bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional autoantibodies against G protein-coupled receptors in hepatic and pulmonary hypertensions in human schistosomiasis
Authors: Botoni Fernando Antonio , Lambertucci José Roberto , Santos Robson Augusto Souza , Müller Johannes , Talvani Andre , Wallukat Gerd 
Published: June 2024

IntroductionSchistosomiasis (SM) is a parasitic disease caused by Schistosoma mansoni. SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma process in the liver, spleen, central nervous system, kidneys, and lungs. Pulmonary arterial hypertension (PAH) is a clinical manifestation characterized by high pressure in the pulmonary circulation and right ventricular overload. This study investigated the production of functional autoantibodies (fAABs) against the second loop of the G-protein-coupled receptor (GPCR) in the presence of hepatic and PAH forms of human SM.MethodsUninfected and infected individuals presenting acute and chronic manifestations (e.g., hepatointestinal, hepato-splenic without PAH, and hepato-splenic with PAH) of SM were clinically evaluated and their blood was collected to identify fAABs/GPCRs capable of recognizing endothelin 1, angiotensin II, and a-1 adrenergic receptor. Human serum was analyzed in rat cardiomyocytes cultured in the presence of the receptor antagonists urapidil, losartan, and BQ123.ResultsThe fAABs/GPCRs from chronic hepatic and PAH SM individuals, but not from acute SM individuals, recognized the three receptors. In the presence of the antagonists, there was a reduction in beating rate changes in cultured cardiomyocytes. In addition, binding sites on the extracellular domain functionality of fAABs were identified, and IgG1 and/or IgG3 antibodies were found to be related to fAABs.ConclusionOur data suggest that fAABs against GPCR play an essential role in vascular activity in chronic SM (hepatic and PAH) and might be involved in the development of hypertensive forms of SM.
Single-cell sequencing of the substantia nigra reveals microglial activation in a model of MPTP
Authors: Liu Qing , Liu Ziyu , Xie Wenmeng , Li Yibo , Wang Hongfang , Zhang Sanbing , Wang Wenyu , Hao Jiaxin , Geng Dandan , Yang Jing , Wang Lei 
Published: June 2024

BackgroundN-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to induce PD models, but the effect of MPTP on the cells and genes of PD has not been fully elucidated.MethodsSingle-nucleus RNA sequencing was performed in the Substantia Nigra (SN) of MPTP mice. UMAP analysis was used for the dimensionality reduction visualization of the SN in the MPTP mice. Known marker genes highly expressed genes in each cluster were used to annotate most clusters. Specific Differentially Expressed Genes (DEGs) and PD risk genes analysis were used to find MPTP-associated cells. GO, KEGG, PPI network, GSEA and CellChat analysis were used to reveal cell type-specific functional alterations and disruption of cell-cell communication networks. Subset reconstruction and pseudotime analysis were used to reveal the activation status of the cells, and to find the transcription factors with trajectory characterized.ResultsInitially, we observed specific DEGs and PD risk genes enrichment in microglia. Next, We obtained the functional phenotype changes in microglia and found that IGF, AGRN and PTN pathways were reduced in MPTP mice. Finally, we analyzed the activation state of microglia and revealed a pro-inflammatory trajectory characterized by transcription factors Nfe2l2 and Runx1.ConclusionOur work revealed alterations in microglia function, signaling pathways and key genes in the SN of MPTP mice.
Prospective cohort study evaluating efficacy and safety of efgartigimod in Chinese generalized myasthenia gravis patients
Authors: Wang Pan , Zhang Bo , Yin Jian , Xi Jianying , Tan Ying , Gao Feng , Zeng Fan , Chang Ting , Zhou Hao , Liang Hui , Zhao Zhongyan , Yang Huan , Zhao Chongbo , Huang Shixiong 
Published: June 2024

BackgroundDespite the efficacy of efgartigimod demonstrated in ADAPT phase 3 trial, data specifically derived from Chinese participants are not available. Therefore, we aimed to evaluate the efficacy and safety of efgartigimod in Chinese patients with generalized myasthenia gravis (gMG).MethodsThis is a prospective cohort study conducted in 8 hospitals across China. gMG patients received weekly intravenous infusions of efgartigimod (10 mg/kg) under a named patient program (NPP). The present study is an 8-week study, consisting of 4 consecutive doses of efgartigimod administered over 3 weeks (one cycle), followed by a 5-week follow-up period to assess the tolerability of efgartigimod’s therapeutic effects. The primary outcome was the mean change in MG activities of daily living (MG-ADL) total score from baseline to 4 weeks. MG-ADL responder was defined as a ≥ 2-point improvement that persisted for 4 weeks, starting by week 4. Safety evaluations encompassed the monitoring of adverse events (AE) and serious AE (SAE) throughout the study.ResultsBetween 5 July 2022 and 25 August 2023, a total of 14 gMG patients were included. The mean age was 57.7 years, with a mean MG-ADL score of 10.86 ± 3.32. At week 4, MG-ADL scores showed a mean reduction of 6 points, reaching a maximum decline of 13 points. Among the patients, 85.7% (12/14) achieved MG-ADL responder status after one cycle of treatment. The most significant reduction in quantitative MG (QMG) scores also occurred at week 4, with a mean decrease of 7 points. Notably, the improvements in MG-ADL and QMG scores persisted until week 8. During treatment and follow-up period, only two mild neck rashes occurred and resolved promptly. No infections or SAE were reported.DiscussionA single cycle of efgartigimod treatment demonstrates effectiveness and the tolerability through week 8, with no new safety signals observed in Chinese gMG patients.
A pan-cancer analysis of EphA family gene expression and its association with prognosis, tumor microenvironment, and therapeutic targets
Authors: Cui Zhe , Liu Chengwang , Wang Xuechao , Xiang Yiping 
Published: June 2024

BackgroundErythropoietin-producing human hepatocellular (Eph) receptors stand out as the most expansive group of receptor tyrosine kinases (RTKs). Accumulating evidence suggests that within this expansive family, the EphA subset is implicated in driving cancer cell progression, proliferation, invasion, and metastasis, making it a promising target for anticancer treatment. Nonetheless, the extent of EphA family involvement across diverse cancers, along with its intricate interplay with immunity and the tumor microenvironment (TME), remains to be fully illuminated.MethodsThe relationships between EphA gene expression and patient survival, immunological subtypes, and TME characteristics were investigated based on The Cancer Genome Atlas (TCGA) database. The analyses employed various R packages.ResultsA significant difference in expression was identified for most EphA genes when comparing cancer tissues and non-cancer tissues. These genes independently functioned as prognostic factors spanning multiple cancer types. Moreover, a significant correlation surfaced between EphA gene expression and immune subtypes, except for EphA5, EphA6, and EphA8. EphA3 independently influenced the prognosis of papillary renal cell carcinoma (KIRP). This particular gene exhibited links with immune infiltration subtypes and clinicopathologic parameters, holding promise as a valuable biomarker for predicting prognosis and responsiveness to immunotherapy in patients with KIRP.ConclusionBy meticulously scrutinizing the panorama of EphA genes in a spectrum of cancers, this study supplemented a complete map of the effect of EphA family in Pan-cancer and suggested that EphA family may be a potential target for cancer therapy.
Nomenclature of the symptoms of head and neck cancer: a systematic scoping review
Authors: Bradley Paula T. , Lee Ying Ki , Albutt Abigail , Hardman John , Kellar Ian , Odo Chinasa , Randell Rebecca , Rousseau Nikki , Tikka Theofano , Patterson Joanne M. , Paleri Vinidh 
Published: June 2024

IntroductionEvolution of a patient-reported symptom-based risk stratification system to redesign the suspected head and neck cancer (HNC) referral pathway (EVEREST-HN) will use a broad and open approach to the nomenclature and symptomatology. It aims to capture and utilise the patient reported symptoms in a modern way to identify patients’ clinical problems more effectively and risk stratify the patient.MethodThe review followed the PRISMA checklist for scoping reviews. A search strategy was carried out using Medline, Embase and Web of Science between January 1st 2012 and October 31st 2023. All titles, abstracts and full paper were screened for eligibility, papers were assessed for inclusion using predetermined criteria. Data was extracted pertaining to the aims, type of study, cancer type, numbers of patients included and symptoms, presenting complaints or signs and symptoms.ResultsThere were 9,331 publications identified in the searches, following title screening 350 abstracts were reviewed for inclusion and 120 were considered for eligibility for the review. 48 publications met the eligibility criteria and were included in the final review. Data from almost 11,000 HNC patients was included. Twenty-one of the publications were from the UK, most were retrospective examination of patient records. Data was extracted and charted according to the anatomical area of the head and neck where the symptoms are subjectively and objectively found, and presented according to lay terms for symptoms, clinical terms for symptoms and the language of objective clinical findings.DiscussionSymptoms of HNC are common presenting complaints, interpreting these along with clinical history, examination and risk factors will inform a clinician’s decision to refer as suspected cancer. UK Head and Neck specialists believe a different way of triaging the referrals is needed to assess the clinical risk of an undiagnosed HNC. EVEREST-HN aims to achieve this using the patient history of their symptoms. This review has highlighted issues in terms of what is considered a symptom, a presenting complaint and a clinical finding or sign.
Case report: Acute severe hyponatremia-induced seizures in a newborn: a community-acquired case and literature review
Authors: Li Haiting , Chen Xiyang , Chen Linlin , Li Jie , Liu Xixi , Chen Caie , Xie Dengpan , Yuan Junhui , Tao Enfu 
Published: June 2024

Severe neonatal hyponatremia represents a critical electrolyte imbalance with potentially severe neurological outcomes, a condition rarely documented in community-acquired, full-term newborns. This report underscores a unique case of a 23-day-old, previously healthy, full-term male neonate experiencing severe hyponatremia that precipitated seizures, underscoring the urgency of prompt recognition and intervention. The neonate presented with symptoms including vomiting, groaning, chills, fixed staring, and limb tremors. Critical findings upon admission encompassed hypothermia, hypotension, tachycardia, and tachypnea accompanied by significant weight loss. The clinical presentation was marked by dehydration, lethargy, weak crying, a fixed gaze, irregular breathing, and coarse lung sounds, yet a distended abdomen, hypertonic limb movements, and recurrent seizures were observed. Immediate interventions included establishing IV access, rewarming, mechanical ventilation, seizure management, volume expansion, dopamine for circulatory support, and initiation of empirical antibiotics. Diagnostic evaluations revealed a sodium ion concentration of 105.9 mmol/L, while amplitude-integrated electroencephalography (aEEG) detected pronounced seizure activity characterized by a lack of sleep-wake rhythmicity, noticeable elevation in both the lower and upper amplitude margins, and a sustained decrease in the lower margin voltage dropping below 5 μV, presenting as sharp or serrated waveforms. The management strategy entailed rapid electrolyte normalization using hypertonic saline and sodium bicarbonate, anticonvulsant therapy, and comprehensive supportive care, with continuous aEEG monitoring until the cessation of seizures. Remarkably, by the third day, the neonate’s condition had stabilized, allowing for discharge in good health 10 days post-admission. At a 16-month follow-up, the child exhibited no adverse neurological outcomes and demonstrated favorable growth and development. Our extensive review on the etiology, clinical manifestations, aEEG monitoring, characteristics of seizures induced by severe neonatal hyponatremia, treatment approaches, and the prognosis for seizures triggered by severe hyponatremia aims to deepen the understanding and enhance clinical management of this complex condition. It stresses the importance of early detection, accurate diagnosis, and customized treatment protocols to improve outcomes for affected neonates. Additionally, this review accentuates the indispensable role of aEEG monitoring in managing neonates at elevated risk for seizures. Yet, the safety and efficacy of swiftly administering hypertonic saline for correcting severe hyponatremia-induced seizures necessitate further investigation through medical research.
Phytochemistry, pharmacology, toxicology and detoxification of Polygonum multiflorum Thunb.: a comprehensive review
Authors: Qian Jiawen , Feng Chenhang , Wu Ziyang , Yang Yuanmei , Gao Xiangfu , Zhu Lingyan , Liu Yang , Gao Yuancheng 
Published: June 2024

BackgroundPolygonum multiflorum Thunb. (PM), a kind of perennial plant, belongs to the genus Polygonum of the family polygonaceae.The dry root of PM (also called Heshouwu), is a traditional Chinese medicine, which has a series of functions and is widely used in clinic for hair lossing, aging, and insomnia. While, PM also has some toxicity, its clinical drug safety has been concerned. In this paper, the chemical components, toxic mechanisms and detoxification strategies of PM were reviewed in order to provide evidence for its clinical application.Materials and methodsWe conducted a systematic review of published literature of PM, including English and Chinese databases, such as PubMed, Web of Science, CNKI, and Wanfang.ResultsPM contains a variety of chemical compounds, including stilbenes, quinones, flavonoids, phospholipids, and has many pharmacological activities such as anti-aging, wound healing, antioxidant, and anti-inflammatory properties. The PE has certain therapeutic effect, and it has certain toxicity like hepatotoxicity, nephrotoxicity, and embryotoxicity at the same time, but.these toxic effects could be effectively reduced by processing and compatibility.ConclusionIt is necessary to further explore the pharmacological and toxicological mechanisms of the main active compounds of PE.This article provides scientific basis for the safe clinical application of PM.
The association between unilateral and bilateral performance-related measures in elite female soccer players: a multifaceted investigation
Authors: Paravlic Armin Huso , Abazovic Ensar , Milanović Zoran , Vučković Goran , Spudić Darjan , Hadzic Vedran , Pajek Maja , Vodičar Janez 
Published: June 2024

PurposeThe present study aimed to investigate a) the associations between bilateral performance utilizing countermovement jump (CMJ), squat jump (SJ), speed and unilateral CMJ, isokinetic peak torque in knee extension and flexion with angular velocities of 60°/s and 180°/s and tensiomyography (TMG) parameters; b) whether the asymmetries derived from unilateral tests are associated with bilateral CMJ, SJ and speed in elite female soccer players.MethodsThirty-five elite female soccer players (average age: 20 ± 5 years) completed CMJ, SJ, speed, isokinetic muscle strength and TMG tests.ResultsCompared to the non-dominant leg, the dominant leg demonstrated greater peak torque output in both knee flexion (7.4%) and knee extension (5.6%) isokinetic tasks, as well as m. vastus medialis contraction time (7.6%), and soccer-specific agility test (4.1%). Conversely, the hamstring to quadriceps peak torque ratio at 180°/s (8.5%) was significantly greater in the non-dominant leg. The associations between CMJ, SJ and speed performance were positive and ranged from weak (r = 0.350) to high (r = 0.710). For speed and TMG-derived variables, correlations were negative and ranged from weak (r = −0.345, p = 0.042, for vastus medialis contraction time) to moderate (r = −0.530, p = 0.001, for biceps femoris contraction time). Furthermore, both bilateral CMJ and SJ negatively correlated with TMG-derived variables, ranging from weak (r = −0.350, p = 0.039, for vastus lateralis contraction time) to moderate (r = −0.537, p = 0.003, for rectus femoris contraction time).ConclusionThe overall significant, albeit inconsistent, correlations between the diverse performance scores obtained highlight the necessity for a multifaceted and thorough diagnostic strategy in female soccer players.
Testing an online screening for autism in the COVID-19 pandemic: a psychometric study of the Q-CHAT-24 in Chilean toddlers
Authors: Gatica-Bahamonde Gabriel , Mendez-Fadol Alejandra , Sánchez-Sepúlveda Francisca , Peñailillo-Diaz Constanza , van Kessel Robin , Czabanowska Katarzyna , Roman-Urrestarazu Andres 
Published: June 2024

BackgroundThe aim of this study was to examine some psychometric characteristics of the Chilean-adapted version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-24) (24) in a group of unselected children (community sample). This version was administered remotely through an online version during the pandemic period to caregivers of children, aged 18–24 months, registered in four primary care polyclinics of the Health Service Araucanía Sur, Chile.MethodsAn intentional non-probabilistic sampling was used. Three hundred and thirteen toddlers were examined. Participants completed an online version of the Q-CHAT-24 which was disseminated through the REDCap platform. Evidence of reliability through internal consistency and evidence of predictive validity through ROC curve analysis were realized.ResultsThe mean age of the children evaluated was 21.16 months. The Shapiro-Wilk test revealed that Q-CHAT-24 scores was normally distributed. 71 cases (23.12%) scored 38 points or more on the Q-CHAT-24, qualifying as Autistic Risk. 48 cases (15.63%) were confirmed as autistic through the ADOS-2 Module T. All items were positively correlated with Q-CHAT-24 total score. All items were positively correlated with Q-CHAT-24 total score. Internal consistency was acceptable for the Q-CHAT-24 (Cronbach ́s α=0.78). The internal consistencies were analyzed for the Q-CHAT-24 Factors, and they were good for factor 1 “Communication and Social Interaction” (Cronbach ́s α=0.85) and acceptable for factor 2 “Restrictive and Repetitive Patterns” (Cronbach ́s α=0.74). Receiver operating characteristic (ROC) curve analyses were performed. The AUC values were 0.93 with statistical significance (p&lt;0.01). For the cut-off point of 38, the Sensitivity, Specificity and Youden index values were 0.89, 0.8 and 0.7, respectively. The Positive Predictive Value (PPV) was 86% and the Negative Predictive Value (NPV) was 85%.ConclusionsIn accordance with the objectives of this study, evidence of reliability and predictive validity was demonstrated for the Q-CHAT-24 in this Chilean population. More importantly, this study provides Sensitivity and Specificity data for a remote application version of an autism screening tool already validated in Chile. The implications of this have to do with the possibility of establishing a remote assessment system for children at risk of autism on a population scale.
Demographic and clinical profile of adolescents suicide attempters admitted to an emergency department during the COVID-19 pandemic – a retrospective cohort study using hospital information system
Authors: Tomaszek Lucyna , Kurleto Paulina , Turkanik Edyta , Bielec Ewa , Milaniak Irena , Dąbrowska-Mędrzycka Wioletta 
Published: June 2024

BackgroundThe prevalence of suicidal attempts among adolescents during COVID-19 significantly increased compared with pre-pandemic estimates. The aim of the study was to explore the demographic and clinical profile of adolescent suicide attempters admitted to the emergency department during the COVID-19 pandemic.Material and methodThe retrospective analysis included, on the basis of electronic medical records in the CliniNet system, sociodemographic and clinical data of patients aged 10–18 years with a diagnosis of suicide attempt. Follow-up period: from March 20, 2020 to May 16, 2023.ResultsDuring the COVID-19 pandemic, there were 425 emergency department visits among adolescents aged 11–17 due to a suicide attempt, with the largest number in the 15–17 (69%) age range. The percentage of emergency department visits was higher among females (80%) and urban residents (75.3%). Self-poisoning was the most common cause of suicide attempts (52.4%), followed by self-harm (41.4%), hanging (3.2%) and jumping from a height (2.1%). The most common toxic substances in self-poisonings were antidepressants and antipsychotics, followed by paracetamol. About 70% of visits were associated with adolescent mental disorders, of which depressive disorder was the most common. One death per 425 visits was recorded (0.2%).ConclusionsAdolescents attempting suicide during COVID-19 were most likely female, aged 15–17, city dwellers, undergoing psychiatric treatment mainly for depressive disorders. The mental health consequences of the pandemic may be more long term, and further monitoring will be needed in the years to come.
Validating self-reported Toxic Release Inventory data using Benford's Law: investigating toxic chemical release hazards in floodplains
Authors: Osiecki Kristin , Hussaini Syed , Sambanis Apostolis , Quinsey Logan , Liew Chloe 
Published: June 2024

IntroductionAcute and long-term health impacts from flooding related toxic chemical releases are a significant local health concern and can disproportionately impact communities with vulnerable populations; reliable release data are needed to quantify this hazard.MethodsIn this paper, we analyze US Federal Emergency Management Agency designated floodplain data and US Environmental Protection Agency Toxic Release Inventory (TRI) data to determine if geographically manipulated databases adhere to Benford's Law.ResultsWe investigated multiple variants and discovered pollution releases adhere to Benford's Law and tests which thereby validates the self-reported toxic release dataset.DiscussionWe find that Benford's Law applies to self-reported toxic chemical release and disposal data, indicating a lack of widespread data errors or manipulation.