bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical students and ChatGPT: analyzing attitudes, practices, and academic perceptions
Authors: Abdelhafiz Ahmed Samir , Farghly Maysa I. , Sultan Eman Anwar , Abouelmagd Moaz Elsayed , Ashmawy Youssef , Elsebaie Eman Hany
Published: February 2025

Background

ChatGPT, a chatbot launched by OpenAI in November 2022, has generated both excitement and concern within the healthcare education, research, and practice communities. This study aimed to explore the knowledge, perceptions, attitudes, and practices of undergraduate medical students regarding the use of ChatGPT and similar chatbots in their academic work.

Methods

An anonymous, structured questionnaire was developed using Google Forms and administered to medical students as part of a cross-sectional study. The survey targeted undergraduate medical students from four governorates in Egypt. The questionnaire link was distributed through social media platforms, including Facebook and WhatsApp. The survey comprised four sections: socio-demographic characteristics, perceptions, attitudes, and practices.

Results

The survey achieved a response rate of 96%, with 614 out of 640 approached students participating. Prior to the study, most respondents (78.5%) had personal experience using it. Overall, respondents demonstrated positive perceptions, attitudes, and practices toward ChatGPT, with mean scores exceeding 3 for all three variables: 3.99 ± 0.60 for perceptions, 3.01 ± 0.46 for attitudes, and 3.55 ± 0.55 for practices. In general, the students exhibited a high degree of trust in the model, with approximately half trusting the accuracy and reliability of the information provided by ChatGPT. However, more than two-thirds expressed apprehension about its potential misuse in medical education, and around 60% were concerned about the accuracy of information ChatGPT might generate on complex medical topics.

Conclusions

Medical students show strong interest and trust in using ChatGPT and similar chatbots for academic purposes but have concerns about the reliability of the information and potential misuse in medical education. The use of AI tools should follow ethical guidelines set by academic institutions, with regular updates to keep pace with technological progress. Future research should focus on the impact of AI on education and personal development, especially among young people.
Ontology-based expansion of virtual gene panels to improve diagnostic efficiency for rare genetic diseases
Authors: Shin Jaemoon , Fujiwara Toyofumi , Saitsu Hirotomo , Yamaguchi Atsuko
Published: February 2025

Background

Virtual Gene Panels (VGP) comprising disease-associated causal genes are utilized in the diagnosis of rare genetic diseases to evaluate candidate genes identified by whole-genome and whole-exome sequencing. VGPs generated by the PanelApp software were utilized in a UK 100,000 Genome Project pilot study to filter candidate genes, thus enhancing diagnostic efficiency for rare diseases. However, PanelApp also filtered out disease-causing genes in nearly 50% of the cases.

Methods

Here, we propose various methods for optimized approach to design VGPs that significantly improve the diagnostic efficiency by leveraging the hierarchical structure of the Mondo disease ontology, without excluding disease-causing genes. We also performed computational experiments on an evaluation dataset comprising 74 patients to determine the optimal VGP design method.

Results

Our results demonstrate that the proposed method can significantly enhance rare disease diagnosis efficiency by automatically identifying candidate genes. The proposed method successfully designed VGPs that improve diagnosis efficiency without excluding disease-causing genes.

Conclusion

We have developed novel methods for VGP design that leverage the hierarchical structure of the Mondo disease ontology to improve rare genetic disease diagnosis efficiency. This approach identifies candidate genes without excluding disease-causing genes, and thereby improves diagnostic efficiency.
Rapid detection of Tulipalin A with SESI-Orbitrap MS: an exploration across spring flowers
Authors: Phan An N. T. , Eerlings Roy , Mengers Hendrik G. , Blank Lars M.
Published: February 2025

Background

Allergic contact dermatitis and chronic actinic dermatitis are frequently observed among florists and gardeners due to exposure to potentially allergenic plants and plant products. Tulipalin A, an alpha-methylene-gamma-butyrolactone, is a common allergen synthesized by Tulipa genera, but its natural occurrence across Plantae remains unexplored.

Results

Here, we demonstrated the secondary electrospray ionization coupled Orbitrap mass spectrometry (SESI-Orbitrap MS) methodology for quantifying tulipalin A release from plants upon injury. By outlining temperature treatment, homogenization strategies and plant organ distribution, we show that processing flower samples stored at room temperature using a garlic press yielded the highest tulipalin A release upon injury. Via real-time monitoring, tulipalin A release was demonstrated to occur immediately upon homogenization. Next, the biosynthesis of tulipalin A across spring flowers was landscaped. Highlighting Rosa, Gerbera, Neapolitanum, Ranunculus, Othocalis, Muscari, Galanthus, Tulipa and Alstroemeria to release detectable amounts of tulipalin A upon injury. Tulipalin A was predominantly released from the Tulipa and Alstroemeria species, both belonging to the Liliales order, as stated in previous clinical and research studies.

Conclusions

In conclusion, a rapid method using the SESI-Orbitrap MS is reported to detect and track tulipalin A synthesis across plant organs and outline its cross-species distribution. Our methodology can be easily adapted for mapping other volatile plant defense metabolites and identify potentially allergenic plants. By addressing these aspects, we can ensure a safer work environment for florists and gardeners.
In vitro micropropagation protocols for two endangered Dianthus species - via in vitro culture for conservation and recultivation purposes
Authors: Farkas Dóra , Csabai Judit , Kolesnyk Angéla , Szarvas Pál , Dobránszki Judit
Published: February 2025

Background

D. giganteiformis subsp. pontederae and D. superbus subsp. superbus are protected or critically endangered species in several European regions; therefore, developing an efficient in vitro micropropagation protocol is essential for germplasm conservation and recultivation purposes.

Results

After germination, one-nodal segments of both species were transferred onto several MS media supplemented with 3% sucrose and different types of cytokinins (at a concentration of 4.5 µM) alongside 0.54 µM 1-naphthaleneacetic acid (NAA) for the multiplication phase for 3 weeks. The shoot clusters were subsequently transferred onto elongation medium (plant growth regulator-free MS medium) for 3 weeks. Individual shoots separated from the shoot clusters were cultured on MS medium supplemented with 0.54 µM NAA and 2% sucrose for 3 weeks for rooting. Taking into account the effects and after-effects of cytokinins, we found that the most suitable cytokinin for D. giganteiformis subsp. pontederae was N-(2-isopentenyl)-adenine (2-iP), while for D. superbus subsp. superbus it was meta-topolin (mT).

Conclusions

In vitro micropropagation methods were developed for two endangered Dianthus species (D. giganteiformis subsp. pontederae and D. superbus subsp. superbus) by determining the optimal type of cytokinin to be used during the multiplication phase. The protocols are designed to produce large quantities of propagation material for recultivation, educational, and research purposes within three months.
Realising health justice in Palestine: beyond humanitarian voices
Authors: Smith James , el-Solh Sara , Hanbali Layth , Abdulrahim Sawsan , Hafez Sali , Abuzerr Samer , Wispelwey Bram , Gilbert Mads , Seyam Mohammed , Hamad Bassam Abu , Gucciardo Dorotea , Haddad Fahd , Khoury Rasha , Nimerawi Amira , Mills David , Abu-Sittah Ghassan
Published: February 2025

In the shadow of Israel’s ongoing genocide throughout occupied Palestine, this article examines the moral, political, and epistemic responsibilities of humanitarian, public health, global health, medical and related communities of practice amid profound violence and injustice. In this paper we offer a three-part critique of a May 2024 commentary by Karl Blanchet and colleagues, ‘Rebuilding the health sector in Gaza: Alternative humanitarian voices’ (Blanchet et al. in Confl Heal 18:42, 2024). We argue that in relation to the post-genocide reconstruction of the health system in Gaza, the authors have failed to adequately contextualise their analysis, or the health system reconstruction policy proposal as commissioned by the Gaza Health Initiative [Gaza Health Rebuilding Initiative (GHRI), Future of the Gaza health system: Needs assessment. https://static1.squarespace.com/static/656c4ff5b219116063f8099e/t/65c30c4d3e80fd21f1165b57/1707281499127/Final+first+draft+-+Gaza+health+system+report.pdf. Accessed 8 November 2024], and as such have failed to elucidate the root causes of what manifests most immediately as an entirely manufactured humanitarian crisis. This in turn undermines the substance and utility of the recovery proposal as it has been presented. We also argue that the authors have failed to afford due recognition to several key health actors in Palestine, in particular the Palestinian Ministry of Health in Gaza and UNRWA, and that this subtle but critical act of erasure further undermines the relevance and applicability of their recovery proposal as presented. In response we emphasise the centrality of Palestinian perspectives, and the need to uphold Palestinian leadership in all stages of the recovery process. Thirdly, we take issue with the suggested chronology and substance of the recovery proposal as presented, which overlooks response and recovery efforts already underway and led by Palestinians in Gaza, and which overstates ultimately harmful intervention strategies such as networks of internationally managed field hospitals. Against the backdrop of a very limited window for what we consider morally justifiable humanitarian engagement in Gaza, we join many others who have called for a paradigm shift away from the inertia of supposed objectivity and claimed neutrality that function to perpetuate injustice. Instead, we call for the collective practice of critical advocacy, solidarity with people affected by injustice and oppression, and an emancipatory politics in pursuit of justice in Palestine.
Transcriptional regulatory network analysis identifies GRN as a key regulator bridging chemotherapy and immunotherapy response in small cell lung cancer
Authors: Yoo Seungyeul , Patel Ayushi S. , Karam Sarah , Zhong Yi , Wang Li , Jiang Feng , Kong Ranran , Bikvan Sharon , Wang Wenhui , Sinha Abhilasha , Powell Charles A. , Zhu Jun , Watanabe Hideo
Published: February 2025

Small cell lung cancer (SCLC) is an aggressive and heterogeneous subtype, representing 15% of lung cancer cases. Although SCLC initially responds to etoposide and platinum (EP) chemotherapy, nearly all patients relapse with resistant tumors. While recent advances in immunotherapy have shown promise, only 10–20% of patients benefit, and effective stratification methods are lacking. The mechanisms of resistance to both therapeutics remain obscure. In this study, we aimed to gain insights into those leveraging a recent surge in the field of SCLC genomics. We constructed a regulatory network for SCLC and identified granulin precursor (GRN) as a hub of EP response associated genes. GRN-low patients showed improved survival with chemotherapy, while GRN-high patients exhibited resistance. GRN overexpression in SCLC cells conferred resistance to EP treatment and suppressed neuroendocrine features. GRN and its associated genes were linked to cancer cell intrinsic immunogenicity, and single-cell RNA-seq data revealed that GRN expression is particularly high in subsets of tumor-associated macrophages. In concordance with these findings, GRN-low tumors showed significantly better survival with chemo-immunotherapy, while GRN-high tumors did not benefit from additional immunotherapy. GRN-high tumors, associated with non-neuroendocrine (non-NE) subtypes, had a higher level of macrophage infiltration, potentially contributing to immunotherapy resistance. These results highlight GRN as a critical regulator of chemo-resistance and a potential biomarker for immunotherapy resistance in SCLC. Targeted therapeutic strategies for GRN-low patients could improve outcomes, while new approaches are needed for GRN-high patients. Overall, our findings implicate GRN as a bridge between chemotherapy and immunotherapy resistance through GRN-mediated mechanisms.
The use of strong analgesics for prehospital pain management in children in the region of Southern Denmark: a register-based study
Authors: Colding-Jørgensen Josefine Tvede , Brandstrup Gina Maj Graven , Nielsen Vibe Maria Laden , Gradman Josefine , Thybo Line Anker Bang , Hansen Peter Martin , Wittrock Daniel , Blomberg Stig Nikolaj Fasmer , Christensen Helle Collatz , Mikkelsen Søren
Published: February 2025

Background

Acute pain in the prehospital setting is frequent and prehospital pain management presents multiple challenges, especially in children. There is a lack of high-level evidence regarding prehospital pain management in the paediatric population worldwide. In Denmark, this lack of evidence particularly concerns the frequency of the prehospital use of strong analgesics. Guidelines are sparse but there is evidence that prehospital fentanyl may be administered up to 5 µg/kg.

Method

This register-based study investigated the prehospital analgesic treatment in the population under 15 years from January 2017 to December 2022 in the Region of Southern Denmark. Data were extracted from electronic prehospital medical records. The analgesic treatment was characterised by the type of medication, dosage, administration method, and cause of ambulance dispatch. Lastly, response- and transport times were registered.

Results

A total of 28,933 prehospital paediatric medical records were examined. In one in seventeen of all prehospital contacts with children, fentanyl, alfentanil, morphine and/or s-ketamine was administered. Three-quarters of the doses of strong analgesics were administered to patients older than 10 years. Fentanyl was the most frequently administered medication (96.4%). The median fentanyl-equipotent doses of opioids were 1.7 µg/kg adjusted according to standardised patient weight. In 63.4% of cases, the analgesic treatment was administered intravenously.

Conclusion

The doses of opioids as administered by the EMS personnel seem safe as 97% of the doses were within the recommended range and even at the lower end of the recommended range. Although apparently safe, the utilisation of strong analgesics points to a risk of under-treating pain in children.
Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats
Authors: Lee Bonnie H. , Cevizci Melike , Lieblich Stephanie E. , Galea Liisa A. M.
Published: February 2025

Background

Alzheimer’s disease (AD) disproportionately and uniquely affects females, and these sex differences are further exacerbated by the presence of Apolipoprotein (APOE) ε4 alleles, the top genetic risk factor for late-onset AD. To expand our understanding about how late-onset AD risk might differentially influence males and females, this study explores how APOEε4 affects hippocampal neurogenesis and microglia, key neuroplastic markers involved in AD pathogenesis, differently by sex in middle-aged rats.

Methods

A rat model expressing the humanized (h) APOEε4 allele was characterized to examine markers of adult neurogenesis (neural progenitor cells and new-born neurons) and immune cells (microglia) in the dentate gyrus of the hippocampus in 13 month-old male and female rats.

Results

We observed basal sex differences in neurogenesis at middle age, as wildtype male rats had greater densities of neural progenitor cells and new-born neurons in the dentate gyrus than wildtype female rats. Male hAPOEε4 rats exhibited fewer neural progenitor cells, fewer new-born neurons, and more microglia than male wildtype rats. On the other hand, female hAPOEε4 rats exhibited more new-born neurons than female wildtype rats. Interestingly, females had more microglia than males regardless of genotype. Correlations were conducted to further elucidate any sex differences in the relationships between these biomarkers. Notably, there was a significant positive correlation between neural progenitor cells and new-born neurons, and a significant negative correlation between new-born neurons and microglia, but only in male rats.

Conclusion

In contrast to the clear pattern of effects of the hAPOEε4 risk factor on hippocampal neurogenesis in males, females had unaltered levels of neural progenitor cells and increased density of new-born neurons. Furthermore, relationships between neurogenesis and microglia were significantly correlated within males, and not females. This suggests that females may be presenting a compensatory response to the hAPOEε4 genotype at middle age. Collectively, these results exemplify the importance of thoroughly examining influences of sex on AD endophenotypes, as it may reveal sex-specific pathways and protective mechanisms relevant to AD.
Supporting primary care clinicians in caring for patients with alcohol use disorder: study protocol for Records for Alcohol Care Enhancement (RACE), a factorial four-arm randomized trial
Authors: Magane Kara M. , Saitz Richard , Fielman Sarah , LaRochelle Marc R. , Shanahan Christopher W. , Pace Christine A. , LaValley Michael , Penington Kaley , Karzhevsky Skylar , Hurstak Emily
Published: February 2025

Background

Unhealthy alcohol use, a spectrum of use inclusive of risky consumption and alcohol use disorder (AUD), is a leading cause of preventable death in the United States. Most people with unhealthy alcohol use do not receive evidence-based treatment. This four-arm factorial design randomized trial will assess whether population health management (PHM) and clinical care management (CCM) support for primary care providers (PCPs) are associated with improved AUD treatment engagement among their patients, beyond electronic health record (EHR) prompting and decision support alone.

Methods

PCPs from an urban safety-net hospital-based primary care clinic are randomized to one of four groups (1) EHR best practice advisory (BPA) and clinical decision support tools for unhealthy alcohol use (BPA), (2) BPA plus population health manager support, (3) BPA plus clinical care manager support, and (4) all three. All PCPs will have access to the EHR BPA and decision support tools which provide chart-based advisories and order set navigation. PCPs assigned to receive PHM support will receive quarterly panel-level feedback on AUD treatment metrics for their patients. PCPs assigned to receive CCM support will receive CCM facilitation of AUD treatment processes including medication counseling, referrals, and support through direct patient interactions. The primary outcome will be the percent of patients engaged in AUD treatment among those with a new AUD diagnosis on a PCP’s panel. Secondary outcomes include the percent of patients with a new diagnosis of AUD who (1) initiated AUD treatment, (2) were prescribed AUD medications within 90 days, and (3) numerical counts of a range of AUD health services (outpatient encounters, specialty AUD care encounters, referrals, and acute healthcare utilization) in this sample. We will assess the primary outcome and the acute healthcare utilization secondary outcomes using Medicaid claims; the remaining secondary outcomes will be assessed using EHR data.

Discussion

The study will evaluate how a targeted EHR innovation alone, compared with population health and care management enhancements alone or in combination, impact engagement in AUD treatment, a national quality of care measure. Findings will advance understanding of supports needed to improve systems of care for AUD in general settings.

Trial registration

ClinicalTrials.gov identifier/registration number (NCT number): NCT05492942
Validation and assessment of the arabic psychological first aid scale among physicians, nurses, and counselors in Jordan
Authors: Alshareef Basma Eid , Alfuqaha Othman A. , Maali Ibraheem B. , Amer Khaled
Published: February 2025

Background

Psychological first aid (PFA) involves strategies to tackle problems that occur as a result of disasters. This study aimed to validate the Arabic version of PFA scale through validity (face, content, convergent, discriminant validity, and confirmatory factor analysis) and reliability (Cronbach’s alpha). Furthermore, it aimed to assess the perceived levels of knowledge, skills, and attitudes of PFA among healthcare providers (HCPs). Moreover, it determined the differences between HCPs based on their knowledge, skills, and attitudes of PFA.

Methods

A sample size of 389 HCPs (physicians = 68, nurses = 173, and counselors = 148) was conveniently selected to participate during the period of 10 December 2023 to 10 February 2024 after completing the translated PFA scale into the Arabic language. Descriptive, translation, validation process, and reliability were conducted.

Results

The translation process was satisfied. The content validity index was 0.91, yielding proper clarity of items. Three constructs were loaded with a total variation of 63.43%, indicating a proper model fit. The goodness-of-fit indices for the PFA model revealed that relative chi-square was 1.47, comparative fit index was 0.91, Tucker-Lewis index was 0.89, and the root mean square of error approximation was 0.046. Cronbach alpha values for knowledge, skills, and attitudes of PFA were 0.90, 0.89, 0.87, respectively. We found that counselors have more knowledge (64.4%), skills (73.4%), and attitudes (73.4%) compared to physicians and nurses. There are significant differences (p < 0.001) between the selected HCP groups, particularly for the counselors’ group in terms of knowledge, skills, and attitudes of PFA.

Conclusions

The Arabic PFA scale is valid and reliable among HCPs. The results highlight the emergent need to provide knowledge, skills, and attitudes of PFA interventions among medical professionals, particularly for physicians and nurses. The Arabic version of PFA helps all HCPs in Arab countries to assess, apply, and implement PFA interventions.
Lithium and strontium isotope hydrogeochemistry in Okayama and Tottori Prefectures, southwest Japan: implications for tracing slab-derived fluid
Authors: Akishiba Manato , Nishio Yoshiro
Published: February 2025

Dehydration of the Philippine Sea Plate during subduction beneath the forearc region of southwest Japan releases fluids into the crust, potentially producing Arima-type fluids, which are characterized by anomalous hydrogen and oxygen isotopic compositions (δD and δ
18O). Arima-type fluids have been identified in limited hot springs near active faults, such as the Arima and Takarazuka hot springs. The aim of our study is to understand why there have been limited reports of Arima-type fluids, despite the likelihood of their formation during slab dehydration. δ
7Li data can be used to identify Arima-type fluids in samples with Cl– concentrations below 3400 mg/L, whereas δD and δ
18O data have difficulty to detect them. In this study, we collected and analyzed samples from Okayama and Tottori Prefectures in southwest Japan, focusing on their chemical compositions and δ
7Li and 87Sr/86Sr values. We found that the δ
7Li and 87Sr/86Sr compositions of some of the water samples from Okayama Prefecture were similar to those of Arima-type fluids and that they are unlikely to be explained by other sources (e.g., local reactions with host rocks, residual hydrothermal/magmatic fluids, or seawater altered by rocks). Our results therefore suggest there may be a more extensive distribution of Arima-type fluids in the forearc region of southwest Japan than has been previously reported.
Predictive value of different baseline optical coherence tomography biomarkers for visual acuity changes in neovascular age-related macular degeneration
Authors: Riazi-Esfahani Hamid , Faghihi Hooshang , Bazvand Fatemeh , Mehrabi Bahar Mohammadreza , Khojasteh Hassan , Husein Ahmed Ahmed , Faghihi Shahin , Fakhraie Ali , Zamani Mohammad Hossein , Ghasemi Samin , Asadi Khameneh Esmaeil , Khalili Pour Elias
Published: February 2025

Background

To evaluate baseline optical coherence tomography (OCT) biomarkers in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) and their correlation with visual acuity changes following intravitreal aflibercept injections.

Methods

A retrospective analysis was conducted on treatment-naïve nAMD patients. Baseline OCT biomarkers, including shallow irregular pigment epithelial detachment (SIPED), subretinal hyperreflective material, subretinal fluid, intraretinal fluid (IRF), hyperreflective foci, and subretinal drusenoid deposits, were assessed. Patients received bimonthly aflibercept injections after three loading doses. Visual acuity changes were evaluated at 3 and 12 months. The maximum height and width of the largest pigment epithelial detachment (PED) were also measured.

Results

Among 89 eyes with nAMD, mean best-corrected visual acuity (BCVA) improved by 6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline to month 3, with sustained improvement through month 12. Baseline IRF was associated with poorer visual acuity improvement at month 12, with patients showing a mean improvement of 1.6 ± 18.2 ETDRS letters versus 11.1 ± 10 ETDRS letters in those without IRF (P = 0.002). Multivariable analysis indicated SIPED was linked to lower visual gains at month 3 (P = 0.025). The largest PED width correlated significantly with lower BCVA gains at months 3 (P = 0.021) and 12 (P = 0.043), suggesting its potential as a prognostic factor.

Conclusion

Baseline OCT biomarkers, including SIPED, IRF, and PED width, may predict visual acuity changes in nAMD patients treated with aflibercept, highlighting the need for individualized monitoring.

Clinical trial number

Not applicable.
A systemic analysis of container terminal layouts
Authors: Rodrigue Jean-Paul
Published: February 2025

The paper provides a systemic analysis of the layout characteristics of a geodatabase comprised of a large sample of 331 global container terminals. Despite the propensity towards terminal standardization that can be expected from containerization, container terminals demonstrate a substantial diversity in measurable attributes such as perimeter, terminal surface, yard surface, and berth length. This is mainly attributed to site characteristics constraining terminal design and operations with clusters arranged along terminal rectangularity level. A further observation concerns the propensity of container terminals to be oriented longitudinally. Geographical factors remain important, including whether the terminal design is a reconversion of an older facility, an adaptation to specific site constraints, or a new land reclamation.
Revealing viral hepatitis epidemiology in the Democratic Republic of Congo: insights from yellow fever surveillance reanalysis
Authors: Mukadi-Kakoni Patrick , Munyeku-Bazitama Yannick , Kashitu-Mujinga Gracia , Manwana-Pemba Marguerite , Zenga-Bibi Niclette , Okitale-Talunda Patient , Mbelu-Kabongo Christelle , Domai-Mbuyakala Fleurette , Pukuta-Simbu Elisabeth , Mutantu-Nsele Pierre , Kubo Yoshinao , Makiala-Mandanda Sheila , Ahuka-Mundeke Steve , Ariyoshi Koya , Muyembe-Tamfum Jean-Jacques
Published: February 2025

Background

Yellow fever surveillance systems are designed to identify cases of acute febrile jaundice, a clinical syndrome used to monitor the emergence of yellow fever outbreaks. However, this syndrome has diverse etiologies, particularly viral hepatitis. This study investigates the seroepidemiology of viral hepatitis A (HAV), B (HBV), C (HCV), and E (HEV) among cases initially suspected to be yellow fever, aiming to elucidate the epidemiology of viral hepatitis in the Democratic Republic of Congo (DRC) and provide insights for improving public health interventions.

Methods

A retrospective cross-sectional study was conducted using serum samples collected between 2017 and 2018 through national yellow fever surveillance in the DRC. Samples from individuals testing negative for yellow fever were tested for IgM antibodies against HAV, HBc, HCV, and HEV and HBs antigen using validated ELISA kits. Acute HBV infection was defined by both HBc IgM and HBs antigen positivity. Multivariable logistic regression was used to assess the association of demographic, geographic, and environmental factors with each hepatitis type.

Results

Among 1239 participants (58.8% male; median age: 16 years), seroprevalence was 16.1, 11.2, 5.0, and 3.1% for HAV, HBV, HCV and HEV, respectively. HAV prevalence was highest in the youngest age group and rural residents. In contrast, the youngest group was most protected from HBV. HCV prevalence was highest in the oldest age groups. HEV exhibited higher prevalence during the dry season and in a humid subtropical climate. Several provinces were identified as hotspots of HAV, HCV and HEV.

Conclusions

Viral hepatitis is a major cause of acute febrile jaundice in the DRC with notable geographic and seasonal trends. National yellow fever surveillance is a valuable resource for understanding hepatitis epidemiology, though careful interpretation is necessary. Tailored interventions are required for mitigating the burden of viral hepatitis in each province.
Epidemiology of urinary tract infections in the Middle East and North Africa, 1990–2021
Authors: Amiri Fatemeh , Safiri Saeid , Aletaha Reza , Sullman Mark J. M. , Hassanzadeh Kamaleddin , Kolahi Ali-Asghar , Arshi Shahnam
Published: February 2025

Objective

This research reports the incidence, mortality, and disability-adjusted life years (DALYs) associated with urinary tract infections (UTIs) in the Middle East and North Africa (MENA) region, stratified by sex, age, and Socio-demographic Index (SDI) from 1990 to 2021.

Methods

Data were sourced from the Global Burden of Disease 2021 study, encompassing all 21 countries in the region. Metrics such as absolute counts, age-standardised rates, and percentage changes from 1990 to 2021 are presented with 95% uncertainty intervals (UIs).

Results

In 2019, the MENA region recorded an incidence rate of 4,033.4 per 100,000 (95% UIs: 3,553.7–4,548.7) and 7,687 deaths (95% UIs: 6,663–8,969). The DALY rate was 41.3 per 100,000 (95% UIs: 36.1–47.2), which was highest among older adults, reaching a peak in the 80–89 age range, and increasing with age, particularly from the 50 + age groups. A non-linear relationship was identified between the burden of UTIs and the SDI, with higher-than-expected rates in lower SDI countries such as Syria and Lebanon.

Conclusion

Despite a substantial increase in the total number of UTI cases and DALYs in the region from 1990 to 2021, the age-standardised rates remained stable. The larger burden in lower SDI countries highlights the urgent need for targeted public health interventions. Improving healthcare access and antibiotic stewardship is crucial to mitigating the growing burden of UTIs, particularly among older populations in the region.
Determination of damaging SNP’s in SHANK3 gene with in silico methods
Authors: Albayrak İrem Gülfem , Yektar Şeyma , Kaya Süeda
Published: February 2025

Background

Asperger's syndrome, autism, and other neurodevelopmental diseases are all included under the general term autism spectrum disorder. The SHANK3 gene has a significant role in autism spectrum disorder; mutations in this gene are seen in roughly 1–2% of patients with both autism and intellectual disability. This genetic association provides insight concerning SHANK3's potential significance in the disorder's development. There is considerable evidence associating SHANK3 mutations to autism spectrum disorder; hence, it is worthwhile to investigate the underlying molecular genetic mechanisms of the disease.

Results

This research uses in silico approaches such as SIFT, PolyPhen-2, I-Mutant 2.0, and Project HOPE to find harmful SNPs, which are the single nucleotide polymorphisms the most prevalent types of genetic variation in humans, in the SHANK3 gene. After the analysis, from the NCBI dbSNP database, 1535 missense SNPs in the SHANK3 gene were identified, with 54 classified as deleterious. Among these, 30 SNPs were confirmed damaging by both SIFT and PolyPhen-2, and 28 led to increased protein stability while two decreased it. In the presented research, effects on protein structure of this SNPs are discussed.

Conclusions

This in silico study improves our understanding of the complicated molecular changes associated with the SHANK3 gene and contributes to a more comprehensive understanding of the genetic landscape. By deepening our knowledge of the genetic basis and molecular pathways linked to SHANK3 mutations, our findings may offer direction for focused experimental validations and treatment strategies for autism spectrum disorder.
Mechanistic insights toward progress in alogliptin beyond glycemic control: translational perspective
Authors: Ahmed Faraha , Ahmad Syed Sufian , Alam M. Mumtaz , Shaqiquzzaman M. , Najmi Abul Kalam , Khan Mohammad Ahmed
Published: February 2025

Background

Alogliptin belongs to gliptin family of drugs that inhibits ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4). Gliptins increase the life-span of incretin hormones that appear to benefit functioning of several organs via various signaling pathways.

Main body

Alogliptin is approved for treatment of type 2 diabetes mellitus (T2DM) in majority of the countries. It is administered orally and efficacious as monotherapy as well as combined therapy with other T2DM drugs, such as pioglitazone and metformin. It has a good safety profile, well-tolerated in elderly patients and in patients with co-morbid conditions including risks of cardiovascular event, renal or hepatic insufficiency. Therefore, alogliptin is incessantly experimented and investigated for its therapeutic benefit. Recent developments have indicated potential of alogliptin in discrete pathological conditions. Emerging evidences suggest prominent cardioprotective, hepatoprotective, reno-protective, anti-inflammatory and lipid-lowering capacity of alogliptin. Apart from inhibiting DPP-4 enzyme, alogliptin also affects several signaling mechanisms to exhibit protective effects in patients with diabetes-induced complications.

Conclusion

This review highlights the potential role of alogliptin and mechanisms involved in amelioration of several other pathological conditions apart from its role in glucose metabolism. Thus, this may provide insights for better utilization and repurposing of alogliptin as a therapeutic agent.
Molecular landscape and therapeutic strategies in pediatric differentiated thyroid carcinoma
Authors: Yang Adeline T , Lai Sin-ting Tiffany , Laetsch Theodore W , Bhatti Tricia , Baloch Zubair , Surrey Lea F , Franco Aime T , Ricarte-Filho Julio C Marques , Mostoufi-Moab Sogol , Adzick N Scott , Kazahaya Ken , Bauer Andrew J
Published: February 2025

There has been significant progress in understanding the molecular landscape of pediatric differentiated thyroid carcinoma over the past two decades. Classification of pediatric differentiated thyroid carcinoma into three-tiers, RAS-like mutant, BRAF-mutant, and kinase-fusions, accurately reflects an increasing risk for invasive behavior, including regional and distant metastasis. In clinical practice, somatic oncogene testing for nodules with indeterminate cytology per the Bethesda System for Reporting Thyroid Cytopathology provides objective data to optimize surgical planning. In addition, knowledge of the somatic oncogene for widely invasive carcinomas allows for incorporation of oncogene-specific inhibitory therapy both in the adjuvant and neoadjuvant setting. In the present review, we review the risk factors, clinical presentation, and evaluation of pediatric DTC, highlighting the correlation among ultrasound features, cytology, and oncogenic driver of the tumor. We subsequently propose an integrated, multi-modal approach that can be used to improve diagnostic accuracy and reliability for pre-operative planning as well as identify and discuss which pediatric patients may benefit from systemic oral targeted therapy.
Hypothalamic Estrogen Receptor α Is Essential for Female Marmoset Sexual Behavior Without Protecting From Obesity
Authors: Kraynak Marissa , Willging Molly M , Uhlrich Daniel J , Shapiro Robert A , Flowers Matthew T , Manning Karen A , John Sara D , Williams Samantha M , Henjum Lukas J , Marrah Rebecca C , Yohnk Hannah R , Berg Carter B , Brunner Kevin , Colman Ricki J , Alexander Andrew L , Abbott David H , Levine Jon E
Published: February 2025

Context

Estrogen receptor α (ERα) in the ventromedial (VMN) and arcuate (ARC) nuclei of female rodent mediobasal hypothalami (MBHs) provides a crucial molecular gateway facilitating estradiol (E2) regulation of sexual behavior, reproductive neuroendocrinology, and metabolic function. In female nonhuman primates (NHPs) and women, however, its hypothalamic counterpart remains unknown.

Objective

We hypothesized that knockdown (KD) of ERα expression in the hypothalamic VMN and ARC of female marmosets would diminish sexual receptivity, while simultaneously disrupting gonadotropic and metabolic homeostasis.

Methods

We ovariectomized (OVX) adult female marmosets of comparable age and weight, immediately replaced E2 at midcycle levels, and approximately 1 month later assigned monkeys to diet-induced obesity (DIO) within group (1) control, receiving scrambled short hairpin RNA (shRNA), or (2) ERαKD, receiving selective ERα gene silencing shRNA. Magnetic resonance imaging–guided neural surgery enabled hypothalamic infusion of viral vector shRNA and subsequent brain immunohistochemistry enabled observer-validated, NIS-elements computer software quantification of ERα knockdown.

Results

ERα expression was significantly diminished in the VMN and ARC, but not the preoptic area (POA), of ERαKD females coincident with elimination of timely female sexual responses, more than 80% loss of female receptivity, modestly elevated gonadotropin levels, hyperglycemia, and diminished calorie consumption. Density and intensity of ERα-expressing cells in the VMN correlated positively with female sexual receptivity and calorie consumption, negatively with timeliness of female sexual responses, and in the ARC, correlated negatively with calorie consumption.

Conclusion

ERα activation in the female NHP MBH is critically important for female sexual behavior and modestly contributes to gonadotropic and metabolic control.
Blood Sample Collection in Randomized Controlled Trials for Biomarker Discovery and Validation: Experience of the PREOPANC-2 Trial
Authors: Dekker Esther N. , Janssen Quisette P. , van Dam Jacob L. , Strijk Gaby J. , Verkolf Eva M. M. , Kandala Sridhar , Dumas Jasper , Fellah Amine , O’Reilly Eileen M. , Besselink Marc G. , van Eijck Casper H. J. , Homs Marjolein Y. V. , van Tienhoven Geert-Jan , Wilmink Johanna W. , Mustafa Dana A. M. , Groot Koerkamp Bas ,   for the Dutch Pancreatic Cancer Group, Beerepoot L. V. , van Bekkum M. L. , Bonsing B. A. , Bos H. , Bosscha K. P. , Bouwense S. A. , Brouwer-Hol L. , Bruynzeel A. M. E. , Busch O. R. , Cirkel G. , Coene P. P. L. O. , de Groot J. W. B. , Haberkorn B. C. M. , de Hingh I. H. J. T. , Karsten T. M. , Kazemier G. , van der Kolk M. B. , Liem M. S. L. , Loosveld O. J. L. , Luelmo S. A. C. , Luyer C. M. , Mieog J. S. D. , Nieuwenhuijs V. B. , Nuyttens J. J. M. E. , ten Oever D. , Patijn G. A. , van Santvoort H. C. , Stommel M. W. J. , Streppel M. M. , ten Tije A. , Versteijne E. , de Vos - Geelen J. , de Wilde R. F.
Published: February 2025

Background

This study aimed to investigate the feasibility and yield of blood sample collection in an investigator-initiated nationwide randomized controlled trial (RCT).

Methods

In the PREOPANC-2 trial, 375 patients with (borderline) resectable pancreatic cancer were randomly assigned to two neoadjuvant regiments in 19 centers in the Netherlands (2018–2021). Blood sample collection was scheduled at seven time points before, during, and after treatment. The primary outcome was the proportion of successfully collected blood samples at each scheduled time point.

Results

Of the 375 randomized patients, 12 were excluded from blood sample collection before any treatment. From the remaining 363 patients, 1513 (87 %) of 1748 blood samples were collected, processed, mailed, and centrally stored. The blood samples were collected before treatment from 347 (96 %) of the 363 patients, after the first neoadjuvant cycle from 322 (94 %) of 343 patients, after neoadjuvant treatment (i.e., before surgery) from 260 (83 %) of 313 patients, and after surgery from 210 (77 %) of 271 patients. During the follow-up visits, blood samples were collected from 147 (82 %) of 179 patients 12 months after randomization and from 83 (77 %) of 108 patients after 24 months. A total of 220 samples (13 %) were missing. The most common causes for missing blood samples were scheduling oversights, unsuccessful blood draw attempts, and mailing failures (151 times, 69 %). Blood sample collection was canceled 69 times (31 %) due to COVID-19.

Conclusion

Blood sample collection in the PREOPANC-2 trial had a yield of 96 % before treatment and an overall yield of 87 %. Collection of blood samples for biomarker studies is feasible in a nationwide RCT.
Knee Ligament Moment Arms Scale with Epicondylar Width and might Contribute to Ligament Injuries in Females
Authors: Rooks Nynke B. , Schneider Marco T. Y. , Besier Thor F.
Published: February 2025

Introduction

Females are prone to knee ligament injuries compared to males. Moment arms describe the mechanical advantage of ligaments to stabilise the knee from injurious moments. Compared to males of the same stature, females have a smaller femoral epicondylar width, which we hypothesised would reduce their knee joint ligament moment arms in the frontal plane.

Methods

To calculate varus-valgus ligament moment arms, we created 26 patient-specific finite element models (17F; 9 M) and simulated an axial load of half body weight. Tibial cartilage contact pressures were obtained and used to define the medial and lateral peak contact pressure, which were assumed to be the point of rotation in the frontal plane. The varus and valgus moment arms of the anterior cruciate (ACL) and the medial (MCL) and lateral collateral ligaments (LCL) were calculated as the perpendicular distance between the point of peak contact pressure and the centroid of each ligament. Multiple linear regression models with sex, height, and epicondylar width as independent variables were produced.

Results

Females had smaller varus-valgus ligament moment arms compared to males, with a mean difference of 7 to 9 mm observed by the MCL and LCL about the lateral and medial contact points, respectively (~12% smaller, p < 0.001). The female cohort exhibited ACL moment arms about the medial and lateral contact points that were ~ 4 mm less than the male cohort (p < 0.05). Correlations between varus-valgus ligament moment arm and epicondylar width were found for all three ligaments using either the medial or lateral points of peak contact pressure.

Conclusions

These findings support our hypothesis that females have smaller varus-valgus ligament moment arms compared to males, which could contribute to the higher rate of female ligament injuries compared to males.
Narrative, drama and the compound stimulus
Authors: Somers John
Published: February 2025

This article is divided into six sections. It highlights the centrality of story to human existence, the key to drama’s effectiveness as a change agent, and then explores the implications for young people and for the drama they create. Section three describes the theory that underpins the use of a “compound stimulus”, a way of drawing participants into the fictional world and the exploration of specific stories. It also outlines the ways in which the compound stimulus should be used and provides case studies of its use. Finally, section six reflects on applications of the compound stimulus.
Evaluating the Cost-Effectiveness of Comprehensive Geriatric Assessment: Protocol for a Systematic Review of Economic Evaluations
Authors: Yigezu Amanuel , Galvin Rose , Trépel Dominic
Published: February 2025

Background Comprehensive Geriatric Assessment (CGA) is a multidimensional interdisciplinary diagnostic process focused on determining an older person's medical, psychological, and functional capabilities to inform a coordinated and integrated health plan. It is a multifactorial intervention requiring longitudinal planning and care coordination, which can utilize variable healthcare resources and have difference health outcomes. This systematic review aims to identify evidence of the cost-effectiveness of CGA in various care settings. Methods and analysis Full economic evaluation studies on CGA will be searched for in the Embase, Medline, CINAHL, CEA registry, and NHSEED databases. Two independent reviewers will screen the studies against the eligibility criteria and extract data using a pretested extraction form. We will include either randomized control trials or model-based economic evaluations, and the outcomes will include the mean costs and effectiveness, incremental cost, and incremental effectiveness. Reporting quality will be assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS-2022) checklist. Narrative summary tables and figures will be used to present the study characteristics. Ethics and dissemination Ethics approval is not required for this systematic review because we will only utilize publicly available economic evaluation studies rather than individual patient data. The findings of this review will be presented at national and international conferences and published in peer-reviewed journals. PROSPERO registration no.: CRD42023492586.
Pre-protocol of the Virtual Spatial Configuration Task (VSCT): A Novel Virtual Reality-Based Tool for Assessing Cognitive Map Formation Abilities
Authors: Umiltà Alberto Massimiliano , Li Pira Giorgio , Burles Ford , Ottoboni Giovanni , Tessari Alessia
Published: February 2025

This study proposes the validation of the Virtual Spatial Configuration Task (VSCT), a novel task designed to evaluate cognitive map formation abilities in participants. Addressing a notable gap in spatial cognition research, particularly in the assessment of higher-level spatial abilities in 3D environments, the VSCT offers a virtual reality (VR) approach that allows users to explore and recall spatial relationships between landmarks. This task is particularly innovative for populations with impaired mobility, as it simplifies navigation by restricting movement to rotational exploration, thus improving accessibility and reducing motion sickness. Furthermore, the VSCT could serve a dual purpose: assessing spatial orientation skills while also providing a platform for training and improving these skills post-injury. The potential applications of this tool extend to neurorehabilitation and other therapeutic interventions, offering an engaging, immersive method for enhancing spatial abilities.