FP counseling during ANC was significantly associated. About 88.4% of women remained unexposed to FP counseling through ANC during their last pregnancy. Missed opportunities in FP counseling during ANC was 80.4% of which 72% points were from qualified providers. The odds of missed opportunities was not associated with provider type, rather significantly increased among women with low education, lower parity, and poor socioeconomic status.

Conclusions
This study highlights the fragile status of FP counseling during ANC and FWA visits in generating ECP awareness. A prominent provider bias is excluding women of the disadvantageous sociodemographic group from receiving FP counseling.
Study protocol and preliminary baseline characteristics of a VA multi-site, mixed methods, randomized controlled study evaluating supported employment provided to veterans with opioid use disorder
Authors: Mumba Mercy , Granger Teresa , Mugoya George , Brackett Stephen , Lu Junfei , Lund Emily , Lynn Charles , Ghera Anchal , Gay Whitney , Davis Lori 
Published: December 2024

AbstractOpioid Use Disorder (OUD) is a pervasive and devastating public health crisis that continues to take a heavy toll on individuals and communities across the United States. In 2021, approximately 473,000 veterans misused opioids in the past year. In the context of their military service and post-service life, Veterans with OUD often encounter unique barriers to recovery, including the reintegration into civilian society and the pursuit of stable, meaningful employment. The path to recovery from OUD is inextricably linked to the restoration of a stable and purposeful life, a fact underscored by the interplay of substance use, mental health, and employment outcomes. These factors necessitate a comprehensive approach to treatment that extends beyond mere pharmacological interventions. One such approach is Individual Placement and Support (IPS), a well-established evidence-based practice that focuses on supporting individuals with severe mental illness in their pursuit of competitive employment. The primary objective of this manuscript is to describe a two-arm, multi-site RCT designed to rigorously evaluate the efficacy of IPS when provided to veterans with OUD and provide the baseline demographics and characteristics of the participants who have enrolled to date. The central hypothesis guiding this research is that IPS can significantly improve vocational, psychosocial, and treatment outcomes of veterans in recovery from OUD, ultimately leading to a more successful reintegration into civilian life. Our study is timely as the VA has expanded IPS services to veterans with SUD this past year. Thus, this study is one of the first to examine IPS in a subpopulation of veterans with a SUD and may provide actionable data to support sustainment of IPS with this population.
Factors that contribute to the perceived treatment effect of spinal manipulative therapy in a chiropractic teaching clinic: a qualitative study
Authors: Boylan Patrick 
Published: December 2024

Abstract
Background
Despite the progress made in better understanding the potential mechanisms of spinal manipulative therapy (SMT) and its treatment effects, a knowledge gap continues to exist when identifying the specific factors that contribute to the perceived treatment effect associated with SMT. The purpose of the study was to explore the perceptions of chiropractic clinicians, interns, and patients regarding what factors during a doctor-patient encounter contribute to the perceived treatment effect associated with SMT.

Methods
This study used convenience sampling to enroll participants from a chiropractic teaching clinic in the United States. Semi-structured interviews were used as the main form of data collection, which took place from January-April 2024. The data was subsequently analyzed using thematic analysis and organized into themes through an iterative open coding process.

Results
Six rounds of interviews were conducted for a total of 18 interviews. Each round consisted of one patient who received treatment including SMT, one intern who performed the treatment, and one clinician who oversaw the treatment. After analyzing the interview data, the following five themes were identified: Treatment Outcome, Therapeutic Alliance, Adjunctive Therapies, Significance of Cavitation, and Psychomotor Skills. Each theme consisted of multiple subthemes which were mentioned by the participant groups at varying frequencies. Patients frequently mentioned the importance of improvement in symptoms following treatment, as well as good communication skills and the use of adjunctive therapies. Interns valued functional change following treatment, while clinicians focused on confidence levels and psychomotor skills. There were differing views on the significance of cavitation, ranging from indifference to an indication of a successful treatment.

Conclusion
This qualitative study identified several themes which describe factors that may contribute to the perceived effect associated with SMT. In addition to the psychomotor skills required to perform SMT, educators and practitioners should consider factors such as the therapeutic alliance between patient and provider, use of adjunctive therapies, and assessment of the outcome associated with the intervention.
Integrated network pharmacology and transcriptomics to explore the mechanism of compound Dihuang granule (CDG) protects dopaminergic neurons by regulating the Nrf2/HMOX1 pathway in the 6-OHDA/MPP+-induced model of Parkinson’s disease
Authors: Sun Xue , Yang Shuai , He Zhuqing , Wang Li , He Jiancheng 
Published: December 2024

Abstract
Background
Parkinson's disease (PD) is a degenerative neurological disease that worsens over time. Ferroptosis has been proven to contribute to PD pathogenesis. CDG exhibits neuroprotective effects. However, CDG's potential mechanism in PD therapy remains uncertain.

Purpose
The purpose of this investigation is to ascertain the specific molecular mechanisms of CDG against neuronal ferroptosis and present an alternative option for PD management.

Methods
Network pharmacology along with LC–MS were used to identify possible targets and candidate pathways. Then RNA-sequencing combined in the in vitro and in vivo experiments were utilized to validate these findings.

Results
According to network pharmacology prediction, NFE2L2, HMOX1 and PTGS2 may be the key genes for ferroptosis in PD. In the in vivo experiments, CDG ultimately improved the neurobehavior of PD rats by alleviating the damage of dopamine neurons, decreasing the levels of MDA, ROS and Fe2+, increasing the GSH level, inhibiting ferroptosis by decreasing ACSL4, TF, and PTGS2 expression levels, and increasing the GPX4, FTH, Nrf2, and HMOX1 levels. RNA-seq analysis showed the differential genes in Model and CDG group were all enriched in Nrf2 and HMOX1, and the enrichment analysis of these differential genes showed they were closely related to the ferroptosis. Subsequently, in vitro experiments, the CDG, OE-Nrf2 and OE-HMOX1 group showed more active cell vitality, with decreasing levels of MDA, ROS, Fe2+, ACSL4, TF and PTGS2, and increasing level GSH, GPX4, FTH, Nrf2 and HMOX1.

Conclusion
CDG has a neuroprotective involvement in alleviating ferroptosis by regulating the Nrf2/HMOX1 pathway. Moreover, this research offers pharmacological evidence supporting the applications of CDG for treating PD.
The UFMylation pathway is impaired in Alzheimer’s disease
Authors: Yan Tingxiang , Heckman Michael G. , Craver Emily C. , Liu Chia-Chen , Rawlinson Bailey D. , Wang Xue , Murray Melissa E. , Dickson Dennis W. , Ertekin-Taner Nilufer , Lou Zhenkun , Bu Guojun , Springer Wolfdieter , Fiesel Fabienne C. 
Published: December 2024

Abstract
Background
Alzheimer’s disease (AD) is characterized by the presence of neurofibrillary tangles made of hyperphosphorylated tau and senile plaques composed of beta-amyloid. These pathognomonic deposits have been implicated in the pathogenesis, although the molecular mechanisms and consequences remain undetermined. UFM1 is an important, but understudied ubiquitin-like protein that is covalently attached to substrates. UFMylation has recently been identified as major modifier of tau aggregation upon seeding in experimental models. However, potential alterations of the UFM1 pathway in human AD brain have not been investigated yet.

Methods
Here we used frontal and temporal cortex samples from individuals with or without AD to measure the protein levels of the UFMylation pathway in human brain. We used multivariable regression analyses followed by Bonferroni correction for multiple testing to analyze associations of the UFMylation pathway with neuropathological characteristics, primary biochemical measurements of tau and additional biochemical markers from the same cases. We further studied associations of the UFMylation cascade with cellular stress pathways using Spearman correlations with bulk RNAseq expression data and functionally validated these interactions using gene-edited neurons that were generated by CRISPR-Cas9.

Results
Compared to controls, human AD brain had increased protein levels of UFM1. Our data further indicates that this increase mainly reflects conjugated UFM1 indicating hyperUFMylation in AD. UFMylation was strongly correlated with pathological tau in both AD-affected brain regions. In addition, we found that the levels of conjugated UFM1 were negatively correlated with soluble levels of the deUFMylation enzyme UFSP2. Functional analysis of UFM1 and/or UFSP2 knockout neurons revealed that the DNA damage response as well as the unfolded protein response are perturbed by changes in neuronal UFM1 signaling.

Conclusions
There are marked changes in the UFMylation pathway in human AD brain. These changes are significantly associated with pathological tau, supporting the idea that the UFMylation cascade might indeed act as a modifier of tau pathology in human brain. Our study further nominates UFSP2 as an attractive target to reduce the hyperUFMylation observed in AD brain but also underscores the critical need to identify risks and benefits of manipulating the UFMylation pathway as potential therapeutic avenue for AD.
Mystery of gamma wave stimulation in brain disorders
Authors: Deng Qianting , Wu Chongyun , Parker Emily , Zhu Jing , Liu Timon Cheng-Yi , Duan Rui , Yang Luodan 
Published: December 2024

AbstractNeuronal oscillations refer to rhythmic and periodic fluctuations of electrical activity in the central nervous system that arise from the cellular properties of diverse neuronal populations and their interactions. Specifically, gamma oscillations play a crucial role in governing the connectivity between distinct brain regions, which are essential in perception, motor control, memory, and emotions. In this context, we recapitulate various current stimulation methods to induce gamma entrainment. These methods include sensory stimulation, optogenetic modulation, photobiomodulation, and transcranial electrical or magnetic stimulation. Simultaneously, we explore the association between abnormal gamma oscillations and central nervous system disorders such as Alzheimer’s disease, Parkinson’s disease, stroke, schizophrenia, and autism spectrum disorders. Evidence suggests that gamma entrainment-inducing stimulation methods offer notable neuroprotection, although somewhat controversial. This review comprehensively discusses the functional role of gamma oscillations in higher-order brain activities from both physiological and pathological perspectives, emphasizing gamma entrainment as a potential therapeutic approach for neuropsychiatric disorders. Additionally, we discuss future opportunities and challenges in implementing such strategies.
miR-3191 promotes the proliferation and metastasis of hepatocellular carcinoma via regulating PAK6
Authors: Xie Anqi , Wang Hengjie , Huang Jingchen , Sun Minmin , Chen Lin 
Published: December 2024

Abstract
Background/Aims
microRNAs (miRNAs) contribute to tumorigenesis, progression and drug resistance of hepatocellular carcinoma (HCC). miR-3191 is a newly discovered miRNA, and its function and mechanism of action in biological processes and diseases are not completely understood.

Methods
miR-3191 expression is determined via quantitative real-time polymerase chain reaction. Knockdown and overexpression of miR-3191 influence the proliferation and metastasis of HCC cells, which is measured by Cell Counting Kit-8 assay, Colony Formation assay and Cell metastasis assay. Protein expression is estimated by Western blot. The interplay between miR-3191 and target is validated by dual-luciferase reporter assay.

Results
Here, we show that miR-3191 is upregulated in HCC tissues and associated with poor prognosis of HCC patients. Mechanistically, p21-activated protein kinase 6 (PAK6) was identified as a direct target of miR‑3191 in HCC. PAK6 knockdown partially recovered interference of miR‑3191‑induced decrease in cell proliferation and invasion. The accuracy of HCC patient prognosis could be improved by employing a combination of miR-3191 and PAK6 values.

Conclusions
miR-3191 promotes the proliferation and metastasis of HCC cells via targeting PAK6 and may serve as a prognostic biomarker and potential therapeutic target.
Serotonin enhances neurogenesis biomarkers, hippocampal volumes, and cognitive functions in Alzheimer’s disease
Authors: Azargoonjahromi Ali ,   For the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2024

AbstractResearch on serotonin reveals a lack of consensus regarding its role in brain volume, especially concerning biomarkers linked to neurogenesis and neuroplasticity, such as ciliary neurotrophic factor (CNTF), fibroblast growth factor 4 (FGF-4), bone morphogenetic protein 6 (BMP-6), and matrix metalloproteinase-1 (MMP-1) in Alzheimer’s disease (AD). This study aimed to investigate the influence of serotonin on brain structure and hippocampal volumes in relation to cognitive functions in AD, as well as its link with biomarkers like CNTF, FGF-4, BMP-6, and MMP-1. Data from 133 ADNI participants with AD included cognitive assessments (CDR-SB), serotonin measurements (Biocrates AbsoluteIDQ p180 kit, UPLC-MS/MS), and neurotrophic factors quantified via multiplex proteomics. Gray matter volume changes were analyzed using Voxel-Based Morphometry (VBM) with MRI. Statistical analyses employed Pearson correlation, bootstrap methods, and FDR-adjusted p-values (< 0.05 or < 0.01) via the Benjamini–Hochberg procedure, alongside nonparametric methods. The analysis found a positive correlation between serotonin levels and total brain (r = 0.229, p = 0.023) and hippocampal volumes (right: r = 0.186, p = 0.032; left: r = 0.210, p = 0.023), even after FDR adjustment. Higher serotonin levels were linked to better cognitive function (negative correlation with CDR-SB, r = −0.230, p = 0.024). Notably, serotonin levels were positively correlated with BMP-6 (r = 0.173, p = 0.047), CNTF (r = 0.216, p = 0.013), FGF-4 (r = 0.176, p = 0.043), and MMP-1 (r = 0.202, p = 0.019), suggesting a link between serotonin and neurogenesis and neuroplasticity. However, after adjusting for multiple comparisons and controlling for confounding factors such as age, gender, education, and APOE genotypes (APOE3 and APOE4), none of the correlations of biomarkers remained statistically significant. In conclusion, increased serotonin levels are associated with improved cognitive function and increased brain volume. However, associations with CNTF, FGF-4, BMP-6, and MMP-1 were not statistically significant after adjustments, highlighting the complexity of serotonin’s role in AD and the need for further research.
Graphical Abstract
Molecular insights unlocking therapeutic potential for multiple myeloma and bone disease management
Authors: Bruno Tiziana , Catena Valeria , Blandino Giovanni , Fanciulli Maurizio , Di Agostino Silvia 
Published: December 2024

AbstractMultiple myeloma (MM), a hematologic malignancy characterized by the clonal expansion of plasma cells within the bone marrow, is associated with severe health complications, including osteolytic bone lesions that significantly increase the risk of fractures, leading to higher morbidity and mortality rates. One intriguing protein in this context is the RNA polymerase binding factor Che-1/AATF (Che-1), which has emerged as a potential player in the survival and proliferation of myeloma cells. Hippo pathway has been shown to be an important mediator of oncogenesis in solid tumors, especially for its role in shaping a tumor microenvironment favorable to cancer maintenance and spread. The Hippo pathway is also implicated in the pathogenesis of the osteolytic lesions that occurs in MM, since it deregulates the activities of mesenchymal populations of the bone matrix. In this commentary we wish to highlight some new molecular aspects elucidated in the paper by Bruno et al. regarding the proliferation of MM and the onset of bone lesions [Leukemia 38:877–882, 1]. A series of recent findings has revealed a crosstalk between the RNA polymerase binding factor Che-1 and the HIPPO downstream co-transcriptional factor TAZ, bringing to light new emerging molecular targets in MM to limit the development of bone lesions.
Methods and equipment available for prehospital treatment of accidental hypothermia: a survey of Norwegian prehospital services
Authors: Barsten Tea Wick , Sunde Emilie , Thomassen Øyvind , Mydske Sigurd 
Published: December 2024

Abstract
Background
Accidental hypothermia is associated with increased morbidity and mortality and poses a significant challenge for both professional and volunteer rescue services in prehospital settings. This study investigated the methods and equipment available to treat patients with cold stress or accidental hypothermia before reaching hospital in Norway.

Methods
We surveyed 156 respondents representing 708 units from both the professional and volunteer Norwegian prehospital chain of care between 2023 and 2024. Professional services included national ground ambulances, boat ambulances, national fixed wing and helicopter air ambulance services, search and rescue helicopter services, and urban search and rescue services. Volunteer services included Norwegian People’s Aid and the Norwegian Red Cross Search and Rescue Corps. The survey queried the availability of active warming equipment, passive insulation materials, thermometers for detecting hypothermia, and preferred sites for temperature measurements. The study also investigated whether there has been a development in available equipment compared to a similar study conducted in 2013.

Results
The survey achieved a response rate of 70.5%. Chemical heat pads were the most frequently used type of equipment for active external warming and were the only equipment used by volunteer rescue services. All services possessed equipment for passive external warming, with duvets, space blankets and wool- or cotton blankets being the most commonly available. Thermometers for detecting hypothermia were found in 86.3% of professional rescue services and 15% of volunteer units. Almost all respondents reported consistent equipment setups year-round.

Conclusion
All Norwegian prehospital services, both professional and volunteer, reported having equipment available for active and passive external warming. Thermometers for detecting hypothermia were reported by all professional services. The most notable change in the equipment available to treat patients with prehospital cold stress and accidental hypothermia in Norway was the increased availability of active external rewarming equipment in 2024 compared with that in 2013.