bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractThe 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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundT-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.MethodsWe 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.ResultsOur 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.ConclusionsOur 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

Abstract
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

Abstract
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

Abstract
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.
Unique clinical and electrophysiological features in the peripheral nerve system in patients with sialidosis – a case series study
Authors: Hsueh Sung-Ju , Lin Chin-Hsien , Lee Ni-Chung , Chang Tung-Ming , Fan Sung-Pin , Huang Wan-De , Lin Yea-Huey , Tsai Li-Kai , Chien Yin-Hsiu , Lee Ming-Jen , Hwu Wuh-Liang , Hsueh Hsueh Wen , Yang Chih-Chao 
Published: May 2024

Abstract
Background
To investigate the peripheral nervous system involvement in S sialidosis with typical features of myoclonus, seizure, and giant waves in somatosensory evoked potentials suggesting hyperexcitability in the central nervous system.

Methods
The clinical presentation of patients with genetically confirmed sialidosis was recorded. Neurophysiological studies, including nerve conduction studies (NCSs), F-wave studies, and needle electromyography (EMG), were performed on these patients.

Results
Six patients (M/F: 2:4) were recruited. In addition to the classical presentation, intermittent painful paresthesia was noted in four patients, and three of whom reported it as the earliest symptom. In the NCSs, one patient had reduced compound muscle action potential amplitudes in the right ulnar nerve, while another patient had prolonged distal motor latency in the bilateral tibial and peroneal nerves. Prolonged F-wave latency (83.3%), repeater F-waves (50%), and neurogenic polyphasic waves in EMG (in 2 out of 3 examined patients) were also noted. Interestingly, a very late response was noted in the F-wave study of all patients, probably indicating lesions involving the proximal peripheral nerve or spinal cord.

Conclusion
In addition to the central nervous system, the peripheral nervous system is also involved in sialidosis, with corresponding clinical symptoms. Further study on these phenomena is indicated.