bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal intraepidermal nerve fiber density in disease: A scoping review
Authors: Thomas Sarah , Enders Jonathan , Kaiser Andrew , Rovenstine Luke , Heslop Lana , Hauser Will , Chadwick Andrea , Wright Douglas 
Published: April 2023

BackgroundIntraepidermal nerve fiber density (IENFD) has become an important biomarker for neuropathy diagnosis and research. The consequences of reduced IENFD can include sensory dysfunction, pain, and a significant decrease in quality of life. We examined the extent to which IENFD is being used as a tool in human and mouse models and compared the degree of fiber loss between diseases to gain a broader understanding of the existing data collected using this common technique.MethodsWe conducted a scoping review of publications that used IENFD as a biomarker in human and non-human research. PubMed was used to identify 1,004 initial articles that were then screened to select articles that met the criteria for inclusion. Criteria were chosen to standardize publications so they could be compared rigorously and included having a control group, measuring IENFD in a distal limb, and using protein gene product 9.5 (PGP9.5).ResultsWe analyzed 397 articles and collected information related to publication year, the condition studied, and the percent IENFD loss. The analysis revealed that the use of IENFD as a tool has been increasing in both human and non-human research. We found that IENFD loss is prevalent in many diseases, and metabolic or diabetes-related diseases were the most studied conditions in humans and rodents. Our analysis identified 73 human diseases in which IENFD was affected, with 71 reporting IENFD loss and an overall average IENFD change of −47%. We identified 28 mouse and 21 rat conditions, with average IENFD changes of −31.6% and −34.7%, respectively. Additionally, we present data describing sub-analyses of IENFD loss according to disease characteristics in diabetes and chemotherapy treatments in humans and rodents.InterpretationReduced IENFD occurs in a surprising number of human disease conditions. Abnormal IENFD contributes to important complications, including poor cutaneous vascularization, sensory dysfunction, and pain. Our analysis informs future rodent studies so they may better mirror human diseases impacted by reduced IENFD, highlights the breadth of diseases impacted by IENFD loss, and urges exploration of common mechanisms that lead to substantial IENFD loss as a complication in disease.
Neurocysticercosis in non-endemic regions: The experience of Qatar
Authors: Haddad Naim , Shaheen Yanal , Abunaib Mohammed , Melikyan Gayane , El Sotouhy Ahmed , Wahbeh Farah , Nauman Areej , Al-Maadid Fatima , Soliman Mohamed , Mesraoua Boulenouar , Elkhider Hisham , Mahfoud Ziyad 
Published: April 2023

ObjectiveTo describe the occurrence and features of Neurocystircercosis (NCC) in Qatar.BackgroundQatar has a mixed population of natives and expats. NCC is not endemic to the region, but clinical practice suggests its occurrence in large numbers.Design/ methodsA database was created to summarize information retrospectively collected on patients with NCC seen through the national health system (HMC) between 2013 and 2018. We identified demographic and disease related variables (clinical manifestations, investigative findings, treatment and outcome) for all patients.ResultsOut of 420 identified NCC patients, 393 (93.6%) were men, and 98.3% were immigrants from NCC endemic countries such as Nepal (63.8%) and India (29.5%). Eighty percent of patients presented with seizures, with the majority (69%) experiencing generalized tonic–clonic seizures. Five percent presented with status epilepticus. Headaches, the second most common complaint, were reported in 18% of subjects. On imaging, 50% had a single lesion while 63% included pathology at the calcified stage. The lesions were parenchymal in 99.5% of cases, predominantly in the frontal lobe (59%). Thirteen percent were diagnosed incidentally on imaging, mainly in the form of isolated calcified non enhancing lesions. Albendazole was received by 55% of patients, and phenytoin was the most prescribed anti-seizure drug (57%). When long term follow up was available, 70% of the patients presenting with seizures were completely seizure free.ConclusionNCC is prevalent in Qatar, mainly within the large Southeast Asian immigrant population. NCC is currently a significant contributor to the epilepsy burden in Qatar, often with a good outcome regarding seizure control. NCC with intraparenchymal single lesion shares a large proportion of our cohort.
Pre- and post-treatment of α-Tocopherol on cognitive, synaptic plasticity, and mitochondrial disorders of the hippocampus in icv-streptozotocin-induced sporadic Alzheimer’s-like disease in male Wistar rat
Authors: Nabavi Zadeh Fatemeh , Nazari Maryam , Amini Abdollah , Adeli Soheila , Barzegar Behrooz Amir , Fahanik Babaei Javad 
Published: April 2023

ObjectiveMost dementia cases in the elderly are caused by Alzheimer’s disease (AD), a complex, progressive neurological disease. Intracerebroventricular (ICV) administration of streptozotocin (STZ) in rat’s results in aberrant brain insulin signaling, oxidative stress, and mitochondrial dysfunction that impair cognition change neural plasticity, and eventually lead to neuronal death. The current study aims to define the neuroprotective action of alpha-tocopherol in enhancing mitochondrial function and the function of synapses in memory-impaired rats brought on by icv-STZ.MethodsMale Wistar rats were pre-treated with (α-Tocopherol 150 mg/kg) orally once daily for 7 days before and 14 days after being bilaterally injected with icv-STZ (3 mg/kg), while sham group rats received the same volume of STZ solvent. After 2 weeks of icv-STZ infusion, rats were tested for cognitive performance using a behaviors test and then were prepared electrophysiology recordings or sacrificed for biochemical and histopathological assays.ResultsThe cognitive impairment was significantly minimized in the behavioral paradigms for those who had taken α-Tocopherol. In the hippocampus of icv-STZ rat brains, α-Tocopherol ocopherol effectively prevented the loss of glutathione levels and superoxide dismutase enzyme activity, lowered mitochondrial ROS and mitochondrial membrane potential, and also brought about a decrease in Aβ aggregation and neuronal death.ConclusionOur findings demonstrated that by lowering neurobehavioral impairments caused by icv-STZ, oxidative stress, and mitochondrial dysfunction, α-Tocopherol enhanced intracellular calcium homeostasis and corrected neurodegenerative defects in the brain. These findings examine the available approach for delaying AD connected to mitochondrial malfunction and plasticity issues.
The TSC2 c.2742+5G>A variant causes variable splicing changes and clinical manifestations in a family with tuberous sclerosis complex
Authors: Fan Kuan , Guo Yi , Song Zhi , Yuan Lamei , Zheng Wen , Hu Xiao , Gong Lina , Deng Hao 
Published: April 2023

BackgroundTuberous sclerosis complex (TSC) is a genetic, variably expressed, multisystem disease characterized by benign tumors. It is caused by pathogenic variants of the TSC complex subunit 1 gene (TSC1) and the TSC complex subunit 2 gene (TSC2). Genetic testing allows for early diagnosis, genetic counseling, and improved outcomes, but it did not identify a pathogenic variant in up to 25% of all TSC patients. This study aimed to identify the disease-causing variant in a Han-Chinese family with TSC.MethodsA six-member, three-generation Han-Chinese family with TSC and three unrelated healthy women were recruited. A comprehensive medical examination, a 3-year follow-up, whole exome sequencing, Sanger sequencing, and segregation analysis were performed in the family. The splicing analysis results obtained from six in silico tools, minigene assay, and patients' lymphocyte messenger RNA were compared, and quantitative reverse transcription PCR was used to confirm the pathogenicity of the variant.ResultsTwo affected family members had variable clinical manifestations including a rare bilateral cerebellar ataxia symptom. The 3-year follow-up results suggest the effects of a combined treatment of anti-epilepsy drugs and sirolimus for TSC-related epilepsy and cognitive deficits. Whole exome sequencing, Sanger sequencing, segregation analysis, splicing analysis, and quantitative reverse transcription PCR identified the TSC2 gene c.2742+5G&gt;A variant as the genetic cause. This variant inactivated the donor splice site, a cryptic non-canonical splice site was used for different splicing changes in two affected subjects, and the resulting mutant messenger RNA may be degraded by nonsense-mediated decay. The defects of in silico tools and minigene assay in predicting cryptic splice sites were suggested.ConclusionsThis study identified a TSC2 c.2742+5G&gt;A variant as the genetic cause of a Han-Chinese family with TSC and first confirmed its pathogenicity. These findings expand the phenotypic and genetic spectrum of TSC and may contribute to its diagnosis and treatment, as well as a better understanding of the splicing mechanism.
Change in cardiometabolic risk factors in a pilot safety-net plant-based lifestyle medicine program
Authors: Albert Stephanie L. , Massar Rachel E. , Correa Lilian , Kwok Lorraine , Joshi Shivam , Shah Sapana , Boas Rebecca , Alcalá Héctor E. , McMacken Michelle 
Published: April 2023

IntroductionInterventions emphasizing healthful lifestyle behaviors are proliferating in traditional health care settings, yet there is a paucity of published clinical outcomes, outside of pay-out-of-pocket or employee health programs.MethodsWe assessed weight, hemoglobin A1c (HbA1c), blood pressure, and cholesterol for 173 patients of the Plant-Based Lifestyle Medicine Program piloted in a New York City safety-net hospital. We used Wilcoxon signed-rank tests to assess changes in means, from baseline to six-months, for the full sample and within baseline diagnoses (i.e., overweight or obesity, type 2 diabetes, prediabetes, hypertension, hyperlipidemia). We calculated the percentage of patients with clinically meaningful changes in outcomes for the full sample and within diagnoses.FindingsThe full sample had statistically significant improvements in weight, HbA1c, and diastolic blood pressure. Patients with prediabetes or overweight or obesity experienced significant improvements in weight and those with type 2 diabetes had significant improvements in weight and HbA1c. Patients with hypertension had significant reductions in diastolic blood pressure and weight. Data did not show differences in non-high-density lipoprotein cholesterol (non-HDL-C), but differences in low-density lipoprotein cholesterol (LDL-C) were approaching significance for the full sample and those with hyperlipidemia. The majority of patients achieved clinically meaningful improvements on all outcomes besides systolic blood pressure.ConclusionOur study demonstrates that a lifestyle medicine intervention within a traditional, safety-net clinical setting improved biomarkers of cardiometabolic disease. Our findings are limited by small sample sizes. Additional large-scale, rigorous studies are needed to further establish the effectiveness of lifestyle medicine interventions in similar settings.
Pelvic floor muscle exercises alleviate symptoms and improve mental health and rectal function in patients with low anterior resection syndrome
Authors: Yuanyuan Wu , Shiyin He , Lei He , Ding Ding 
Published: April 2023

BackgroundPelvic floor rehabilitation has been reported to be effective in improving fecal incontinence. The aim of this study was to prospectively evaluate the effectiveness of combined pelvic floor muscle exercises (PFMEs) and loperamide treatment on rectal function and mental health for low anterior resection syndrome (LARS) patients after sphincter-saving operation (SSO) for rectal cancer.MethodsA total of 60 inpatients diagnosed with LARS were enrolled and randomly assigned to one of two groups: patients in Group A (n = 30) were treated with a PFME intervention and those in Group B (n = 30) with a control intervention for 4 weeks. High-resolution anorectal manometry (HRAM) was performed for all LARS patients. Demographic information was collected for all patients, and they subsequently also completed several questionnaires, including the Hospital Anxiety and Depression Scale (HADS), a measure of Wexner score, a measure of stool frequency per day, and the Bristol Stool Form Scale (BSFS).ResultsNo significant differences between the groups were observed in baseline data. With regard to rectal function, we found significant improvements at week 4 in maximal resting pressure (MRP) (39.93 ± 5.02 vs. 28.70 ± 5.40 mmH2O, p &lt; 0.001) and maximal squeeze pressure (MSP) (132.43 ± 8.16 mmH2O vs. 113.33 ± 9.87 mmH2O, p &lt; 0.001) among Group A patients compared to Group B patients. Additionally, Wexner scores were significantly lower in Group A than in Group B at week 4 (8.10 ± 1.24 vs. 9.87 ± 1.29 ml, p = 0.018), as were stool frequency (6.47 ± 0.90 vs. 7.83 ± 0.93, p &lt; 0.001) and BSFS scores (5.17 ± 0.65 vs. 6.10 ± 0.80, p = 0.020). Notably, HADS scores were also significantly lower in Group A than in Group B at week 4 (8.25 ± 2.36 vs. 10.48 ± 3.01, p &lt; 0.001). Additionally, both anxiety scores (4.16 ± 1.38 vs. 5.33 ± 1.69, p &lt; 0.001) and depression scores (4.09 ± 1.56 vs. 5.15 ± 1.89, p &lt; 0.001) were significantly lower in Group A than in Group B at week 4.ConclusionPelvic floor muscle exercises are an effective treatment that can alleviate symptoms and improve rectal function and mental health in patients with low anterior resection syndrome.
A new model based on gamma-glutamyl transpeptidase to lymphocyte ratio and systemic immune-inflammation index can effectively predict the recurrence of hepatocellular carcinoma after liver transplantation
Authors: Zhang Weiqi , Bi Yi , Yang Kai , Xie Yan , Li Zhaoxian , Yu Xinghui , Zhang Li , Jiang Wentao 
Published: April 2023

BackgroundLiver transplantation (LT) is one of the most effective treatment modalities for hepatocellular carcinoma (HCC), but patients with HCC recurrence after LT always have poor prognosis. This study aimed to evaluate the predictive value of the gamma-glutamyl transpeptidase-to-lymphocyte ratio (GLR) and systemic immune-inflammation index (SII) in terms of HCC recurrence after LT, based on which we developed a more effective predictive model.MethodsThe clinical data of 325 HCC patients who had undergone LT were collected and analyzed retrospectively. The patients were randomly divided into a development cohort (n = 215) and a validation cohort (n = 110). Cox regression analysis was used to screen the independent risk factors affecting postoperative recurrence in the development cohort, and a predictive model was established based on the results of the multivariate analysis. The predictive values of GLR, SII and the model were evaluated by receiver operating characteristic (ROC) curve analysis, which determined the cut-off value for indicating patients’ risk levels. The Kaplan-Meier survival analysis and the competing-risk regression analysis were used to evaluate the predictive performance of the model, and the effectiveness of the model was verified further in the validation cohort.ResultsThe recurrence-free survival of HCC patients after LT with high GLR and SII was significantly worse than that of patients with low GLR and SII (P&lt;0.001). Multivariate Cox regression analysis identified GLR (HR:3.405; 95%CI:1.954-5.936; P&lt;0.001), SII (HR: 2.285; 95%CI: 1.304-4.003; P=0.004), tumor number (HR:2.368; 95%CI:1.305-4.298; P=0.005), maximum tumor diameter (HR:1.906; 95%CI:1.121-3.242; P=0.017), alpha-fetoprotein level (HR:2.492; 95%CI:1.418-4.380; P=0.002) as independent risk factors for HCC recurrence after LT. The predictive model based on these risk factors had a good predictive performance in both the development and validation cohorts (area under the ROC curve=0.800, 0.791, respectively), and the performance of the new model was significantly better than that of single GLR and SII calculations (P&lt;0.001). Survival analysis and competing-risk regression analysis showed that the predictive model could distinguish patients with varying levels of recurrence risk in both the development and validation cohorts.ConclusionsThe GLR and SII are effective indicators for evaluating HCC recurrence after LT. The predictive model based on these indicators can accurately predict HCC recurrence after LT and is expected to guide preoperative patient selection and postoperative follow-up.
Drug-related problems among transfusion-dependent thalassemia patients: A real-world evidence study
Authors: Chun Geok Ying , Mohd Tahir Nurul Ain , Islahudin Farida , Selvaratnam Veena , Li Shu Chuen 
Published: April 2023

Introduction: Thalassemia is among the most common genetic disorders globally and many patients suffer from iron overload (IOL) complications that mainly affect the heart, liver and endocrine system. These events may be further complicated by drug-related problems (DRP), an inherent issue among patients with chronic diseases.Objective: The study aimed to evaluate the burden, associated factors and impacts of DRP in transfusion-dependent thalassemia (TDT) patients.Method: Eligible TDT patients under follow-up in a tertiary hospital between 01 March 2020 to 30 April 2021 were interviewed and their medical records were reviewed retrospectively to identify any DRP. DRPs were classified using the Pharmaceutical Care Network Europe (PCNE) classification version 9.1. The incidence and preventability of DRP were assessed and the associated risk factors were estimated by univariate and multivariate logistic regression.Results: A total of 200 patients were enrolled with a median (interquartile range: IQR) age of 28 years at enrolment. Approximately 1 in 2 patients were observed to suffer from thalassemia-related complications. Throughout the study period, 308 DRPs were identified among 150 (75%) participants, with a median DRP per participant of 2.0 (IQR 1.0–3.0). Of the three DRP dimensions, treatment effectiveness was the most common DRP (55.8%) followed by treatment safety (39.6%) and other DRP (4.6%). The median serum ferritin level was statistically higher in patients with DRP compared with patients without DRP (3833.02 vs. 1104.98 μg/L, p &lt; 0.001). Three risk factors were found to be significantly associated with the presence of DRP. Patients with frequent blood transfusion, moderate to high Medication Complexity Index (MRCI) and of Malay ethnicity were associated with higher odds of having a DRP (AOR 4.09, 95% CI: 1.83, 9.15; AOR 4.50, 95% CI: 1.89, 10.75; and AOR 3.26, 95% CI: 1.43, 7.43, respectively).Conclusion: The prevalence of DRP was relatively high amongst TDT patients. Increased medication complexity, more severe form of the disease and Malay patients were more likely to experience DRP. Hence, more viable interventions targeted to these groups of patients should be undertaken to mitigate the risk of DRP and achieve better treatment outcomes.
Hurdles and signposts on the road to virtual control groups—A case study illustrating the influence of anesthesia protocols on electrolyte levels in rats
Authors: Gurjanov A. , Kreuchwig A. , Steger-Hartmann T. , Vaas L. A. I. 
Published: April 2023

Introduction: Virtual Control Groups (VCGs) represent the concept of using historical control data from legacy animal studies to replace concurrent control group (CCG) animals. Based on the data curation and sharing activities of the Innovative Medicine Initiatives project eTRANSAFE (enhancing TRANSlational SAFEty Assessment through Integrative Knowledge Management) the ViCoG working group was established with the objectives of i) collecting suitable historical control data sets from preclinical toxicity studies, ii) evaluating statistical methodologies for building adequate and regulatory acceptable VCGs from historical control data, and iii) sharing those control-group data across multiple pharmaceutical companies. During the qualification process of VCGs a particular focus was put on the identification of hidden confounders in the data sets, which might impair the adequate matching of VCGs with the CCG.Methods: During our analyses we identified such a hidden confounder, namely, the choice of the anesthetic procedure used in animal experiments before blood withdrawal. Anesthesia using CO2 may elevate the levels of some electrolytes such as calcium in blood, while the use of isoflurane is known to lower these values. Identification of such hidden confounders is particularly important if the underlying experimental information (e.g., on the anesthetic procedure) is not routinely recorded in the standard raw data files, such as SEND (Standard for Exchange of Non-clinical Data). We therefore analyzed how the replacement of CCGs with VCGs would affect the reproducibility of treatment-related findings regarding electrolyte values (potassium, calcium, sodium, and phosphate). The analyses were performed using a legacy rat systemic toxicity study consisting of a control and three treatment groups conducted according to pertinent OECD guidelines. In the report of this study treatment-related hypercalcemia was reported. The rats in this study were anesthetized with isoflurane.Results: Replacing the CCGs with VCGs derived from studies comprising both anesthetics resulted in a shift of control electrolyte parameters. Instead of the originally reported hypercalcemia the use of VCG led to fallacious conclusions of no observed effect or hypocalcemia.Discussion: Our study highlights the importance of a rigorous statistical analysis including the detection and elimination of hidden confounders prior to the implementation of the VCG concept.