bluuebunny/crossref_metadata_2025 huggingface dataset:
A suposta entronização de Alexandre Magno no Egito (332 a.C.): entre fragmentos de historiadores gregos, relatos helenístico-romanos e especulação historiográfica
Authors: Sant'Anna Henrique Modanez de
Published: May 2024

Commentators on the Alexander Romance (AR) have often countered the reservations of modern historians on using the text as a historical source for the life of Alexander the Great. This is particularly relevant with regard to the king’s purported enthronement at Memphis. Historical biographies of Alexander as well as recent studies on his Egyptian royal titles lend support to the use of the AR as a source for this particular event, by arguing that an Egyptian enthronement can be defended. These studies make use of a complete onomastic protocol in archaeological evidence that dates from Alexander’s time. The present article offers a systematic discussion of ancient accounts of his first stay in Memphis to emphasize that the reservations of modern historians are based on the silence on the first by historians from the time of Alexander, whose works (preserved only in fragments) were used by writers of the main corpus of Hellenistic-Roman sources. I argue that there is evidence of a Macedonian strategy that sought to align its monarchical experience with older Egyptian traditions as well as the inclination of the Memphite priestly elite to fulfill a messianic expectation disseminated since the disappearance of Nectanebo II. Both, however, for reasons including both the length of Alexander’s stay in Egypt and the special solemnity of the coronation of Egyptian kings, seem not to have resulted in his formal enthronement in Memphis. The silence of the Hellenistic-Roman sources remains imperative.
A Sociedade Ipiranga do Rio de Janeiro: tensões e limites da emergência do associativismo abolicionista gradual no Brasil Imperial (1855-1863)
Authors: Ferretti Danilo José Zioni
Published: May 2024

The article deals with the Ipiranga Society (SI) of Rio de Janeiro, dedicated to the celebration of national independence through the granting of manumissions and its relationship with slavery. It seeks to understand whether there was abolitionism in the practices of the IS and how to characterize it. In broader terms, the relationship between slavery and the constitution of modern public space in mid-nineteenth-century Brazil is discussed, assessing its potentialities and limitations. The ambiguities of the IS’s practices of gradual abolitionism, their unfolding at the national and transnational levels, as well as the internal tensions within the association that led to the end of such practices, reinforced by state intervention, through the application of the “law of obstacles” of 1860, are indicated.
On the Unexpected Abilities of Large Language Models
Authors: Nolfi Stefano
Published: May 2024

Large Language Models (LLMs) are capable of displaying a wide range of abilities that are not directly connected with the task for which they are trained: predicting the next words of human-written texts. In this article, I review recent research investigating the cognitive abilities developed by LLMs and their relation to human cognition. I discuss the nature of the indirect process that leads to the acquisition of these cognitive abilities, their relation to other indirect processes, and the implications for the acquisition of integrated abilities. Moreover, I propose the factors that enable the development of abilities that are related only very indirectly to the proximal objective of the training task. Finally, I discuss whether the full set of capabilities that LLMs could possibly develop is predictable.
Adaptation mechanism of three Impatiens species to different habitats based on stem morphology, lignin and MYB4 gene
Authors: Li Xin-Yi , Li Ze-Feng , Zhang Xiao-Li , Yang Meng-Qing , Wu Pei-Qing , Huang Mei-Juan , Huang Hai-Quan
Published: May 2024

Background

Impatiens is an important genus with rich species of garden plants, and its distribution is extremely extensive, which is reflected in its diverse ecological environment. However, the specific mechanisms of Impatiens’ adaptation to various environments and the mechanism related to lignin remain unclear.

Results

Three representative Impatiens species,Impatiens chlorosepala (wet, low degree of lignification), Impatiens uliginosa (aquatic, moderate degree of lignification) and Impatiens rubrostriata (terrestrial, high degree of lignification), were selected and analyzed for their anatomical structures, lignin content and composition, and lignin-related gene expression. There are significant differences in anatomical parameters among the stems of three Impatiens species, and the anatomical structure is consistent with the determination results of lignin content. Furthermore, the thickness of the xylem and cell walls, as well as the ratio of cell wall thickness to stem diameter have a strong correlation with lignin content. The anatomical structure and degree of lignification in Impatiens can be attributed to the plant's growth environment, morphology, and growth rate. Our analysis of lignin-related genes revealed a negative correlation between the MYB4 gene and lignin content. The MYB4 gene may control the lignin synthesis in Impatiens by controlling the structural genes involved in the lignin synthesis pathway, such as HCT, C3H, and COMT. Nonetheless, the regulation pathway differs between species of Impatiens.

Conclusions

This study demonstrated consistency between the stem anatomy of Impatiens and the results obtained from lignin content and composition analyses. It is speculated that MYB4 negatively regulates the lignin synthesis in the stems of three Impatiens species by regulating the expression of structural genes, and its regulation mechanism appears to vary across different Impatiens species. This study analyses the variations among different Impatiens plants in diverse habitats, and can guide further molecular investigations of lignin biosynthesis in Impatiens.
Systematic review and meta-analysis of hepatitis E seroprevalence in Southeast Asia: a comprehensive assessment of epidemiological patterns
Authors: Mirzaev Ulugbek Khudayberdievich , Ouoba Serge , Ko Ko , Phyo Zayar , Chhoung Chanroth , Ataa Akuffo Golda , Sugiyama Aya , Akita Tomoyuki , Tanaka Junko
Published: May 2024

The burden of hepatitis E in Southeast Asia is substantial, influenced by its distinct socio-economic and environmental factors, as well as variations in healthcare systems. The aim of this study was to assess the pooled seroprevalence of hepatitis E across countries within the Southeast Asian region by the UN division.

The study analyzed 66 papers across PubMed, Web of Science, and Scopus databases, encompassing data from of 44,850 individuals focusing on anti-HEV seroprevalence. The investigation spanned nine countries, excluding Brunei and East Timor due to lack of data. The pooled prevalence of anti-HEV IgG was determined to be 21.03%, with the highest prevalence observed in Myanmar (33.46%) and the lowest in Malaysia (5.93%). IgM prevalence was highest in Indonesia (12.43%) and lowest in Malaysia (0.91%). The study stratified populations into high-risk (farm workers, chronic patients) and low-risk groups (general population, blood donors, pregnant women, hospital patients). It revealed a higher IgG—28.9%, IgM—4.42% prevalence in the former group, while the latter group exhibited figures of 17.86% and 3.15%, respectively, indicating occupational and health-related vulnerabilities to HEV.

A temporal analysis (1987–2023), indicated an upward trend in both IgG and IgM prevalence, suggesting an escalating HEV burden.

These findings contribute to a better understanding of HEV seroprevalence in Southeast Asia, shedding light on important public health implications and suggesting directions for further research and intervention strategies.

Key points

Research Question

Investigate the seroprevalence of hepatitis E virus (HEV) in Southeast Asian countries focusing on different patterns, timelines, and population cohorts.

Findings

Sporadic Transmission of IgG and IgM Prevalence:

• Pooled anti-HEV IgG prevalence: 21.03%

• Pooled anti-HEV IgM prevalence: 3.49%

Seroprevalence among specific groups:

High-risk group (farm workers and chronic patients):

• anti-HEV IgG: 28.9%

• anti-HEV IgM: 4.42%

Low-risk group (general population, blood donors, pregnant women, hospital patients):

• anti-HEV IgG: 17.86%

• anti-HEV IgM: 3.15%

Temporal Seroprevalence of HEV:

Anti-HEV IgG prevalence increased over decades (1987–1999; 2000–2010; 2011–2023): 12.47%, 18.43%, 29.17% as an anti-HEV IgM prevalence: 1.92%, 2.44%, 5.27%

Importance

Provides a comprehensive overview of HEV seroprevalence in Southeast Asia.

Highlights variation in seroprevalence among different population groups.

Reveals increasing trend in HEV seroprevalence over the years.

Distinguishes between sporadic and epidemic cases for a better understanding of transmission dynamics.
Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up
Authors: Zhang Li-Yuan , Guo Wei , Du Han-Ze , Pan Hui , Sun Yun-Chuan , Zhu Hui-Juan , Song Shuai-Hua , Guo Xiao-Yuan , Jiang Yue , Sun Qian-Qian
Published: May 2024

Objective

Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs.

Materials and methods

The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis.

Results

According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2–3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level.

Conclusion

In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.
Health policy and regulations in Seychelles – barriers and opportunities for oral health inclusion
Authors: Noshir C. Y. S. , Brijlal P.
Published: May 2024

Background

Successful and inclusive policies that embrace oral health as part of the health agenda have the potential to alleviate the burden of oral diseases and to promote dental public health. This study aimed to understand the factors influencing the inclusion of oral health in health and public policy and regulations in the Seychelles. The barriers and opportunities for inclusion / non-inclusion as well as the impact thereof were explored.

Methodology

A qualitative approach was adopted using document analysis and interviews as data collection strategies to allow for a complete analysis of the research problem. Using a purposive sampling approach, individual face to face interviews were conducted with patients, dental staff and representatives of the upper management. Policy and related oral health statistical documents were reviewed to ascertain how oral health was located and implemented from a national to a district level. Thematic analysis and content analysis were used to analyse and interpret the qualitative data.

Results

The study provided insight on how oral health is contextualised in the Seychelles and how public policy and strategic documents influences the oral health outcomes. There is fragmentation in how the health and oral health agendas are managed and it is coupled with a severe lack of involvement and commitment to address the latter.

Conclusion

Oral health needs to be integrated in all relevant policies and public health programmes as part of the broader national NCDs in Seychelles in order reduce the incidence of oral diseases in the population.
Astragalus polysaccharides augment BMSC homing via SDF-1/CXCR4 modulation: a novel approach to counteract peritoneal mesenchymal transformation and fibrosis
Authors: Wang Funing , Dai Huibo , Zhou Ziren , Shan Yun , Yu Manshu , Sun Jinyi , Sheng Li , Huang Liyan , Meng Xiaohui , You Yongqing , Sheng Meixiao
Published: May 2024

Purpose

This study aimed to evaluate the potential of astragalus polysaccharide (APS) pretreatment in enhancing the homing and anti-peritoneal fibrosis capabilities of bone marrow mesenchymal stromal cells (BMSCs) and to elucidate the underlying mechanisms.

Methods

Forty male Sprague-Dawley rats were allocated into four groups: control, peritoneal dialysis fluid (PDF), PDF + BMSCs, and PDF + APSBMSCs (APS-pre-treated BMSCs). A peritoneal fibrosis model was induced using PDF. Dil-labeled BMSCs were administered intravenously. Post-transplantation, BMSC homing to the peritoneum and pathological alterations were assessed. Stromal cell-derived factor-1 (SDF-1) levels were quantified via enzyme-linked immunosorbent assay (ELISA), while CXCR4 expression in BMSCs was determined using PCR and immunofluorescence. Additionally, a co-culture system involving BMSCs and peritoneal mesothelial cells (PMCs) was established using a Transwell setup to examine the in vitro effects of APS on BMSC migration and therapeutic efficacy, with the CXCR4 inhibitor AMD3100 deployed to dissect the role of the SDF-1/CXCR4 axis and its downstream impacts.

Results

In vivo and in vitro experiments confirmed that APS pre-treatment notably facilitated the targeted homing of BMSCs to the peritoneal tissue of PDF-treated rats, thereby amplifying their therapeutic impact. PDF exposure markedly increased SDF-1 levels in peritoneal and serum samples, which encouraged the migration of CXCR4-positive BMSCs. Inhibition of the SDF-1/CXCR4 axis through AMD3100 application diminished BMSC migration, consequently attenuating their therapeutic response to peritoneal mesenchyme-to-mesothelial transition (MMT). Furthermore, APS upregulated CXCR4 expression in BMSCs, intensified the activation of the SDF-1/CXCR4 axis’s downstream pathways, and partially reversed the AMD3100-induced effects.

Conclusion

APS augments the SDF-1/CXCR4 axis’s downstream pathway activation by increasing CXCR4 expression in BMSCs. This action bolsters the targeted homing of BMSCs to the peritoneal tissue and amplifies their suppressive influence on MMT, thereby improving peritoneal fibrosis.
For the rural curious: mixed methods evaluation of a rural pharmacy practice elective
Authors: Stratton Timothy P.
Published: May 2024

Background

As of 2020, 20% of people residing in the United States of America (U.S.) lived in rural communities. Despite rural residents tending to be older, poorer, and having greater disease burden than their urban counterparts, the number of rural primary care providers continues to decline. Nearly 66% of U.S. Primary Care Health Professional Shortage Areas are designated as rural. Pharmacists can help address this shortage of rural primary care providers, often serving as providers of first-contact care; however, only 12% of U.S. pharmacists practice in rural communities. To help address this gap, in 2022 an elective Rural Pharmacy course was created at the University of Minnesota College of Pharmacy by a faculty member who has rural practice experience.

Methods

The course combines formal lectures, guest presentations by rural pharmacists and student interviews with additional rural pharmacists. For the 42 students enrolled in the course in 2022 and 2023, non-parametric statistics were used to compare the percentage of students who were raised in rural communities or who otherwise had extensive exposure to rural, and compare student interest ratings (1 to 7) about practicing/living rural at the beginning and end of the course. Students also wrote end-of-course reflection papers, commenting on the course and their interviews with rural pharmacists.

Results

Across both years, 45% of the enrolled students had previous experience in rural communities. The net change in Rural Interest scores among students completing both questionnaires was + 5 in 2022 and + 2 in 2023, both non-significant differences. The largest shifts in student interest were from “Not Sure” at the start of the course to “Interested” or “Not Interested” at the end of the course, and from “Interested” to “Very Interested.” In their reflection papers nearly 60% of students reported being most impressed by their interviews with rural pharmacists.

Conclusions

A course addressing the benefits and challenges of practicing pharmacy in rural communities was well-received by pharmacy students. Even students who have little interest in living in a rural community can benefit from being introduced to rural culture, enabling them to provide more culturally-responsive care for patients from rural communities.
The impact of distance education on the socialization of college students in the Covid-19 era: problems in communication and impact on mental health
Authors: Liu Qingxia , Lin Douxiu
Published: May 2024

Background

The problems of students’ social interaction and psychological well-being associated with online learning dependent on self-directed learning have become an important topic of research in recent years worldwide due to the COVID-19 pandemic, affecting their Social Emotional Learning. This paper aimed to compare the students’ loneliness, social anxiety, social interaction, and general psychological well-being at different stages of online learning (at the beginning and the height of the pandemic), considering their criteria (presence/absence of a job and own family).

Methods

For this, the researchers conducted an electronic survey of students (n = 320) twice, in February and May 2020, using four questionnaires: UCLA loneliness scale-3, Social Anxiety Scale for E-Learning Environments, Social Interaction Scale, and Brief Adjustment Scale. The responses at different stages of online learning were compared using Student’s t-test. Differences between employed and unemployed students with or without their own families were determined using the analysis of variance (ANOVA).

Results

The findings showed that unemployed students without their families suffered the most from loneliness. Social interaction online was rated higher by students with their own families; psychological well-being at the beginning of the distance period and social anxiety at the height of the distance period were higher among unemployed students.

Conclusions

This research can become a theoretical basis for a phase-by-phase study of social predictors for the psychological well-being of higher education students and is of practical value for teachers and administrators of online learning aimed at students’ socialization. In addition, it provides education officials with information about how students perceive psychological well-being, anxiety, social interaction, and loneliness during distance learning, which can help officials direct their decisions and reforms to improve interaction in the online environment.
The influence of socio-cognitive mindfulness, moral sensitivity and dementia communication behaviors on dementia nursing performance of nurses in long-term care hospitals: a cross-sectional study
Authors: Bong Hyun Ju , Lee Mikyoung
Published: May 2024

Background

By incorporating socio-cognitive mindfulness which has been under-examined in the nursing field, this study investigated the relationships between socio-cognitive mindfulness, moral sensitivity, dementia communication behaviors, and dementia nursing performance of nurses in long-term care hospitals. This study also examined the factors influencing nurses’ dementia nursing performance.

Methods

A cross-sectional study was conducted with 209 nurses from long-term care hospitals in Korea. Data were collected between August 1 and August 31, 2022. Participants completed the questionnaire assessing their socio-cognitive mindfulness, moral sensitivity, dementia communication behaviors, and dementia nursing performance. Pearson’s correlation and hierarchical multiple regression analysis were performed for data analysis.

Results

Dementia nursing performance of the nurses in long-term care hospitals was positively related to their socio-cognitive mindfulness, moral sensitivity, and dementia communication behaviors. Furthermore, nurses’ dementia communication behaviors, moral sensitivity, and total clinical career, in that order, were found to be the factors influencing their dementia nursing performance.

Conclusion

The findings indicate that the higher socio-cognitive mindfulness, moral sensitivity, and dementia communication behaviors, the higher dementia nursing performance, and that higher dementia nursing performance is associated with better dementia communication behaviors, greater moral sensitivity, and more extensive clinical experiences. This study provides a foundation for developing effective interventions to enhance dementia nursing performance in the future. To improve dementia nursing performance of nurses in long-term care hospitals, it is necessary to improve dementia communication behaviors and moral sensitivity, and prepare multilateral countermeasures to maintain nurses’ clinical careers.
Considerations, barriers and enablers of deprescribing among healthcare professionals in Ogun State, Southwest, Nigeria: a cross-sectional survey
Authors: Saka Sule Ajibola , Osineye Tolulope Ruth
Published: May 2024

Background

Deprescribing is a clinical intervention aimed at managing polypharmacy and improving older adults’ health outcomes. However, evidence suggests that healthcare professionals (HCPs) may face challenges in implementing the intervention. This study aimed to explore the considerations, barriers and enablers of deprescribing among HCPs in Southwest Nigeria.

Methods

A quantitative cross-sectional survey was carried out among consecutively sampled HCPs including physicians, pharmacists and nurses in two public tertiary healthcare hospitals in Ogun State, Southwest, Nigeria. A structured 43-item self-administered questionnaire was used to explore the participants’ sociodemographics, HCPs’ experience, considerations, barriers and enablers of deprescribing in older adults. The data were summarised using descriptive statistics including frequency and percentage. The Kruskal–Wallis test was used to determine differences in perceptions among the groups on a Likert scale. A p-value < 0.05 was considered significant.

Results

Overall, 453 copies of the questionnaire were analysed. Of the participants 204 (45.0%) were within the age group of 20–30 years; 173 (38.2%) claimed that older adults occasionally requested deprescribing of their medications. The majority (417; 92.1%) considered patients’ quality of life to be very important in deprescribing; 423 (93.4%) opined that having a care goal known to members of the HCP team is an enabler for deprescribing while 308 (68.0%) disagreed or strongly disagreed that lack of incentives and remuneration for HCPs that de-prescribe is a barrier to deprescribing. There is a significant difference among the participants across professional groups on the assertion that pressure from pharmaceutical companies is a barrier to deprescribing in older adults (p = 0.037).

Conclusions

The participants in this study had various considerations for deprescribing medication in older adults including patients’ quality of life. Having a care goal known to every HCP involved in managing a patient is an enabler for deprescribing while the lack of incentives and remuneration for HCPs that de-prescribe may not necessarily be a barrier to deprescribing. There is a need for regulations and policies to support the identified enablers among HCPs and reduce the barriers to effective deprescribing process.
Association between characteristics of employing healthcare facilities and healthcare worker infection rates and psychosocial experiences during the COVID-19 pandemic
Authors: Lusk Jay B. , Manandhar Pratik , Thomas Laine E. , O’Brien Emily C.
Published: May 2024

Background

Healthcare facility characteristics, such as ownership, size, and location, have been associated with patient outcomes. However, it is not known whether the outcomes of healthcare workers are associated with the characteristics of their employing healthcare facilities, particularly during the COVID-19 pandemic.

Methods

This was an analysis of a nationwide registry of healthcare workers (the Healthcare Worker Exposure Response and Outcomes (HERO) registry). Participants were surveyed on their personal, employment, and medical characteristics, as well as our primary study outcomes of COVID-19 infection, access to personal protective equipment, and burnout. Participants from healthcare sites with at least ten respondents were included, and these sites were linked to American Hospital Association data to extract information about sites, including number of beds, teaching status, urban/rural location, and for-profit status. Generalized estimating equations were used to estimate linear regression models for the unadjusted and adjusted associations between healthcare facility characteristics and outcomes.

Results

A total of 8,941 healthcare workers from 97 clinical sites were included in the study. After adjustment for participant demographics, healthcare role, and medical comorbidities, facility for-profit status was associated with greater odds of COVID-19 diagnosis (aOR 1.76, 95% CI 1.02–3.03, p = .042). Micropolitan location was associated with decreased odds of COVID-19 infection after adjustment (aOR = 0.42, 95% CI 0.24, 0.71, p = .002. For-profit facility status was associated with decreased odds of burnout after adjustment (aOR = 0.53, 95% CI 0.29–0.98), p = .044).

Conclusions

For-profit status of employing healthcare facilities was associated with greater odds of COVID-19 diagnosis but decreased odds of burnout after adjustment for demographics, healthcare role, and medical comorbidities. Future research to understand the relationship between facility ownership status and healthcare outcomes is needed to promote wellbeing in the healthcare workforce.

Trial registration

The registry was prospectively registered: ClinicalTrials.gov Identifier (trial registration number) NCT04342806, submitted April 8, 2020.
Pamidronate-induced irreversible symptomatic hypocalcemia in a dog with hypercalcemia after glucocorticoid withdrawal: a case report
Authors: Oh Ye-In , An Ju-Hyun , Lim Ga-Hyun , Park Su-Min , Kim Tae-Hee , Seo Kyoung-Won , Youn Hwa-Young
Published: May 2024

Background

Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog.

Case presentation

An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner’s request because of worsened hypocalcemia and renal failure.

Conclusions

Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient’s underlying conditions. Therefore, the patient’s condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate.
Re-evaluating the placebo response in recent canine dietary epilepsy trials
Authors: Schmidt Teresa , Meyerhoff Nina , Meller Sebastian , Twele Friederike , Charalambous Marios , Berk Benjamin A. , Law Tsz H. , Packer Rowena M. A. , Zanghi Brian , Pan Yuanlong , Fischer Andrea , Volk Holger A.
Published: May 2024

The placebo response is a common phenomenon. Limited evidence is available about its magnitude in canine epilepsy trials, even though it can significantly influence the efficacy evaluation of new treatments. It was hypothesised that the placebo response is diminished when epilepsy trials are conducted in a prospective crossover design. Seizure data spanning six months from three previous multicenter epilepsy studies were analysed. The monthly seizure frequency of 60 dogs diagnosed with idiopathic epilepsy was calculated, comparing baseline data with placebo treatment. Furthermore, differentiation was made between dogs randomised to the placebo group early (Phase 1: first 3 months) or later during the study (Phase 2: second 3 months).

The analysis did not reveal any placebo response in terms of monthly seizure frequency. Instead, an increase was noted during the placebo treatment period, with a mean of 2.95 seizures per month compared to 2.30 seizures per month before study entry (p = 0.0378). Additionally, a notable phase effect was observed. Dogs receiving the placebo in the second study phase exhibited a significant increase in monthly seizure frequency compared to baseline (p = 0.0036). Conversely, no significant difference from baseline was observed for dogs receiving the placebo in the first study phase. These findings underscore the considerable variability in placebo responses observed in trials for canine epilepsy, contrasting with previous limited data. The identified phase effect should be carefully considered in the design and evaluation of canine epilepsy trials to ensure a more accurate assessment of efficacy for new treatments.
Endoscopic endonasal transsphenoidal approach improves endocrine function and surgical outcome in primary craniopharyngioma resection: a systematic review and meta-analysis
Authors: Li Shuang , Ye Youfan , Nie Chuansheng , Huang Xing , Yan Kaixuan , Zhang Fangcheng , Jiang Xiaobing , Wang Haijun
Published: May 2024

Background

Craniopharyngiomas (CPs) are generally derived from the craniopharyngeal duct epithelium, accounting for 38% and 24.5% of mortality in pediatric and adult patients, respectively. At present, the widespread application of the endoscopic endonasal transsphenoidal approach (EEA) has led to controversy between the traditional microscopic transcranial approach (TCA) and EEA in relation to the surgical management of CPs.

Object and method

We performed a systematic review and meta-analysis comparing the complications, surgical outcomes, and endocrine functions of patients with CPs to provide evidence-based decision-making in their surgical management.

Result

Overall, 11 observational studies with 12,212 participants were included in the meta-analysis, in which five of them only included an adult population, three of them only included a child population, and the other three studies included a mixed population (adult and child). In pediatric patients, the EEA achieved a higher gross total resection (GTR) rate (odds ratio (OR) = 5.25, 95%CI: 1.21–22.74), lower recurrence rate (OR = 0.54, 95%CI: 0.31–0.94, p = 0.030), and less hypopituitarism (OR = 0.34, 95%CI: 0.12–0.97, p = 0.043). In adult patients, EEA significantly improved mortality (OR = 0.09, 95%CI: 0.06–0.15, p < 0.001) and visual outcomes (visual improvement: OR = 3.42, 95%CI: 1.24–9.40, p = 0.017; visual deficit: OR = 0.30, 95%CI: 0.26–0.35) with decreases in postoperative stroke (OR = 0.58, 95%CI: 0.51–0.66, p < 0.001), hydrocephalus, and infections (OR = 0.32, 95%CI: 0.24–0.42, p < 0.001).

Conclusion

Compared with the traditional TCA in primary CP resection, the development and wide application of EEA optimistically decreased the recurrence rate of CP, alleviated hypopituitarism with improvement in the GTR rate of pediatric patients, and significantly improved the visual outcomes, hydrocephalus, postoperative stroke, survival, and infection rates of the patients. Therefore, EEA is an optimal approach for primary CP resection.
Medical expenses and its determinants in female patients with urological disorder
Authors: Park Sewon , Ji Seokmin , Lee Hyunseo , Choi Hangseok , Choi Mankyu , Lee Munjae , Jakovljevic Mihajlo
Published: May 2024

Background

The rising older adult population has led to an increase in the prevalence of chronic diseases and medical expenses. Women tend to have a longer healthy life expectancy than men and are more likely to be exposed to urological disorders around the age of 50, resulting in substantial healthcare expenses throughout their lifetime. Urological disorders often require continuous treatment owing to their high risk of recurrence, contributing to an increased financial burden from medical costs. This study aimed to identify factors influencing medical expense in female patients with urological disorders and propose strategies to alleviate the associated financial burden.

Methods

We used data from the Korea Health Panel Survey conducted from 2011 to 2016. The final sample comprised 2,932 patients who visited hospitals for urological disorders. To identify the factors influencing medical expense among female patients with urological disorders, we employed a generalized estimating equation model.

Results

The results indicated that younger people and patients with middle-income levels tended to incur higher medical expenses. Furthermore, patients receiving treatment at tertiary hospitals and those enrolled in National Health Insurance also incurred higher health expenses.

Conclusions

This study suggests that effective management of medical expenses related to urological disorders in women requires improvements in healthcare accessibility to facilitate early detection and continuous disease management. In addition, the findings highlight the potential benefits of digital health and non-face-to-face treatments in addressing these needs.
Cost-effectiveness of differentiated care models that incorporate economic strengthening for HIV antiretroviral therapy adherence: a systematic review
Authors: Liang Annie , Wilson-Barthes Marta , Galárraga Omar
Published: May 2024

Background

There is some evidence that differentiated service delivery (DSD) models, which use a client-centered approach to simplify and increase access to care, improve clinical outcomes among people living with HIV (PLHIV) in high HIV prevalence countries. Integrating economic strengthening tools (e.g., microcredit, cash transfers, food assistance) within DSD models can help address the poverty-related barriers to HIV antiretroviral therapy (ART). Yet there is minimal evidence of the cost-effectiveness of these types of multilevel care delivery models, which potentially prohibits their wider implementation.

Methods

Using a qualitative systematic review, this article synthesizes the literature surrounding the cost-effectiveness of differentiated service delivery models that employ economic strengthening initiatives to improve HIV treatment adherence in low- and middle-income countries. We searched three academic databases for randomized controlled trials and observational studies published from January 2000 through March 2024 in Sub-Saharan Africa. The quality of each study was scored using a validated appraisal system.

Results

Eighty-nine full texts were reviewed and 3 met all eligibility criteria. Two of the three included articles were specific to adolescents living with HIV. Economic strengthening opportunities varied by care model, and included developmental savings accounts, microenterprise workshops, and cash and non-cash conditional incentives. The main drivers of programmatic and per-patient costs were ART medications, CD4 cell count testing, and economic strengthening activities.

Conclusion

All economic evaluations in this review found that including economic strengthening as part of comprehensive differentiated service delivery was cost-effective at a willingness to pay threshold of at least 2 times the national per capita gross domestic product. Two of the three studies in this review focused on adolescents, suggesting that these types of care models may be especially cost-effective for youth entering adulthood. All studies were from the provider perspective, indicating that additional evidence is needed to inform the potential cost-savings of DSD and economic strengthening interventions to patients and society. Randomized trials testing the effectiveness of DSD models that integrate economic strengthening should place greater emphasis on costing these types of programs to inform the potential for bringing these types of multilevel interventions to scale.
The CD6 interactome orchestrates ligand-independent T cell inhibitory signaling
Authors: Santos Rita F. , de Sousa Linhares Annika , Steinberger Peter , Davis Simon. J. , Oliveira Liliana , Carmo Alexandre M.
Published: May 2024

Background

T-cell membrane scaffold proteins are pivotal in T cell function, acting as versatile signaling hubs. While CD6 forms a large intracellular signalosome, it is distinguished from typical scaffolds like LAT or PAG by possessing a substantial ectodomain that binds CD166, a well-characterized ligand expressed on most antigen-presenting cells (APC), through the third domain (d3) of the extracellular region. Although the intact form of CD6 is the most abundant in T cells, an isoform lacking d3 (CD6∆d3) is transiently expressed on activated T cells. Still, the precise character of the signaling transduced by CD6, whether costimulatory or inhibitory, and the influence of its ectodomain on these activities are unclear.

Methods

We expressed CD6 variants with extracellular deletions or cytosolic mutations in Jurkat cells containing eGFP reporters for NF-κB and NF-AT transcription factor activation. Cell activation was assessed by eGFP flow cytometry following Jurkat cell engagement with superantigen-presenting Raji cells. Using imaging flow cytometry, we evaluated the impact of the CD6-CD166 pair on cell adhesiveness during the antigen-dependent and -independent priming of T cells. We also examined the role of extracellular or cytosolic sequences on CD6 translocation to the immunological synapse, using immunofluorescence-based imaging.

Results

Our investigation dissecting the functions of the extracellular and cytosolic regions of CD6 revealed that CD6 was trafficked to the immunological synapse and exerted tonic inhibition wholly dependent on its cytosolic tail. Surprisingly, however, translocation to the synapse occurred independently of the extracellular d3 and of engagement to CD166. On the other hand, CD6 binding to CD166 significantly increased T cell:APC adhesion. However, this activity was most evident in the absence of APC priming with superantigen, and thus, in the absence of TCR engagement.

Conclusions

Our study identifies CD6 as a novel ‘on/off’ scaffold-receptor capable of modulating responsiveness in two ways. Firstly, and independently of ligand binding, it establishes signaling thresholds through tonic inhibition, functioning as a membrane-bound scaffold. Secondly, CD6 has the capacity for alternative splicing-dependent variable ligand engagement, modulating its checkpoint-like activity.
IL-37 ameliorates myocardial fibrosis by regulating mtDNA-enriched vesicle release in diabetic cardiomyopathy mice
Authors: Huang Qingyu , Chen Tongqing , Li Jian , Wang Yiming , Shi Huairui , Yu Yifei , Ji Qingwei , Shen Xiaoyan , Sun Tao , Shi Haiming , Luo Xinping , Jin Bo , You Yan , Wu Bangwei
Published: May 2024

Background

Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities of the heart and ultimately evolves to heart failure. IL-37 exerts a substantial influence on the regulation of inflammation and metabolism. Whether IL-37 is involved in DCM is unknown.

Methods

The plasma samples were collected from healthy controls, diabetic patients and DCM patients, and the level of IL-37 and its relationship with heart function were observed. The changes in cardiac function, myocardial fibrosis and mitochondrial injury in DCM mice with or without IL-37 intervention were investigated in vivo. By an in vitro co-culture approach involving HG challenge of cardiomyocytes and fibroblasts, the interaction carried out by cardiomyocytes on fibroblast profibrotic activation was studied. Finally, the possible interactive mediator between cardiomyocytes and fibroblasts was explored, and the intervention role of IL-37 and its relevant molecular mechanisms.

Results

We showed that the level of plasma IL-37 in DCM patients was upregulated compared to that in healthy controls and diabetic patients. Both recombinant IL-37 administration or inducing IL-37 expression alleviated cardiac dysfunction and myocardial fibrosis in DCM mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling and the cGAS-STING pathway to initiate pro-fibrotic process and adverse remodeling. However, the presence of IL-37 ameliorated mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, resulting in a reduction in release of mtDNA-enriched vesicle and ultimately attenuating the progression of DCM.

Conclusions

Collectively, our study demonstrates a protective role of IL-37 in DCM, offering a promising therapeutic agent for this disease.

Graphical abstract

Hyperglycemia aggravates mitochondrial injury through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA in DCM mice. Fibroblasts then engulf these mtDNA-enriched vesicles, activating TLR9 signaling and the cGAS-STING pathway to initiate profibrotic process and adverse remodeling. However, both exogenous and endogenous IL-37 ameliorate mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, and reducing the release of mtDNA-enriched vesicles, which attenuates the progression of DCM
Visual training after central retinal loss limits structural white matter degradation: an MRI study
Authors: Kozak Anna , Ninghetto Marco , Wieteska Michał , Fiedorowicz Michał , Wełniak-Kamińska Marlena , Kossowski Bartosz , Eysel Ulf T. , Arckens Lutgarde , Burnat Kalina
Published: May 2024

Background

Macular degeneration of the eye is a common cause of blindness and affects 8% of the worldwide human population. In adult cats with bilateral lesions of the central retina, we explored the possibility that motion perception training can limit the associated degradation of the visual system. We evaluated how visual training affects behavioral performance and white matter structure. Recently, we proposed (Kozak et al. in Transl Vis Sci Technol 10:9, 2021) a new motion-acuity test for low vision patients, enabling full visual field functional assessment through simultaneous perception of shape and motion. Here, we integrated this test as the last step of a 10-week motion-perception training.

Results

Cats were divided into three groups: retinal-lesioned only and two trained groups, retinal-lesioned trained and control trained. The behavioral data revealed that trained cats with retinal lesions were superior in motion tasks, even when the difficulty relied only on acuity. 7 T-MRI scanning was done before and after lesioning at 5 different timepoints, followed by Fixel-Based and Fractional Anisotropy Analysis. In cats with retinal lesions, training resulted in a more localized and reduced percentage decrease in Fixel-Based Analysis metrics in the dLGN, caudate nucleus and hippocampus compared to untrained cats. In motion-sensitive area V5/PMLS, the significant decreases in fiber density were equally strong in retinal-lesioned untrained and trained cats, up to 40% in both groups. The only cortical area with Fractional Anisotropy values not affected by central retinal loss was area V5/PMLS. In other visual ROIs, the Fractional Anisotropy values increased over time in the untrained retinal lesioned group, whereas they decreased in the retinal lesioned trained group and remained at a similar level as in trained controls.

Conclusions

Overall, our MRI results showed a stabilizing effect of motion training applied soon after central retinal loss induction on white matter structure. We propose that introducing early motion-acuity training for low vision patients, aimed at the intact and active retinal peripheries, may facilitate brain plasticity processes toward better vision.
An ethnobotanical survey on the medicinal and edible plants used by the Daur people in China
Authors: Bi Yaqiong , Gao Feng , Guo Jingxia , Yao Xia , Wang Aixiang , Liu Haolin , Sun Yahong , Yao Ruyu , Li Minhui
Published: May 2024

Background

The Daur people are one of the 55 minority ethnic groups in China and have lived in Northern China for 300 years. In traditional Daur medicine, medicinal and edible plants (MEPs) are utilised for health benefits and therapeutic purposes; however, related ethnobotanical knowledge is rarely reported, which is disadvantageous for the sustainable development of these MEPs.

Methods

Semi-structured interviews with 122 informants, six focus group discussions, and a resource survey were conducted in a Daur minority nationality area in Inner Mongolia from 2015 to 2020, and the data statistics were analysed. In this study, we simulated a system dynamics model aimed at understanding the multiple feedback mechanisms involved in the relationships between the cultural influences and socioeconomic factors, sustainable environment, and development of MEPs.

Results

A total of 52 species of MEPs were identified and relevant ethnobotanical knowledge was assessed using Daur medicinal species data from Inner Mongolia and the Xinjiang region, with the literature and Ewenki ethnic group data used for comparison. The most commonly used medicinal plant species by the Daur were found to be Betula pendula subsp. mandshurica, Artemisia integrifolia, Crataegus pinnatifida, Saposhnikovia divaricata, Artemisia argyi, and Jacobaea cannabifolia. The MEPs most frequently targeted the digestive and rheumatic immunity systems, as well as infectious diseases or parasitic infections and other common diseases and basic health issues. MEP knowledge was primarily limited to older generations; thus, the valuable ethnobotanical knowledge on traditional medicines must be protected from future losses.

Conclusions

Our findings provide insights for future research aimed at exploiting the rich phytochemical diversity in traditional medicine and promote its use in modern lifestyles. Effective assessment and management of plant resources will lead to their application for the improvement of dietary diversity, nutrition, and health care.