bluuebunny/crossref_metadata_2025 huggingface dataset:
Building a research agenda on preventing and addressing sexual assault and intimate partner violence against trans people: a two-stage priority-setting exercise
Authors: Du Mont Janice , Cheung Rachel , Burley Joseph Friedman , Kosa Sarah Daisy , Kelly C. Emma , Jakubiec Brittany A. E. , Brouillard-Coyle Sydney , Macdonald Sheila
Published: December 2024

Background

Transgender (trans) people experience high rates of sexual assault (SA) and intimate partner violence (IPV) and seldom receive the care and supports they need post-victimization. However, there is little to no research that aids in the development or improvement of related interventions. We undertook a study to build a novel Canadian research agenda on SA/IPV against trans people to guide future work and address these profound gaps in knowledge.

Methods

Guided by the Child Health and Nutrition Research Initiative (CHNRI) method for research priority-setting, we developed and circulated two consecutive surveys to a multi-stakeholder group of government decision makers; mental health, health and social service providers, researchers and trans communities, among others, who proposed research questions related to preventing and addressing SA/IPV against trans persons. The initial survey launched March 2021 garnered responses from 213 stakeholders. These items were cleaned and collated into 20 final questions that fell within seven thematic areas. The refined research questions were evaluated in August 2021 on predefined criteria for answerability, feasibility, impact and equity by 79 of 95 survey 1 respondents who agreed to participate in the second survey (response rate = 83.2%). The questions were ranked using a research priority score calculated by dividing the sum of all the answers for each question across the four criteria by the number of answers received.

Results

All questions were highly rated on each individual criterion and each had an overall research priority score of above 80%, with the most highly ranked question falling within the theme, “improving quality and implementation of education and training: How can training (e.g., for university/college students, educators, nurses, physicians, social workers, police, lawyers, security guards) be improved to better support trans survivors of sexual assault and intimate partner violence?”.

Conclusions

These questions form Canada’s first research agenda on SA/IPV against trans people. Together, they reflect the insights of stakeholder groups who have been historically excluded from research priority-setting processes and will guide future and much-needed work on the topic. Actionable information on preventing and addressing SA/IPV against trans persons will help reduce negative outcomes associated with being victimized.
Targeting cellular senescence in kidney diseases and aging: A focus on mesenchymal stem cells and their paracrine factors
Authors: Hejazian Seyyedeh Mina , Hejazian Seyyed Sina , Mostafavi Seyyedeh Mina , Hosseiniyan Seyed Mahdi , Montazersaheb Soheila , Ardalan Mohammadreza , Zununi Vahed Sepideh , Barzegari Abolfazl
Published: December 2024

Cellular senescence is a phenomenon distinguished by the halting of cellular division, typically triggered by DNA injury or numerous stress-inducing factors. Cellular senescence is implicated in various pathological and physiological processes and is a hallmark of aging. The presence of accumulated senescent cells, whether transiently (acute senescence) or persistently (chronic senescence) plays a dual role in various conditions such as natural kidney aging and different kidney disorders. Elevations in senescent cells and senescence-associated secretory phenotype (SASP) levels correlate with decreased kidney function, kidney ailments, and age-related conditions. Strategies involving senotherapeutic agents like senolytics, senomorphics, and senoinflammation have been devised to specifically target senescent cells. Mesenchymal stem cells (MSCs) and their secreted factors may also offer alternative approaches for anti-senescence interventions. The MSC-derived secretome compromises significant therapeutic benefits in kidney diseases by facilitating tissue repair via anti-inflammatory, anti-fibrosis, anti-apoptotic, and pro-angiogenesis effects, thereby improving kidney function and mitigating disease progression. Moreover, by promoting the clearance of senescent cells or modulating their secretory profiles, MSCs could potentially reverse some age-related declines in kidney function.

This review article intends to shed light on the present discoveries concerning the role of cellular senescence in kidney aging and diseases. Furthermore, it outlines the role of senotherapeutics utilized to alleviate kidney damage and aging. It also highlights the possible impact of MSCs secretome on mitigating kidney injury and prolonging lifespan across various models of kidney diseases as a novel senotherapy.
Does optimizing Choose to Move – a health-promoting program for older adults – enhance scalability, program implementation and effectiveness?
Authors: Nettlefold Lindsay , Macdonald Heather M. , Sims Gould Joanie , Bauman Adrian , Szewczyk Zoe , McKay Heather A.
Published: December 2024

Background

Investment in scale-up and sustainment of effective health-promoting programs is often hampered by competing demands on scarce health dollars. Thus, optimizing programs to reduce resource use (e.g., delivery costs) while maintaining effectiveness is necessary to promote health at scale. Using a phased approach (2015–2024), we adapted and scaled-up an evidence-based, health-promoting program for older adults (Choose to Move; CTM). For CTM Phase 4 we undertook a systematic, data-driven adaptation process to reduce resource use. In this paper we: 1) describe the CTM Phase 4 program (‘CTM Phase 4’) and assess its 2) implementation and 3) effectiveness.

Methods

For CTM Phase 4 (30-min one-on-one consultation and 8, 60-min group meetings with an activity coach), we reduced activity coach hours by 40% compared to Phase 3. To evaluate effectiveness of CTM Phase 4 we conducted a type 2 hybrid effectiveness-implementation study involving 137 programs (1126 older adults; 59–74 years, 75 + years) delivered by 29 activity coaches. We assessed implementation indicators (e.g., dose, fidelity, adaptation, participant responsiveness, self-efficacy) via survey in activity coaches and older adults. We assessed older adults’ physical activity (PA), mobility, social isolation, and loneliness before and after (0, 3 months) the program.

Results

Implementation indicators demonstrated that CTM Phase 4 was delivered successfully. Post-intervention, PA (+ 1.4 days/week; 95% CI 1.3, 1.6), mobility limitations (-6.4%), and scores for mobility (+ 0.7; 95% CI: 0.4, 1.3), social isolation (+ 0.9; 95% CI: 0.67, 1.17), and loneliness (-0.23; 95% CI: -0.34, -0.13) were improved in those < 75 years. Among those ≥ 75 years, PA (+ 1.0 days/week; 95% CI, 0.7, 1.2), mobility score (+ 1.1; 95% CI: 0.4, 1.8), and social isolation score (+ 0.5; 95% CI: 0.08, 0.86) were improved post-intervention. Participant-level benefits were comparable to, or greater (PA and social isolation in those < 75) than, those observed in Phase 3.

Conclusions

CTM was co-designed as a flexible program, adapted over time based on user group needs and preferences. This flexibility enabled us to reduce activity coach delivery hours without compromising implementation or benefits to older adults’ health. Optimizing effective health-promoting programs to enhance their scalability and sustainability provides an important pathway to improved population health.

Trial Registration

ClinicalTrials.gov, NCT05678985. Registered 10 January 2023 – Retrospectively registered,
https://clinicaltrials.gov/study/NCT05678985.
Prospective associations of infant food exposures and appetitive traits with early childhood diet quality
Authors: Nansel Tonja R. , Channell-Doig Amara , Lipsky Leah M. , Burger Kyle , Shearrer Grace , Siega-Riz Anna Maria , Ma Yong
Published: December 2024

Background

Early-life food exposures may influence food preferences and receptivity, thereby impacting long-term diet quality. Infant exposure to discretionary foods may be more detrimental for infants with high food approach traits; conversely, early exposure to fruits and vegetables may be more important for those with high food avoidance traits. This study investigated associations of infant food exposures with early childhood diet quality and whether these associations are modified by infant appetitive traits.

Methods

Data are from the Pregnancy Eating Attributes Study (PEAS) and Sprouts follow-up study, a prospective cohort assessed from the first trimester of pregnancy through early childhood. Birthing parents completed the Baby Eating Behavior Questionnaire assessing food-approach and food-avoidance appetitive traits at 6 months and food frequency questionnaires assessing infant age at introduction to and frequency of consuming food groups at ages 6 months, 1 year, and 2 years. At child ages 3.5 and 5 years, parents provided two 24-h dietary recalls, from which the Healthy Eating Index-2020 was calculated to measure diet quality. Structural equation models using maximum likelihood estimation examined associations of age at introduction to, and intake frequency of, fruit/vegetables and discretionary foods, and their interactions with food-approach and food-avoidance appetitive traits, on child diet quality at ages 3.5 & 5 years, controlling for income, education, and breastfeeding duration.

Results

Higher childhood diet quality was associated with later infant age at introduction to discretionary foods, lower intake of discretionary foods at ages 1 and 2 years, and greater intake of fruits and vegetables at age 2 years. Childhood diet quality was not associated with infant age at introduction to fruits and vegetables. Intake of fruits and vegetables at age 1 year interacted with food avoidance traits, indicating that the association of fruit and vegetable intake with childhood diet quality was magnified by greater food avoidance.

Conclusions

Exposure to discretionary food in the first two years of life was consistently associated with lower diet quality in early childhood regardless of the strength of appetitive traits. Findings suggest that improving child diet quality may require stronger efforts to limit exposure to discretionary foods in infancy.
Longitudinal relationship between 24-Hour Movement behavior patterns and physical function and quality of life after stroke: a latent transition analysis
Authors: Zhang Yi , Yao Lin , Chen Lei , Zhong Weiying , Li Jiaxuan , Xu Lan , Pan Xi
Published: December 2024

Background

24-hour movement behavior, including Physical activity (PA), Sedentary behavior (SB), and sleep, is independently associated with health after stroke. Few studies have explored 24-hour movement behavior patterns in stroke survivors and their transitions, as well as the health implications of the transitions. This study aimed to explore the different subgroups and stability of 24-hour movement behavior patterns in people after stroke and the relationship of profile transitions with physical function and health-related quality of life (HRQoL).

Methods

In this study, 131 people with first-ever stroke were investigated at one week (T1), one month (T2), three months (T3), and six months (T4) after discharge. The participants were asked to wear a wristband smartwatch for 7 consecutive days during each pe riod to collect 24-hour exercise data. After each period, their physical function and HRQoL were assessed. Latent profile analysis (LPA) identified typologies of 24-hour movement behaviors, and latent transition analysis (LTA) examined the stability and change in these profiles over time. The relationship of transition types with physical function and HRQoL was analyzed using a generalized linear regression model.

Results

108 participants were categorized into 3 latent profiles of 24-hour movement behavior: “Active, Non-sedentary, and Short sleep,” “Active and Sedentary,” and “Inactive and Sedentary.” The LTA results indicated that the proportion of participants with the “Active, Non-sedentary, and Short Sleep” profile and “Active and Sedentary” profile staying in the original latent profile was high. However, participants in the “Inactive and Sedentary” profile showed a high probability of transitioning to “Active and Sedentary” profile (T1→T2: 65.2%; T2→T3: 76.3%; T3→T4: 51.7%;T1→T4: 54.2%). Transition types are associated with physical function and HRQoL.

Conclusions

The results demonstrated substantial transitions in 24-hour movement behaviors within 6 months of rehabilitation after discharge, associated with later physical function and HRQoL. Furthermore, the participants’ sedentary behavior was highly stable within 24-hour movement behaviors, necessitating prompt diagnosis and intervention.
Diet, physical activity, and sleep in relation to postprandial glucose responses under free-living conditions: an intensive longitudinal observational study
Authors: Yao Jiali , Brugger Victoria K. , Edney Sarah M. , Tai E-Shyong , Sim Xueling , Müller-Riemenschneider Falk , van Dam Rob M.
Published: December 2024

Background

It remains unclear what lifestyle behaviors are optimal for controlling postprandial glucose responses under real-world circumstances in persons without diabetes. We aimed to assess associations of diet, physical activity, and sleep with postprandial glucose responses in Asian adults without diabetes under free-living conditions.

Methods

We conducted an observational study collecting intensive longitudinal data using smartphone-based ecological momentary assessments, accelerometers, and continuous glucose monitors over nine free-living days in Singaporean men and women aged 21–69 years without diabetes. The outcome was the 2-h postprandial glucose incremental area under the curve (mmol/l*min). Associations were estimated using linear mixed-effect models.

Results

The analyses included 11,333 meals in 789 participants. Greater variations in glucose and lifestyle measures were observed within individuals than between individuals. Higher consumption of carbohydrate-rich and deep-fried foods and lower consumption of protein-rich foods were significantly associated with higher postprandial glucose levels (incremental area under the curve). The strongest association was observed for including refined grains (46.2 [95% CI: 40.3, 52.1]) in meals. Longer postprandial light-intensity physical activity (-24.7 [(-39.5, -9.9] per h) and moderate-to-vigorous-intensity physical activity (-58.0 [-73.8, -42.3]) were associated with substantially lower postprandial glucose levels. Longer daily light-intensity physical activity (-7.5 [-10.7, -4.2]) and sleep duration (-2.7 [-4.4, -1.0]) were also associated with lower postprandial glucose levels. Furthermore, postprandial glucose levels were the lowest in the morning and the highest in the afternoon. The results were largely consistent for males and females and for participants with and without prediabetes.

Conclusions

Consuming less refined grains and more protein-rich foods, getting more physical activity (particularly during the postprandial period), and having a longer sleep duration were associated with lower postprandial glucose levels in Asian adults without diabetes. Our findings support multi-component lifestyle modifications for postprandial glucose control and highlight the importance of the timing of eating and physical activity.
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

Traumatic 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

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

Opioid 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

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

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

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

Neuronal 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

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

Research 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

Multiple 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

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.
Non-prescription antibiotic use and its predictors among children in low- and middle-income countries: a systematic review and meta-analysis
Authors: Zewdie Segenet , Kassa Assefa Andargie , Yayehrad Ashagrachew Tewabe , Bizuneh Mekonnen Melkie , Ayenew Wondim , Zewudie Melkamu , Mulat Selomie , Bitew Bayih Endalew , Zewudie Serkalem , Meharie Birhanu Geta , Tesfaye Tegenu Chanie , Zerga Aregash Abebayehu , Ayele Fanos Yeshanew , Toleha Husein Nurahmed , Workineh Birhanu Demeke , Bayked Ewunetie Mekashaw
Published: December 2024

Globally antibiotics are among the most commonly used drugs. Non-prescription use of antibiotics is a major factor for the emergence and spread of antimicrobial resistance one of the top global public health and development threats. This systematic review and meta-analysis aim to assess non-prescription antibiotic use and predictors among children in Low and middle-income countries.

A comprehensive search of electronic databases was conducted from PubMed, Scopus and HINARI to identify primary studies published between 2000 and 2024. Observational studies conducted among children ≤ 18 years old and published in English language were included in the review. After screening, the studies were assessed using Joanna Briggs Institute (JBI) critical appraisal tool and data were extracted using a checklist. Heterogeneity was assessed using forest plot, Chocran’s Q Test and I2. The random effects meta-analysis model was employed to pool the prevalence of non-prescription antibiotic use among children in low-and middle-income countries. Sub-group analysis and meta-regression were performed to identify the sources of heterogeneity. Publication bias was assessed using funnel plots with Egger’s test.

The review was conducted among 32 cross-sectional studies with a sample size of 80,133 participants. The pooled prevalence of non-prescription antibiotic use among children in low-and middle-income countries was 38.86% (95% CI 34.32, 43.40; P < 0.0001) with high heterogeneity (I2 = 99.38%, p < 0.001). The prevalence of non-prescribed antibiotic use among studies conducted in upper middle-income countries (30.85% (24.49%, 37.21%)) was low when compared to studies conducted in LMICs (44.00% (37.72%, 52.09%). Penicillin was the most often antibiotic class used without prescription, while upper respiratory infections were the most prevalent illness/symptoms that prompted non-prescription antibiotic use.

The pooled prevalence of non-prescription antibiotic use among children in low-and middle-income countries is high indicating that two out of five children used non-prescribed antibiotics. This review is important for international organizations, ministry of health of the low-and middle- income countries, regulatory bodies and researchers.
GenomeDelta: detecting recent transposable element invasions without repeat library
Authors: Pianezza Riccardo , Haider Anna , Kofler Robert
Published: December 2024

We present GenomeDelta, a novel tool for identifying sample-specific sequences, such as recent transposable element (TE) invasions, without requiring a repeat library. GenomeDelta compares high-quality assemblies with short-read data to detect sequences absent from the short reads. It is applicable to both model and non-model organisms and can identify recent TE invasions, spatially heterogeneous sequences, viral insertions, and hotizontal gene transfers. GenomeDelta was validated with simulated and real data and used to discover three recent TE invasions in Drosophila melanogaster and a novel TE with geographic variation in Zymoseptoria tritici.
STABLE trial of spectacle provision and driving safety among myopic motorcycle users in Vietnam: study protocol for a stepped-wedge, cluster randomised trial
Authors: Le Vinh Chi , To Kien Gia , Le Van Dat , Nguyen Le , MacKenzie Graeme , Sigwadhi Lovemore Nyasha , Piyasena Prabhath , Tran Mai , Chan Ving Fai , Khanna Rohit C. , Clarke Mike , Lohfeld Lynne , Dickey Heather , Azuara-Blanco Augusto , Mettla Asha Latha , Rayasam Sridevi , Doan Han Thi Ngoc , Van Do Dung , Le Phuoc Hong , Klauer Charlie , Hanowski Richard , Bowden Zeb , Murphy Lynn , Thompson Joanne , McMullan Susan , McDowell Cliona , Narayanan Raja , Little Julie-Anne , Ha Huong Thu , Yoon Sangchul , Goel Rahul , Luong Lan , Nguyen Xuan , Congdon Nathan
Published: December 2024

Background

Traffic crashes are the leading cause of death globally for people aged 5–29 years, with 90% of mortality occurring in low- and middle-income countries (LMICs). The STABLE (Slashing Two-wheeled Accidents by Leveraging Eyecare) trial was designed to determine whether providing spectacles could reduce risk among young myopic motorcycle users in Vietnam.

Methods

This investigator-masked, stepped-wedge, cluster randomised naturalistic driving trial will recruit 625 students aged 18–23 years, driving ≥ 50 km/week, with ≥ 1-year driving experience and using motorcycles as their primary means of transport, in 25 clusters of 25 students in Ho Chi Minh City, Vietnam. Motorcycles of consenting students who have failed self-testing on the WHOeyes app will be fitted with Data Acquisition Systems (DAS) with video cameras and accelerometers. Video clips (± 30 s) of events flagged by the accelerometer will be reviewed for crash and near-crash events per 1000 km driven (main outcome). Five clusters of 25 students will be randomly selected every 12 weeks to undergo ocular examination and an estimated 40% of these will have bilateral spherical equivalent < − 0.5 D, and better-eye presenting distance visual acuity < 6/12, correctable bilaterally to ≥ 6/7.5. They will be given free distance spectacles and their driving data before receiving spectacles will be analysed as the control condition and subsequent data as the intervention condition. Secondary outcomes include visual function, cost-effectiveness and self-reported crash events.

Discussion

STABLE will be the first randomised trial of vision interventions and driving safety in a LMIC.

Trial registration

ClinicalTrials.gov, NCT05466955. Initial registration: 20 July 2022, most recent update: 9 July 2024.
Perceived barriers and facilitators of staff recruiting participants to a randomised controlled trial of a community rehabilitation intervention following hip fracture
Authors: Harvey Kathryn , Ralph Penelope , Spencer Llinos Haf , Doungsong Kodchawan , Morrison Val , Lemmey Andrew , Golding-Day Miriam , Dodd Susanna , Hardwick Ben , Dorkenoo Shanaz , Hennessey Sophie , Williams Nefyn
Published: December 2024

Background

Randomised controlled trials (RCTs) often struggle with recruitment and many need extensions which leads to delayed implementation of effective interventions. Recruitment to complex intervention trials have similar difficulties. Alongside this, the COVID-19 pandemic had a major impact upon trial recruitment. Research has shown that many other recruitment issues can be anticipated, for example overestimating target population prevalence; however, a range of factors may play a role. The aim of this study is to investigate facilitators and barriers to recruitment from the perspective of the recruiter.

Methods

Fracture in the Elderly Multidisciplinary Rehabilitation – phase III (FEMuR III) was a RCT of a complex intervention post-surgery for hip fracture in patients over 60 years old. A process evaluation was undertaken, and semi-structured interviews were conducted with seven recruiters between November 2022 and March 2023 to identify barriers and facilitators to recruitment. A thematic analysis was undertaken in NVIVO (Version 12) using a critical realist perspective.

Results

The trial took place mostly during the COVID-19 pandemic, and the unique impact of this on reported barriers is considered. A key finding included recruiter reluctance to approach patients that they felt would not benefit from the trial due to other factors (e.g. comorbidities or complex living situations). A possible barrier to recruiting carers appeared to be that family members did not relate to the label of ‘carer’ and so did not take part. Facilitators included recruiters approaching patients with other clinical or research staff. This approach, which included tailored initial information on the trial, reduced participant stress by increasing patient familiarity with recruiting staff and allowing staff time to develop relationships with patients.

Conclusion

This paper identifies barriers and facilitators of recruitment to FEMuR III with six broad themes for both barriers and facilitators identified in the qualitative data synthesis. The impact of the COVID-19 pandemic was the main, but not sole, barrier to recruitment. Key findings concern reluctance to approach some eligible patients, the label of ‘carer’, the involvement of clinical staff and patient preference for trial group. Strategies to identify and overcome recruitment problems are highlighted and should be implemented and evaluated in further RCTs of complex interventions.

Trial registration

ISRCTN28376407. November 23, 2018.