bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of the pediatric population with gender incongruence attending specialized care in Cali, Colombia: an observational, descriptive and retrospective study
Authors: Gutiérrez Kenny , Moreno Mabel , Sierra Jimena Alexandra , Lemus Rodrigo , Apraez Karen , Angulo Mario 
Published: January 2024

Abstract
Background
Gender incongruence can often manifest itself from early childhood [Olson KR, Gülgöz S. Child Dev Perspect. 2018;12:93–7. https://doi.org/10.1111/cdep.12268] with a significant psychological impact, altering social and school dynamics without the appropriate care.[Tordoff DM, et al. JAMA Netw Open. 2022;5(2): e220978. https://doi.org/10.1001/jamanetworkopen.2022.0978] Early identification and gender–affirming care are essential to reduce adverse mental health outcomes, such as depression and self-harm [Tordoff DM, et al. JAMA Netw Open. 2022;5(2): e220978. https://doi.org/10.1001/jamanetworkopen.2022.0978]..This study aims to analyze characteristics and to estimate relative frequencies of gender incongruence in a population of children and adolescents receiving gender-affirming care at a high-complexity university hospital located in the third largest city in Colombia.

Methods
This was a retrospective descriptive study of patients under 18 with gender incongruence that received gender-affirming care between January 2018 and June 2022 at Fundacion Valle del Lili in Cali, Colombia. Sociodemographic and clinical characteristics of 43 patients were assessed, as well as the relative frequencies of gender incongruence. Data analysis was performed with the statistical package STATA®. To determine significant differences between the characteristics of the patients who participated in the study, the Mann‒Whitney U test was performed for numerical variables with non-parametric distribution, while either Pearson's Chi-2 test or Fisher's exact test was performed for categorical variables.

Results
For every ten individuals assigned female at birth, who manifested gender incongruence, there were eight assigned male at birth. The median age of onset of gender incongruence was ten years (IQR: 5–13 years), and the median time elapsed between the reported onset of gender incongruence and the first consultation with a multidisciplinary gender-affirming team was three years (IQR: 1–10 years).
The frequency of transgender identity was notable in participants with ages between 15 and 17 years. Depressive symptoms, anxiety, and psychotropic drug use were significantly higher in individuals assigned female at birth. Among 25 individuals assigned female at birth who participated in this study, 60% self-recognized as transgender men.18 individuals assigned male at birth, 67% self-recognized as transgender women. The most frequent treatment was a referral to mental health services (46.51%).

Conclusion
Based on the cohort of our study, we can conclude that patients consult for gender-affirming treatment 3 years after the onset of gender incongruence. Anxiety and depression were higher in individuals assigned female at birth. Additionally, they presented at a later stage of sexual maturation, reducing the possibility of using puberty blockers.
The hazards of genotype imputation when mapping disease susceptibility variants
Authors: Lau Winston , Ali Aminah , Maude Hannah , Andrew Toby , Swallow Dallas M. , Maniatis Nikolas 
Published: January 2024

Abstract
Background
The cost-free increase in statistical power of using imputation to infer missing genotypes is undoubtedly appealing, but is it hazard-free? This case study of three type-2 diabetes (T2D) loci demonstrates that it is not; it sheds light on why this is so and raises concerns as to the shortcomings of imputation at disease loci, where haplotypes differ between cases and reference panel.

Results
T2D-associated variants were previously identified using targeted sequencing. We removed these significantly associated SNPs and used neighbouring SNPs to infer them by imputation. We compared imputed with observed genotypes, examined the altered pattern of T2D-SNP association, and investigated the cause of imputation errors by studying haplotype structure. Most T2D variants were incorrectly imputed with a low density of scaffold SNPs, but the majority failed to impute even at high density, despite obtaining high certainty scores. Missing and discordant imputation errors, which were observed disproportionately for the risk alleles, produced monomorphic genotype calls or false-negative associations. We show that haplotypes carrying risk alleles are considerably more common in the T2D cases than the reference panel, for all loci.

Conclusions
Imputation is not a panacea for fine mapping, nor for meta-analysing multiple GWAS based on different arrays and different populations. A total of 80% of the SNPs we have tested are not included in array platforms, explaining why these and other such associated variants may previously have been missed. Regardless of the choice of software and reference haplotypes, imputation drives genotype inference towards the reference panel, introducing errors at disease loci.
Effectiveness of peer-led intervention in control of non-communicable diseases in rural areas of Khordha district: study protocol for a cluster randomized controlled trial
Authors: Behera Priyamadhaba , Patro Binod Kumar , Singh Arvind Kumar , Dora Susmita , Bandhopadhyay Debapriya , Saharia Gautom Kumar , Dey Anupam , Behera Surama Manjari , Subba Sonu H. 
Published: January 2024

Abstract
Background
The main contributors to death and disability from chronic illnesses in developing nations are elevated blood pressure (hypertension), blood sugar (diabetes mellitus), and blood cholesterol (dyslipidaemia). Even though there are affordable treatments, the treatment gap for these conditions is still significant. Few pilot studies from industrialized nations discuss the value of peer-led interventions for achieving community-level management of blood pressure and blood sugar. This study aims to evaluate the effectiveness of peer-led intervention compared to standard care in achieving control of selected non-communicable diseases (NCDs) in Indian context at 1 year of intervention among people of 30–60 years with hypertension and/or diabetes mellitus and/or dyslipidaemia.

Methods
A cluster-randomized controlled trial will be conducted in villages of two rural blocks of the Khordha district of Odisha from August 2023 to December 2024. A total of 720 eligible participants (360 in the intervention group and 360 in the control group) will be recruited and randomized into two study arms. The participants in the intervention arm will receive a peer-led intervention model for 6 months in addition to standard care. The sessions will be based on the six domains of NCDs — self-care, follow-up care, medication, physical activity, diet, limiting substance use, mental health and co-morbidities. The mean reduction in blood pressure, HbA1C, and blood cholesterol in the intervention arm compared to the standard care arm will be the main outcome.

Discussion
The increasing burden of NCDs demands for newer strategies for management. Peer-led interventions have proven to be useful at the international level. Incorporating it in India will have remarkable results in controlling NCDs.

Trial registration
Clinical Trial Registry of India (CTRI) CTRI/2023/02/050022. Registered on 23 February 2023.
Targeting apoptosis; design, synthesis and biological evaluation of new benzoxazole and thiazole based derivatives
Authors: Helmy Sama W. , Shahin Mai I. , Samir Nermin , Lasheen Deena S. , Ella Dalal A. Abou El 
Published: January 2024

Abstract
Several novel approaches to target Bcl-2 proteins and apoptotic pathways have been identified in recent years for the treatment of different types of cancer including colorectal cancer. However, no effective treatments were yet developed for colorectal cancer. Twenty two novel benzoxazole and thiazole−based compounds were designed, synthesized, and evaluated as potential Bcl-2 inhibitors with anti−proliferative activity. Compounds 8g, 12e and 13d showed good to moderate anti−proliferative activity against most of the NCI 60 cell line panel with mean growth inhibition percent of 45.13, 42.29 and 29.25%, respectively. They showed the greatest cell growth inhibition percent to HCT-116 cell line with the values of 68.0, 59.11 and 43.44%, respectively. The aforementioned compounds were furtherly investigated for their effect on HCT-116 cell cycle, and they showed increase in the total apoptosis with 17, 22, and 5%, respectively. Also, the apoptotic effect of compounds 8g, 12e and 13d, were tested by their effect on altering caspase-3 expression level in HCT-116 human cell line. The three compounds showed an increase in the caspase-3 levels by 6, 8 and 3 folds, respectively in comparison with the same untreated ones. Moreover, they were evaluated for their in–vitro Bcl-2 inhibitory activity and they showed percent inhibition of 60.2, 69.2 and 50.0%, respectively. Finally, the most potent compounds 8g and 12e showed 3.864 and 2.834 folds increase in Bax level compared to the control respectively. On the other hand, Bcl-2 was down−regulated to 0.31 and 0.415 folds compared to the control. The induction of apoptosis through increase in caspase 3 expression and down−regulation of Bcl-2 is the suggested mechanism of action.
Olive industry liquid waste from trash to metal adsorbent for wastewater purification
Authors: Ishraydeh Isra , Hamed Othman , Deghles Abdalhadi , Jodeh Shehdeh , Azzaoui Khalil , Hasan Abdelfattah , Assali Mohyeddin , Jaseer Ataa , Mansour Waseem , Hacıosmanoğlu Gül Gülenay , Can Zehra Semra , Algarra Manuel 
Published: January 2024

AbstractThe development of biobased polymeric materials for wastewater purification has become a demand due to the growing need for water free of hazardous metal ions for safe purposes. The organic components of the OLLW including carbohydrates, phenolics, aromatic acids and others are cost-effective and sustainable choices for this application. This work focuses on a method for turning the organic components of liquid waste from the olive industry (OILW) into a foam-based value-added polymer that has several metal ion binding sites. The process of making the target polymers involved reacting the components of the OILW with hexamethylene diisocyante and 1,4-phnyelene diisocynate to create the polymeric materials LHMIDIC and LPDIC that are in foam forms with urethane linkages, respectively. The adsorption competence of the polymeric foams toward Pb(II) was evaluated as a function of various parameters including adsorbent dose, pH, temperature, initial ion concentration and time. The optimum parameters values that led to a quantitative removal of Pb(II) were identified. The obtained thermodynamic parameters showed that the adsorption by the two foams was spontaneous at room temperature. The isothermal and kinetic values showed that the adsorption by synthesized foams follows a second order kinetic and obeys the Langmuir isothermal model. The foams showed a high tendency for removing multi metal ions present in a real sample of wastewater. The original nature of the starting material used in making the foam, cost and the obtained results showed the potential of using the foam in a large-scale plants of wastewater purification.Graphical Abstract
Bacterial transformation of lignin: key enzymes and high-value products
Authors: Gu Jinming , Qiu Qing , Yu Yue , Sun Xuejian , Tian Kejian , Chang Menghan , Wang Yibing , Zhang Fenglin , Huo Hongliang 
Published: January 2024

AbstractLignin, a natural organic polymer that is recyclable and inexpensive, serves as one of the most abundant green resources in nature. With the increasing consumption of fossil fuels and the deterioration of the environment, the development and utilization of renewable resources have attracted considerable attention. Therefore, the effective and comprehensive utilization of lignin has become an important global research topic, with the goal of environmental protection and economic development. This review focused on the bacteria and enzymes that can bio-transform lignin, focusing on the main ways that lignin can be utilized to produce high-value chemical products. Bacillus has demonstrated the most prominent effect on lignin degradation, with 89% lignin degradation by Bacillus cereus. Furthermore, several bacterial enzymes were discussed that can act on lignin, with the main enzymes consisting of dye-decolorizing peroxidases and laccase. Finally, low-molecular-weight lignin compounds were converted into value-added products through specific reaction pathways. These bacteria and enzymes may become potential candidates for efficient lignin degradation in the future, providing a method for lignin high-value conversion. In addition, the bacterial metabolic pathways convert lignin-derived aromatics into intermediates through the “biological funnel”, achieving the biosynthesis of value-added products. The utilization of this “biological funnel” of aromatic compounds may address the heterogeneous issue of the aromatic products obtained via lignin depolymerization. This may also simplify the separation of downstream target products and provide avenues for the commercial application of lignin conversion into high-value products.
Salicylic acid enhances cell growth, fatty acid and astaxanthin production in heterotrophic Chromochloris zofingiensis without reactive oxygen species elevation
Authors: Zhang Xinwei , Zhang Zhao , Peng Yanmei , Zhang Yushu , Li Qingyang , Sun Dongzhe 
Published: January 2024

Abstract
Background
The induction of lipid and astaxanthin accumulation in microalgae is often achieved through abiotic stress. However, this approach usually leads to oxidative stress, which results in relatively low growth rate. Phytohormones, as important small molecule signaling substances, not only affect the growth and metabolism of microalgae but also influence the intracellular reactive oxygen species level. This study aimed to screen phytohormones that could promote the fatty acids and astaxanthin yield of heterotrophic Chromochloris zofingiensis without causing oxidative damage, and further investigate the underlying mechanisms.

Results
In the present study, among all the selected phytohormones, the addition of exogenous salicylic acid (SA) could effectively promote cell growth along with the yield of total fatty acids (TFA) and astaxanthin in heterotrophic C. zofingiensis. Notably, the highest yields of TFA and astaxanthin were achieved at 100 μM SA, 43% and 97.2% higher compared with the control, respectively. Interestingly, the intracellular reactive oxygen species (ROS) levels, which are usually increased with elevated TFA content under abiotic stresses, were significantly decreased by SA treatment. Comparative transcriptome analysis unveiled significant alterations in overall carbon metabolism by SA. Specifically, the upregulation of fatty acid synthesis pathway, upregulation of β-carotene-4-ketolase (BKT) in carotenoid synthesis aligned with biochemical findings. Weighted gene co-expression network analysis highlighted ABC transporters and GTF2B-like transcription factor as potential key regulators.

Conclusion
This study found that salicylic acid can serve as an effective regulator to promote the celling growth and accumulation of fatty acids and astaxanthin in heterotrophic C. zofingiensis without ROS elevation, which provides a promising approach for heterotrophic production of TFA and astaxanthin without growth inhibition.

Graphical Abstract
Association between triglyceride glucose index and all-cause mortality in patients with cerebrovascular disease: a retrospective study
Authors: Jiang Yong’An , Chen Peng , Zhao YangYang , Cai JiaHong , Liang JiaWei , Cheng ShiQi , Zhang Yan 
Published: January 2024

Abstract
Background
Triglyceride glucose (TyG) is associated with stroke, atherosclerosis, and adverse clinical outcomes. However, its correlation with cerebrovascular disease (CVD) mortality remains unclear. This study aimed to investigate the relationship between TyG index and mortality in patients with CVD.

Methods
Patient data sourced from the Medical Information Mart for Intensive Care -IV database were categorized based on TyG quartiles. Kaplan–Meier survival analysis was used to estimate survival disparities among the TyG subgroups. Cox proportional risk modeling was used to examine the association between the TyG index and mortality. Generalized summation models were applied to fit the smoothed curves. log-likelihood ratio test were used to analyze the non-linear relationship.

Results
The study comprised 1,965 patients (50.18% were male). The 28-day and 90-day mortality rates were 20.10% and 24.48%, respectively. The TyG index exhibited a linear relationship with the 28-day mortality (Hazards ratio (HR), 1.16; 95% confidence interval (CI), 0.99–1.36) and the 90-day mortality (HR, 1.18; 95% CI, 1.02–1.37). In the TyG Q4 group, each 1 mg/dl increase was linked to a 35% rise in the risk of 28-day mortality and a 38% increase in the risk of 90-day mortality. Subgroup analyses highlighted a more substantial association between TyG index and 90-day mortality in the diabetic group.

Conclusion
Our findings underscore the positive association between TyG and the 28- and 90-day mortality rates in patients with CVD. This insight may prove pivotal for identifying at-risk populations and enhancing risk prediction in the clinical management of CVD.
Current views on selenoprotein S in the pathophysiological processes of diabetes-induced atherosclerosis: potential therapeutics and underlying biomarkers
Authors: Yu Shan-shan , Du Jian-ling 
Published: January 2024

AbstractAtherosclerotic cardiovascular disease (ASCVD) consistently ranks as the primary mortality factor among diabetic people. A thorough comprehension of the pathophysiological routes and processes activated by atherosclerosis (AS) caused by diabetes mellitus (DM), together with the recognition of new contributing factors, could lead to the discovery of crucial biomarkers and the development of innovative drugs against atherosclerosis. Selenoprotein S (SELENOS) has been implicated in the pathology and progression of numerous conditions, including diabetes, dyslipidemia, obesity, and insulin resistance (IR)—all recognized contributors to endothelial dysfunction (ED), a precursor event to diabetes-induced AS. Hepatic-specific deletion of SELENOS accelerated the onset and progression of obesity, impaired glucose tolerance and insulin sensitivity, and increased hepatic triglycerides (TG) and diacylglycerol (DAG) accumulation; SELENOS expression in subcutaneous and omental adipose tissue was elevated in obese human subjects, and act as a positive regulator for adipogenesis in 3T3-L1 preadipocytes; knockdown of SELENOS in Min6 β-cells induced β-cell apoptosis and reduced cell proliferation. SELENOS also participates in the early stages of AS, notably by enhancing endothelial function, curbing the expression of adhesion molecules, and lessening leukocyte recruitment—actions that collectively reduce the formation of foam cells. Furthermore, SELENOS forestalls the apoptosis of vascular smooth muscle cells (VSMCs) and macrophages, mitigates vascular calcification, and alleviates inflammation in macrophages and CD4+ T cells. These actions help stifle the creation of unstable plaque characterized by thinner fibrous caps, larger necrotic cores, heightened inflammation, and more extensive vascular calcification—features seen in advanced atherosclerotic lesion development. Additionally, serum SELENOS could function as a potential biomarker, and SELENOS single nucleotide polymorphisms (SNPs) rs4965814, rs28628459, and rs9806366, might be effective gene markers for atherosclerosis-related diseases in diabetes. This review accentuates the pathophysiological processes of atherosclerosis in diabetes and amasses current evidence on SELENOS's potential therapeutic benefits or as predictive biomarkers in the various stages of diabetes-induced atherosclerosis.
Histone acetylation: a key determinant of acquired cisplatin resistance in cancer
Authors: Natu Abhiram , Verma Tripti , Khade Bharat , Thorat Rahul , Gera Poonam , Dhara Sangita , Gupta Sanjay 
Published: January 2024

AbstractCisplatin is an alkylating class of chemotherapeutic drugs used to treat cancer patients. However, cisplatin fails in long-term treatment, and drug resistance is the primary reason for tumor recurrence. Hence, understanding the mechanism of acquirement of chemoresistance is essential for developing novel combination therapeutic approaches. In this study, in vitro cisplatin-resistant cancer cell line models were developed. Gene ontology and GSEA of differentially expressed genes between parental and resistant cells suggest that PI3K-AKT signaling, central carbon metabolism, and epigenetic-associated phenomenon alter in cisplatin-resistant cells. Further, the data showed that increased glucose transport, alteration in the activity of histone-modifying enzymes, and acetyl-CoA levels in resistant cells paralleled an increase in global histone acetylation. Enrichment of histone acetylation on effectors of PI3K-AKT and glycolysis pathway provides evidence of epigenetic regulation of the key molecules in drug resistance. Moreover, cisplatin treatment to resistant cells showed no significant changes in histone acetylation marks since drug treatment alters cell epigenome. In continuation, targeting PI3K-AKT signaling and glycolysis leads to alteration in histone acetylation levels and re-sensitization of resistant cells to chemo-drug. The data provide evidence of histone acetylation's importance in regulating pathways and cisplatin-resistant cells' cell survival. Our study paves the way for new approaches for developing personalized therapies in affecting metabolic pathways and epigenetic changes to achieve better outcomes for targeting drug-resistant cells.
Switching from zonisamide to perampanel improved the frequency of seizures caused by hyperthermia in Dravet syndrome: a case report
Authors: Horiuchi Kazuhiro , Kudo Akihiko , Nakamura Shuntaro , Yamada Kazuki , Inoue Takashi , Fujii Shintaro , Oshima Yuki 
Published: January 2024

Abstract
Background
Dravet syndrome is a severe epilepsy disorder characterized by drug-resistant seizures and cognitive dysfunction, often caused by SCN1A gene mutations. It leads to neurodevelopmental delays and motor, behavioral, and cognitive impairments, with a high mortality rate. Treatment options include sodium valproate, clobazam, and newer agents such as cannabidiol and fenfluramine. Zonisamide, which is used in some cases, can cause hyperthermia and oligohydrosis. Herein, we present a case of a patient with Dravet syndrome whose seizures were controlled by treating infections and switching from zonisamide to perampanel.

Case presentation
A 24-year-old Japanese man with Dravet syndrome presented to our department with aspiration pneumonia. The patient had been treated with valproate, sodium bromide, and zonisamide for a long time. His seizures were triggered by hyperthermia. The patient was experiencing a sustained pattern of hyperthermia caused by infection, zonisamide, and persistent convulsions, which caused a vicious cycle of further seizures. In this case, the control of infection and switching from zonisamide to perampanel improved seizure frequency.

Conclusion
Dravet syndrome usually begins with generalized clonic seizures in its infancy because of fever and progresses to various seizure types, often triggered by fever or seizure-induced heat due to mutations in the SCN1A gene that increases neuronal excitability. Seizures usually diminish with age, but the heat sensitivity remains. In this case, seizures were increased by repeated infections, and hyperthermia was induced by zonisamide, resulting in status epilepticus. Perampanel, an aminomethylphosphonic acid receptor antagonist, decreased seizures but caused psychiatric symptoms. It was effective in suppressing seizures of Dravet syndrome in this patient.