bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: Novel ACTN4 variant of uncertain significance in a pediatric case of steroid-resistant nephrotic syndrome requesting kidney transplantation
Authors: Alarcón Ignacio , Peralta Carolina , Cammarata-Scalisi Francisco , Araya Castillo Maykol , Cano Francisco , Rojo Angélica , Ceballos María Luisa , Krall Paola 
Published: January 2025

BackgroundSteroid-resistant nephrotic syndrome (SRNS) is a rare kidney disease commonly characterized histopathologically by focal and segmental glomerulosclerosis (FSGS) or minimal change disease. One-third of SRNS-FSGS cases are attributed to a genetic cause ultimately leading to end-stage kidney disease (ESKD) during childhood or adulthood. ACTN4 variants, although rare, typically manifest in early adulthood as SRNS-FSGS with autosomal dominant inheritance pattern and are associated with variable progression toward ESKD.Case–diagnosis/treatmentA 10-year-old Chilean male patient, born to a complicated pregnancy without any history of prenatal care, was incidentally found to have mild proteinuria during pre-surgery analysis. He was diagnosed with nephrotic syndrome and treatment with prednisone was started, but 12 months later, he persisted with hyperlipidemia, hypoalbuminemia, and proteinuria. Within a few weeks, proteinuria rapidly increased, and a kidney biopsy exhibited FSGS features. At the age of 12, he reached ESKD and initiated peritoneal dialysis, experiencing an episode of posterior reversible encephalopathy syndrome. Exome sequencing identified a novel variant of uncertain significance (VUS), ACTN4 c.625_633del that predicted the in-frame deletion p.L209_E211del in a highly conserved functional domain. He requested to be considered for kidney transplantation and the VUS in ACTN4 was re-analyzed to assess potential risks, resulting in a reclassification as likely pathogenic (PM1+PM2+PM4 criteria). At 14 years old, he received a deceased donor kidney allograft without recurrence during the subsequent 5 months.ConclusionsIdentifying VUS is a recurring challenge in routine clinical genetics, particularly for patients with rare diseases or atypical phenotypes in underrepresented populations. This case underscores the benefit of timely genetic diagnosis taking into account the patient’s request. VUS reassessment becomes more relevant when considering a kidney transplant not only as an appropriate procedure, but as the therapy of choice, especially considering the patient’s history of complications with variable long-term consequences.
Clinical analysis and case series report on autoimmune glial fibrillary acidic protein astrocytopathy presenting with autonomic dysfunction
Authors: Wu Xiao Ke , Zhai Guojie , Zhang Jin Ru , Du Hua Ping , Hu Lan , Yu Shu Ye , Hang Hai Lun , Han Sirui , Zhang Yanlin , Xu Yuan 
Published: January 2025

Background and purposeThe incidence of autonomic dysfunction is frequently underestimated and often overlooked in patients with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). This study comprehensively analyzes the clinical manifestations, laboratory and imaging findings, and treatment modalities for patients demonstrating GFAP-A involvement in the autonomic nervous system. The present article primarily elucidates the prevalence and prognosis of diverse autonomic system symptoms while examining the associated laboratory and imaging indicators. These findings aim to establish a foundation for personalized diagnosis and treatment strategies in such patients.MethodWe performed a retrospective data analysis from three cases of GFAP-A involvement in autonomic nerves from the Ninth People’s Hospital of Suzhou and the Second Affiliated Hospital of Soochow University from 2020 to 2023. After an extensive literature review, we identified 39 cases involving GFAP-A and autonomic nervous system dysfunction. We also comprehensively analyzed the patient’s clinical manifestations, laboratory biomarkers, and imaging findings.ResultThe study included a total of 42 patients, consisting of 15 females and 27 males. The primary manifestations of autonomic dysfunction included bladder dysfunction (41/42 cases), gastrointestinal dysfunction (18 /42 cases), heart rate variability (4/42 cases), unusual sweating (2/42 cases), and blood pressure fluctuations (1/42 cases). Other neurological symptoms comprised headache (12 /42 cases), limb weakness presentation (30/42 cases). Blood pressure variability is related to cerebrospinal fluid pressure and convulsive seizures. Heart rate variability is related to disorders of consciousness. unusual sweating was associated to age, gender, cerebrospinal fluid protein content and convulsive seizures. Gastrointestinal disorders have associations with gender, sleep disturbances, protein content in the cerebrospinal fluid, and brain MRI lesions. The prognosis of autonomic nerve dysfunction is associated to sleep disorder and cerebrospinal fluid protein content. The higher the cerebrospinal fluid protein level, the worse the prognosis of autonomic nervous system.ConclusionBladder dysfunction and gastrointestinal dysfunction are the primary manifestations of autonomic dysfunction in GFAP-A patients, with a subset also experiencing abnormalities in heart rate, blood pressure, and sweating. These additional symptoms have implications for prognosis, necessitating heightened attention from clinicians toward GFAP-A patients.
Identifying the predictors of ultra early neurological improvement and its role in functional outcome after endovascular thrombectomy in acute ischemic stroke
Authors: Lai Yuzheng , Mofatteh Mohammad , Baizabal-Carvallo José Fidel , He Jianfeng , Wu Wenhao , Wang Daohong , Yan Wenshan , Ma Jicai , Zhou Sijie , Sun Yu , He Yi , Li Shumei , Sun Hao 
Published: January 2025

Background and purposeUsing post-treatment methods to predict functional outcomes of acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) is crucial in stroke medicine. The National Institute of Health Stroke Scale (NIHSS) score at 24 h has been widely used; however, there is a paucity of data on using earlier NIHSS scores and their association with outcome. In this study, we aimed to investigate the usage of NIHSS at 1-h time window -ultra-early neurological improvement (UENI)- as a surrogate marker associated with the functional outcomes of AIS patients treated with EVT.MethodsWe included 485 adults (≥18 years old) who underwent emergency EVT at four academic comprehensive stroke centers between 2020 and 2021. Patients with pre-EVT Alberta Stroke Program Early CT Score (ASPECTS) &lt; 6, missing follow-up data, and missing data of the first hour NIHSS were excluded (n = 20). UENI was defined as post-EVT NIHSS reduction of 4 points or more or NIHSS as 0–1 within 1-h post-EVT. An mRS score of 0–2 after three months was defined as favorable outcome, and independent walking independence was defined as mRS of 3.ResultsA total of 465 patients were included in our final analysis. We identified 122 (26.2%) patients with UENI. While 82.79% of the patients with UENI achieved favorable functional outcomes at 3-months, only 32.36% of patients without UENI had favorable functional outcome (p &lt; 0.0001). In addition, lower hospitalization costs were associated with patients who had UENI, compared to No-UENI (p = 0.003). A multivariate logistic regression analysis revealed that younger age (p &lt; 0.0001), shorter last know normal to puncture time (LKNPT) (p = 0.013), higher pre-treatment ASPECTS (p = 0.039), final modified thrombolysis in cerebral infarction (mTICI) ≥2b (p = 0.002), and fewer number of EVT attempts (p = 0.002) were variables independently associated with UENI. The presence of UENI was independently associated with a better outcome OR: 7.999 (95% C.I. 4.415–14.495).ConclusionUENI was observed in about a quarter of patients with AIS undergoing EVT. Younger age, shorter LKNPT, higher pre-treatment ASPECTS, final mTICI≥2b, and fewer number of EVT attempts, were independently associated with UENI. The presence of UENI was independently associated with better functional outcome at 3 months.
Association between the atherogenic index of plasma and non-alcoholic fatty liver disease in Korean pregnant women: secondary analysis of a prospective cohort study
Authors: Shuai Rong , He Yuxing , Yang Dongqian , Zhang Yingying , Zhang Li 
Published: January 2025

BackgroundRecent studies have shown an association between atherogenic index of plasma (AIP) and nonalcoholic fatty liver disease (NAFLD), but the association in a population of pregnant women remains unclear.ObjectivesOur study aimed to examine the association between AIP and NAFLD in pregnant Korean women.MethodsOur study used publicly available data from Korea, which recruited singleton pregnant women between November 2014 and September 2016 who were at 10–14 weeks of gestation. The presence of NAFLD was diagnosed by liver ultrasound. AIP was calculated as log10 (TG/HDL). Participants were grouped according to AIP tertile: T1 (&lt; 0.16, n = 195), T2 (0.16–0.32, n = 195), and T3 (&gt;0.32, n = 196). Logistic regression models were used to estimate the relationship between AIP and NAFLD. Subgroup and sensitivity analyses were conducted to explore the stability of this relationship. Restricted cubic spline (RCS) curve fitting was employed to investigate potential non-linear associations.ResultsAfter excluding data on missing variables, 586 singleton pregnant women were finally included. The subjects included in the study had an average AIP of 0.22 (0.11, 0.37), and NAFLD occurred in 110 (18.8%) pregnant women. We observed a positive linear association between AIP and NAFLD (OR = 1.33, 95% CI: 1.19–1.48), which persisted after adjusting for potential confounders (OR = 1.2, 95% CI: 1.06–1.37). When AIP was used as a categorical variable, after adjusting for covariates, the NAFLD risk was significantly higher in the highest tertile of AIP than in the lowest group (OR = 2.02, 95% CI: 1.11–3.68). Their correlations were stable across subgroups and sensitivity analyses.ConclusionIn this secondary analysis of a prospective cohort study of pregnant Korean women, AIP was found to be positively associated with NAFLD. These outcomes might be used to screen for NAFLD in pregnant women.
Intracranial germ cell tumors: advancement in genomic diagnostics and the need for novel therapeutics
Authors: Yeo Kee Kiat , Gell Joanna , Dhall Girish , Lau Ching 
Published: January 2025

IntroductionThe outcomes for patients with intracranial germ cell tumors (GCT) has improved over the past few decades. However, there remains a lack of a consensus on a standard diagnostic and treatment approach of these tumors. The diagnostic work-up of intracranial GCT remains variable, and the treatment for patients with recurrent disease remains challenging.MethodsWe review the current approach in the diagnosis and treatment of intracranial GCT. Given the heterogeneity of these tumors, we highlight the challenges and controversy with these conventional approaches.ResultsWe discuss the advancements in the understanding of the underlying genetic changes in intracranial GCT and the utility of novel molecular techniques in the diagnosis and classification of intracranial germ cell tumors as well as development of potential novel therapeutics.DiscussionDevelopment of liquid biopsy platforms for diagnosis and management of malignancies is a rapidly growing field. Current approach utilizing traditional tumor markers have significant limitations. In this review, we will discuss profiling of intracranial GCTs for genetic and epigenetic signatures, which are emerging as promising biomarkers to assist in the diagnosis and management of intracranial GCTs. Various studies have shown that activating mutations in MAPK pathway are common alterations in intracranial GCTs, with KIT expression seen in most germinomas. Development of targeted therapeutics against KIT has led to the prospect of targeted therapy in germinoma. Other treatment modalities being considered for clinical development include immunotherapy and the use of immune checkpoint inhibitors, especially in NGGCT. In this review, we will discuss the potential novel therapeutics and the clinical trials that are currently under development.
Study on the value of gastrin 17 and aldehyde dehydrogenase 1 in gastric juice for early diagnosis in gastric cancer
Authors: Wang Yanfang , Liu Hui , Li Xiang , Jin Juan , Yan Bo 
Published: January 2025

ObjectiveTo investigate the diagnostic utility of aldehyde dehydrogenase 1 (ALDH1) and gastrin 17 (G-17) levels in the gastric juice of patients with gastric cancer and to track changes in the levels of these markers in the gastric juice of these patients.Methods126 individuals were diagnosed via gastroscopy. This trial includes gastric mucosal histology and gastroscopy performed at Hefei Second People’s Hospital between March 2023 and March 2024. On the basis of the results of gastroscopy and gastric mucosal histology, all the participants were categorized into three groups: 30 patients with gastric cancer (GC), 34 patients with gastric ulcer (GU) and 62 patients with gastritis. Thirty patients with chronic nonatrophic gastritis were chosen from the physical examination center, and thirty-two patients with chronic atrophic gastritis (CAG) composed the gastritis group. As the control group, they were chosen at the physical testing center. An enzyme-related immunosorbent assay (ELISA) was used to quantify the levels of G-17 and ALDH1 in each group. A correlation study was performed on the levels of ALDH1 and G-17 in the gastric juice. By using binomial logistic regression analysis, the impact of G-17 and ALDH1 in gastric juice on the incidence of gastric cancer was examined. To illustrate the predictive usefulness of G-17 and ALDH1 in gastric juice for GC diagnosis, a receiver operating characteristic (ROC) curve was generated.ResultsThe gastric juice of the gastric cancer group had higher levels of ALDH1 and G-17 than did the gastric juice of the gastritis group and GU group (P &lt; 0.05). The levels of ALDH1 and G-17 in gastric juice of gastric ulcer group were higher than those of atrophic gastritis group and control group (P &lt; 0.05). The levels of ALDH1 and G-17 in gastric juice of atrophic gastritis group were statistically significant compared with those of control group (P &lt; 0.05). The development of gastric cancer was significantly influenced by elevated levels of ALDH1 and G-17 in gastric juice (OR= 1.095, 1.018; both P &lt;0.05); the AUCs for the combined diagnosis of gastric cancer and elevated levels of G-17 and ALDH1 in gastric juice were 0.792, 0.757, and 0.695, respectively.ConclusionThe development of gastric cancer is influenced by increased levels of ALDH1 and G-17 in gastric juice. The diagnosis of gastric cancer may be made more accurately by combining the two gastric fluid markers, which can be found in gastric juice.
Epidemiology of neonatal disorders attributable to low birthweight-global burden of disease research, 1990–2021
Authors: Zhang Qi , Luo Lan , Yan Lai-lai , Guo Jing , Wu Hui-jun , Zhang Zi-wei , Zhu Yu-hua , Qiao Rui 
Published: January 2025

BackgroundTo evaluate global, regional, and national trends in the burden of neonatal diseases attributable to LBW, as well as associated health inequalities, from 1990 to 2021.MethodsUsing data from the Global Burden of Disease Study (GBD2021), we analyzed deaths and DALYs due to LBW-attributable neonatal diseases. Data were stratified by gender, geographic region, epidemiological characteristics, and SDI levels. Trends and influencing factors were investigated through Joinpoint regression, health inequality analysis, and frontier modeling.ResultsIn 2021, the global age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life year (DALY) rate (ASDR) for neonatal diseases associated with low birth weight (LBW) were 22.76 [95% uncertainty interval (UI): 19.63–26.40] and 2,227.54 (95% UI: 1,939.96–2,563.52) per 100,000, respectively. Over the past 32 years, these rates have consistently declined, with average annual percentage changes (AAPCs) of −1.40 [95% confidence interval (CI): −1.48 to −1.33] for ASMR and −1.27 (95% CI: −1.34 to −1.21) for ASDR. Notably, absolute health inequality related to the Socio-demographic Index (SDI) has decreased, as indicated by a reduction in DALY disparities between the most and least developed countries from −4,216.49 (95% CI: −4,558.27 to −3,874.71) in 1990 to −2,635.35 (95% CI: −2,868.40 to −2,402.30) in 2021. However, relative health inequality has worsened, with the relative disease burden in low-SDI countries increasing from −33.46% (95% CI: −36.29% to −30.63%) to −40.20% (95% CI: −44.02% to −36.39%). The burden of neonatal diseases remains disproportionately concentrated in low-SDI regions. Frontier analyses highlight opportunities for improvement across development levels. Some low-SDI countries have achieved minimal theoretical disease burdens, whereas certain high-SDI countries lag in reducing their neonatal disease burdens.ConclusionOver the past 32 years, the global burden of neonatal diseases attributable to LBW has significantly decreased, but inequality in disease burden has intensified. Addressing this disparity requires sustained international and governmental efforts to improve the accessibility, equality, and quality of healthcare for pregnant women and newborns.
Hu-lu-su-pian ameliorates hepatic steatosis by regulating CIDEA expression in AKT-driven MASLD mice
Authors: Ren Rumeng , Wang Qi , Deng Dongjie , Guo Aoao , Chen Xin , Meng Yan , Fang Ying , Zheng Guohua , Xu Zhong , Li Man , Hu Junjie 
Published: January 2025

IntroductionHu-lu-su-pian (HLSP) is an oral tablet derived from the active compounds of Cucumis melo L., a traditional Chinese medicine. This contemporary formulation is frequently employed in clinical settings for the management of liver ailments. However, the molecular mechanism by which HLSP affects metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. This study aimed to explore the therapeutic potential of HLSP on MASLD and the underlying mechanism.MethodsThe researchers used ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) to identify the primary chemical components of HLSP. A mouse model of MASLD induced by AKT was established through hydrodynamic transfection with activated forms of AKT. Serum biochemical indices and liver pathological assessments were employed to evaluate the pharmacodynamic effects of HLSP on MASLD. Transcriptomic analysis of the liver was conducted to detect differentially expressed genes (DEGs). Further examination of significant DEGs and proteins was performed using quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry (IHC) techniques, respectively. The efficacy and molecular mechanisms of HLSP in MASLD were further explored in HepG2 and Huh-7 cells in the presence of gene overexpression.ResultsFrom the UPLC-Q-TOF-MS/MS results, we detected fifteen components from HLSP. From the results of serum biochemical indices and hepatic pathology analyses, it is clear that HLSP is effective in treating MASLD. The findings from hepatic transcription studies revealed CIDEA as an essential DEG that facilitates lipid droplet (LD) fusion and enhances de novo fatty acid synthesis from scratch in cases of hepatic steatosis, which HLSP has the potential to counteract. In addition, HLSP significantly reduced lipid accumulation and expression of critical genes for de novo fatty acid synthesis in HepG2 and Huh-7 cells overexpressing CIDEA.DiscussionThe present study preliminarily suggests that HLSP can ameliorate hepatic steatosis by inhibiting CIDEA-mediated de novo fatty acid synthesis and LD formation, which may offer a potential strategy for treating MASLD.
Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson’s disease
Authors: Nies Yong Hui , Lim Wei Ling , Abd Karim Norwahidah , Yahaya Mohamad Fairuz , Teoh Seong Lin 
Published: January 2025

IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder primarily affecting motor function due to progressive loss of dopaminergic neurons in the substantia nigra. Current therapies offer symptomatic relief but fail to halt disease progression, highlighting the need for novel therapeutic strategies. This study explores the neuroprotective potential of exogenous human metallothionein 2 (hMT2) peptide in a rotenone-induced PD zebrafish model.MethodsAdult zebrafish were divided into four groups: control, rotenone-treated, hMT2 pre-treatment, and hMT2 co-treatment. PD model was established by exposing zebrafish to 5 µg/L rotenone water for 28 days. hMT2 (0.2 µg) was administered intracranially either one day before or seven days after rotenone exposure.ResultsThe novel tank test demonstrated that rotenone exposure significantly impaired locomotor activity (p &lt; 0.05) and increased anxiety-like behavior (p &lt; 0.001). Additionally, PD model zebrafish exhibited reduced dopamine levels, decreased dopaminergic neuron population, elevated oxidative stress, heightened inflammatory response and mitochondrial dysfunction. Treatment with hMT2, especially in the co-treatment group, ameliorated these deficits by restoring locomotor activity, dopamine levels, and dopaminergic neuron counts while reducing oxidative stress and inflammation, and improving mitochondrial function.DiscussionThese results suggest that hMT2 exhibited neuroprotective effect in the PD model zebrafish. These findings support the potential of MT as a therapeutic agent for PD.
Development and validation a methodology model for traditional Chinese medicine good practice recommendation: an exploratory sequential mixed methods study
Authors: Li Su , Zhang Luan , Wang Yangyang , Xie Runsheng , Chen Wenjia , Lee Myeong Soo , Amer Yasser Sami , Sharifan Amin , Hussein Heba , Li Hui 
Published: January 2025

BackgroundTo develop a rational and standardized traditional Chinese medicine (TCM) good practice recommendation (GPR) methodology model that guides the formulation of recommendations grounded in clinical experience.MethodsWe adopted an exploratory sequential mixed-method to develop a methodology model by coding systematically collected literature on methodology and TCM guidelines related to TCM GPR using a best-fit framework synthesis. Then based on real-world data (published TCM guidelines), saturation tests, structural rationality validation, and discriminability tests were conducted to validate methodology model.ResultsA total of 35 methodological literature and 190 TCM guidelines were included. A TCM GPR methodology model was developed, including 3 themes, 10 sub-themes, and the relationships between themes and subthemes. The information of TCM GPR methodology model achieved data saturation. The fit indices were within the acceptable range, and were able to distinguish the overall differences between guidelines from different literature sources, development organizations, guideline types, discipline categories, and funding categories.ConclusionThe study developed a TCM GPR methodology model which describes the definition of a TCM GPR, how to formulate it, and how to report it. The methodology modeldemonstrates good fit, discriminability, and data saturation. It can standardize the specific formulation of TCM GPRs, facilitate the scientific and rational formation of TCM GPRs, and provide theoretical and methodological guidance for the formation of TCM GPRs.