bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of a coach-guided personalized depression risk communication program on the risk of major depressive episode: study protocol for a randomized controlled trial
Authors: Wang JianLi , Feng Cindy , Hajizadeh Mohammad , Lesage Alain
Published: December 2024

Background

Depression is a highly prevalent and disabling mental health problem. Self-help has been strongly advocated for dealing with depression. Built upon the research on risk prediction modeling and risk communication, we developed a coach-guided, personalized depression risk communication tool (PDRC) for sharing information about individualized depression risk and evidence-based self-help strategies. The primary objective of this project is to evaluate the impact of the PDRC on the 12-month risk of major depressive episode (MDE) in Canadians who are at high risk of MDE.

Methods

This is an assessor-blinded randomized controlled trial (RCT) with two arms. We will recruit 500 males and 500 females in the communities across the country. Individuals are eligible, if they: (1) are 18 years or older, (2) have not had a depressive episode in the past two months, (3) are at high risk of MDE based on the sex-specific risk predictive algorithms for MDE (predicted risk of 6.5% + for men and of 11.2% + for women), (4) can communicate in either English or French, and (5) agree to be contacted for follow-up interviews. After screening and baseline assessment, participants will be randomized by sex into intervention and control group in a 1:1 ratio. Participants in the intervention group will receive the coach-guided PDRC. The participants are assessed at baseline, 3 and 12 months via computer assisted telephone interview system, regarding the presence of MDE, depressive and anxiety symptoms, use of self-help strategies, mental health services use and self-efficacy.

Discussion

The coach-guided PDRC may empower users to actively engage in self-management, leading to reduced risk of MDE. If successful, the coach-guided PDRC will lead to a novel selective prevention program that is closely aligned with the tiered mental health services model, contributing to early prevention of depression and better mental health wellbeing.

Date of trial registration

: 2024-10-02.

Protocol version and date

December 6, 2024. Version #1.

Trial registration

: NCT06619366.
How could 20-minute neighbourhoods impact health and health inequalities? A policy scoping review
Authors: Pollack Roxana , Olsen Jonathan R , Heppenstall Alison , Hoehn Andreas , Boyd Jennifer , Hardy Vicki Ponce , Littlejohn Jennifer , Stevenson Amy , Mitchell Richard , Meier Petra , Stokes Jonathan
Published: December 2024

Background

‘Twenty-minute neighbourhoods’ (or variations, such as 15-minute cities) are receiving increasing policy attention with anticipated impacts on population health (inequalities) outcomes alongside sustainability improvements. Yet, factors contributing to possible health impacts are not well understood. This scoping review aimed to identify proposed and evidenced pathways to health (inequality) outcomes from international policy plans.

Methods

We first identified relevant academic literature, searching Scopus, (Ovid) Medline and Embase databases. A second search aimed to identify local or national planning or policy documents on government websites and related organisations. We followed a snowball search strategy to retrieve examples identified from the academic literature search and from the C40 cities network. These policy documents were our primary target for extraction, and we extracted and analysed by individual place. Pathways to health and health inequality outcomes identified in these documents were inductively coded thematically. We used Sankey diagrams to visually aggregate the thematic codes for each place relating to pathways to health outcomes and social determinants (mechanisms).

Results

In total, 36 places across 17 countries were included, described across 96 academic articles, policy plans and reports. While different health improvement outcomes were included as a goal in nearly all policy plans, most frequently references were to health in general rather than specific health outcomes. Pathways to health were discussed in numerous policy plans across three overarching themes: proximity, place redesign, and environmental action. Proximity pathways were most frequently outlined as the means to achieve health outcomes, with active travel acting through increased physical activity/reduced obesity as the most frequent individual pathway. However, few plans specified what would actually be implemented in practice to achieve the increased proximity to services. Health inequalities were only mentioned by six places specifically, although nearly half of all places mentioned broader inequality aims (e.g., poverty reduction). Possible unintended consequences to health inequalities also received some attention, for example through displacement of residents.

Discussion

Pathways to assumed health (inequality) outcomes require better specification and evidence. Health inequalities are particularly under-explored, and scenario modelling might provide a means to explore the dynamic aspects necessary to examine these important outcomes pre-implementation.
Digital learning of clinical skills and its impact on medical students’ academic performance: a systematic review
Authors: McGee Richard G. , Wark Stuart , Mwangi Felista , Drovandi Aaron , Alele Faith , Malau-Aduli Bunmi S. ,   The ACHIEVE Collaboration
Published: December 2024

Background

The constraints imposed by the COVID-19 pandemic has led to the rapid development and implementation of digital methods for teaching clinical skills in medical education. This systematic review presents both the benefits, challenges, and effectiveness of this transition.

Methods

A systematic search of six electronic databases (SCOPUS, Medline, CINAHL, PsycINFO, ERIC & Informit) was conducted on 1st October 2023 and updated on 1st April 2024 to identify peer- reviewed articles, from 2019 onwards, which used any type of digital tool (online or otherwise) to teach clinical skills to medical trainees (undergraduate or postgraduate) and were published in English language. The primary outcome synthesised was the reported effectiveness of these digital tools in the development of clinical skills. Risk of bias of included studies was assessed using the Quality Assessment With Diverse Studies (QuADS) tool.

Results

Twenty-seven studies involving 3,895 participants were eligible for inclusion in this review. The QuADS quality assessment scores ranged from 22 to 35, indicating medium quality and thirteen of the studies were randomized trials. Overall, digital teaching of clinical skills demonstrated improved or comparable outcomes to in-person teaching. There was a beneficial effect of digital learning tools on assessment outcomes, with meta-analysis showing a mean difference increase of 1.93 (95% CI 1.22 to 2.64), albeit with a high amount of statistical heterogeneity I2 97%, P < 0.001. Digital clinical skills teaching also resulted in improved student satisfaction scores in many situations and was also shown in one study to be cost effective.

Conclusion

Teaching of clinical skills using digital tools is an important alternative to the traditional format of face-to-face delivery, which is resource intensive and difficult to implement during a pandemic. This review demonstrates their potential efficacy in improving education outcomes, student satisfaction and potentially reducing costs. However, the integration of traditional and innovative digital teaching methods appeared to provide the most comprehensive learning experience. Future research could focus on longitudinal studies to assess the long-term impact and efficacy of different digital and blended learning modalities on the acquisition of clinical skills and professional competencies.
Social anxiety, loneliness, and mobile phone addiction among nursing students: latent profile and moderated mediation analyses
Authors: Jiang Yingting , Shen Zhenrong , Zeng Yihao , Li Shuhan , Li Hongman , Xiong Ying , Ye Zengjie
Published: December 2024

Background

The overutilization of mobile devices by nursing students has been found to adversely affect their physical and cognitive health, potentially impeding the cultivation of a proficient nursing workforce. Previous research has identified social anxiety and loneliness as influential contributors to mobile phone addiction, but the relationship between these three factors has not been extensively examined. The objective of this research was to investigate the role of loneliness in mediating the relationship between social anxiety and mobile phone addiction, as well as the moderating influence of sleep duration on the relationship between social anxiety, loneliness, and mobile phone addiction among nursing students.

Methods

We enrolled 437 students from the Be Resilient to Nursing Career program (BRNC) between October and December 2023. Surveys were employed to evaluate the levels of social anxiety, loneliness, and mobile phone addiction among nursing students. Three types of analyses were performed: latent profile analysis, mediation analysis, and moderation analysis.

Results

The following three profiles of social anxiety were identified: low social anxiety (23.8%), middle social anxiety (42.8%), and high social anxiety (33.4%). The significant mediating effect of loneliness in the relationship between social anxiety based on latent profile analysis and mobile phone addiction was observed (SE = 0.709, 95%CI = 1.821, 4.618; SE = 0.561, 95%CI = 1.161, 3.345, respectively). The moderating role of sleep duration between social anxiety, loneliness, and mobile phone addiction was not significant (P > 0.05).

Conclusion

Heterogeneity exists in social anxiety among nursing students. Loneliness serves as a significant mediating factor between social anxiety and mobile phone addiction. The moderating influence of sleep duration should be validated in future research.
Methodological report of a cross-sectional survey of abortion-related knowledge, attitudes and practices amongst health professionals in Britain, strategies adopted and lessons learned: evidence from the SACHA Study
Authors: French R. S. , Palmer M. J. , McCarthy O. , Salaria N. , Meiksin R. , Shawe J. , Lewandowska M. , Scott R. , Wellings K. ,   the SACHA Study Team, Aronsson A. , Baraitser P. , Cameron S. , Free C. , Keogh L. , Lohr P. A. , Murphy C. , Norman W. V. , Reiter J. , Sheldon S. , Wong G.
Published: December 2024

Background

Most surveys examining health professionals’ knowledge, attitudes and practices around abortion have used convenience samples and have targeted doctors. Our goal in the SACHA Study, drawing on evidence-based strategies to maximise response rates, was to achieve a representative sample of a wider range of health professionals, working in general practice, maternity services, pharmacies, sexual and reproductive health (SRH) clinics and specialist abortion services in Britain, to explore the knowledge, attitudes and experience of abortion care and views on future models of delivery.

Methods

A cross-sectional questionnaire-based survey of midwives, doctors, nurses and pharmacists in England, Scotland and Wales was undertaken between November, 2021 and July, 2022. We used a stratified cluster sampling approach to select a random sample of sites and all eligible staff within those services were asked to respond to the survey. Evidence-based strategies to maximise completion rates were adopted, including postal delivery of the one-page questionnaire with personal letter of invitation and a stamped address envelope for return, inclusion of an unconditional voucher and follow-up.

Results

Overall, 147 of the 314 (46.8%) health service sites randomly selected took part in the survey. Reasons for non-participation included local Research and Development (R&D) Department non-response, lack of resources or insufficient time to support or approve the study, lack of interest in or perceived relevance of the topic and insufficient capacity to take part, exacerbated by work demands during the COVID epidemic. Of the 1370 questionnaires sent to eligible identified participants within these services, 771 were completed and returned (56.3%). At the service level the highest proportion of returns was from SRH clinics (81.0%) and the lowest from general practice (32.4%). In relation to profession, returns were highest amongst midwives (69.6%) and lowest amongst pharmacists (36.5%).

Conclusions

Obtaining information about health professional knowledge, attitudes and practices is key to guide service development and policy and to identify gaps in training and service provision in abortion. Despite our attempts to gain a representative sample of health professionals, the challenges we experienced limited the representativeness of the sample, despite the use of an evidence-based strategy.
Patient characteristics and healthcare use for high-cost patients with musculoskeletal disorders in Norway: a cohort study
Authors: Amundsen Olav , Moger Tron Anders , Holte Jon Helgheim , Haavaag Silje Bjørnsen , Bragstad Line Kildal , Hellesø Ragnhild , Tjerbo Trond , Vøllestad Nina Køpke
Published: December 2024

Background

A high proportion of healthcare costs can be attributed to musculoskeletal disorders (MSDs). A small proportion of patients account for most of the costs, and there is increasing focus on addressing service overuse and high costs. We aimed to estimate healthcare use contributing to high costs over a five-year period at the individual level and to examine if healthcare use for high-cost patients is in accordance with guidelines and recommendations. These findings contribute to the understanding of healthcare use for high-cost patients and help in planning future MSD-care.

Methods

This study combined Norwegian registries on healthcare use, diagnoses, demographic, and socioeconomic factors. Patients (≥ 18 years) were included by their first MSD-contact in 2013–2015. We analysed healthcare use during the subsequent five years. Descriptive statistics were used to compare high-cost (≥ 95th percentile) and non-high-cost patients. Total healthcare contacts and costs for high-cost patients were examined stratified by number of hospitalisations and surgical treatments. Healthcare use of General Practitioners (GPs), physiotherapy, chiropractor and Physical Medicine and Rehabilitation physicians prior to the first hospitalisation or surgical treatment for a non-traumatic MSD was registered.

Results

High-cost patients were responsible for 61% of all costs. Ninety-four percent of their costs were related to hospital treatment. Ninety-nine percent of high-cost patients had at least one hospitalisation or surgical procedure. Out of the high-cost patients, 44% had one registered hospitalisation or surgical procedure, 52% had two to four and 4% had five or more. Approximately 30–50% of patients had seen any healthcare personnel delivering conservative treatment other than GPs the year prior to their first hospitalisation/surgical treatment for a non-traumatic MSD.

Conclusion

Most healthcare costs were concentrated among a small proportion of patients. In contrast to guidelines and recommendations, less than half had been to a healthcare service focused on conservative management prior to their first hospitalisation or surgical treatment for a non-traumatic MSD. This could indicate that there is room for improvement in management of patients before hospitalisation and surgical treatment, and that ensuring sufficient capacity for conservative care and rehabilitation can be beneficial for reducing overall costs.
The human Dicer helicase domain is capable of ATP hydrolysis and single-stranded nucleic acid binding
Authors: Ciechanowska Kinga , Szczepanska Agnieszka , Szpotkowski Kamil , Wojcik Klaudia , Urbanowicz Anna , Kurzynska-Kokorniak Anna
Published: December 2024

Background

Vertebrates have one Dicer ortholog that generates both microRNAs (miRNAs) and small interfering RNAs (siRNAs), in contrast to the multiple Dicer-like proteins found in flies and plants. Here, we focus on the functions of the human Dicer (hDicer) helicase domain. The helicase domain of hDicer is known to recognize pre-miRNA substrates through interactions with their apical loop regions. Besides interacting with canonical substrates, the hDicer helicase domain has also been suggested to bind many different cellular RNAs; however, a comprehensive study of the biochemical activities and substrate specificity of the hDicer helicase domain towards different nucleic acids has yet to be undertaken.

Results

Here, we reveal that full-length hDicer, through its helicase domain, hydrolyzes ATP. The ATPase activity of hDicer can only be observed under low-turnover conditions. To the best of our knowledge, this is the first time this activity has been reported for vertebrate Dicers. We also show that the hDicer helicase domain binds single- but not double-stranded RNAs and DNAs and that this binding activity presumably is not nucleotide-dependent. Moreover, the hDicer helicase domain may influence the structure of the RNA to which it binds.

Conclusions

Preservation of ATPase activity by hDicer suggests that this enzyme performs many more functions in the cell than is currently assumed. Our findings open new avenues for future studies aimed at defining the cellular activities of hDicer that may be associated with these newly described biochemical properties: ATP hydrolysis and single-stranded nucleic acid binding activities.
The burden and clinical trajectory of immune checkpoint inhibitor-induced endocrinopathies: an 8-year experience
Authors: Ata Fateen , Khan Adeel Ahmad , Algorani Emad , Alsharafi Amr Faisal Musaed , Shdid Reham Abo , Nofal Mohammad , Ibrahim Ayman R. , Abdullah Loai , Annan Khalil Youssef El , Al-Bkoor Tareq Emad Hawash , Rasul Kakil Ibrahim , Elhadd Tarik , Surchi Haval
Published: December 2024

Background

Immune checkpoint inhibitors (ICIs) have revolutionized the management of cancer patients, but the emergence of ICI-related endocrinopathies (IREs) has introduced new clinical challenges. Despite worldwide recognition of these adverse effects, data from the Middle East is scarce.

Methods

This retrospective-observational study included adult cancer patients who received at least one dose of ICI between January 2015 and January 2023. Descriptive statistics and multivariable regression (MVR) models were applied to delineate the incidence and clinical impact of IREs.

Results

The median age of 649 included patients was 55 years, with male preponderance (70.7%). The incidence of IREs was 26.7%, dominated by primary hypothyroidism (62.4%), insulin deficiency (15%), and primary hyperthyroidism (13.9%). Pembrolizumab (62%) was the most utilized ICI among the study cohort, followed by nivolumab (23.7%), atezolizumab (12.5%), durvalumab (0.9%), avelumab (0.6%) and ipilimumab (0.1%). The mortality rates in the cohort and the IRE subgroup were 43.4% and 42.2%. MVR revealed age (OR 1.02, 95% CI (1.003–1.03), P = 0.02), pre-ICI white-cell (WBC) count (OR 0.94, 95% CI (0.89–0.99), P = 0.04), pembrolizumab (OR 2.6, 95% CI (1.05–6.3), P = 0.04), and nivolumab use (OR 2.6, 95% CI (1.04–6.6), P = 0.04) as significant predictors of IREs. After MVR, factors influencing mortality in the subgroup with IREs included a higher age (OR 1.1, 95% CI 1.04–1.2, P = 0.001) and platelet-to-lymphocyte ratio (OR 1.004, 95% CI 0.7–1.4, P = 0.006).

Conclusions

This first extensive Middle Eastern and South Asian cohort reported a higher-than-previously known incidence of IREs. Hypothyroidism, insulin deficiency, and hyperthyroidism were the commonest IREs, with pembrolizumab being the commonest ICI. IRE development was associated with higher age, a low WBC count, pembrolizumab, and nivolumab use. The development of IREs did not seem to influence mortality. Further research on IREs is imperative to optimize management guidelines in the era of precision medicine.
Incidence, risk factors, and epidemiological trends of tracheal cancer: a global analysis
Authors: Huang Junjie , Chen Mingtao , Zhang Lin , Lin Xu , Lucero-Prisno Don Eliseo , Zhong Claire Chenwen , Xu Wanghong , Zheng Zhi-Jie , Withers Mellissa , Wong Martin C. S. ,   N. C. D. Global Health Working Group,   Association of Pacific Rim Universities (APRU)
Published: December 2024

Background

Tracheal cancer is a rare malignancy with limited research but high mortality rates. This study aims to analyse recent data to understand the global burden, trends, and risk factors for tracheal cancer, facilitating improved prevention and treatment strategies.

Methods

We conducted a study on tracheal cancer using data from the Global Cancer Observatory and the Cancer Incidence in Five Continents databases. We collected information on the incidence of tracheal cancer, risk factors, and the Human Development Index (HDI) at the country level. The univariate linear regression was used to explore the relationship between tracheal cancer and the various risk factors. We utilised joinpoint regression analysis to calculate the Average Annual Percentage Change (AAPC) in tracheal cancer incidence.

Results

The global age-standardised rate of incidence of tracheal cancer was 2.9 per 10 million (3,472 cases in total) in 2022, with the highest regional incidence observed in Central and Eastern Europe (ASR = 9.0) and the highest national incidence in Hungary (12.5). Higher incidence was found among the males (3.8) than females (2.0); among the older adults aged 50-74 (11.9) than the younger population aged 15-49 (1.2). A higher tracheal cancer incidence ratio was associated with higher levels of smoking, alcohol drinking, diabetes, lipid disorders, and HDI. Despite the overall decreasing trends for all population groups (highest decrease in Thailand; AAPC: -15.06, 95% CI: -21.76 to -7.78, p = 0.002), there was an increase in some female populations (highest increase in Colombia, AAPC: 19.28, 95% CI: 16.48 to 22.15, p < 0.001) and younger populations (highest increase in Ireland; AAPC: 29.84, 95% CI: 25.74 to 34.06, p < 0.001).

Conclusion

This study provides a comprehensive analysis of tracheal cancer, focusing on risk factors and population-level trends. There has been an overall decreasing trend in the incidence of tracheal cancer, particularly among males and older adults, while the decline is less pronounced in females and younger individuals. Further research is needed to explore the underlying drivers of these epidemiological trends.
The plasma lipidome varies with the severity of metabolic dysfunction-associated steatotic liver disease
Authors: Heymann Clément J. F. , Mak Anne Linde , Holleboom Adriaan G. , Verheij Joanne , Shiri-Sverdlov Ronit , van Mil Saskia W. C. , Tushuizen Maarten E. , Koek Ger H. , Grefhorst Aldo
Published: December 2024

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with many aspects of disturbed metabolic health. MASLD encompasses a wide spectrum of liver diseases, ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), up to fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Limited noninvasive diagnostic tools are currently available to distinguish the various stages of MASLD and as such liver biopsy remains the gold standard for MASLD diagnostics. We aimed to explore whether the plasma lipidome and its variations can serve as a biomarker for MASLD stages.

Methods

We investigated the plasma lipidome of 7 MASLD-free subjects and 32 individuals with MASLD, of whom 11 had MASH based on biopsy scoring.

Results

Compared with the MASLD-free subjects, individuals with MASLD had higher plasma concentrations of sphingolipids, glycerolipids, and glycerophospholipids. Only plasma concentrations of ceramide-1-phosphate C1P(d45:1) and phosphatidylcholine PC(O-36:3), PC(O-38:3), and PC(36:2) differed significantly between presence of MASH in individuals with MASLD. Of these lipids, the first three have a very low relative plasma abundance, thus only PC(36:2) might serve as a biomarker with higher plasma concentrations in MASLD individuals without MASH compared to those with MASH.

Conclusions

Plasma lipids hold promise as biomarkers of MASLD stages, whereas plasma PC(36:2) concentrations would be able to distinguish individuals with MASH from those with MASLD without MASH.
Lessons from an intervention study on the sustainability of after-school comprehensive sexuality education in Zambia: the perspectives of teachers, health workers and guardians
Authors: Svanemyr Joar , Zulu Joseph Mumba , Munsaka Ecloss , Sandøy Ingvild Fossgard
Published: December 2024

Background

Comprehensive sexuality education (CSE) has been introduced in many sub-Saharan African countries, but limited political interest and insufficient funding have resulted in many CSE initiatives being dependent on donor funding or non-governmental organisations (NGOs) supporting its implementation. This has created concerns about the sustainability of the programmes. The objective of this study was to explore factors affecting the sustainability of CSE delivered through a youth club organized after school hours in Zambia.

Methods

We interviewed teachers and community health workers (CHWs) who had implemented CSE as part of an after-school youth club set up as part of a cluster randomized controlled trial. The trial evaluated the effectiveness of economic support for adolescent girls, CSE and community dialogue meetings on adolescent childbearing. Teachers and CHWs in 63 schools were trained to facilitate the CSE youth clubs, and they were given economic incentives during the trial´s two-year intervention period to organize meetings every fortnight. Two years after the external support for the youth clubs ended, we conducted qualitative interviews with the facilitators in 15 of the 63 schools, interviews with some head teachers, and focus group discussions with guardians of adolescent girls.

Results

Whereas CHWs were generally supportive of teaching adolescents about contraception, some of the teachers stressed that abstinence was the most effective method to avoid pregnancy and diseases. The respondents’ diverging points of view did not affect their willingness to continue teaching CSE, including contraception. However, the youth club meetings were only continued in a few schools after the external support period ended. This was attributed to transfers of trained teachers and a lack of training among the remaining staff; lapse of moral support, resources and incentives; limited involvement of the school management in the CSE initiative; and attention shifting to other projects.

Conclusion

To ensure the sustainability of CSE initiatives for adolescents, emphasis should be placed on training several teachers in each school, and continued moral support and encouragement also appeared essential.

Trial registration: ISRCTN (ISRCTN12727868).
Knockout of AMPA receptor binding protein Neuron-specific gene 2 (NSG2) enhances associative learning and cognitive flexibility
Authors: Zimmerman Amber J. , Serrano-Rodriguez Antonio , Sun Melody , Wilson Sandy J. , Linsenbardt David N. , Brigman Jonathan L. , Weick Jason P.
Published: December 2024

The vast majority of gene mutations and/or gene knockouts result in either no observable changes, or significant deficits in molecular, cellular, or organismal function. However, in a small number of cases, mutant animal models display enhancements in specific behaviors such as learning and memory. To date, most gene deletions shown to enhance cognitive ability generally affect a limited number of pathways such as NMDA receptor- and translation-dependent plasticity, or GABA receptor- and potassium channel-mediated inhibition. While endolysosomal trafficking of AMPA receptors is a critical mediator of synaptic plasticity, mutations in genes that affect AMPAR trafficking either have no effect or are deleterious for synaptic plasticity, learning and memory. NSG2 is one of the three-member family of Neuron-specific genes (NSG1-3), which have been shown to regulate endolysosomal trafficking of a number of proteins critical for neuronal function, including AMPAR subunits (GluA1-2). Based on these findings and the largely universal expression throughout mammalian brain, we predicted that genetic knockout of NSG2 would result in significant impairments across multiple behavioral modalities including motor, affective, and learning/memory paradigms. However, in the current study we show that loss of NSG2 had highly selective effects on associative learning and memory, leaving motor and affective behaviors intact. For instance, NSG2 KO animals performed equivalent to wild-type C57Bl/6n mice on rotarod and Catwalk motor tasks, and did not display alterations in anxiety-like behavior on open field and elevated zero maze tasks. However, NSG2 KO animals demonstrated enhanced recall in the Morris water maze, accelerated reversal learning in a touch-screen task, and accelerated acquisition and enhanced recall on a Trace Fear Conditioning task. Together, these data point to a specific involvement of NSG2 on multiple types of associative learning, and expand the repertoire of pathways that can be targeted for cognitive enhancement.
Dynamic changes in the hippocampal neuronal circuits activity following acute stress revealed by miniature fluorescence microscopy imaging
Authors: Gerasimov Evgenii , Pchitskaya Ekaterina , Vlasova Olga , Bezprozvanny Ilya
Published: December 2024

Coordinated activity of neuronal ensembles is a basis for information processing in the brain. Recent development of miniscope imaging technology enabled recordings of neuronal circuits activity in vivo in freely behaving animals. Acute stress is believed to affect various hippocampal functions, especially memory. In the current study, we utilized miniscope imaging to investigate the hippocampal neuronal circuits properties in a mouse as function of time and immediately in response to an acute stress, induced by passive restraint, 3 h and 10 days after. Comprehensive quantitative analysis of network activity changes at the neuronal ensembles level revealed highly stable neuronal activity parameters, which exhibited a rapid and robust shift in response to acute stress stimulation. This shift was accompanied by the restructuring of the pairwise-correlated neuronal pairs. Remarkably, we discovered that ensembles activity characteristics returned to the initial state following recovery period, demonstrating hippocampal homeostatic stability at the neuronal circuits level. Obtained results provide an evidence about hippocampal neuronal ensembles activity in response to acute stress over time.
Parvovirus B19 infection in children: a comprehensive review of clinical manifestations and management
Authors: Bloise Silvia , Cocchi Enrico , Mambelli Lorenzo , Radice Caterina , Marchetti Federico
Published: December 2024

Parvovirus B19 (B19V) is a significant pathogen responsible for a wide range of clinical manifestations, particularly in children and pregnant women. While B19V is most commonly recognized as the cause of Fifth disease, a mild erythematous illness in children, its clinical impact extends far beyond this condition. B19V can lead to severe complications, including transient aplastic crisis in individuals with chronic hemolytic anemias, arthralgia, and more severe joint diseases. During pregnancy, B19V infection poses serious risks, such as spontaneous abortion, non-immune hydrops fetalis, and fetal anemia, particularly when infection occurs between 9 and 20 weeks of gestation. Moreover, B19V is associated with a variety of organ system involvements, including cardiac, neurological, hepatic, and renal complications. These manifestations can range from mild to life-threatening, necessitating a broad spectrum of therapeutic approaches, including symptomatic care, immunoglobulins, corticosteroids, and supportive therapies. Despite the significant clinical burden posed by B19V, no specific antiviral treatment or vaccine is currently available, making early recognition and prompt management crucial for improving patient outcomes. This review provides a comprehensive overview of the diverse clinical presentations of B19V infection, with a focus on pediatric and pregnancy-related complications. It underscores the need for ongoing research into targeted therapies and highlights the importance of vigilant clinical management to mitigate the severe consequences of this pervasive virus.
EpiGePT: a pretrained transformer-based language model for context-specific human epigenomics
Authors: Gao Zijing , Liu Qiao , Zeng Wanwen , Jiang Rui , Wong Wing Hung
Published: December 2024

The inherent similarities between natural language and biological sequences have inspired the use of large language models in genomics, but current models struggle to incorporate chromatin interactions or predict in unseen cellular contexts. To address this, we propose EpiGePT, a transformer-based model designed for predicting context-specific human epigenomic signals. By incorporating transcription factor activities and 3D genome interactions, EpiGePT outperforms existing methods in epigenomic signal prediction tasks, especially in cell-type-specific long-range interaction predictions and genetic variant impacts, advancing our understanding of gene regulation. A free online prediction service is available at http://health.tsinghua.edu.cn/epigept.
The NExT trial: Protocol for a two-phase randomized controlled trial testing transcranial magnetic stimulation to augment exposure therapy for youth with OCD
Authors: Conelea Christine , Breitenfeldt Claire , Wilens Alixandra , Carpenter Linda , Greenberg Benjamin , Herren Jennifer , Jacob Suma , Lewis Charles , McLaughlin Nicole , Mueller Bryon A. , Nelson Steve , O’Connor Erin , Righi Giulia , Widge Alik S. , Fiecas Mark , Benito Kristen
Published: December 2024

Background

Exposure with Response Prevention (ERP) is a first-line treatment for OCD, but even when combined with first-line medications it is insufficiently effective for approximately half of patients. Compulsivity in OCD is thought to arise from an imbalance of two distinct neural circuits associated with specific subregions of striatum. Targeted modulation of these circuits via key cortical nodes (dorsolateral prefrontal cortex [dlPFC] or presupplementary motor area [pSMA]) has the potential to improve ERP efficacy by decreasing compulsions during therapy.

Methods

The NExT (Neuromodulation + Exposure Therapy) trial is a two-phase, multisite early-stage randomized controlled trial designed to examine whether TMS augmentation of ERP alters activity in dlPFC and/or pSMA-associated circuitry and reduces compulsions during therapy in youth with OCD age 12–21 years. Phase 1 (N = 60) will compare two different active TMS regimens with sham: A. continuous theta burst stimulation (cTBS) to pSMA vs. B. intermittent theta burst stimulation (iTBS) to dlPFC. A priori “Go/No-Go” criteria will inform a decision to proceed to Phase 2 and the choice of TMS regimen. Phase 2 (N = 60) will compare the selected TMS regimen vs. sham in a new sample.

Discussion

This trial is the first to test TMS augmentation of ERP in youth with OCD. Results will inform the potential of TMS to enhance ERP efficacy and enhance knowledge about mechanisms of change.

Trial registration

ClinicalTrials.gov NCT05931913. Registered prospectively on July 5, 2023.
Strategies to improve recruitment in mental health clinical trials: a scoping review (RE-MIND study)
Authors: Iflaifel Mais , Hall Charlotte L. , Green Heidi R. , Willis Andrew , Rennick-Egglestone Stefan , Juszczak Edmund , Townsend Mark , Martin Jennifer , Sprange Kirsty
Published: December 2024

Background

Lower-than-expected recruitment continues to be one of the major causes of trial delays, and trials to improve mental health are no exception. Indeed, recruitment challenges in trials of vulnerable populations, such as those living with mental health illness, can even be exacerbated. To address this, researchers are turning to digital and online recruitment strategies, e.g. web-based approaches and multi-media in order to (1) increase recruitment efficiency (recruit to target and on time) and (2) improve diversity in mental health clinical trials to be more inclusive and reduce health inequity. There is, however, inconclusive evidence on the success of digital and online recruitment strategies in mental health clinical trials. The RE-MIND study comprised a scoping review to assess the impact of using such recruitment strategies in mental health clinical trials to inform a more systematic scoping review.

Methods

A cohort of 191 recently published RCTs and randomised feasibility studies were identified from the NIHR Journals Library and top two mental health journals (based on citation metrics), Lancet Psychiatry and JAMA Psychiatry. Population characteristics including gender, ethnicity and age were summarised for inclusivity using descriptive statistics, and recruitment strategies were compared to examine differences in their success in recruiting to target.

Results

After screening, 97 articles were included for review. The review findings showed no evidence that offline or mixed strategies were superior for achieving recruitment targets in mental health trials. However, there was a suggestion that trials using a mixed recruitment strategy improved inclusivity and tended to recruit closer to the target.

Conclusions

The key finding was that consideration should be given to a mixed methods approach to recruitment not only to enable wider and more diverse participation in mental health trials but also to realize greater efficiency.
Borrelia miyamotoi and Borrelia burgdorferi sensu lato widespread in urban areas of the Czech Republic
Authors: Balážová Alena , Václavík Tomáš , Baláž Vojtech , Široký Pavel
Published: December 2024

Background

Borrelia miyamotoi and Borrelia burgdorferi sensu lato (s.l.) are important zoonotic agents transmitted by Ixodes ricinus ticks, which are widely distributed across Central Europe. Understanding the spatial distribution of these pathogens’ prevalence will help identify areas with increased infection risk and facilitate the implementation of effective preventive measures.

Methods

We analysed 12,955 I. ricinus ticks collected from 142 towns in the Czech Republic between 2016 and 2018. The ticks were pooled into 2591 groups of five and tested using duplex quantitative polymerase chain reaction (qPCR) for the presence of B. burgdorferi s.l. and B. miyamotoi. For each location, we estimated the overall prevalence of both agents using the EpiTools Epidemiological Calculator for pooled samples and calculated the minimum infection rate (MIR). To assess the potential risk of infection, we combined data on the abundance of nymphs and females with pathogen prevalence at each sampled site. Using a geographic information system (GIS), we mapped the MIR and infection risk of both Borrelia species across all 142 sampled locations and employed a geostatistical method (ordinary kriging) to predict MIR values and infection risk as continuous surfaces across the entire country.

Results

We detected B. miyamotoi in 110 localities and B. burgdorferi s.l. in all 142 localities. The estimated prevalence of B. miyamotoi and B. burgdorferi s.l. in the collected ticks was 2.1% (95% confidence interval [CI] 1.8–2.3) and 27.1% (95% CI 26.0–28.3), respectively. For B. miyamotoi, we identified previously unknown, geographically distinct hotspots of MIR up to 8.3%, with MIR slightly higher in females (2.3%) than in males (1.9%) and nymphs (1.8%), though the difference was not statistically significant. In contrast, B. burgdorferi s.l. exhibited ubiquitous presence, with consistently high prevalence nationwide, showing similar MIRs in females (16.2%) and males (16.1%), and slightly lower in nymphs (15.6%). The highest infection risk for B. miyamotoi was 12.4 infected vectors per hour in southeastern Moravia, while the highest risk for B. burgdorferi s.l. reached 78.6 infected vectors per hour in the Bohemian-Moravian Highlands.

Conclusions

Borrelia miyamotoi is widespread, forming distinct high-prevalence areas in certain regions. Borrelia burgdorferi s.l. demonstrates consistently high prevalence across most of the country, except for a few localized areas such as southwestern Czechia. Both pathogens exhibit natural nidality, forming regions with elevated prevalence and infection risk. Long-term time-series data are needed to confirm the spatio-temporal stability of these hotspots.

Graphical Abstract
Hosts and vectors of scrub typhus in Chile: epidemiological study and molecular analyses of Orientia infection in rodents and rodent-associated mites
Authors: Martínez-Valdebenito Constanza , Acosta-Jamett Gerardo , Abello Rayitray , Jiang Ju , Richards Allen L. , Abarca Katia , Weitzel Thomas
Published: December 2024

Candidatus Orientia chiloensis causes scrub typhus over a wide geographical range in southern Chile. The life cycle, including vectors and reservoirs of this novel rickettsial pathogen, is incompletely understood. We analyzed rodent tissue and rodent-associated mite samples collected during a field study in six localities on Chiloé Island, where human scrub typhus cases have occurred. Using molecular methods, we detected Orientia DNA in 24.8% of rodents, belonging to five of seven captured species. Orientia-infection rates showed geographical variations, but were not influenced by rodent species, sex, age, and mite infestation. Phylogenetic analysis showed that Orientia sequences from trombiculid mites (Proschoengastia eloisae) were identical to those from scrub typhus patients from the same region. The results suggest that these rodent-associated mites serve as vectors and play an important role in the ecology of scrub typhus in southern Chile. Further studies are required to determine whether Orientia-infected rodents can also serve as reservoir of Orientia in Chile.

Graphical Abstract
Microfluidic chip systems for characterizing glucose-responsive insulin-secreting cells equipped with FailSafe kill-switch
Authors: Izadifar Mohammad , Massumi Mohammad , Prentice Kacey J. , Oussenko Tatiana , Li Biao , Elbaz Judith , Puri Mira , Wheeler Michael B. , Nagy Andras
Published: December 2024

Background

Pluripotent cell-derived islet replacement therapy offers promise for treating Type 1 diabetes (T1D), but concerns about uncontrolled cell proliferation and tumorigenicity present significant safety challenges. To address the safety concern, this study aims to establish a proof-of-concept for a glucose-responsive, insulin-secreting cell line integrated with a built-in FailSafe kill-switch.

Method

We generated β cell-induced progenitor-like cells (βiPLCs) from primary mouse pancreatic β cells through interrupted reprogramming. Then, we transcriptionally linked our FailSafe (FS) kill-switch, HSV-thymidine kinase (TK), to Cdk1 gene using a CRISPR/Cas9 knock-in strategy, resulting in a FailSafe βiPLC line, designated as FSβiPLCs. Subsequently we evaluated and confirmed the functionality of the drug-inducible kill-switch in FSβiPLCs at different ganciclovir (GCV) concentrations using our PDMS-based transcapillary microfluidic system. Finally, we assessed the functionality of FSβiPLCs by characterizing the dynamics of insulin secretion in response to changes in glucose concentration using our microfluidic perfusion glucose-stimulated insulin secretion (GSIS) assay-on- chip.

Results

The βiPLCs exhibited Ins1, Pdx1 and Nkx6.1 expression, and glucose responsive insulin secretion, the essential properties of pancreatic beta cells. The βiPLCs were amenable to genome editing which allowed for the insertion of the kill-switch into the 3’UTR of Cdk1, confirmed by PCR genotyping. Our transcapillary microfluidic system confirmed the functionality of the drug-inducible kill-switch in FSβiPLCs, showing an effective cell ablation of dividing cells from a heterogeneous cell population at different ganciclovir (GCV) concentrations. The Ki67 expression assessment further confirmed that slow- or non-dividing cells in the FSβiPLC population were resistant to GCV. Our perfusion glucose-stimulated insulin secretion (GSIS) assay-on-chip revealed that the resistant non-dividing FSβiPLCs exhibited higher levels of insulin secretion and glucose responsiveness compared to their proliferating counterparts.

Conclusions

This study establishes a proof-of-concept for the integration of a FailSafe kill-switch system into a glucose-responsive, insulin-secreting cell line to address the safety concerns in stem cell-derived cell replacement treatment for T1D. The microfluidic systems provided valuable insights into the functionality and safety of these engineered cells, demonstrating the potential of the kill-switch to reduce the risk of tumorigenicity in pluripotent cell-derived insulin-secreting cells.
Matrix-free human lung organoids derived from induced pluripotent stem cells to model lung injury
Authors: Budeus Bettina , Kroepel Chiara , Stasch Lisa Marie , Klein Diana
Published: December 2024

Background

Organoids, as near-physiological 3D culture systems, offer new opportunities to study the pathogenesis of various organs in mimicking the cellular complexity and functionality of human organs.

Method

Here we used a quite simple and very practicable method to successfully generate induced pluripotent stem cell (iPSC)-derived human lung organoids (LuOrg) in a matrix-free manner as an alternative to the widely used preclinical mouse models in order to investigate normal lung damage in detail and as close as possible to the patient. We performed detailed morphological and molecular analyses, including bulk and single cell RNA sequencing, of generated lung organoids and evaluated the quality and robustness of our model as a potential in vitro platform for lung diseases, namely radiation-induced lung injury.

Results

A matrix-free method for differentiation of iPSCs can be used to obtain lung organoids that morphologically reflect the target tissue of the human lung very well, especially with regard to the cellular composition. The different cellular fates were investigated following the genotoxic stress induced by radiation and revealed further insights in the radiation-sensitivity of the different lung cells. Finally, we provide cellular gene sets found to be induced in the different lung organoid cellular subsets after irradiation, which could be used as additional RT response and particularly senescence gene sets in future studies.

Conclusion

By establishing these free-floating LuOrgs for the investigation of cancer therapeutic approaches as a new and patient-oriented in vitro platform particularly in experimental radiooncology, not only a reduction in the number of experimental animals, but also an adequately and meaningfully replacement of corresponding animal experiments can be achieved.