bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergent reductions in interhemispheric functional, structural and callosal connectivity in Parkinson’s disease
Authors: Wang Erlei , Jia Yujing , Cheng Luqi , Mao Chengjie , Bao Yiqing , Shen Junkang , Zhang Yuanchao , Fan Guohua 
Published: February 2025

BackgroundAbnormal interhemispheric functional connectivity is frequently reported in Parkinson’s disease (PD), but its structural basis remains unclear. This study aimed to investigate changes in interhemispheric functional, structural, and callosal connectivity, as well as their interrelationships, in PD patients.MethodsThe study included 57 PD patients and 50 healthy controls (HCs). Interhemispheric functional connectivity was evaluated using voxel mirrored homotopic connectivity (VMHC) derived from resting-state functional MRI, while structural connectivity was measured through homotopic cortical thickness covariance from T1-weighted MRI. The corpus callosum (CC), connecting bilateral regions with VMHC differences, was assessed using fractional anisotropy (FA) from diffusion MRI. Pearson’s correlation was used to evaluate the interrelationships among imaging data and their clinical relevance.ResultsCompared to HCs, PD patients showed reduced VMHC and interhemispheric structural connectivity in similar brain regions, displaying a positive correlation trend between these measures. The affected regions encompassed the bilateral sensorimotor cortices (precentral gyrus, postcentral gyrus, and paracentral lobule) and posterior cortical areas, including the superior parietal lobule, supramarginal gyrus, precuneus, middle occipital gyrus, fusiform gyrus, as well as the superior and middle temporal gyri. FA in the CC, connecting regions with reduced VMHC, was also lower in PD patients. Additionally, interhemispheric structural, functional, and callosal connectivity reductions were, respectively, related to cognitive impairment, motor dysfunctions, and disease duration in PD.ConclusionThe study identified convergent reductions in interhemispheric functional, structural and callosal connectivity in PD patients, emphasizing the strong link between structural and functional brain abnormalities. Our findings may provide new insights into the pathophysiology of PD.
Congenital cytomegalovirus screening in neonates born after 35 weeks gestation—is targeted screening beneficial?
Authors: Aldon Mary Liza , Raveentheran Gayatiri , Amin Zubair , Chan Si Min , Aoyama Rie , Tee Nancy , Ng Sau Yoke , Lee Chun Kiat , Ng Pick Gate , Low Jia Ming 
Published: February 2025

IntroductionCongenital Cytomegalovirus (cCMV) is the most common congenital viral infection and leading cause of non-genetic sensorineural hearing loss in children. Timely treatment within the first months of life can prevent hearing loss. We evaluated utility, feasibility, and short-term cost implications of targeted cCMV screening in a tertiary public healthcare institution in Singapore.MethodsWe analyzed data from neonates born at ≥35 weeks gestation from 1st February 2022 to 31st January 2023, at the National University Hospital, Singapore. Screening criteria for CMV testing were neonates who failed hearing screening at birth, had a birth weight &lt;2.5 kg, small for gestational age (SGA), or had clinical suspicion for cCMV. Urine samples were obtained within two weeks of birth for CMV polymerase chain reaction (PCR) testing. We collected clinical, ophthalmological, neuroimaging, laboratory, and audiological data. A limited, short-term cost analysis was performed to compare costs of three cCMV screening strategies (universal, targeted, and no screening) two years after implementation.ResultsOut of 5,277 neonates, 305 (6%) met the screening criteria. Among those screened, 70.5% (215/305) were SGA or had a birth weight &lt;2.5 kg, and 23.3% (71/305) failed the hearing screen. The overall diagnostic yield was 0.06% (3/5,277). There was one false positive result (0.3%; 1/305). Three neonates (0.98%; 3/305) were diagnosed with cCMV by urine PCR. One was SGA without intracranial abnormality, and two had low birth weight with intracranial calcifications. None had cytopenia or transaminitis, and all ophthalmology screenings were normal. All infected neonates were started on Valganciclovir. One neonate failed the hearing test at one month of age but passed repeat assessments by three months. Two neonates exhibited upper motor neuron signs in the lower limbs and are on long-term follow-up. The total estimated direct treatment-related cost without cCMV screening was S$104,445.79. In the targeted screening model, the total cost was S$146,656.30, compared to S$853,890.16 in the universal screening model.ConclusionWe demonstrated the feasibility of targeted cCMV screening, which complements universal newborn hearing screening in a tertiary neonatal center in Singapore. Targeted cCMV screening can be implemented cost-effectively during the neonatal period, enabling early detection and intervention.
Entrectinib can induce nerve cell damage by inhibiting PI3K-AKT and TGF-β signaling pathways
Authors: Tang Qingshan , Dong Jiachen , Zhang Feng , Zhao Dan , Yang Qi , Wen Jiayu , Sun Yuhao , Wei Jifu , Liu Zhixian 
Published: February 2025

BackgroundThe tyrosine receptor kinase inhibitor (TRKi) entrectinib is used to treat neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumors and ROS1-positive patients. Despite its impressive efficacy against cancer, the clinical application is still limited by the central nervous system (CNS)-related toxicities. However, the precise mechanism of such CNS-related toxicities remains elusive.MethodsThe effect of entrectinib-induced nerve cell damage was evaluated by the nerve cells (PC12, HT22 and SK-N-SH) based in vitro models. Various assays, including CCK-8, colony formation and EdU incorporation assays were utilized to estimate the cellular viability and proliferation ability. Cell apoptosis was measured by flow cytometry. Next, transcriptome sequencing technology was performed to identify differentially expressed genes (DEGs). Gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) analysis and gene set enrichment analysis (GSEA) were applied to predict the potential functions of DEGs. Quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting assays were performed to measure the expressions of thrombospondin-1 (THBS1), TGF-β1, PI3K, AKT and phosphorylated AKT (p-AKT) in the entrectinib-treated nerve cells. Additionally, we Preliminary observed and validated whether THBS1 overexpression could rescue nerve cell damage and the abnormalities in PI3K-AKT and TGF-β signaling pathways.ResultsEntrectinib significantly inhibited the nerve cells proliferation and colony formation, and induced nerve cells apoptosis. Transcriptome sequencing analysis and qRT-PCR revealed that THBS1 was downregulated within entrectinib treatment. KEGG and GSEA analysis also suggested that entrectinib directly caused the abnormalities in proliferation-related signaling pathway like PI3K-AKT pathway, and apoptosis-related signaling pathway including TGF-β pathway. We further demonstrated that THBS1, TGF-β1, PI3K, AKT and p-AKT were downregulated by entrectinib. Meanwhile, pretreatment with THBS1 overexpression plasmids significantly rescued nerve cells (PC12, HT22 and SK-N-SH) from cell death and the abnormalities in PI3K-AKT and TGF-β signaling pathways.ConclusionThese results identified a critical role of entrectinib in promoting nerve cell damage by downregulating the expression of THBS1 while also inhibiting PI3K-AKT and TGF-β signaling pathways. Our findings will provide potential therapeutic targets for CNS-related toxicities.
Network analysis and experimental validation to investigate chenpi against functional dyspepsia through TLR4/MyD88 by regulating the gut microbial structure
Authors: Hu Jinfang , Wang Xu , Guo Xiaoqiu , Wen Wen , Xue Jin , Liao Zhengzheng , Chen Lihua 
Published: February 2025

Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder characterized by the absence of organic lesions; it affects nearly one-fifth of the global population. There is currently no specific drug for treating it. Citri reticulatae Pericarpium (CRP) has been utilized in China for millennia as a therapeutic agent for alleviating bloating and spleen–stomach disharmony. Nonetheless, the curative efficacy and precise molecular mechanisms implicated in FD warrant further investigation. This study aims to address this gap by investigating the potential mechanisms of CRP against FD using HPLC-ESI-QTOF-MS, network analysis prediction, and experimental validation. In this study, 90 CRP metabolites were identified by HPLC-ESI-QTOF-MS; 70 common targets of CRP and FD were extracted, and the top ten overlapped targets included MAPK1, MAPK2, and MAPK3. KEGG enrichment analysis revealed that the MAPK pathways were predominant and involved the TLR4 signaling pathway. In vivo experiments demonstrated that after 14 days of treatment, CRP improved body weight, gastric emptying rate, intestinal transit rate, and the pathological structure of the gastric tissue. Serum IL-6, TNF-α, and IL-1β were downregulated, and the expressions of TLR4, MyD88, p-NF-κB, and MAPKs were suppressed in gastric tissue. Furthermore, CRP increased the relative abundance of Patescibateria and Bacteroidota, accompanied by a reduction in the relative abundance of Verrucomicrobota and Proteobacteria. In brief, CRP could attenuate dyspepsia by reducing the activation of inflammation-related TLR4/MyD88 and MAPK signaling pathways and by mediating gut microbial structure and composition. This study provides a unique perspective for further research on drugs for treating FD.
Real-world pharmacovigilance investigation of imipenem/cilastatin: signal detection using the FDA Adverse Event Reporting System (FAERS) database
Authors: Jia Peng , Zhou Yusen , Gao Yuan , Wang Shangyu , Yin Jiangliu , Lian Yixiang , Lai Quanyou 
Published: February 2025

BackgroundAlthough imipenem/cilastatin (IMI/CIL) has demonstrated favorable therapeutic efficacy against various infections, the incidence of potential adverse events (AEs) has escalated in parallel with its increased utilization and has been documented in clinical trials. However, a comprehensive understanding of real-world implications remains lacking.MethodsBy conducting a comprehensive search in the FDA Adverse Event Reporting System (FAERS) database, AE reports associated with IMI/CIL as the primary suspect (PS) were selected for analysis, spanning from the first quarter of 2004 to the fourth quarter of 2023. Utilizing disproportionality analysis techniques, potential signals of AE s were identified through reported odds ratio (ROR), proportional report ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM). The obtained results were systematically classified using Medical Dictionary for Regulatory Activities (MedDRA).ResultFrom the first quarter of 2004 to the fourth quarter of 2023, a total of 2,574 reports documenting AEs associated with IMI/CIL were obtained, with more than half (n = 1,517, 58.94%) involving individuals aged over 60 years old. Descriptive analysis was conducted based on age groups and time to onset, revealing that the majority of AEs occurred within 3 days. Adverse drug reactions caused by IMI/CIL were classified into 24 system organ classes (SOCs) at the preferred term (PT) level. Furthermore, previously unreported and clinically significant AEs such as cerebral atrophy, and delirium were also identified at the PT level.ConclusionThis study offers a more comprehensive insight into the monitoring, supervision, and management of adverse drug reactions associated with IMI/CIL. Clinicians should pay further attention to the implications of numerous AEs and their corresponding signal intensities, as well as unrecorded signals of severe AEs. This holds significant value in enhancing the clinical safety profile of IMI/CIL.
Identifying network state-based Parkinson’s disease subtypes using clustering and support vector machine models
Authors: Nguchu Benedictor Alexander , Han Yifei , Wang Yanming , Shaw Peter 
Published: February 2025

IntroductionParkinson’s disease (PD) heterogeneity poses challenges to the current development of discovering the best therapeutic targets.MethodsHere, we employ K-means and hierarchical clustering algorithms on data from the Parkinson’s Progression Markers Initiative (PPMI) to identify network-specific patterns that describe PD subtypes using the optimal number of brain features. The features were specifically the gray matter volume and dopaminergic features of the neostriatum, i.e., the caudate, putamen, and anterior putamen. We use machine learning (ML) algorithms, including Random Forest, Logistic Regression, and Support Vector Machine, to evaluate the diagnostic power of the brain features and network patterns in differentiating the PD subtypes and distinguishing PD from HC. Finally, we assessed whether PD subtypes described through network-specific patterns are dependent on the APOE genotype.ResultsUsing data from 2396 subjects, we show that PD (n=2037) is highly associated with APOE ϵ2/ϵ4. Our findings reveal a significant DAT deficit in the left and right structures of the caudate, putamen, and anterior putamen in subjects with PD compared to subjects with SWEDD(n=137) or HC(n=222), and that APOE ϵ2/ϵ4 may accelerate DAT deficits and brain alterations in both PD and SWEDD. Furthermore, clinical symptoms of PD in subjects (SWEDD), which hardly validated by DAT scan data, can be explained by variations in APOE genotypes and other brain features beyond DAT. We show the existence of three networks states for the whole data, with the first network state describing the subjects in HC, while the remaining two network states describing the two PD subtypes—one network state typified by a mildly sparsely connected network (patterns) and the other network state characterized by a more intensified sparsity in their network. We also show that the two subtypes of PD are characterized by distinctly different levels of total gray matter volume and DAT deficit. ML models show that features extracted from brain structure and network patterns can serve as reliable biomarkers for PD and its subtypes, with the highest performance (100% AUC, 99.3% accuracy, 0.993 F1) demonstrated by the fine-tuned SVM model.ConclusionOur findings suggest that, while PD is generally associated with a larger DAT deficit in specific brain structures of the neostriatum, it exhibits intrinsic heterogeneity across individuals, which may stem from genetic factors. Such heterogeneity can be characterized by ML models and optimally mapped into network states, providing new insights to consider when developing personalized drugs.
Unraveling the occupational exposure to mycotoxins in a waste management setting: results from a case study in Norway
Authors: Martins Carla , Viegas Carla , Eriksen Elke , Graff Pål , Afanou Anani Komlavi , Straumfors Anne , Twarużek Magdalena , Grajewski Jan , Kosicki Robert , Viegas Susana 
Published: February 2025

IntroductionWaste management represents an occupational setting where fungi are significant contaminants. This study aimed to assess the exposure of waste workers to mycotoxins through a human biomonitoring study.MethodsA total of 33 workers and 19 controls provided spot urine samples to determine 10 mycotoxins’ urinary biomarkers using liquid chromatography coupled with mass spectrometry. Risk characterization was performed using hazard quotient and margin of exposure assessments.ResultsThe results indicated that workers were exposed to six out of the 10 mycotoxins tested, with the following detection rates: deoxynivalenol (91%, 30/33), ochratoxin A (33%, 11/33), zearalenone (17%, 5/33), α-zearalenol (12%, 4/33), β-zearalenol (12%, 4/33), and HT-2 toxin (3%, 1/33). Within controls and outwith controls, were exposed to 5/10 and 2/10 mycotoxins, respectively. All participants exhibited hazard quotients for deoxynivalenol and zearalenone below one, indicating that the exposure is unlikely to pose a health risk. However, when considering the margin of exposure determined for ochratoxin A, 18% of the total participants presented results below 200 for non-neoplastic effects, and 100% of the total participants presented values below 10,000 for neoplastic effects, suggesting potential health concerns that require further assessment.DiscussionThis study highlights the need for future research on occupational exposure to mycotoxins in waste management settings.
Using in-house 3D technology for optimal spatial positioning of elongation devices for distraction osteogenesis—a cost-effective alternative
Authors: Rachmiel Adi , Shilo Dekel , Hija Ahmad , Capucha Tal , Zeineh Nidal , Emodi Omri , Krasovsky Andrei 
Published: February 2025

IntroductionMandibular distraction osteogenesis is globally accepted as the gold-standard surgical solution for various craniofacial deformities and syndromes. Stock device evolution has advanced into complex designs to achieve the most accurate three-dimensional distraction vector of elongation. Today's cutting-edge solution is patient-specific distractors designed by virtual surgical planning (VSP) to facilitate surgical performance and ensure the most predictable clinical results. However, tailoring patient-specific distractors comes with a significant price tag.MethodsUsing VSP technology, we developed an inexpensive stepwise method of precisely directing the distraction vector by adapting off-the-shelf distractors for the individual contour of the patients’ mandibles based on the in-house designed and printed cutting guides.ResultsThe virtual planning sequence and clinical application are described in detail. The final results are assessed by 3D analysis to confirm the method's precision and predictability.DiscussionThe final positions of the adapted off-the-shelf distractors were found to match the pre-operative virtual planning precisely, resulting in excellent clinical results. This method can be easily reproduced in similar clinical cases with reduced cost.
Distance and orientation of hydrophones influence the received soundscape in shallow coral reefs
Authors: Azofeifa-Solano Juan Carlos , Erbe Christine , Tollefsen Cristina , McCauley Robert D. , Brooker Rohan M. , Pygas Daniel , Parsons Miles J. G. 
Published: February 2025

IntroductionAcoustic monitoring and soundscape analysis provide valuable data for the conservation and restoration of underwater habitats. However, before these methods can be widely implemented for management purposes, it is crucial to validate the ecological relevance of different sampling methodologies and quantify potential biases.MethodsWe investigated how the distance and orientation of an acoustic sensor relative to a target habitat influence the received soundscape. Using a spatial array of hydrophones, we recorded sound at different distances (1 m, 2 m, 5 m) and orientations (vertical vs. horizontal) from a shallow coral reef.ResultsHydrophones oriented horizontally toward the reef exhibited the expected decrease in sound levels with increasing distance. In contrast, hydrophones oriented vertically showed an inverse trend, with lower sound pressure levels at closer distances and higher levels further away.DiscussionThese findings indicate that sensor directivity significantly influences the received soundscape, introducing a potential methodological bias within and across acoustic datasets. To improve the accuracy and comparability of acoustic sampling in coastal habitats, sensor beam patterns should be carefully considered in experimental design.
Проблемы сброса сточных вод на рельеф местности и возможные их решения (в порядке обсуждения)
Authors: Пукемо М.М. 
Published: February 2025

Рассматриваются проблемы и риски, связанные со сбросом очищенных сточных вод на рельеф местности, а также возможные пути решения этих проблем. Представлен комплексный анализ экологических рисков, связанных с данным способом утилизации сточных вод, который давно получил широкое распространение, но в настоящее время не урегулирован законодательно. Основная проблема заключается в том, что загрязненные сточные воды, попадая в грунт, могут просачиваться в подземные водоносные горизонты, что может привести к долгосрочным экологическим катастрофам. Подчеркивается, что данный способ может применяться только в исключительных случаях, когда другие варианты невозможны, и только при строгом соблюдении ряда условий и технических требований. Важнейшими из них являются технологии очистки, например биопруды, с более жесткими технологическими нормативами и постоянным контролем качества сточных вод. Сделан вывод, что при соблюдении всех необходимых мер и ограничений сброс очищенных сточных вод на рельеф местности может быть оправдан в конкретных ситуациях, но требует тщательной подготовки и контроля с целью минимизации возможных негативных последствий для окружающей среды.
The problems and risks associated with the land disposal of effluents, as well as possible solutions to these problems, are considered. A comprehensive analysis of the environmental risks associated with this method of wastewater disposal, which has long been widespread, however, up to now is not regulated by law so far, is presented. The main problem is that contaminated wastewater, getting into the soil, can infiltrate into underground aquifers resulting in long-term environmental disasters. It is emphasized that this method can only be used in exceptional cases, when other options are impossible, and only in strict compliance with a number of conditions and technical requirements. The most important of these are treatment technologies, such as lagoons, with more stringent technological standards and constant monitoring of wastewater quality. It is concluded that, if all the necessary measures and restrictions are observed, the land disposal of effluents may be justified in specific situations; however, provided thorough preparation and control in order to minimize possible negative consequences for the environment.