bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of novel Plasmodium falciparum coronin gene mutations in a recrudescent ACT-treated patient in South-Western Nigeria
Authors: Ajibaye Olusola , Olukosi Yetunde Adeola , Oriero Eniyou C. , Oboh Mary Aigbiremo , Iwalokun Bamidele , Nwankwo Ikechukwu Chidiebere , Nnam Chinaza Favour , Adaramoye Olawunmi Victoria , Chukwemeka Somadina , Okanazu Judith , Gabriel Eniafe , Balogun Emmanuel Oluwadare , Amambua-Ngwa Alfred 
Published: April 2024

BackgroundRoutine surveillance for antimalarial drug resistance is critical to sustaining the efficacy of artemisinin-based Combination Therapies (ACTs). Plasmodium falciparum kelch-13 (Pfkelch-13) and non-Pfkelch-13 artemisinin (ART) resistance-associated mutations are uncommon in Africa. We investigated polymorphisms in Plasmodium falciparum actin-binding protein (Pfcoronin) associated with in vivo reduced sensitivity to ART in Nigeria.MethodsFifty-two P. falciparum malaria subjects who met the inclusion criteria were followed up in a 28-day therapeutic efficacy study of artemether-lumefantrine in Lagos, Nigeria. Parasite detection was done by microscopy and molecular diagnostic approaches involving PCR amplification of genes for Pf18S rRNA, varATS, telomere-associated repetitive elements-2 (TARE-2). Pfcoronin and Pfkelch-13 genes were sequenced bi-directionally while clonality of infections was determined using 12 neutral P. falciparum microsatellite loci and msp2 analyses. Antimalarial drugs (sulfadoxine-pyrimethamine, amodiaquine, chloroquine and some quinolones) resistance variants (DHFR_51, DHFR_59, DHFR_108, DHFR_164, MDR1_86, MDR1_184, DHPS_581 and DHPS_613) were genotyped by high-resolution melting (HRM) analysis.ResultsA total of 7 (26.92%) cases were identified either as early treatment failure, late parasitological failure or late clinical failure. Of the four post-treatment infections identified as recrudescence by msp2 genotypes, only one was classified as recrudescence by multilocus microsatellites genotyping. Microsatellite analysis revealed no significant difference in the mean allelic diversity, He, (P = 0.19, Mann-Whitney test). Allele sizes and frequency per locus implicated one isolate. Genetic analysis of this isolate identified two new Pfcoronin SNVs (I68G and L173F) in addition to the P76S earlier reported. Linkage-Disequilibrium as a standardized association index, IAS, between multiple P. falciparum loci revealed significant LD (IAS = 0.2865, P=0.02, Monte-Carlo simulation) around the neutral microsatellite loci. The pfdhfr/pfdhps/pfmdr1 drug resistance-associated haplotypes combinations, (108T/N/51I/164L/59R/581G/86Y/184F), were observed in two samples.ConclusionPfcoronin mutations identified in this study, with potential to impact parasite clearance, may guide investigations on emerging ART tolerance in Nigeria, and West African endemic countries.
Mendelian randomization reveals the impact of diet on infertility in men and women
Authors: Chen Xiangyu , Ren Congzhe , Wu Changgui , Liu Xiaoqiang 
Published: April 2024

BackgroundAlthough studies on the effects of diet on fertility has progressed, some cumulative evidence has piled against popular hypotheses. The aim of our study was to investigate the effects of 31 diets including 23 individual dietary intakes and 8 dietary habits on infertility in men and women.MethodsThe datas of diets and infertility were collected from genome-wide association studies (GWAS). Mendelian randomization (MR) methods were used to analyze causal relationships. Multivariate MR (MVMR) adjusted for the effects of other exposures on causality. And MR-Egger, Cochran’s Q, radial MR, and MR-PRESSO tests were employed to assess heterogeneity and horizontal pleiotropy.ResultsOur study found that coffee intake (OR, 3.6967; 95% CI, 1.0348 – 13.2065; P = 0.0442) and cooked vegetable intakes (OR, 54.7865; 95% CI, 2.9011 – 1030.5500; P = 0.0076) increased the risk of male infertility. For women, beer was a risk factor for infertility (OR, 4.0932; 95% CI, 1.8728 – 8.9461; P = 0.0004); but processed meat was negatively associated with infertility (OR, 0.5148; 95% CI, 0.2730 – 0.9705; P = 0.0401). MVMR demonstrated selenium as a protective factor against female infertility (OR, 7.4474e-12; 95% CI, 5.4780e-22 – 1.0125e-01; P = 0.0314).ConclusionWe found the causal relationships between four diets and infertility. We look forward to more high-quality epidemiologic studies to prove our conclusions.
A retrospective multicenter study on clinical and serological parameters in patients with MuSK myasthenia gravis with and without general immunosuppression
Authors: Koneczny Inga , Mané-Damas Marina , Zong Shenghua , De Haas Sander , Huda Saif , van Kruining Daan , Damoiseaux Jan , De Rosa Anna , Maestri Michelangelo , Guida Melania , Molenaar Peter , Van Damme Philip , Fichtenbaum Andreas , Perkmann Thomas , De Baets Marc , Lazaridis Konstantinos , Zouvelou Vasiliki , Tzartos Socrates , Ricciardi Roberta , Losen Mario , Martinez-Martinez Pilar 
Published: April 2024

IntroductionMuscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of the IgG4 subclass. The first-line treatment for MuSK-MG is general immunosuppression with corticosteroids, but the effect of treatment on IgG4 and MuSK IgG4 levels has not been studied.MethodsWe analyzed the clinical data and sera from 52 MuSK-MG patients (45 female, 7 male, median age 49 (range 17–79) years) from Italy, the Netherlands, Greece and Belgium, and 43 AChR-MG patients (22 female, 21 male, median age 63 (range 2–82) years) from Italy, receiving different types of immunosuppression, and sera from 46 age- and sex-matched non-disease controls (with no diagnosed diseases, 38 female, 8 male, median age 51.5 (range 20–68) years) from the Netherlands. We analyzed the disease severity (assessed by MGFA or QMG score), and measured concentrations of MuSK IgG4, MuSK IgG, total IgG4 and total IgG in the sera by ELISA, RIA and nephelometry.ResultsWe observed that MuSK-MG patients showed a robust clinical improvement and reduction of MuSK IgG after therapy, and that MuSK IgG4 concentrations, but not total IgG4 concentrations, correlated with clinical severity. MuSK IgG and MuSK IgG4 concentrations were reduced after immunosuppression in 4/5 individuals with before-after data, but data from non-linked patient samples showed no difference. Total serum IgG4 levels were within the normal range, with IgG4 levels above threshold (1.35g/L) in 1/52 MuSK-MG, 2/43 AChR-MG patients and 1/45 non-disease controls. MuSK-MG patients improved within the first four years after disease onset, but no further clinical improvement or reduction of MuSK IgG4 were observed four years later, and only 14/52 (26.92%) patients in total, of which 13 (93.3%) received general immunosuppression, reached clinical remission.DiscussionWe conclude that MuSK-MG patients improve clinically with general immunosuppression but may require further treatment to reach remission. Longitudinal testing of individual patients may be clinically more useful than single measurements of MuSK IgG4. No significant differences in the serum IgG4 concentrations and IgG4/IgG ratio between AChR- and MuSK-MG patients were found during follow-up. Further studies with larger patient and control cohorts are necessary to validate the findings.
Efficacy and safety of ciprofol for sedation in outpatient gynecological procedures: a phase III multicenter randomized trial
Authors: Xu Jing , Yang Mengchang , Zeng Yuan , Zou Xiao-Hua , Ren Jing-Hua , Xia Zhongyuan , Xie Hai-Hui , Yu Yong-Hao , Xu Ming-Jun , Chen Wei , Wang Dong-Xin 
Published: April 2024

ObjectiveCiprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures.MethodsThis phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18–65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at −8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain.ResultsA total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, −4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p &lt; 0.001), and required more time to reach full awake (MD, 2.3 min; 95% CI, 1.4 to 3.1; p &lt; 0.001) and discharge criteria (MD, 2.3 min; 95% CI, 1.5 to 3.2; p &lt; 0.001). Fewer patients in the ciprofol group were dissatisfied with sedation (relative risk, 0.21; 95% CI, 0.06 to 0.77; p = 0.024). Patients given ciprofol sedation had lower incidences of treat-emergent adverse events (34.4% [31/90] vs. 79.5% [35/44]; p &lt; 0.001) and injection pain (6.7% [6/90] vs. 61.4% [27/44]; p &lt; 0.001).ConclusionCiprofol for sedation in ambulatory gynecological procedures was non-inferior to propofol, with less adverse events and injection pain.Clinical trial registrationClinicalTrials.gov, identifier NCT04958746.
Construction of a nomogram to predict the probability of new vertebral compression fractures after vertebral augmentation of osteoporotic vertebral compression fractures: a retrospective study
Authors: Gao Yan , Zheng Jianhu , Yao Kang , Wang Weiguo , Tan Guoqing , Xin Jian , Li Nianhu , Chen Yungang 
Published: April 2024

ObjectiveThis study aimed to develop and validate a new nomogram model that can predict new vertebral fractures after surgery for osteoporotic compression fractures to optimize surgical plans and reduce the incidence of new vertebral compression fractures.Methods420 patients with osteoporotic vertebral compression fractures were randomly sampled using a computer at a fixed ratio; 80% of the patients were assigned to the training set, while the remaining 20% were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression method was applied to screen the factors influencing refracture and construct a predictive model using multivariate logistic regression analysis.ResultsThe results of the multivariate logistic regression analysis showed a significant correlation between bone cement leakage, poor cement dispersion, the presence of fractures in the endplate, and refractures. The receiver operating characteristic curve (ROC) results showed that the area under the ROC curve (AUC) of the training set was 0.974 and the AUC of the validation set was 0.965, which proves that this prediction model has a good predictive ability. The brier score for the training set and validation set are 0.043 and 0.070, respectively, indicating that the model has high accuracy. Moreover, the calibration curve showed a good fit with minimal deviation, demonstrating the model’s high discriminant ability and excellent fit. The decision curve indicated that the nomogram had positive predictive ability, indicating its potential as a practical clinical tool.ConclusionCement leakage, poor cement dispersion, and presence of fractures in the endplate are selected through LASSO and multivariate logistic regressions and included in the model development to establish a nomogram. This simple prediction model can support medical decision-making and maybe feasible for clinical practice.
Moringa oleifera-based feed supplement protects against renal ischaemia/reperfusion injury via downregulation of Bax/caspase 3 signaling
Authors: Afolabi Oladele A. , Akhigbe Tunmise M. , Hammed Sodiq. O. , Hamed Moses A. , Ekundina Victor O. , Ajike Richard A. , Alabi Babatunde A. , Akhigbe Roland E. 
Published: April 2024

IntroductionIschaemia/reperfusion (I/R) may lead to acute kidney injury via the induction of oxidative stress. On the other hand, Moringa oleifera has been reported to exert antioxidant activities. This study was designed to assess whether or not Moringa oleifera-based feed supplement could prevent I/R-induced renal injury.Materials and methodsRenal I/R was induced by occluding the right renal artery for 30  min followed by a 2-h reperfusion.ResultsRenal I/R led to increased absolute renal weight and renal organo-somatic weight index. Renal I/R also caused distortion of renal histoarchitecture and impaired renal function evidenced by elevated serum creatinine and blood urea nitrogen. In addition, renal I/R significantly elevated renal levels of hydrogen peroxide, MDA, and advanced oxidation protein products, but suppressed the levels of reduced glutathione, protein thiol, and non-protein thiol, and the activities of superoxide dismutase and glutathione peroxidase. In addition, renal I/R up-regulated myeloperoxidase activity and the renal levels of NO, TNF-α, and IL-6. Renal I/R also up-regulated Bax and caspase 3 expression in the kidney. Furthermore, I/R-driven structural and biochemical alterations were markedly inhibited by Moringa oleifera-based feed supplement.DiscussionThese results suggest that Moringa oleifera-based feed supplement may preserve the gross and histoarchitectural integrity of the kidney as well as renal function via downregulation of Bax/caspase 3 signaling by targeting oxidative stress, inflammation and apoptosis in the kidney of I/R rat.
ALK-rearranged and EGFR wild-type lung adenocarcinoma transformed to small cell lung cancer: a case report
Authors: Chen Rui , Jian Yan , Liu Yuzhen , Xie Junping 
Published: April 2024

BackgroundCases of ALK-rearranged EGFR wild-type lung adenocarcinoma (LUAD) transforming into small cell lung cancer (SCLC) are rarely reported, and diagnosis is often delayed. The emergence of this transformation phenomenon is often regarded as a consequence of acquired resistance mechanisms.Case presentationA 47-year-old male diagnosed with poorly differentiated adenocarcinoma of the right middle lung (pT2N2M0, stage IIIA) achieved a 46-month progression-free survival (PFS) following surgery and adjuvant chemotherapy. During routine follow-up, tumor recurrence and metastasis was detected. Genetic testing revealed ALK rearrangement and wild-type EGFR, prompting treatment with ALK-TKIs. In May 2023, abdominal CT scans showed significant progression of liver metastases and abnormal elevation of the tumor marker NSE. Immunohistochemical results from percutaneous liver biopsy indicated metastatic SCLC.ResultsAfter resistance to ALK-TKIs and transformation to SCLC, the patient received chemotherapy combined with immunotherapy for SCLC, but the patient’s disease progressed rapidly. Currently, the patient is being treated with albumin-bound paclitaxel in combination with oral erlotinib and remains stable.ConclusionHistological transformation emerges as a compelling mechanism of resistance to ALK-TKIs, necessitating the utmost urgency for repeat biopsies in patients displaying disease progression after resistance. These biopsies are pivotal in enabling the tailor-made adaptation of treatment regimens to effectively counteract the assorted mechanisms of acquired resistance, thus optimizing patient outcomes in the battle against ALK-driven malignancies.
Rice mutants, selected under severe drought stress, show reduced stomatal density and improved water use efficiency under restricted water conditions
Authors: Phunthong Chutima , Pitaloka Mutiara K. , Chutteang Cattleya , Ruengphayak Siriphat , Arikit Siwaret , Vanavichit Apichart 
Published: April 2024

IntroductionRice is among the least water-use-efficient crops, and rice plants utilise most of their water uptake for transpirational cooling via stomata. To improve water-use efficiency (WUE) in rice, reducing stomatal density and size could help optimise transpiration and photosynthesis. MethodologyIn this study, we compared two series of purple rice stomata mutants: the Stomatal Model Mutant (SMM) identified by microscopic observation of flag-leaf stomata, and the Drought-selected Model Mutant (DMM) generated through screening under severe water stress. After undergoing two rounds of severe water stress between -60 to -80 Ym, right before the R1–2 reproductive stage, three DMMs were selected based on their rapid recovery rate and % filled-grain percentage.ResultThe three DMMs displayed 618–697 stomatal units per mm2, similar to the SMMs low-density stomata mutant (JHN 8756 (LD)). Furthermore, the four SMMs, three DMMs and the Jao Hom Nin wild type (JHN WT) were treated with two restricted water condition schemes from seedlings to harvest. The total amount of irrigation and precipitation during the experiment was 78.1 L/plant (69.1 mm/plant) for the less restricted water condition (LR) and 47.5 L/plant (42 mm/plant) for the more restricted water condition (MR). Water condition treatments had no effects on stomatal density and stomatal index. In contrast, genotypes and restricted water condition schemes affected plant height, tillers/plant, % filled grains and shoot dry weight (SDW). The three DMMs and the JHN 8756 (LD), the SMM's low-density stomata mutant, displayed greater resilience towards more restricted water conditions than the SMMs and the JHN wild type. Particularly, DMMs were tolerant to more restricted water condition treatments, showing no SDW penalties. Together, the DMMs and the JHN 8756 (LD) displayed higher WUE under these conditions of more restricted water conditions. ConclusionA rigorous screening process to distinguish tolerant mutants with a rapid drought recovery rate from severe water stress could pave the way to isolate more mutants with better stomatal functionality and resilience in preparation for imminent climate changes.
Experiences using an online therapist-guided psychotherapy platform (OPTT) in correctional workers with depression, anxiety, and PTSD
Authors: Moghimi Elnaz , Gutierrez Gilmar , Stephenson Callum , Gizzarelli Tessa , Jagayat Jasleen , Holmes Christina , Patel Charmy , Omrani Mohsen , Simpson Alexander Ian Frederic , Alavi Nazanin 
Published: April 2024

IntroductionCorrectional workers (CWs) are frequently exposed to potentially traumatic events in the workplace, leading to an increased prevalence of mental health concerns. Online psychotherapy can address many of the barriers CWs face when seeking adequate mental health care. Despite their benefits, CWs’ experience using digital mental health interventions is relatively unknown. This information could be valuable in developing enhanced care delivery to improve recruitment, retention, satisfaction, and treatment outcomes.MethodsThis study investigated the experiences of a sample of CWs enrolled in a clinical trial evaluating the efficacy of the Online Psychotherapy Tool (OPTT) in this population. Participants were surveyed and interviewed to capture their opinions and feedback on the program. Survey analysis was conducted through Qualtrics statistical analysis software. The interview transcripts and open-ended survey questions were analyzed using thematic analysis methods in NVivo.ResultsParticipants (n=14) were cis-gender, predominantly white, with an average age of 38 years. While most respondents preferred in-person therapy, they also reported the benefits of the online psychotherapy program. Specifically, they expressed positive perceptions of the platform, the quality and interaction of their care provider, and the homework assignments and skills learned. Lack of motivation to complete weekly homework assignments was a frequently cited challenge. Unhelpful aspects of the therapy noted issues with the online format and frustration with certain program elements.DiscussionParticipants expressed a positive outlook on the program, the platform, and treatment outcomes. A preference for in-person therapy was still indicated, demonstrating the need to focus on engagement in digital mental health interventions. In addition, the findings of this study shed light on the factors that can influence help-seeking in this population, including stigma in the work environment, demanding work schedules, workplace perceptions, and previous experiences accessing mental health services.
BERT-based language model for accurate drug adverse event extraction from social media: implementation, evaluation, and contributions to pharmacovigilance practices
Authors: Dong Fan , Guo Wenjing , Liu Jie , Patterson Tucker A. , Hong Huixiao 
Published: April 2024

IntroductionSocial media platforms serve as a valuable resource for users to share health-related information, aiding in the monitoring of adverse events linked to medications and treatments in drug safety surveillance. However, extracting drug-related adverse events accurately and efficiently from social media poses challenges in both natural language processing research and the pharmacovigilance domain.MethodRecognizing the lack of detailed implementation and evaluation of Bidirectional Encoder Representations from Transformers (BERT)-based models for drug adverse event extraction on social media, we developed a BERT-based language model tailored to identifying drug adverse events in this context. Our model utilized publicly available labeled adverse event data from the ADE-Corpus-V2. Constructing the BERT-based model involved optimizing key hyperparameters, such as the number of training epochs, batch size, and learning rate. Through ten hold-out evaluations on ADE-Corpus-V2 data and external social media datasets, our model consistently demonstrated high accuracy in drug adverse event detection.ResultThe hold-out evaluations resulted in average F1 scores of 0.8575, 0.9049, and 0.9813 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively. External validation using human-labeled adverse event tweets data from SMM4H further substantiated the effectiveness of our model, yielding F1 scores 0.8127, 0.8068, and 0.9790 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively.DiscussionThis study not only showcases the effectiveness of BERT-based language models in accurately identifying drug-related adverse events in the dynamic landscape of social media data, but also addresses the need for the implementation of a comprehensive study design and evaluation. By doing so, we contribute to the advancement of pharmacovigilance practices and methodologies in the context of emerging information sources like social media.