bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of trimethoprim- sulfamethoxazole for treating Pneumocystis jirovecii pneumonia in a patient with glucose-6-phosphate dehydrogenase deficiency: a case report
Authors: Wang Linyu , Xie Xianlong , Li Zhe , Li Yan 
Published: September 2024

BackgroundPneumocystis jirovecii pneumonia (PJP) is an opportunistic infection caused by the yeast-like fungus P. jirovecii. As recommended by some guidelines, the first-line treatment for this infection is trimethoprim-sulfamethoxazole (TMP-SMX), and the second-line treatment includes drugs such as dapsone, pentamidine, primaquine, Atovaquone, clindamycin, and caspofungin. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked gene disorder in which treatment with oxidizing drugs, such as sulfonamides, dapsone, primaquine, can directly destroy hemoglobin present in red blood cells (RBCs), thereby inducing methemoglobin and hemolysis.Case presentationHere, we present the case of a lymphoma patient with previous G6PD deficiency who was admitted to ICU for the treatment of severe pneumonia combined with respiratory failure. PJP was detected by the next-generation sequencing of the bronchoalveolar lavage fluid. The patient was initially treated with the antifungal drug caspofungin; however, this treatment showed poor therapeutic effect. Based on the evaluation of G6PD enzyme activity and the patient’s previous history of G6PD deficiency, we finally treated the patient with low-dose TMP-SMX combined with caspofungin and provided rigorous medical care to the patient. Following this treatment, the patient’s clinical symptoms improved, lung computed tomography showed reduced pulmonary inflammation, and the fungal β-(1,3)-D-glucan test (G test) showed decreased levels of fungal D-glucan. After 57 days, the TMP-SMX treatment was discontinued. No symptoms related to G6PD deficiency, such as hemolysis, hematuria, and anemia, occurred during the treatment course.ConclusionThis is the first report mentioning the successful treatment of Pneumocystis jirovecii pneumonia with a double-drug regimen with low-dose TMP-SMX and caspofungin in a T-lymphoblastic leukemia/lymphoma patient with previous G6PD deficiency. Enzyme activity detection is the first step for anti-PJP treatment in patients with G6PD deficiency. Although patients with mild enzyme deficiency may not show any adverse reactions, we still recommend the regular monitoring of the levels of RBCs, hemoglobin, and hematocrit before and after the use of sulfonamides or sulfoxides and other oxidizing drugs in patients with G6PD deficiency. Among other things, early and correct diagnosis of Pneumocystis jirovecii pneumonia in hematological malignancies patients is very important. Relevant oncologists should be alert to the risk of Pneumocystis jirovecii pneumonia in these patients.
Metabolomic changes in tear fluid following zinc biofortification in the BiZiFED nutritional study: a feasibility study
Authors: Brown Connor N. , Shahzad Babar , Zaman Mukhtiar , Pan Xiaobei , Green Brian D. , Lowe Nicola M. , Lengyel Imre 
Published: September 2024

BackgroundBiofortified Zinc Flour to Eliminate Deficiency in Pakistan (BiZiFED) is a nutritional research program that evaluates the impact of consuming zinc biofortified wheat flour on zinc status and associated health outcomes of vulnerable communities in northwest Pakistan. Measuring zinc status from blood samples is fraught with problems. This feasibility study evaluated whether metabolite changes in tear biofluids could be used to understand zinc status.MethodsZinc deficiency is particularly prevalent amongst the female population in Pakistan. Therefore, a crossover trial was developed in which 25 women of reproductive age received standard, wheat flour, and another 25 received zinc-biofortified wheat flour for 8 weeks. At the end of this period, the nutritional intervention was switched between the groups for another 8 weeks. Tear biofluid was collected using Schirmer strips at baseline and after 8 and 16 weeks. Metabolomic analysis was conducted using the MxP® Quant 500 kit on the tear biofluid from a subset of the study participants.ResultsTwo metabolites had a significantly negative correlation with plasma zinc concentration: tiglylcarnitine and valine. Compared to baseline metabolite concentrations, acetylcarnitine, glutamine, two lysophosphatidylcholines (lysoPC a C16:0 and lysoPC a C18:1), and four sphingomyelins (SM (OH) C16:1, SM C16:0, SM C16:1, and SM C24:0) were all significantly decreased post-zinc intervention, whilst a ceramide (Cer(d18:1/18:0) was significantly increased.ConclusionThese results highlight the potential of using tear biofluids as an alternative source for metabolomic biomarkers, both for the assessment of the zinc status of individuals enrolled in nutritional studies and for indicating physiological changes that arise from nutritional supplementation.
Neuroprotective effects of ellorarxine in neuronal models of degeneration
Authors: Kouchmeshky Azita , Whiting Andrew , McCaffery Peter 
Published: September 2024

IntroductionRetinoic acid (RA) was first recognised to be important for the central nervous system (CNS) in its developmental regulatory role and, given this action, it has been proposed in the adult CNS to regulate plasticity and promote regeneration. These types of roles have included support of neurogenesis, induction of neurite outgrowth, and protection from neuronal death. These functions are predominantly mediated by the retinoic acid receptor (RAR) transcription factor, and hence agonists for the RARs have been tested in a variety of models of neurodegeneration. This present study employs several in vitro models less explored for the action of RAR agonists to reverse neurodegeneration.MethodsA series of assays are used in which neuronal cells are placed under the types of stress that have been linked to neurodegeneration, in particular amyotrophic lateral sclerosis (ALS), and the neuroprotective influence of a new potent agonist for RAR, ellorarxine, is tested out. In these assays, neuronal cells were subjected to excitotoxic stress induced by glutamate, proteostasis disruption caused by epoxomicin, and oxidative stress leading to stress granule formation triggered by sodium arsenite.ResultsEllorarxine effectively reversed neuronal death in excitotoxic and proteostasis disruption assays and mitigated stress granule formation induced by sodium arsenite. This study also highlights for the first time the novel observation of RAR modulation of stress granules, although it is unknown whether this change in stress granules will be neuroprotective or potentially regenerative. Furthermore, the distribution of RAR agonists following intraperitoneal injection was assessed in mice, revealing preferential accumulation in the central nervous system, particularly in the spinal cord, compared to the liver. Gene expression studies in the spinal cord demonstrated that ellorarxine induces transcriptional changes at a low dose (0.01 mg/kg).DiscussionThese findings underscore the therapeutic potential of RAR agonists, such as ellorarxine, for ALS and potentially other neurodegenerative diseases.
Different types and numbers metabolic abnormalities and risk of gallbladder stone disease in adults
Authors: Yang Tingting , Zhong Jianqin , Zhang Renhua , Xiao Fei , Wang Yuan , Tao Huimin , Hong Feng 
Published: September 2024

BackgroundMetabolic abnormalities in the body increase the risk of gallbladder stones and their complications, which brings a great economic and social burden. The relationship between different types and amounts of metabolic abnormalities and gallstone risk in different sexes is poorly documented and controversial.MethodsBased on the baseline survey data of the Chinese Multi-Ethnic Cohort (CMEC) study, 4,075 Chinese adults aged 30–79 years with complete abdominal ultrasound results and metabolic index data. Logistic regression model was used to evaluate the correlation between five metabolic abnormalities and gallstones, and to explore the gender difference.ResultsThe detection rate of gallbladder stones was found to be 7.0%, with a higher rate in women (8.6%) than in men (4.1%). Logistic results showed adjustment odds ratio (ORs) and 95% confidence interval (95% CI) of dysglycemia + hypertension + central obesity in 3 metabolic combinations was 4.459 (1.653, 12.029). The four metabolic combinations, dysglycemia + dyslipidemia + hypertension + central obesity, dysglycemia + dyslipidemia + hypertension + abnormal blood uric acid and dysglycemia + dyslipidemia + central obesity + abnormal blood uric acid adjusted OR and 95%CI were 3.342 (1.459, 7.659), 5.439 (1.555, 19.018) and 2.971 (1.187, 7.435), respectively. Gender-stratified analysis found that “any three or more metabolic abnormalities and their components were associated with gallstone risk, more significantly in women.ConclusionDifferent types and amounts of five metabolic abnormalities were associated with the risk of gallstone development, and the differences were more significant in women than men.
A machine learning model based on CHAT-23 for early screening of autism in Chinese children
Authors: Lu Hengyang , Zhang Heng , Zhong Yi , Meng Xiang-Yu , Zhang Meng-Fei , Qiu Ting 
Published: September 2024

IntroductionAutism spectrum disorder (ASD) is a neurodevelopmental condition that significantly impacts the mental, emotional, and social development of children. Early screening for ASD typically involves the use of a series of questionnaires. With answers to these questionnaires, healthcare professionals can identify whether a child is at risk for developing ASD and refer them for further evaluation and diagnosis. CHAT-23 is an effective and widely used screening test in China for the early screening of ASD, which contains 23 different kinds of questions.MethodsWe have collected clinical data from Wuxi, China. All the questions of CHAT-23 are regarded as different kinds of features for building machine learning models. We introduce machine learning methods into ASD screening, using the Max-Relevance and Min-Redundancy (mRMR) feature selection method to analyze the most important questions among all 23 from the collected CHAT-23 questionnaires. Seven mainstream supervised machine learning models were built and experiments were conducted.ResultsAmong the seven supervised machine learning models evaluated, the best-performing model achieved a sensitivity of 0.909 and a specificity of 0.922 when the number of features was reduced to 9. This demonstrates the model's ability to accurately identify children for ASD with high precision, even with a more concise set of features.DiscussionOur study focuses on the health of Chinese children, introducing machine learning methods to provide more accurate and effective early screening tests for autism. This approach not only enhances the early detection of ASD but also helps in refining the CHAT-23 questionnaire by identifying the most relevant questions for the diagnosis process.
A single exposure to brivaracetam or perampanel does not cause cell death in neonatal rats
Authors: Witherspoon Eric , Zuczek Nicholas , Williams Gabrielle , Bernstein Briana , Ghosh Anjik , Culjat Marko , Kaushal Suhasini , Forcelli Patrick A. 
Published: September 2024

IntroductionExposure to a range of anti-seizure medications (ASMs) during early brain development adversely impacts neurodevelopmental outcomes in both animal models and in clinical studies. Many ASMs, including phenobarbital, phenytoin, valproate (VPA), and benzodiazepines, are associated with acute neurotoxicity (cell death), impaired synaptic development, and long-term behavioral changes following gestational or neonatal exposure in animals. This is mirrored in clinical studies which show lasting neurodevelopmental deficits following early-life or gestational exposure to these drugs. Brivaracetam (BRV) and perampanel (PER) are two newer generation anti-seizure medications and are of interest based on their mechanisms of action (SV2A modulator, AMPA antagonist, respectively), as other drugs with these mechanisms of action do not trigger acute neurotoxicity. Both BRV and PER show anti-seizure efficacy in developing animals, but potential neurotoxicity of these drugs is unexplored.MethodsTo address this gap, we treated postnatal day (P)7 Sprague-Dawley rats with BRV (20, 40, 80 mg/kg) and PER (0.1, 0.9, 2.7 mg/kg), and assessed the induction of cell death across a range of vulnerable brain regions 24 h after exposure. Cell death was assessed using pathogreen staining.ResultsIn each of the regions examined (dorsal striatum, nucleus accumbens, motor cortex, cingulate cortex, lateral thalamus, septum, hippocampus), VPA, which served as a positive control, significantly increased cell death as measured by the numer of pathogreen positive cells. By contrast, neither BRV nor PER increased the number of pathogreen positive cells in any region examined.DiscussionOur results suggest that BRV and PER may have a positive safety profile–at least with respect to acute induction of cell death - and therefore may offer a safer option for the treatment of early life seizures.
Mechanisms of action of Sappan lignum for prostate cancer treatment: network pharmacology, molecular docking and experimental validation
Authors: Li Wenna , Jiang Honglin , Zhang Weina , Sun Qiuyue , Zhang Qiaoli , Xu Jingnan , Huang Jinchang , Wan Yuxiang 
Published: September 2024

BackgroundProstate cancer (PCa) is the most common non-cutaneous malignancy in men globally. Sappan lignum, which exists in the heartwood of Caesalpinia sappan L., has antitumor effects; however, its exact mechanism of action remains unclear. This study elucidated the underlying mechanisms of Sappan lignum in PCa through network pharmacology approaches and molecular docking techniques. Moreover, the therapeutic effects of Sappan lignum on PCa were verified through in vitro experiments.MethodsThe constituent ingredients of Sappan lignum were retrieved from the HERB database. Active plant-derived compounds of Sappan lignum were screened based on gastrointestinal absorption and gastric drug properties. Disease targets for PCa were screened using unpaired and paired case datasets from the Gene Expression Omnibus. Intersection targets were used for gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Core targets were identified through topological analysis parameters and their clinical relevance was validated through The Cancer Genome Atlas database. The affinity between the phytochemicals of Sappan lignum and core proteins was verified using the molecular docking technique. Validation experiments confirmed the significant potential of Sappan lignum in treating PCa.ResultsTwenty-one plant-derived compounds of Sappan lignum and 821 differentially expressed genes associated with PCa were collected. Among 32 intersection targets, 8 were screened according to topological parameters. KEGG analysis indicated that the antitumor effects of Sappan lignum on PCa were primarily associated with the p53 pathway. The molecular docking technique demonstrated a strong affinity between 3-deoxysappanchalcone (3-DSC) and core proteins, particularly cyclin B1 (CCNB1). CCNB1 expression correlated with clinicopathological features in patients with PCa. Experimental results revealed that 3-DSC exhibited anti-proliferative, anti-migratory, and pro-apoptotic effects on 22RV1 and DU145 cells while also causing G2/M phase cell cycle arrest, potentially through modulating the p53/p21/CDC2/CCNB1 pathway.ConclusionThis research highlights the promising therapeutic potential of Sappan lignum in treating PCa, with a particular focus on targeting the p53 pathway.
Ethnobotanical survey and scientific validation of liver-healing plants in northeastern Morocco
Authors: Bencheikh Noureddine , Elbouzidi Amine , Baraich Abdellah , Bouhrim Mohamed , Azeroual Abdelhamid , Addi Mohamed , Mothana Ramzi A. , Al-Yousef Hanan M. , Eto Bruno , Elachouri Mostafa 
Published: September 2024

IntroductionLiver diseases represent a significant global health challenge, with primary causes including excessive alcohol consumption, infections, chemotherapy, and autoimmune disorders. Medicinal plants, due to their natural bioactive compounds, hold promise for developing effective treatments and preventive measures against liver ailments. This study aimed to document the use of herbal remedies in northeastern Morocco for liver diseases and correlate these uses with scientific evidence through a bibliometric analysis.MethodsAn ethnobotanical survey was conducted in remote communities of northeastern Morocco from October 2020 to January 2022. A total of 189 informants were interviewed using semi-structured questionnaires to gather information on local medicinal plants used for liver ailments. The data were analyzed using four ethnobotanical quantitative indices: use value (UV), familial use value (FUV), informant consensus factor (ICF), and fidelity level (FL). Additionally, a bibliometric analysis was performed to evaluate the scientific support for the ethnopharmacological uses documented.ResultsThe survey identified 45 plant species from 26 different families used in the treatment of liver diseases. The most frequently utilized species were Cuminum cyminum L. (UV = 0.1065), Allium sativum L. (UV = 0.1015), Salvia officinalis L. (UV = 0.0761), Asparagus officinalis L. (UV = 0.0558), and Ziziphus lotus (L.) Lam. (UV = 0.0457). The Apiaceae family showed the highest familial use value (FUV = 0.1066), followed by Alliaceae (FUV = 0.1015). Liver congestion had the highest informant consensus factor (ICF = 0.83), followed by hepatic colic (ICF = 0.80). Bibliometric analysis revealed that 61% of the plants identified had documented pharmacological effects related to liver health.DiscussionThe study demonstrates that traditional knowledge in northeastern Morocco encompasses a rich diversity of medicinal plants used to treat liver diseases. The high ICF values indicate a strong consensus among informants on the efficacy of these remedies. The correlation between ethnopharmacological use and scientific validation for a significant portion of these plants suggests their potential as reliable therapeutic agents for liver conditions. However, further scientific investigations are necessary to confirm their efficacy and safety in clinical settings. This research contributes valuable information for future studies on the therapeutic potential of these plants.ConclusionThis ethnobotanical survey provides a comprehensive database of medicinal plants used in northeastern Morocco for liver diseases. The findings highlight the potential of these plants in developing novel treatments for hepatic conditions, although further research is essential to substantiate their therapeutic claims.
Individualized dosing parameters for tacrolimus in the presence of voriconazole: a real-world PopPK study
Authors: Zhao Yi-Chang , Sun Zhi-Hua , Li Jia-Kai , Liu Huai-Yuan , Zhang Bi-Kui , Xie Xu-Biao , Fang Chun-Hua , Sandaradura Indy , Peng Feng-Hua , Yan Miao 
Published: September 2024

ObjectivesSignificant increase in tacrolimus exposure was observed during co-administration with voriconazole, and no population pharmacokinetic model exists for tacrolimus in renal transplant recipients receiving voriconazole. To achieve target tacrolimus concentrations, an optimal dosage regimen is required. This study aims to develop individualized dosing parameters through population pharmacokinetic analysis and simulate tacrolimus concentrations under different dosage regimens.MethodsWe conducted a retrospective study of renal transplant recipients who were hospitalized at the Second Xiangya Hospital of Central South University between January 2016 and March 2021. Subsequently, pharmacokinetic analysis and Monte Carlo simulation were employed for further analysis.ResultsNineteen eligible patients receiving tacrolimus and voriconazole co-therapy were included in the study. We collected 167 blood samples and developed a one-compartment model with first-order absorption and elimination to describe the pharmacokinetic properties of tacrolimus. The final typical values for tacrolimus elimination rate constant (Ka), apparent volume of distribution (V/F), and apparent oral clearance (CL/F) were 8.39 h−1, 2690 L, and 42.87 L/h, respectively. Key covariates in the final model included voriconazole concentration and serum creatinine. Patients with higher voriconazole concentration had lower tacrolimus CL/F and V/F. In addition, higher serum creatinine levels were associated with lower tacrolimus CL/F.ConclusionOur findings suggest that clinicians can predict tacrolimus concentration and estimate optimal tacrolimus dosage based on voriconazole concentration and serum creatinine. The effect of voriconazole concentration on tacrolimus concentration was more significant than serum creatinine. These findings may inform clinical decision-making in the management of tacrolimus and voriconazole therapy in solid organ transplant recipients.
Applying neural network algorithms to ascertain reported experiences of violence in routine mental healthcare records and distributions of reports by diagnosis
Authors: Mason Ava J. C. , Bhavsar Vishal , Botelle Riley , Chandran David , Li Lifang , Mascio Aurelie , Sanyal Jyoti , Kadra-Scalzo Gioulaina , Roberts Angus , Williams Marcus , Stewart Robert 
Published: September 2024

IntroductionExperiences of violence are important risk factors for worse outcome in people with mental health conditions; however, they are not routinely collected be mental health services, so their ascertainment depends on extraction from text fields with natural language processing (NLP) algorithms.MethodsApplying previously developed neural network algorithms to routine mental healthcare records, we sought to describe the distribution of recorded violence victimisation by demographic and diagnostic characteristics. We ascertained recorded violence victimisation from the records of 60,021 patients receiving care from a large south London NHS mental healthcare provider during 2019. Descriptive and regression analyses were conducted to investigate variation by age, sex, ethnic group, and diagnostic category (ICD-10 F chapter sub-headings plus post-traumatic stress disorder (PTSD) as a specific condition).ResultsPatients with a mood disorder (adjusted odds ratio 1.63, 1.55-1.72), personality disorder (4.03, 3.65-4.45), schizophrenia spectrum disorder (1.84, 1.74-1.95) or PTSD (2.36, 2.08-2.69) had a significantly increased likelihood of victimisation compared to those with other mental health diagnoses. Additionally, patients from minority ethnic groups (1.10 (1.02-1.20) for Black, 1.40 (1.31-1.49) for Asian compared to White groups) had significantly higher likelihood of recorded violence victimisation. Males were significantly less likely to have reported recorded violence victimisation (0.44, 0.42-0.45) than females.DiscussionWe thus demonstrate the successful deployment of machine learning based NLP algorithms to ascertain important entities for outcome prediction in mental healthcare. The observed distributions highlight which sex, ethnicity and diagnostic groups had more records of violence victimisation. Further development of these algorithms could usefully capture broader experiences, such as differentiating more efficiently between witnessed, perpetrated and experienced violence and broader violence experiences like emotional abuse.