bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term effects of tocilizumab on retinal and choroidal inflammation in Birdshot uveitis
Authors: zur Bonsen Lynn S. , Schulze Daniel , Künzel Steffen E. , Rübsam Anne , Pleyer Uwe , Pohlmann Dominika 
Published: November 2024

Abstract
Background
Tocilizumab (TCZ), an interleukin-6 receptor antagonist, is approved for treating rheumatic diseases and has demonstrated efficacy in managing refractory non-infectious uveitis (NIU). This retrospective study aimed to investigate the long-term effects of TCZ on inflammation in the retinal and choroidal compartments in Birdshot NIU.

Methods
Eight patients (16 eyes) received TCZ and were included in the analysis. The primary outcomes measured were inflammatory activity in the retina and choroid, assessed by fluorescein angiography (FA) and indocyanine green angiography (ICGA) using the Angiography Scoring for Uveitis Working Group at baseline, 6, 12, 24, and 36 months.

Results
The mean follow-up time with TCZ treatment was 33 months. At baseline, the median FA score was 14 (quartiles: 10.25, 15.25), which significantly decreased over time (at 36 months: 8 (5.5, 11); p = 0.004). In contrast, the ICGA score significantly increased within the first year (median at baseline: 5 (4.75, 7.25); at 6 months: 7 (6, 9.25); at 12 months: 7 (6.5, 9.25); p = 0.002), but returned to baseline levels after two years (at 24 months: 5 (5, 6.5); at 36 months: 5.5 (4, 7.5)). Central retinal thickness (CRT) improved significantly after 6 months (median at baseline: 295 µm (275, 322); at 6 months: 275 µm (251, 308); p = 0.01).

Conclusion
TCZ is effective in reducing retinal vasculitis and CRT in refractory Birdshot uveitis over time, but might be less effective in managing choroidal inflammation. Further studies are needed to determine the optimal treatment strategies for TCZ therapy in NIU.
Preferences for attributes of an artificial intelligence-based risk assessment tool for HIV and sexually transmitted infections: a discrete choice experiment
Authors: Latt Phyu M. , Soe Nyi N. , King Alicia J. , Lee David , Phillips Tiffany R. , Xu Xianglong , Chow Eric P. F. , Fairley Christopher K. , Zhang Lei , Ong Jason J. 
Published: November 2024

Abstract
Introduction
Early detection and treatment of HIV and sexually transmitted infections (STIs) are crucial for effective control. We previously developed MySTIRisk, an artificial intelligence-based risk tool that predicts the risk of HIV and STIs. We examined the attributes that encourage potential users to use it.

Methods
Between January and March 2024, we sent text message invitations to the Melbourne Sexual Health Centre (MSHC) attendees to participate in an online survey. We also advertised the survey on social media, the clinic's website, and posters in affiliated general practice clinics. This anonymous survey used a discrete choice experiment (DCE) to examine which MySTIRisk attributes would encourage potential users. We analysed the data using random parameters logit (RPL) and latent class analysis (LCA) models.

Results
The median age of 415 participants was 31 years (interquartile range, 26–38 years), with a minority of participants identifying as straight or heterosexual (31.8%, n = 132). The choice to use MySTIRisk was most influenced by two attributes: cost and accuracy, followed by the availability of a pathology request form, level of anonymity, speed of receiving results, and whether the tool was a web or mobile application. LCA revealed two classes: "The Precisionists" (66.0% of respondents), who demanded high accuracy and "The Economists" (34.0% of respondents), who prioritised low cost. Simulations predicted a high uptake (97.7%) for a tool designed with the most preferred attribute levels, contrasting with lower uptake (22.3%) for the least preferred design.

Conclusions
Participants were more likely to use MySTIRisk if it was free, highly accurate, and could send pathology request forms. Tailoring the tool to distinct user segments could enhance its uptake and effectiveness in promoting early detection and prevention of HIV and STIs.
Perceived stress among graduate students in health sciences at a military university: a mixed-method approach
Authors: Mushtaq Omar , Soh Michael , Dong Ting , Durning Steven J. , Melton John , McCants Khalilah M. , Taylor Laura , Baumann Laura , Olapeju Bolanle 
Published: November 2024

Abstract
Background
There is a gap in the literature about the experiences of active-duty military students pursuing a graduate degree in health sciences at a university that emphasizes a military context. This exploratory study investigates how graduate students navigate stress in the context of a military university.

Method
The study applied a mixed-methods approach including a survey (N = 59) and in-depth interviews (N = 16) of students enrolled in a graduate program at the School of Medicine (368 students) and School of Nursing (187 students). Survey data was collected via email blasts to various health science departments. In the survey, students could opt-in to complete in-depth interviews. Survey data were analyzed using cross-tabulations while a transcendental phenomenological approach was employed to code and analyze qualitative data.

Results
Survey findings showed that more civilian students (70.6%) felt more noticeably and severely stressed than their active-duty counterparts (64.3%). Active-duty students were more likely to see their grades as a source of stress (76.2%) than their civilian counterparts (64.7%). Active-duty students were less likely to see finances as a source of stress (67.7%) than their civilian counterparts. Active-duty students were not as connected to their families and friends as their civilian counterparts were. The interviews found that active-duty students anticipated the coursework and were adept at juggling multiple demands; whereas, the civilian students centered their concerns around culture and collaboration. Active-duty students saw their program as less of a “big deal;” whereas, civilian students highlighted how they were concerned about the program and financial situations. Active-duty students relied on technical knowledge to understand their well-being; whereas, civilian students understood their well-being in holistic terms. Active-duty students focused on the idea of the individual, and how they take personal responsibility; whereas, civilian students focused more on self-care and compassion.

Conclusion
The study found how civilian and active-duty students experienced stress, stressors, and other aspects that contextualize their experience with stress. Study findings may inform the design of interventions to improve student well-being and resilience mechanisms among similar graduate school contexts.
Schools of public health as a cornerstone for pandemic preparedness and response: the Africa COVID-19 experience
Authors: Ndejjo Rawlance , Mitonga Honore Kabwebwe , Amde Woldekidan , Lubega Grace Biyinzika , Muula Adamson S. , Mariam Damen Haile , Kabwama Steven N. , Patrick Sean Mark , Haufiku Desderius , Amour Maryam , Bosonkie Marc , Mukama Trasias , Bello Segun , Dwomoh Duah , Nja Glory Mbe Egom , Bulafu Douglas , Halake Dabo Galgalo , Frumence Gasto , Leye Mamadou Makhtar Mbacke , Katangolo-Nakashwa Ndasilohenda , Abaya Samson Wakuma , Diallo Issakha , Egbende Landry , Worku Netsanet , Bassoum Oumar , Mbunga Branly , Musoke David , Mohamed Hussein , Seck Ibrahima , Fobil Julius , Kiwanuka Suzanne N. , Fawole Olufunmilayo I. , Mapatano Mala Ali , Alfven Tobias , Gilson Lucy , Syombua Muinde Jacinta Victoria , van Marwijk Harm , Lehmann Uta , Speybroeck Niko , Kaseje Margaret , Wanyenze Rhoda K. 
Published: November 2024

Abstract
Background
The Coronavirus disease (COVID-19) pandemic caused significant morbidity and mortality in Africa, in addition to other socio-economic consequences. Across the continent, Schools of Public Health (SPHs) played several roles in supporting national, regional, and global response to the pandemic. Following a published and grey literature search, this paper reviews and analyses the contribution of SPHs in Africa during the COVID-19 pandemic.

Contribution of the Schools of Public Health
SPH faculty in most countries contributed their expertise through COVID-19 task forces and advisory committees where they guided and supported decision-making. Faculty also supported the identification, review, and synthesis of rapidly evolving global and local evidence, adapting it to the local context to guide policy decisions. Through research, SPHs contributed to a better understanding of the disease epidemiology, response interventions, as well as prevention and control measures. SPHs engaged in training field epidemiologists, frontline health workers, and district response teams. SPH staff, students and field epidemiology trainees also supported field activities including surveillance, contact tracing, as well as managing quarantine facilities and points of entry. SPHs engaged in public education and awareness-raising initiatives to share information and dispel misinformation. In partnership with other stakeholders, SPHs also developed important innovations and technologies.

Conclusion
SPHs are a critical pillar for pandemic prevention, preparedness, and response, that support health systems with important functions. To further enhance their capacity, efforts to improve coordination of SPHs, strengthen collaboration among schools, harmonize training and curricula, and enhance capacity for advanced research are needed. There is also a need to bridge the inequities in capacity and resources that exist among SPHs across regions and countries.
Advancing understanding of human variability through toxicokinetic modeling, in vitro-in vivo extrapolation, and new approach methodologies
Authors: Kreutz Anna , Chang Xiaoqing , Hogberg Helena T. , Wetmore Barbara A. 
Published: November 2024

AbstractThe merging of physiology and toxicokinetics, or pharmacokinetics, with computational modeling to characterize dosimetry has led to major advances for both the chemical and pharmaceutical research arenas. Driven by the mutual need to estimate internal exposures where in vivo data generation was simply not possible, the application of toxicokinetic modeling has grown exponentially in the past 30 years. In toxicology the need has been the derivation of quantitative estimates of toxicokinetic and toxicodynamic variability to evaluate the suitability of the tenfold uncertainty factor employed in risk assessment decision-making. Consideration of a host of physiologic, ontogenetic, genetic, and exposure factors are all required for comprehensive characterization. Fortunately, the underlying framework of physiologically based toxicokinetic models can accommodate these inputs, in addition to being amenable to capturing time-varying dynamics. Meanwhile, international interest in advancing new approach methodologies has fueled the generation of in vitro toxicity and toxicokinetic data that can be applied in in vitro-in vivo extrapolation approaches to provide human-specific risk-based information for historically data-poor chemicals. This review will provide a brief introduction to the structure and evolution of toxicokinetic and physiologically based toxicokinetic models as they advanced to incorporate variability and a wide range of complex exposure scenarios. This will be followed by a state of the science update describing current and emerging experimental and modeling strategies for population and life-stage variability, including the increasing application of in vitro-in vivo extrapolation with physiologically based toxicokinetic models in pharmaceutical and chemical safety research. The review will conclude with case study examples demonstrating novel applications of physiologically based toxicokinetic modeling and an update on its applications for regulatory decision-making. Physiologically based toxicokinetic modeling provides a sound framework for variability evaluation in chemical risk assessment.
Muscularity-oriented disordered eating: investigating body image concerns and the moderating role of emotion dysregulation in cyclists
Authors: Mazaraki Jack , Bussey Kay , Cunningham Mitchell , Jewell Tom , Trompeter Nora 
Published: November 2024

AbstractA lean muscular body of low weight is often associated with performance for cyclists and can be difficult to achieve. Disordered eating for some cyclists may develop in the pursuit of lean muscularity which is perceived to be beneficial to performance. Further, emotion dysregulation may exacerbate negative feelings about body image, increasing the risk of developing disordered eating as a means of controlling weight and shape. While research in athlete populations has been substantial, disordered eating in cyclists is relatively under-explored. The current study examined whether shape and weight concern and drive for leanness were associated with muscularity-oriented disordered eating and whether these relationships were moderated by emotion dysregulation. Interactions between these factors were also investigated. Participants were 139 Australian competitive cyclists (112 males, 27 females, aged 18–68 years) who completed a self-report questionnaire comprised of measures of shape and weight concern, drive for leanness, muscularity-oriented eating and emotion dysregulation variables. Both shape and weight concern and drive for leanness had a unique association with muscularity-oriented disordered eating. Emotion dysregulation was found to have a unique association with muscularity-oriented disordered eating when controlling for drive for leanness, but not when shape and weight concern was controlled. Additionally, emotion dysregulation moderated the association between shape and weight concern and muscularity-oriented disordered eating, whereby the relationship was intensified at higher levels of emotion dysregulation. Our study has extended the literature by indicating that cyclists’ desire to attain a lean body is associated with muscularity-oriented disordered eating. Further, emotion dysregulation moderated this link, suggesting it could be a maintaining factor worth addressing.
Depression like-behavior and memory loss induced by methylglyoxal is associated with tryptophan depletion and oxidative stress: a new in vivo model of neurodegeneration
Authors: Md. Samsuzzaman  , Hong Seong-Min , Lee Jae Hyuk , Park Hyunjun , Chang Keun-A , Kim Hyun-Bum , Park Myoung Gyu , Eo Hyeyoon , Oh Myung Sook , Kim Sun Yeou 
Published: November 2024

Abstract
Background
Depression and memory loss are prevalent neurodegenerative disorders, with diabetic patients facing an elevated risk of brain dysfunction. Methylglyoxal (MGO) formation, which is heightened in diabetes owing to hyperglycemia and gut dysbiosis, may serve as a critical link between diabetes and brain diseases. Despite the high prevalence of MGO, the precise mechanisms underlying MGO-induced depression and memory loss remain unclear.

Results
We investigated the effect of MGO stress on depression like-behavior and memory loss to elucidate the potential interplay between MGO-induced tryptophan (Trp) metabolism impairment and oxidative stress in the brain. It demonstrates that MGO induces depression-like behavior in mice, as confirmed by the OFT, TST, FST, SPT, and EPM behavioral tests. MGO led to the depletion of Trp and related neurotransmitters as 5-HT, EPI, and DA in the mouse brain. Additionally, MGO reduced the cell count in the DG, CA1, and CA3 hippocampal regions and modulated TPH2 levels in the brain. Notably, co-treatment with MGO and Trp mirrored the effects observed after Trp-null treatment in neurons, including reduced TPH1 and TPH2 levels and inhibition of neuronal outgrowth. Furthermore, MGO significantly altered the expression of key proteins associated with neurodegeneration, such as p-Tau, p-GSK-3β, APP, oAβ, BDNF, NGF, and p-TrkB. Concurrently, MGO activated MAPKs through ROS induction, triggering a redox imbalance by downregulating Nrf-2, Ho-1, TXNRD1, Trx, Sirt-3, and Sirt-5 expression levels, NAD+, and CAT activity in the mouse brain. This led to an accelerated neuroinflammatory response, as evidenced by increased expression of Iba-1, p-NF-κB, and the secretion of IL-6 and TNF-α. Importantly, Trp treatment ameliorated MGO-induced depression like-behavior and memory loss in mice and markedly mitigated increased expression of p-Tau, APP, p-ERK1/2, p-pJNK, and p-NF-κB in the brain. Likewise, Trp treatment also induced the expression of MGO detoxifying factors GLO-I and GLO-II and CAT activity, suggesting the induction of an antioxidant system and reduced inflammation by inhibiting IL-6 and TNF-α secretion.

Conclusions
Our data revealed that MGO-induced depression like-behavior and memory deficits resulted from disturbances in Trp, 5-HT, BDNF, and NGF levels, increased p-Tau and APP expression, neuroinflammation, and impaired redox status (Nrf-2/Ho-1/TXNRD1/Sirt3/5) in the brain.
New insights on the Xylaria species (Ascomycota, Xylariales) with bright-coloured exudates: Xylaria aurantiorubroguttata sp. nov. and revision of X. haemorrhoidalis and X. anisopleura type collections
Authors: Forin Niccolò , Vizzini Alfredo , Amalfi Mario , Voyron Samuele , Ercole Enrico , Marcolini Simone , Moschin Silvia , Baldan Barbara 
Published: November 2024

AbstractA new species of Xylaria is described based on morphological characters of both sexual and asexual morphs, and molecular data based on nuclear rDNA internal transcribed spacer, α-actin, β-tubulin and RNA polymerase subunit II sequences. Xylaria aurantiorubroguttata is characterized by the presence of both upright, cylindrical, long-stipitate and globose to subglobose, short-stipitate stromata, immature stromatal stages producing at first orange and then red drops, and ascospores with a slightly oblique, straight half spore-length germ slit. We provide also new morphological descriptions for X. haemorrhoidalis (holotype) and X. anisopleura (isosyntype), two Xylaria species belonging to X. polymorpha complex together with X. aurantiorubroguttata.
Computational and experimental insights into glycyrrhizin-loaded nanostructured lipid carriers: docking, dynamics, design optimization, and anticancer efficacy in lung cancer cells
Authors: Kumar Amit , Tiwari Abhishek , Tiwari Varsha 
Published: November 2024

Abstract
Background
Lung cancer (LC) remains a predominant global health concern, especially with escalating tobacco-smoking rates. Present study provides computational screening, molecular dynamics, DFT and simulation analysis of phytoconstituents on EGFR receptors (2ITY and W2O), followed by selection of highest docking score phytoconstituents among 45 for further analysis. The formulation was optimized by Central composite design. Nanostructured-lipid carriers were prepared by high-speed homogenization, combining a 1:1 ratio of liquid lipid (Castor oil) and melted solid lipid (glyceryl monostearate) with 4% surfactant (tween 80) in a water phase containing Glycyrrhizin. The resulting mixture underwent high-speed homogenization at 8000 rpm for 40 min, followed by sonication for 15 min to achieve formulation development of GNLC. The anticancer potential of GNLC have been proved by experimental analysis through MTT assay using A549 Cell lines.

Results
Glycyrrhizin was found to possess maximum docking score − 8.863 and − 8.837 on both 2ITY and W2O respectively. The study unveils Glycyrrhizin’s interactions with EGFR pivotal in cancer progression and treatment. Molecular dynamics simulations highlighted the structural and dynamic interactions within a protein–ligand complex, indicating both stability and flexibility characteristics. DFT analysis of Glycyrrhizin revealed its molecular properties, suggesting stability and potential reactivity. Glycyrrhizin loaded nanostructured lipid carriers (GNLC) have been developed and analysed by various parameters like particle size and drug release zeta potential, SEM analysis, and solubility analysis reveals critical insights into their optimization for effective drug delivery. Both GNLC and Doxorubicin (0.78–50 µg/ml) were used for the activity. The anticancer potential at 12.50, 25 and 50 µg/ml pf GNLC was found to be statistically significant and was comparable with that of standard group Doxorubicin. The observed structural transformations in Glycyrrhizin into a lipid matrix indicate potential enhancements in its drug release.

Conclusions
GNLC shows promising anti-cancer potential in lung cancer, further pre-clinical and clinical studies, is crucial to validate its efficacy, safety, and integration into standard therapeutic regimens.

Graphical abstract
Timeliness of Breast Cancer Patients' Presentation to Health Care Facilities in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Wendimu Debisa Eshatu , Degefa Mosisa Bekele , Achalu Daniel Legese , Mamo Biniyam Tedla , Daba Derese Bekele , Meshesha Solomon Getnet 
Published: November 2024

PURPOSE
Low breast cancer survival rates are often linked to late-stage diagnosis. The patient interval, the time between symptom detection and the first health care visit, is a key indicator of early diagnosis. This study aimed to assess the prevalence of patient delay and its associated factors in Ethiopia.

METHODS
This systematic review used a combined approach of meta-analysis and meta-synthesis of quantitative and qualitative data, respectively. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.

RESULTS
Eleven studies that satisfied the eligibility criteria were included in the review. More than half (58.48%) of the patients with breast cancer delayed seeking medical help at health facilities, with a median delay time of 120 days. Presence of a painful breast ulcer/wounded mass (odds ratio [OR], 0.23 [95% CI, 0.09 to 0.58]), having swelling or a lump in the armpit (OR, 0.27 [95% CI, 0.15 to 0.46]), residing in urban area (OR, 0.27 [95% CI, 0.15 to 0.49]), and having a secondary school education or higher (OR, 0.28 [95% CI, 0.12 to 0.64]) were less likely to delay in seeking formal health care. However, patients who travel more than 5 km (OR, 6.33 [95% CI, 4.10 to 9.75]) were more likely to delay in our meta-analysis. Moreover, the meta-synthesis showed that the nature and progression of symptoms, symptom disclosure, social support, emotional responses, use of alternative therapies, misconceptions about breast cancer, financial limitations, accessibility issues, and other personal-environmental factors were associated with patient delay.

CONCLUSION
Nearly three fifths of patients with breast cancer delayed seeking health care at health facilities. Inaccessibility, low awareness, cultural beliefs, and socioeconomic factors contributed to these delays. Increasing public awareness, especially in rural areas, and improving health care access could encourage earlier presentation.