bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of endovascular thrombectomy in patients with cerebral venous thrombosis: A cohort study of 325 patients
Authors: Malhotra Aryan , Jain Ankita , Spirollari Eris , Kaddoura Rachid , Arthur Melinda Christine , Sacknovitz Ariel , Nawaiseh Mohammed B , Medicherla Chaitanya , Kaur Gurmeen , Gandhi Chirag D , Al-Mufti Fawaz
Published: February 2025

Background

Cerebral venous thrombosis (CVT) is a rare condition that presents with significant treatment challenges and has traditionally been managed with anticoagulation. However, for patients who fail anticoagulation or present with severe symptoms, endovascular thrombectomy (EVT) has emerged as a favorable treatment modality. This study examines the outcomes, complications, and comorbidities associated with EVT in patients with CVT.

Methods

A query of the 2015-2019 National (Nationwide) Inpatient Sample was performed for patients admitted to hospitals with ICD-10 diagnosis codes for CVT and ICD-10 procedure codes for usage of EVT. Demographic information, baseline comorbidities, complications, and discharge dispositions were compared between patients who underwent EVT and those who were managed medically.

Results

A total of 36,005 patients diagnosed with CVT were identified from 2015(Q4) to 2019. Of these patients, 325 (0.9%) received EVT. Patients who underwent EVT were older (<0.001), more likely to be female (p = 0.016), and had higher rates of diabetes mellitus (p = 0.012), hypertension (p < 0.001), and obesity (p < 0.001). These patients also presented with more severe neurological symptoms, including higher National Institutes of Health Stroke Scale scores (p < 0.001), coma (p < 0.001), and cerebral edema (p < 0.001). Patients undergoing EVT had a higher incidence of in-hospital mortality (p = 0.007) and were less likely to be discharged routinely (p < 0.001).

Conclusions

This study found that patients with CVT who underwent EVT were older, more likely to be female, and presented with more severe neurological conditions. After controlling for severity, EVT in patients with CVT was associated with significant risks, including higher rates of complications and inpatient mortality. Although EVT is associated with significant risks, the findings of this study suggest that its outcomes may reflect the severity of the underlying condition rather than the procedure itself. Careful patient selection and individualized management strategies are essential for optimizing outcomes in this high-risk population.
Quest for the optimal venous access in a complex skull base dural fistula: Case illustrations and principles
Authors: Almallouhi Eyad , Sattur Mithun G. , Abo Kasem Rahim , Muthana Ahmed , Wood Robert E. , Spiotta Alejandro M.
Published: February 2025

Treatment of dural arteriovenous fistulae (DAVFs) is dynamic and evolves between diagnostic and therapeutic angiography.

A 79-year-old man with a left jugular foramen DAVF presented with new onset cranial nerve XII palsy. The DAVF progressed from Cognard grade I to IIa + b. A transvenous approach was chosen. Attempts to access the left inferior petrosal sinus (IPS) via the left internal jugular vein failed due to occlusion. An alternative route through the left superior ophthalmic vein and left cavernous sinus to the IPS was devised. Successful coil occlusion of the IPS was achieved. Postoperatively, symptoms resolved, and angiography showed no cortical venous reflux.
Panic attacks
Authors: Chandio Rida Rauf , Rashid Ujala Sadaf
Published: February 2025

A panic attack is a sudden, intense episode of anxiety and fear that often occurs without warning. It may be accompanied by severe physical symptoms, such as a racing heart, rapid breathing and sweating. The exact cause of panic attacks is unknown, but risk factors have been identified. Recurring unexpected panic attacks over a period of 4 weeks is termed panic disorder. Panic attacks that occur in specific situations or scenarios are known as phobias, including agoraphobia and social phobia, and are commonly seen in patients with panic disorder. This article gives an overview of panic attacks, their assessment, criteria for diagnosis and an approach to management in primary care.
Perineural Invasion Unveiled: Deciphering the Prognostic Impact of Diameter and Quantity Subcategories in Oral Cancer
Authors: Cheng Hui-Wen , Lin Li-Han , Lin Hung-Pin , Liu Chung-Ji
Published: February 2025

Importance

Perineural invasion (PNI) is an established prognostic factor in oral squamous cell carcinoma (OSCC), but the impact of its subcategories on survival is not fully understood. This study quantifies the number and diameter of PNI foci to assess their prognostic relevance in OSCC.

Objective

To evaluate the prognostic significance of PNI subcategories, specifically the number and diameter of PNI foci, as predictors of overall survival (OS) and disease-free survival (DFS) in OSCC patients.

Design

Retrospective cohort study, adhering to STROBE guidelines.

Setting

Single-center study at MacKay Memorial Hospital, Taiwan, including patients diagnosed with OSCC from 2005 to 2018.

Participants

Nine hundred twenty-six patients with biopsy-proven OSCC, excluding those with perioperative mortality or incomplete follow-up.

Exposure

Histological evaluation of PNI, including quantifying the number and diameter of invaded nerves, along with clinicopathological features such as tumor stage and lymphovascular invasion (LVI).

Main Outcome Measures

OS and DFS, assessed via Cox proportional hazards models, Kaplan–Meier survival analysis, and receiver operating characteristic curve analysis for PNI foci subcategories.

Results

PNI was present in 138 (14.9%) patients and was significantly associated with adverse histologic features, advanced tumor stage, nodal involvement, metastasis, and LVI. Multivariate analysis revealed that both the number of PNI foci greater than 4 and nerve diameters exceeding 0.21 mm were significantly associated with poorer OS and DFS ( P < .05). After adjusting for clinical variables, PNI remained an independent predictor of worse OS [hazard ratio (HR): 1.37] and DFS (HR: 1.46).

Conclusions and Relevance

PNI is a significant independent prognostic factor in OSCC. Patients with more than 4 PNI foci or nerve involvement greater than 0.21 mm in diameter experienced significantly worse survival outcomes. These findings suggest that detailed assessment of PNI subcategories should be incorporated into OSCC management, guiding treatment decisions and potentially informing the need for adjuvant therapies.
Dialogues among ‘necrolocutors’ and fugitives
Authors: Ruette-Orihuela Krisna
Published: February 2025

This exploratory commentary invites readers to situate ‘the necrolocutor’ in dialogue with ‘the fugitive’ – an agent uncovered by Fred Moten and Stephano Harney in The Undercommons: Fugitive Planning and Black Study (Harney and Moten, 2013). I aim to briefly examine how the necrolocutor not only administers power, knowledge, and death (in line with the ant logic carefully dissected by Gibson) but also co-produces multiple scales and modes of fugitivity, refusing to engage in participatory practices.
Effects of a 12-week digital training equipment program on cognitive function and mental health in older women: a randomized controlled trial
Authors: Lee Byung-Sun , Choi Bong Du , Park Ho Sung , Seo Chae Won , Kim Kyung-Ae
Published: February 2025

Objective

Combined interventions of physical activity and cognitive training have been shown to effectively enhance physical and mental factors in older adults. Digital-based tools offer various social advantages and may be more effective in improving the physical and mental well-being of older adults. As digital health content can simultaneously provide physical activity and cognitive training, this study aims to investigate the effects of a digital-based physical and cognitive training program on the physical and mental health of older women and to explore the potential of digital tools for older adults.

Methods

The participants, older women, engaged in the program three times a week for 12 weeks, with each session lasting 30 minutes (10 minutes for each of the three components). The content included digital health tools such as VR, motion tracking, and touchscreens designed for cognitive and physical fitness. Measurements were taken one week before and after the intervention for both groups, assessing body composition, cognitive function, depression, and quality of life.

Results

Data from 36 participants were analyzed. Interaction effects were observed in body fat mass ( P = .011) and body fat percentage ( P = .01), with improvements noted in the digital intervention group. Cognitive function ( P = .017) and depression ( P = .017) also showed significant improvements in the digital intervention group. Quality of life subdomains, including Physical Function ( P = .009), Limitation of Physical Function ( P = .004), and Pain ( P = .002), demonstrated significant interaction effects, though no interaction effects were found in other subdomains.

Conclusion

This study found that digital-based combined interventions did not significantly impact body comb position but did improve cognitive function and depression in older women. These findings suggest that digital tools can be effectively utilized for the comprehensive management of cognitive function and mental health well-being. Such insights contribute to promoting healthy aging and provide an efficient method for managing the mental and physical health of older adults.
Cost-effectiveness of the Floodlight® MS app in Austria. Unlocking the mystery of costs and outcomes of a digital health application for patients with multiple sclerosis
Authors: Walter Evelyn , Traunfellner Matthäus , Meyer Franz , Enzinger Christian , Guger Michael , Bsteh Christian , Altmann Patrick , Hegen Harald , Goger Christoph , Mikl Veronika
Published: February 2025

Objective

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting 2.9 million people worldwide, often leading to permanent disability. MS patients frequently use eHealth tools due to their relatively young age. The Floodlight® MS app is a scientifically designed smartphone application that helps patients monitor hand motor skills, walking ability and cognition between medical appointments. This study assesses the cost-effectiveness of using the Floodlight® MS app alongside standard-of-care (SoC) versus SoC alone in patients with relapsing-remitting MS (RRMS) from the perspective of the healthcare system.

Methods

A 10-year decision-analytic model was developed to assess the cost-effectiveness of incorporating the Floodlight® MS app alongside SoC. The analysis included treatment-naive individuals and those already on drug therapy, modelling the app's role in early detection of disease progression and relapses to improve quality-of-life.

Results

For treatment-naive patients, using the Floodlight® MS app resulted in a 2,660 € increase in total costs but yielded potential medical-cost savings of 786 € through health improvements. These patients experienced fewer relapses and slower disability progression, translating to a quality-of-life improvement of 4.5 months in perfect health and an incremental-cost-effectiveness-ratio (ICER) of 7,071 €. Pre-treated patients showed similar trends, with medical-cost savings of 718 €, an ICER of 7,864 €, and a quality-of-life improvement of 4.2 months. Higher effectiveness (+5%) led to an additional 8.3 months in perfect health and a reduction in overall costs.

Conclusion

The analysis demonstrates that the Floodlight® MS app is a cost-effective digital health application, encouraging broader discussions on maximizing the potential of software-as-medical-devices within the care pathway.
Is the Welfare State Bad for Citizens’ Moral Character? Beliefs and Evidence
Authors: Eriksson Kimmo , Simpson Brent
Published: February 2025

Conservative thinkers have long warned that the welfare state may weaken society’s moral fiber. But this claim has not been empirically examined. The authors link publicly available data on the sizes of welfare states with behavioral data from a recent study in which thousands of lost wallets were distributed in 40 countries to measure how often they were returned to their owners. A preregistered study ( n = 194) confirmed that U.S. Republicans perceive returning lost wallets as a good indicator of moral character and believe that people’s moral character is worse in countries where the welfare state is larger. Contrary to this belief, the linked data indicate a strong positive relationship between the size of welfare states and moral character: rates of returned wallets were higher in countries with historically large welfare states, net of economic prosperity and economic inequality. The authors conclude with tentative implications and suggestions for further work.
Durable responses to immune checkpoint inhibitor-based regimens for metastatic clear cell renal cell carcinoma stratified by IMDC risk groups: A pooled analysis of four randomized phase 3 trials
Authors: Jang Albert , Zhong Jeffrey Y. , Kumar Hamsa L.S. , Zarrabi Kevin K. , Zhu Alec , Grier Abby L. , Calaway Adam , Shoag Jonathan E. , Bukavina Laura , Jia Angela Y. , Mendiratta Prateek , Sheng Iris Y. , Rao Santosh , Brown Jason R. , Garcia Jorge A. , Margevicius Seunghee , Fu Pingfu , Barata Pedro C.
Published: February 2025

Background

An immune checkpoint inhibitor (ICI) backbone is a standard of care for frontline metastatic clear cell renal cell carcinoma, involving either ICI doublet or tyrosine kinase inhibitor (TKI) with ICI. These phase 3 trials used a sunitinib control arm. The optimal regimen is uncertain.

Objective

To compare long-term responders of these trials using extended follow-up data stratified by International Metastatic RCC Database Consortium risk group.

Methods

Phase 3 trial data (CheckMate 214, KEYNOTE-426, CheckMate 9ER, and CLEAR) with a minimum follow-up of four years was used. Pseudo individual patient data (IPD) was obtained from Kaplan-Meier curves using the graph digitizer software IPDfromKM R package to extract coordinates of points on the curves and to apply a numerical algorithm to reconstruct progression-free survival (PFS) and overall survival (OS) results. Durable response (DR) was defined as PFS ≥ 24 months, extreme durable response (EDR) as PFS ≥ 36 months, and long-term OS as OS ≥ 48 months.

Results

For the favorable risk group, lenvatinib-pembrolizumab had the highest DR and EDR, while ipilimumab-nivolumab had the lowest DR, and cabozantinib-nivolumab had the lowest EDR; there was no difference in long-term OS among the regimens ( p = 0.11). For the intermediate/poor risk group, lenvatinib-pembrolizumab also had the highest DR and EDR compared to other regimens with similar DR and EDR; there was also no difference in long-term OS among the regimens ( p = 0.22).

Conclusion

TKI-ICI was overall associated with higher DR and EDR regardless of risk status compared to ICI doublet. Yet, OS at 48 months were similar when stratified by favorable versus intermediate/poor risk.
Mitochondrial-ER Contact Sites and Tethers Influence the Biosynthesis and Function of Coenzyme Q
Authors: Novales Noelle Alexa , Meyer Hadar , Asraf Yeynit , Schuldiner Maya , Clarke Catherine F.
Published: February 2025

Coenzyme Q (CoQ) is an essential redox-active lipid that plays a major role in the electron transport chain, driving mitochondrial ATP synthesis. In Saccharomyces cerevisiae (yeast), CoQ biosynthesis occurs exclusively in the mitochondrial matrix via a large protein-lipid complex, the CoQ synthome, comprised of CoQ itself, late-stage CoQ-intermediates, and the polypeptides Coq3-Coq9 and Coq11. Coq11 is suggested to act as a negative modulator of CoQ synthome assembly and CoQ synthesis, as its deletion enhances Coq polypeptide content, produces an enlarged CoQ synthome, and restores respiration in mutants lacking the CoQ chaperone polypeptide, Coq10. The CoQ synthome resides in specific niches within the inner mitochondrial membrane, termed CoQ domains, that are often located adjacent to the endoplasmic reticulum-mitochondria encounter structure (ERMES). Loss of ERMES destabilizes the CoQ synthome and renders CoQ biosynthesis less efficient. Here we show that deletion of COQ11 suppresses the respiratory deficient phenotype of select ERMES mutants, results in repair and reorganization of the CoQ synthome, and enhances mitochondrial CoQ domains. Given that ER-mitochondrial contact sites coordinate CoQ biosynthesis, we used a Split-MAM (Mitochondrial Associated Membrane) artificial tether consisting of an ER-mitochondrial contact site reporter, to evaluate the effects of artificial membrane tethers on CoQ biosynthesis in both wild-type and ERMES mutant yeast strains. Overall, this work identifies the deletion of COQ11 as a novel suppressor of phenotypes associated with ERMES deletion mutants and indicates that ER-mitochondria tethers influence CoQ content and turnover, highlighting the role of membrane contact sites in regulating mitochondrial respiratory homeostasis.
Experiences With a Novel Micro-Choice-Based Concentrated Group Intervention for People With Type 2 Diabetes: A Qualitative Study
Authors: Bendixen Bente Elisabeth , Wilhelmsen-Langeland Ane , Lomborg Kirsten , Måkestad Eirin , Skogheim Trine L. , Schønberg Anne , Iversen Marjolein M. , Kvale Gerd , Søfteland Eirik , Haugstvedt Anne
Published: February 2025

Purpose:

The purpose of this study was to explore experiences with an interdisciplinary micro-choice-based concentrated group intervention for people with type 2 diabetes.

Methods:

A qualitative study with individual semistructured interviews were conducted with 14 adults (8 women, ages 45-74 years) with type 2 diabetes. Purposive sampling was used, and participants from 3 different intervention groups in the micro-choice-based concentrated group intervention were recruited. Thematic analysis was used for the data analysis.

Results:

Three main themes were identified: (1) group intervention tailored to individual needs through friendly and skilled professionals, (2) valuable social interactions and an experience of fellowship, and (3) commitment to change through goal setting and conscious micro-choices. The participants described a readiness for change that was met by important knowledge from skilled professionals in the concentrated intervention. They reported that new knowledge, particularly about micro-choices and the focus on how insulin works in the body, led to change in their awareness and self-management. The concentrated group intervention was a preferred setting that contained a sense of community without compromising on meeting individual needs. Participants described internalized changes after the intervention and a willingness to adhere to changes necessary for their self-management.

Conclusion:

Study findings showed that a micro-choice-based concentrated group intervention for people with type 2 diabetes can be a valuable approach contributing to improved patient activation and diabetes self-management. The findings underpin the importance of increased diabetes knowledge and support from an interprofessional team to bring about significant changes in everyday life.
Does the “state of disaster” response have a downside? Hospital incident command group leaders’ experiences of a terrorist-induced major incident: a qualitative study
Authors: Murphy Jason P. , Hörberg Anna , RN Monica Rådestad , Kurland Lisa , Jirwe Maria
Published: February 2025

Aim

This study explores HICGs’ experience of disaster response during a terrorist-induced major incident major incident.

Design

A qualitative descriptive design with individual semi-structured interviews was used.

Methods

This was a qualitative study based on seven individual interviews. Participants were members of hospital incident command groups during a terror attack. The interviews were transcribed verbatim and analyzed using deductive content analysis. The SRQR checklist was used to report the findings.

Results

The data created from the interviews identified barriers and facilitators for hospital response as well as aligned with previously established categories: Expectations, prior experience, and uncertainty affect hospital incident command group response during a Major Incident and three categories, (I) Gaining situational awareness (containing two subcategories), (II) Transitioning to management (containing three subcategories) and (III) Experiences of hospital incident command group response (containing two subcategories). In addition, the results suggest that an exaggerated response may have led to unanticipated adverse events.

Clinical trial number

Not applicable.
Strengthening identification and characterization of causes of perinatal deaths in Kaski district of Nepal (Perinatal MITS Nepal)
Authors: Subedi Nuwadatta , Ranabhat Sunita , Regmi Sanjib Mani , Mallik Mukesh , Singh Dela , Shrestha Shree Krishna , Gurung Bandana , Bhattarai Arjun , Baral Madan Prasad , Parajuli Sudhir Raman , Bastola Ramchandra , Shrestha Junu , Basnet Sahisnuta , Gauchan Eva , Paudel Sabita
Published: February 2025

Background

Three million babies die in the early neonatal period while 2.6 million are stillborn per year worldwide, and one of three deaths can be prevented. The perinatal mortality rate in Nepal is around 31 per 1000 births. Although the perinatal and neonatal death rates have decreased recently, it still poses a major challenge to the health system of Nepal. The objective of the study is to determine the causes of perinatal deaths by integrating Minimally Invasive Tissue Sampling (MITS) in hospital perinatal deaths and incorporating verbal autopsy in community deaths in Kaski district of Nepal.

Methods

The study will be conducted among the perinatal deaths reported in the five hospitals implementing the Maternal and Perinatal Death Surveillance and Response (MPDSR) system in Kaski district of Nepal. We will also conduct verbal autopsy (VA) among community perinatal deaths reported in the district. All the perinatal deaths reported in the study sites will be enrolled in the first stage of the study. Minimally Invasive Tissue Sampling (MITS) will be conducted among the consenting cases of perinatal deaths to retrieve relevant tissue samples and specimens. The specimens will undergo standard histopathological, microbiological, biochemical, and molecular tests. The “Cause of Death Panel” will finalize MITS informed cause of death following the customized protocol for the project and the cause so derived will be compared with that obtained by the review of deaths by the MPDSR committees of the hospitals. The Female Community Health Volunteers will be trained and mobilized to identify community perinatal deaths and trained personnel will conduct VA. Community engagement activities will be conducted to provide awareness to prevent perinatal deaths.

Discussion

The mechanism of counting and accounting for deaths in a systematic manner is important and it can provide evidence to determine changes in clinical practice and to develop guidelines and training packages for preventive measures. The outcome will be helpful to standardize methods to establish the accurate causes of perinatal deaths and develop strategies to minimize the deaths. The selected pathological investigations can be integrated into the existing death surveillance system in order to effectively determine the causes of death.
Subclinical systolic dysfunction in children with steroid-resistant nephrotic syndrome identified by speckle tracking echocardiography
Authors: Mahgoob Mohamed Hashem , Setouhi Amr Mostafa
Published: February 2025

Background

Steroid resistant nephrotic syndrome (SRNS) is a clinical phenotype of nephrotic syndrome (NS) that does not respond to steroid therapy and usually results in kidney failure. The aim of this study was to determine whether children with SRNS have subclinical left ventricular systolic dysfunction and, if so, to identify the risk factors for myocardial involvement in those children.

Methods

This prospective case-control study included of 35 children with SRNS, 40 children in the healthy control group, and 40 children with NS during the initial episode as the diseased control group. Conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography (STE) were performed on all the studied children.

Results

No statistically significant difference in conventional echocardiography’s parameters were detected between the patient and control groups. TDI revealed that the E/E′ ratio was significantly greater in the SRNS group than in both the healthy and diseased control groups (P = 0.001). The left ventricle global longitudinal strain (LV GLS) was markedly lower in children with SRNS than in healthy controls and NS patients (the diseased controls) (P = 0.001). Multiple binary regression analysis for the predictors of systolic dysfunction in SRNS patients revealed that the serum albumin is the only variable that predicts systolic dysfunction in these children.

Conclusions

Subclinical systolic and diastolic LV dysfunction should be screened in NS especially SRNS children.
Food choice motivations and perceptions of healthy eating: a cross-sectional study among consumers in the UAE
Authors: Cheikh Ismail Leila , Osaili Tareq M. , Obaid Reyad Shaker , Hashim Mona , Ahmed Marya , Al-Fayadh Fatma , Farah Aisha , Sad Hanin , Alghanem Humood , Mohamad Maysm N. , Saleh Sheima T. , Al Daour Rameez , Masuadi Emad , Stojanovska Lily , Ali Habiba I. , Al Dhaheri Ayesha S.
Published: February 2025

Background

Investigating consumer food choice motivations is crucial for planning effective policies and targeted interventions. This study aimed to examine the food choice motivations and perceptions of healthy eating among adults in the United Arab Emirates (UAE) and to segment consumers based on their motivations.

Methods

A web-based, cross-sectional study was conducted among adults in the UAE (n = 1209). An overall perception of healthy eating score was calculated based on the sum of the responses to the perception statements. Food motivation scores were calculated with a higher score indicating more influence of the food motivation group. Hierarchical Cluster Analysis (HCA) and K-means cluster analysis were used to identify and determine the optimal number of clusters. Differences between clusters were evaluated using an Independent sample t-test, One-Way ANOVA test, and Chi-square analysis.

Results

Participants mostly agreed that a healthy diet should be balanced, varied, and complete (84.4%), that fruit and vegetables are essential to a practice of healthy eating (82.8%), and that they can eat everything as long as it is in small quantities (60.1%). Females, younger adults, those with higher education levels, and those with normal BMI tended to have a slightly more positive perception of a healthy diet than their counterparts (p < 0.05). Health motivation (mean = 3.43, SD ± 0.78) exhibited the highest influence on the participants’ food choices, followed by emotional motivations (mean = 3.26, SD ± 0.68). Health-related motivations mainly influenced food choices among participants in both identified clusters but were notably more emphasised in Cluster 1. Cluster 1 demonstrated significantly higher mean scores in all other categories than Cluster 2 (p < 0.001). Cluster 1 encompasses more female participants than males, while Cluster 2 comprises a more significant proportion of males and individuals falling within higher income brackets (p < 0.001).

Conclusions

The results of the current study offer valuable insights into various crucial aspects that impact the decisions of individuals' food choices. Based on distinct motivational structures identified through cluster analysis, personalised approaches can encourage healthier dietary practices. A holistic approach acknowledging emotional, economic, environmental, alongside health-related factors is vital.
Adolescent girls’ explanations of high rates of low mood and anxiety in their population: a co-produced qualitative study
Authors: Demkowicz Ola , Jefferson Rebecca , Nanda Pratyasha , Foulkes Lucy , Lam Jo , Pryjmachuk Steven , Evans Rhiannon , Dubicka Bernadka , Neill Liz , Winter Laura Anne , Nnamani Georgina
Published: February 2025

Background

From early adolescence, girls face greater risk of experiencing low mood and anxiety relative to boys, with recent evidence that this may be worsening. There is a paucity of mental health research that meaningfully progresses understanding of these gender disparities, including that engages adolescent girls’ own perspectives, limiting our ability to direct further research and enhance intervention approaches.

Aims

We examined low mood and anxiety from the perspective of adolescent girls, asking: What do adolescent girls perceive to be causing their population’s high rates of low mood and anxiety?

Methods

We adopted a co-produced qualitative design, guided by ecological systems theory, conducting focus groups in 2022 with 32 adolescent girls aged 16 to 18 years in England. Data were analysed using reflexive thematic analysis.

Analysis

Participants framed low mood and anxiety among adolescent girls as “normal”, and discussed potential explanations including persistent reiteration and expectation of gendered norms, intense educational pressures in ways that can be gendered, difficulties within peer relationships, and comparison and insecurity in social media contexts. Throughout, participants highlighted how complex these issues are, including nuances around individual differences, sociodemographic contexts, and societal contexts.

Conclusions

The study offers a critically important contribution to evidence on gendered inequalities in low mood and anxiety, drawing attention to the interwoven and complex nature of girls’ lives and illuminating various aspects that would benefit from greater research. The insights gained through exploration with girls themselves hold policy and practical relevance to enhance systems to meet girls’ needs.
Heterochrony in orthodenticle expression is associated with ommatidial size variation between Drosophila species
Authors: Torres-Oliva Montserrat , Buchberger Elisa , Buffry Alexandra D. , Kittelmann Maike , Guerrero Genoveva , Sumner-Rooney Lauren , Gaspar Pedro , Bullinger Georg C. , Jimenez Javier Figueras , Casares Fernando , Arif Saad , Posnien Nico , Nunes Maria D. S. , McGregor Alistair P. , Almudi Isabel
Published: February 2025

Background

The compound eyes of insects exhibit extensive variation in ommatidia number and size, which affects how they see and underlies adaptations in their vision to different environments and lifestyles. However, very little is known about the genetic and developmental bases of differences in eye size. We previously showed that the larger eyes of Drosophila mauritiana compared to D. simulans are generally caused by differences in ommatidia size rather than number. Furthermore, we identified an X-linked chromosomal region in D. mauritiana that results in larger eyes when introgressed into D. simulans.

Results

Here, we used a combination of fine-scale mapping and gene expression analysis to further investigate positional candidate genes on the X chromosome. We found earlier expression of orthodenticle (otd) during ommatidial maturation in D. mauritiana than in D. simulans, and we show that this gene is required for the correct organisation and size of ommatidia in D. melanogaster. We discovered that the activity of an otd eye enhancer is consistent with the difference in the expression of this gene between species, with the D. mauritiana enhancer sequence driving earlier expression than that of D. simulans. When otd expression is driven prematurely during D. melanogaster eye development, the ommatidia grow larger, supporting a possible role for the timing of otd expression in regulating ommatidial size. We also identified potential direct targets of Otd that are differentially expressed between D. mauritiana and D. simulans during ommatidial maturation.

Conclusions

Taken together, our results suggest that differential timing of otd expression may contribute to natural variation in ommatidia size between D. mauritiana and D. simulans, which provides new insights into the mechanisms underlying the regulation and evolution of compound eye size in insects.
Transitioning from wet lab to artificial intelligence: a systematic review of AI predictors in CRISPR
Authors: Abbasi Ahtisham Fazeel , Asim Muhammad Nabeel , Dengel Andreas
Published: February 2025

The revolutionary CRISPR-Cas9 system leverages a programmable guide RNA (gRNA) and Cas9 proteins to precisely cleave problematic regions within DNA sequences. This groundbreaking technology holds immense potential for the development of targeted therapies for a wide range of diseases, including cancers, genetic disorders, and hereditary diseases. CRISPR-Cas9 based genome editing is a multi-step process such as designing a precise gRNA, selecting the appropriate Cas protein, and thoroughly evaluating both on-target and off-target activity of the Cas9-gRNA complex. To ensure the accuracy and effectiveness of CRISPR-Cas9 system, after the targeted DNA cleavage, the process requires careful analysis of the resultant outcomes such as indels and deletions. Following the success of artificial intelligence (AI) in various fields, researchers are now leveraging AI algorithms to catalyze and optimize the multi-step process of CRISPR-Cas9 system. To achieve this goal AI-driven applications are being integrated into each step, but existing AI predictors have limited performance and many steps still rely on expensive and time-consuming wet-lab experiments. The primary reason behind low performance of AI predictors is the gap between CRISPR and AI fields. Effective integration of AI into multi-step CRISPR-Cas9 system demands comprehensive knowledge of both domains. This paper bridges the knowledge gap between AI and CRISPR-Cas9 research. It offers a unique platform for AI researchers to grasp deep understanding of the biological foundations behind each step in the CRISPR-Cas9 multi-step process. Furthermore, it provides details of 80 available CRISPR-Cas9 system-related datasets that can be utilized to develop AI-driven applications. Within the landscape of AI predictors in CRISPR-Cas9 multi-step process, it provides insights of representation learning methods, machine and deep learning methods trends, and performance values of existing 50 predictive pipelines. In the context of representation learning methods and classifiers/regressors, a thorough analysis of existing predictive pipelines is utilized for recommendations to develop more robust and precise predictive pipelines.
Acid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathway
Authors: Yuan Huiqi , Xu Yanan , Jiang Hailun , Jiang Meizhu , Zhang Luofei , Wei Shifeng , Li Cao , Zhao Zhigang
Published: February 2025

Recent studies have shown that abnormal activity of acid sphingomyelinase (Asm) has been associated with a range of psychiatric disorders including schizophrenia and depression. However, the role of Asm in the regulation of anxiety remains unclear. In the present study, we employed Asm-knockout (Asm KO) mice to investigate the association between Asm and anxiety using behavioral tests, RNA sequencing, q-PCR, immunohistochemical staining, and other methods. The behavioral results showed that Asm KO mice exhibit enhanced anxiety-like behaviors, such as restricted activity, reduced cumulative times in the central area, diminished exploratory interest, delayed latency to feed, through behavioral tests including open field, novelty-suppressed feeding test, elevated plus maze test, ect. Transcriptional profiling combined with bioinformatics analysis revealed the upregulation of Toll-like receptor signaling pathway related gene including Tlr1/2, Ccl3, Ccl4, Ccl5 and Cd86 in Asm KO mice, which was further confirmed by the detection of activated microglia and astrocytes through iba-1 and GFAP immunohistochemical staining. Collectively, our findings uncover a role for Asm in regulating anxiety-like behavior and suggest that it may be essential for the maintenance of emotional stability, indicating its potential as a promising target for treating anxiety disorders.
Learn from international recommendations and experiences of countries that have successfully implemented monoclonal antibody prophylaxis for prevention of RSV infection
Authors: Manti Sara , Baraldi Eugenio
Published: February 2025

Respiratory syncytial virus (RSV)-mediated bronchiolitis causes a significant global health burden. Despite this, for several years, the only approved agent for RSV prophylaxis was the anti-RSV monoclonal antibody Palivizumab, reserved for a small population of infants at high risk of developing severe RSV disease. Recently, the availability and approval of nirsevimab to immunize all infants against RSV infection since their first RSV season represented a crucial paradigm shift in RSV prevention. Nirsevimab has been shown to be safe and effective (> 80%) against RSV lower respiratory tract infections (LRTIs) in all infants and children at their first season of RSV. Surveillance studies have demonstrated 90% effectiveness in reducing all-cause hospitalizations, all-cause LRTI hospitalizations, RSV-related LRTI hospitalizations, and severe RSV-related LRTIs. Moreover, the consistency and reproducibility of the beneficial outcomes coming from the prophylaxis with nirsevimab highlights its potential to deliver substantial health benefits, positioning monoclonal antibody administration as a cornerstone in the fight against RSV-related morbidity and mortality. Implementing immunization strategies for infants and children is crucial to align the international experiences and guarantee universal protection. This review provided an updated overview of the monoclonal antibody strategy for preventing RSV infection.
Bioassays for the evaluation of the attractiveness of attractive targeted sugar bait (ATSB) against Anopheles mosquitoes in controlled semi-field systems
Authors: Tenywa Frank S. C. , Kibondo Ummi A. , Entwistle Julian , Dogan Osward , Haruna Mapipi , Phisoo Restuta P. , Moore Jason , Machange Jane J. , Makame Haji , Tripet Frederic , Müller Pie , Mondy Mathias , Nimmo Derric , Stevenson Jennifer C. , Moore Sarah J.
Published: February 2025

Background

Sugar feeding is an essential aspect of mosquito biology that may be exploited for mosquito control by adding insecticides to sugar attractants, so-called ‘attractive targeted sugar baits’ (ATSBs). To optimize their effectiveness, ATSB products need to be maximally attractive at both short and long range and induce high levels of feeding. This study aimed to assess the attractiveness and feeding success of Anopheles mosquitoes exposed to attractive sugar baits (ASBs).

Method

Experiments were conducted in 2 × 5 × 2-m cages constructed within the semi-field systems (SFS) at Ifakara Health Institute, Bagamoyo, Tanzania. Male and female Anopheles gambiae s.s. and An. funestus s.s. mosquitoes were exposed to either 20% sucrose or different ASB station prototypes produced by Westham Co. in either (1) no-choice experiments or (2) choice experiments. Mosquitoes were exposed overnight and assessed for intrinsic or relative olfactory attraction using fluorescent powder markers dusted over the ASB stations and 20% sucrose and for feeding using uranine incorporated within the bait station and food dye in 20% sucrose controls.

Results

Both male and female An. gambiae and An. funestus mosquitoes were attracted to the ASBs, with no significant difference between the sexes for each of the experiments conducted. Older mosquitoes (3–5 days) were more attracted to the ASBs (OR = 8.3, [95% CI 6.6–10.5] P < 0.001) than younger mosquitoes (0–1 day). Similarly, older mosquitoes responded more to 20% sucrose (OR = 4.6, [3.7–5.8], P < 0.001) than newly emerged Anopheles. Of the four prototypes tested, the latest iteration, ASB prototype v1.2.1, showed the highest intrinsic attraction of both Anopheles species, attracting 91.2% [95% CI 87.9–94.5%]. Relative to ATSB v1.1.1, the latest prototype, v.1.2.1, had higher attraction (OR = 1.19 [95% CI 1.07–1.33], P < 0.001) and higher feeding success (OR = 1.71 [95% CI 1.33–2.18], P < 0.001).

Conclusions

Data from these experiments support using ASBs v1.2.1, deployed in large-scale epidemiological trials, as it is the most attractive and shows the highest feeding success of the Westham prototypes tested. The findings indicate that future bioassays to evaluate ATSBs should use mosquitoes of both sexes, aged 3–5 days, include multiple species in the same cage or chamber, and utilize both non-choice and choice tests with a standard comparator.
Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate
Authors: Wang Shuang , Ma Ruishuang , Gao Chong , Tian Yu-Nong , Hu Rong-Gui , Zhang Han , Li Lan , Li Yue
Published: February 2025

Background

Tuberous sclerosis complex is a genetic disorder caused by mutations in the TSC1 or TSC2 genes, affecting multiple systems. These genes produce proteins that regulate mTORC1 activity, essential for cell function and metabolism. While mTOR inhibitors have advanced treatment, maintaining long-term therapeutic success is still challenging. For over 20 years, significant progress has linked TSC1 or TSC2 gene mutations in stem cells to tuberous sclerosis complex symptoms.

Methods

A comprehensive review was conducted using databases like Web of Science, Google Scholar, PubMed, and Science Direct, with search terms such as “tuberous sclerosis complex,” “TSC1,” “TSC2,” “stem cell,” “proliferation,” and “differentiation.” Relevant literature was thoroughly analyzed and summarized to present an updated analysis of the TSC1-TSC2 complex’s role in stem cell fate determination and its implications for tuberous sclerosis complex.

Results

The TSC1-TSC2 complex plays a crucial role in various stem cells, such as neural, germline, nephron progenitor, intestinal, hematopoietic, and mesenchymal stem/stromal cells, primarily through the mTOR signaling pathway.

Conclusions

This review aims shed light on the role of the TSC1-TSC2 complex in stem cell fate, its impact on health and disease, and potential new treatments for tuberous sclerosis complex.

Graphical abstract
MyD88 inhibitor TJ-M2010-5 alleviates spleen impairment and inflammation by inhibiting the PI3K/miR-136-5p/AKT3 pathway in the early infection of Trichinella spiralis
Authors: Bai Huifang , Dang Qianqian , Chen Guoliang , Xie Lingfeng , Wang Saining , Jiang Ning , Wu Xiaoxia , Zhang Shuyan , Wang Xuelin
Published: February 2025

Trichinella spiralis (T. spiralis) has been reported to induce inflammation, which can cause immune system dysregulation. Myeloid differentiation primary response gene 88 (MyD88) is implicated in inflammation signalling pathways. TJ-M2010-5 is a novel MyD88 inhibitor with remarkable protective effects against several diseases. However, the precise mechanism of TJ-M2010-5’s involvement in spleen impairment and inflammation in the early infection of T. spiralis has yet to be fully elucidated. This study analysed histological, inflammation, and macrophage polarisation of the early T. spiralis-infected mice treated with TJ-M2010-5. MyD88 promoter methylation results showed that the methylation levels in the 5 d group were lower compared to the control group (P < 0.05). Furthermore, the methylation led to an imbalance in anti-inflammatory regulation in the infected mice. After TJ-M2010-5 treatment, spleen impairment was reduced. Sequencing analysis showed that TJ-M2010-5 significantly up-regulated 9 and down-regulated 10 miRNAs compared with the 5 d group. A dual-luciferase reporter assay further revealed that miR-136-5p is involved in the TJ-M2010-5 treatment by targeting AKT3. In RAW264.7 cells, TJ-M2010-5 pre-treatment significantly reversed the M1 polarisation and inhibited nitric oxide (NO) production. LC–MS/MS results showed TJ-M2010-5 was hepatosplenic-targeted. In conclusion, the study demonstrates that TJ-M2010-5 could effectively alleviate spleen impairment and reduce inflammation in mice infected with T. spiralis in its early stages by blocking the activation of PI3K/miR-136-5p/AKT3.
Perspectives of substance use disorder counselors on the benefits and drawbacks of medications for opioid use disorder
Authors: Cardamone Nicholas C. , Stewart Rebecca E. , Kampman Kyle M. , Marcus Steven C.
Published: February 2025

Background

Medications for opioid use disorder (MOUD) are among the best tools available to combat the opioid epidemic. Yet, use of MOUD among people with opioid use disorder (OUD) remains low. Interventions to increase MOUD access in the United States have largely focused on improving organizational capacity and addressing funding barriers, yet stigma toward MOUD may inhibit uptake even where MOUD is readily available. Non-prescribing substance use disorder (SUD) treatment professionals (e.g. counselors) likely have considerable influence on a client’s choice to initiate and adhere to MOUD, but beliefs that counselors convey about MOUD in interaction with clients are understudied. The current study explores what advantages and disadvantages that counselors communicate about buprenorphine, methadone, and naltrexone.

Methods

From June to December 2021, we surveyed counselors from publicly-funded SUD treatment agencies under a municipality-wide mandate to offer MOUD to all clients with OUD. Counselors were asked to describe, in a free-response format, the most important advantages and disadvantages to communicate to their clients about taking buprenorphine, methadone, and naltrexone. Counselor responses were coded for one or more advantage and disadvantage.

Results

A total of 271 SUD counselors from 29 agencies in the Philadelphia Metropolitan Area completed the survey, generating 1,995 advantages and disadvantages across three types of MOUD. The most frequently reported advantage across all three types of MOUD was their ability to reduce cravings and illicit drug use. The most frequently reported disadvantage related to the potential for some types of MOUD to develop long-term medication dependence.

Conclusions

As the availability and variety of MOUD treatment options continue to expand, it is important that SUD counselors are equipped with evidence-based recommendations for OUD care. We identified misalignments with the MOUD-prescribing evidence base and stigmatizing language toward MOUD within counselors’ responses, highlighting the potential to refine training materials for MOUD and mitigate stigmatizing beliefs.