bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and feasibility of home-based transcranial alternating current stimulation in youths with 22q11.2 deletion syndrome
Authors: Latrèche Caren , Mancini Valentina , McGinn Nova , Rochas Vincent , Férat Victor , Forrer Silas , Schneider Maude , Eliez Stephan 
Published: October 2024

Neurodevelopmental disorders such as attention deficit and/or hyperactivity disorder (ADHD) and schizophrenia are characterized by core impairment in executive functions (EF). Despite the development of various behavioral interventions to enhance EF, the evidence is still scarce. Alternatively, non-invasive brain stimulation tools such as transcranial alternating current stimulation (tACS) has emerged as a potential strategy to alleviate cognitive deficits. Previous studies have demonstrated the safety, feasibility, and efficacy of one single tACS session in different clinical populations. However, the effects of tACS appear limited and need to be sustained to be considered an effective cognitive neurorehabilitation tool. Recent studies have used home-based, repeated tACS sessions in individuals with neurodegenerative diseases. To our knowledge, the safety and feasibility of such an intensive protocol remains to be tested in a younger population with neurodevelopmental disorders. Using a randomized double-blind sham-controlled design, we administered home-based, repeated tACS sessions to seven individuals aged 14–25 with 22q11.2 deletion syndrome (22q11.2DS), which confers an increased risk for neurodevelopmental disorders. We aimed to assess the safety, tolerability, and feasibility of tACS. Findings from this ongoing clinical trial revealed a favorable safety profile, with frequent yet transient and mainly mild adverse effects. The intervention proved to be feasible, shown by very high adherence rates and positive user experiences. Future studies should therefore investigate whether prolonged exposure to tACS can lead to long-lasting cognitive outcomes.Clinical trial registrationClinicalTrials.gov, identifier NCT05664412.
Dissection of signaling pathways regulating TrkB-dependent gephyrin clustering
Authors: Wüstner Lisa-Sophie , Beuter Simone , Kriebel Martin , Volkmer Hansjürgen 
Published: October 2024

IntroductionThe TrkB receptor is known for its role in regulating excitatory neuronal plasticity. However, accumulating evidence over the past decade has highlighted the involvement of TrkB in regulating inhibitory synapse stability and plasticity, particularly through regulation of the inhibitory scaffold protein gephyrin, although with contradicting results.MethodsIn this study, we extended on these findings by overexpressing rat TrkB mutants deficient in either Shc-or PLCγ-dependent signaling, as well as a kinase-dead mutant, to dissect the contributions of specific TrkB-dependent signaling pathways to gephyrin clustering.ResultsOur results demonstrate that TrkB signaling is required for gephyrin clustering on the perisomatic area of granule cells in the dentate gyrus in vivo. To further investigate, we expressed TrkB wild-type and mutants in hippocampal neurons in vitro.DiscussionUnder basal conditions, TrkB-Shc signaling was important for the reduction of gephyrin cluster size, while TrkB-PLCγ signaling accounts for gephyrin clustering specifically at synaptic sites. Concomitant, impaired PLCγ signaling was associated with disinhibition of transduced neurons. Moreover, chemically induced inhibitory long-term potentiation (chem iLTP) depended on TrkB signaling and the activation of both Shc and PLCγ pathways.ConclusionOur findings suggest a complex, pathway-specific regulation of TrkB-dependent gephyrin clustering, both under basal conditions and during chem iLTP.
Plasma cell-free DNA as predictor of disease status in patients with differentiated thyroid cancer - a prospective study from a tertiary care institution
Authors: Goel Rashi , Satapathy Swayamjeet , Chandekar Kunal Ramesh , Ballal Sanjana , Agarwal Shipra , Deo Suryanarayan S. V. , Tripathi Madhavi , Bal Chandrasekhar 
Published: October 2024

IntroductionPlasma cell-free DNA (cfDNA) estimation offers a non-invasive method to potentially diagnose, monitor, and prognosticate patients with malignancy. This prospective study aimed to assess plasma cfDNA levels in patients with differentiated thyroid cancer (DTC) to determine its role in predicting disease status in the post-operative setting.Materials and methodsThis was a single-center prospective observational study conducted at a public medical research university and hospital in New Delhi, India. 254 patients with DTC in the post-operative setting were included: 95 in Group 1 (active structural disease) and 159 in Group 2 (disease-free). Blood samples were collected for plasma separation and cfDNA extraction. The cfDNA concentrations were quantified and compared across various disease states.ResultsMedian values of plasma cfDNA (ng/µL) in groups 1 and 2 were found to be 0.272 (IQR: 0.137-0.442) and 0.222 (IQR: 0.123-0.398), respectively with no significant difference (p=0.122). cfDNA levels were significantly higher in patients in the age group ≥55 years (p=0.016). However, the cfDNA levels were not significantly associated with any of the other known prognostic markers of DTC.DiscussionBased on the results of this study, plasma cfDNA levels did not significantly predict disease status in patients with DTC in the post-operative setting.
Machine learning-based prediction of 5-year survival in elderly NSCLC patients using oxidative stress markers
Authors: Chen Hao , Xu Jiangjiang , Zhang Qiang , Chen Pengfei , Liu Qiuxia , Guo Lianyi , Xu Bindong 
Published: October 2024

BackgroundOxidative stress plays a significant role in aging and cancer, yet there is currently a lack of research utilizing machine learning models to examine the relationship between oxidative stress and prognosis in elderly non-small cell lung cancer (NSCLC) patients.MethodsThis study included elderly NSCLC patients who underwent radical lung cancer resection from January 2012 to April 2018, exploring the relationship between Oxidative Stress Score (OSS) and prognosis. Machine learning techniques, including Decision Trees (DT), Random Forest (RF), and Support Vector Machine (SVM), were employed to develop predictive models for 5-year overall survival (OS).ResultsThe datasets consisted of 1647 patients in the training set, 705 in the internal validation set, and 516 in the external validation set. An OSS was formulated from six systemic oxidative stress biomarkers, such as albumin, total bilirubin, and blood urea nitrogen, among others. Boruta variable importance analysis identified low OSS as a key indicator of poor prognosis. The OSS was subsequently integrated into the DT, RF, and SVM models for training. These models, optimized through hyperparameter tuning on the training set, were then evaluated on the internal and external validation sets. The RF model demonstrated the highest predictive performance, with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.794 in the internal validation set, compared to AUCs of 0.711 and 0.760 for the DT and SVM models, respectively. Similarly, in the external validation set, the RF model achieved an AUC of 0.784, outperforming the DT and SVM models, which had AUCs of 0.699 and 0.730, respectively. Calibration plots confirmed the RF model’s superior calibration, followed by the SVM model, with the DT model performing the poorest.ConclusionThe OSS-based clinical prediction model, constructed using machine learning methodologies, effectively predicts the prognosis of elderly NSCLC patients post-radical surgery.
Low miR-936-mediated upregulation of Pim-3 drives sorafenib resistance in liver cancer through ferroptosis inhibition by activating the ANKRD18A/Src/NRF2 pathway
Authors: Li Xiao , Cui Mengna , Xu Long , Guo Qie 
Published: October 2024

ObjectiveSorafenib, a multikinase inhibitor, is currently the standard treatment for advanced liver cancer. However, its application has become limited by the development of drug resistance. We intended to explore the mechanisms underlying the development of sorafenib resistance, therefore identifying an effective strategy to overcome sorafenib resistance remain challenges.MethodsHere, the follow-up of liver cancer patients undergoing sorafenib therapy, as well as animal tumor challenge and treatment were performed. The sorafenib-resistant liver cancer cell lines Huh7/SOR and HepG2/SOR were also established. miRNA and mRNA microarray analyses, TargetScan prediction, dual luciferase reporter assay, RNA pull-down assay, co-mmunoprecipitation (Co-IP) and pull-down assays, a transcription factor-specific NRF2 assay, an iron detection assay, a lipid peroxidation quantification assay, a ROS measurement assay, and GSH/GSSG and GSH-px standard quantitative assays were used.ResultsWe showed that upregulation of the provirus-integrating site for Moloney murine leukemia virus 3 (Pim-3) predicted poor response and unsatisfactory prognosis in sorafenib-treated liver cancer patients. Similarly, Pim-3 expression was positively associated with sorafenib resistance in liver cancer cells. Furthermore, microRNA-936 (miR-936) targeted the 3’-noncoding region (3'-UTR) of Pim-3 but exhibited lower expression in sorafenib-resistant liver cancer cells than in their parental cells. The high expression of Pim-3 mediated by miR-936 insufficiency activated the ANKRD18A/Src/NRF2 pathway which rearranged the expression of the indicated markers involved in iron distribution and lipid peroxidation homeostasis. MiR-936 overexpression and GV102-Pim-3-shRNA significantly attenuated the activity of the ANKRD18A/Src/NRF2 pathway to decrease the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A), Src, and Nuclear factor (erythroid-derived 2)-like 2 (NRF2), especially decreasing NRF2 nuclear retention and transcriptional activity. The transcriptional activity of NRF2 prompted cell ferroptosis because the transfection of miR-936 mimics, GV102-Pim-3-shRNA and GV102-NRF2-shRNA plasmid increased the expression of transferrin receptor 1 (TFR1) and divalent metal transporter 1 (DMT1) but decreased the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1), thus facilitating the accumulation of intracellular Fe2+, lipid peroxides, and reactive oxygen species (ROS) but reducing the glutathione (GSH) level. Moreover, the elevated expression of Pim-3, resulting from the absence of miR-936 enhances sorafenib resistance in liver cancer by inhibiting cell ferroptosis.ConclusionPim-3 can be regarded as a target in the treatment of sorafenib-resistant liver cancer.
The addition of PD-1 inhibitor overcame trastuzumab resistance in patients with HER2 positive, PD-L1 negative metastatic gastric cancer: Case report and review of literature
Authors: Wen Zhenpeng , Ye Daoli , Hu Qiancheng , Gou Hongfeng 
Published: October 2024

Gastric cancer (GC) is a malignancy with poor prognosis and high heterogeneity. For HER2-positive, PD-L1 negative metastatic GC patients, chemotherapy plus trastuzumab is the first-line therapy. However, such patients soon acquired resistance to treatment, especially to trastuzumab during the treatment. Improving the therapeutic resistance of HER2-positive, PD-L1 negative metastatic GC is still a dilemma. We present the case of a metastatic GC patient with HER2-positive and PD-L1-negative expression who suffered progression after a short remission with trastuzumab plus chemotherapy. The patient exhibited strong heterogeneity in the primary and metastatic lesions. His resistance to trastuzumab was overcome after the addition of a PD-1 inhibitor, after which he received a durable response for more than 8 months. In HER2-positive, PD-L1-negative metastatic GC, the addition of PD-1 inhibitors after first-line chemotherapy and trastuzumab treatment resistance may be an option.
Thymol and carvacrol against Klebsiella: anti-bacterial, anti-biofilm, and synergistic activities—a systematic review
Authors: Farhadi Kousha , Rajabi Erta , Varpaei Hesam Aldin , Iranzadasl Maryam , Khodaparast Sepideh , Salehi Mohammadreza 
Published: October 2024

IntroductionKlebsiella poses a significant global threat due to its high antibiotic resistance rate. In recent years, researchers have been seeking alternative antimicrobial agents, leading to the introduction of natural compounds such as monoterpenes, specifically thymol and carvacrol. This review aims to illustrate the potential antimicrobial, anti-biofilm, and synergistic traits of thymol and carvacrol in combat against Klebsiella.MethodsSearching PubMed, Scopus, and Web of Science, we reviewed available evidence on the antibacterial effects of thymol, carvacrol, or combined with other compounds against Klebsiella until May 2024. Reference checking was performed after the inclusion of studies. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), fractional inhibitory concentration (FIC), and anti-biofilm activity were gathered, and the MBC/MIC ratio was calculated to assess the bactericidal efficacy.ResultsWe retrieved 38 articles out of 2,652 studies screened. The gathered data assessed the anti-microbial activity of thymol, carvacrol, and both compounds in 17, 10, and 11 studies, respectively. The mean (± standard deviation) non-weighted MIC was 475.46 μg/mL (±509.95) out of 60 MIC for thymol and 279.26 μg/mL (±434.38) out of 68 MIC for carvacrol. Thymol and carvacrol showed anti-biofilm activities in the forms of disruption, inhibition, and mass reduction of biofilms. The MBC/MIC ratio was lower than 4 in 45 out of 47 cases, showing high bactericidal efficacy. FIC values were gathered for 68 combinations of thymol and carvacrol with other compounds, and they were mostly synergistic or additive.ConclusionThymol and carvacrol alone or in combination with other compounds, specifically known antibiotics, show great antimicrobial activity.
The work challenges faced by primary healthcare workers in Guangzhou during the COVID-19 pandemic prevention and control period of 2021–2022: a qualitative study
Authors: Jin Yuqing , Feng Huiyao , Xiao Qin , Tian Fenglin , Yao Huan , Zhang Runquan , Wu Qiqi , Zhu Haiyuan , Zheng Wanshan , Chen Jin , Liu Tao , Ma Wenjun , Chen Xiongfei , Dong Xiaomei 
Published: October 2024

BackgroundPrimary healthcare workers in China were vital in controlling COVID-19, facing unprecedented challenges due to the pandemic’s suddenness and transmissibility. This paper analyzed their work in Guangzhou, highlighting key difficulties in past epidemic control efforts.MethodsSemi-structured qualitative interviews were conducted with selected primary healthcare workers in Guangzhou City and audio-recorded until saturation of themes was reached. The data were analyzed independently for themes using NVivo V.12.ResultsThematic analysis of qualitative interview data revealed that challenges and difficulties encountered in grassroots epidemic prevention and control work during the COVID-19 pandemic were primarily categorized into seven dimensions: human resource allocation, material and vehicle support, epidemic prevention subsidies and compensation, humanistic care, upper-level management, horizontal collaboration, and resident cooperation.ConclusionBased on the findings, the research team recommends that administrative departments and institutions related to primary healthcare should appropriately schedule personnel work and rest time, adjust work content flexibly, optimize the allocation of medical and logistical resources, and increase investment in primary healthcare work as well as staff protection.
Longitudinal analysis of culture of patient safety survey results in surgical departments
Authors: Butler Logan R. , Lashani Shaian , Mitchell Cody , Ra Jin H. , Greenberg Caprice , Marks Lawrence B. , Ivester Thomas , Mazur Lukasz 
Published: October 2024

BackgroundThere is a need for improved methodologies on how to longitudinally analyze, interpret and learn from the Surveys on Patient Safety Culture™ (SOPS), developed by the Agency for Healthcare Research and Quality (AHRQ). Typically, SOPS quantify results by the percentage of positive responses, but this approach may miss insights from neutral or negative feedback.Study designThe SOPS were distributed every two years from 2011 to 2022 to all hospital staff at one academic institution from perioperative services. Differences between rates of “positive” and “negative” scores (“Delta”), and “neutral” responses over time were calculated. The coefficient of determination (R2) was used to assess the correlation strength of the positive scores as the primary outcomes provided by the SOPS and Delta values over time. Finally, we evaluated patterns (crossing and converging [indicating “worrisome” patterns] vs. diverging [suggesting “desirable” pattern] vs. stable [suggesting “neutral” pattern]) of the longitudinal scores.ResultsA total of 1,035 responses were analyzed [51 and 40 survey items for SOPS v1 and v2 (2022 only), respectively]. Comparing the R2 values of the positive only scores to the Delta scores demonstrated a change in effect size for “Nonpunitive Response to Error” (R2 = 0.290 vs. 0.420). Of the 13 specific categories measured through SOPS, plotting negative vs. positive values elucidated 2 crossing, 2 converging and 2 diverging patterns indicating both a decrease in positive responses and an increase in negative responses rather than neutral.ConclusionLongitudinal analysis of the SOPS using the directional measures, Delta and pattern trends can provide organizations with additional key insights regarding culture of patient safety.
Evaluation of the urban sponge stormwater regulation effectiveness based on SWMM: a case study of Wuhan, China
Authors: Lin Yuru , Liang Xiayuan , Xu Jijun , Song Zhihong , Lou Yu , Yu Yaoguo 
Published: October 2024

BackgroundRapid population growth, urbanization, and high-intensity infrastructure development have challenged cities sustainable development. Surface water flooding occurs as a result of heavy rainfall which generates runoff that exceeds infiltration rates and local drainage capacity. In China, 70 cities have been chosen as pilot cities for sponge city construction building to address this challenge.MethodThis paper takes the South Trunk Canal in Qingshan Demonstration Area of Wuhan Sponge City as the study area. Based on construct a Stormwater Management Model (SWMM), simulate and analyze the runoff process and the drainage capacity of the pipe network before and after the construction of the sponge city in typical years with high, normal and low water flows and different return periods.ResultThe results show that the construction of sponge cities can significantly regulate the annual runoff in various typical target years and mitigate the overflow in 1- and 5- year return period. However, when faced with the short-duration storm events, the measures involved in urban sponge regulations are only effective for rainfall with 1-year return period. As the scale of the flood events increases, the effectiveness of urban sponge regulations becomes more limited.DiscussionTo address these issues, the National Water Network Project is proposed for the construction of water system connections. The aim of this project is to rectify the shortcomings of sponge cities while also making better use of water resources to improve overall resilience.
Surviving the summer: foot-and-mouth disease virus survival in U.S. regional soil types at high ambient temperatures
Authors: Bessler Andrea L. , Nayee Serena , Garabed Rebecca , Krug Peter , Obrycki John , Rodriguez Luis 
Published: October 2024

IntroductionFoot-and-mouth disease (FMD) is one of the most economically significant global livestock diseases. In the U.S., economic optimization models run in 2011 demonstrate the highest mean epidemic impact of a potential FMD outbreak in California would occur in livestock-dense regions, resulting in national agriculture losses of $2.3 to $69.0 billion. In the case that an FMD outbreak occurred in the U.S., mass depopulation, carcass disposal, and disinfection protocols for infected premises have been designed to prevent further viral spread. Because the FMD virus (FMDV) is spread mechanically via the environment, characteristics of viral environmental stability are important. Temperature and adsorption to soil particles are reported to be the most important factors affecting general virus survival; however, how much these factors alter FMDV survival has not been tested.MethodsSoil samples were examined from typical U.S. regions containing the highest cattle population densities: Tennessee, Georgia, Nebraska, California, Pennsylvania, Kentucky, and Iowa. Soils were spiked with known quantities of FMDV and FMDV stability was evaluated over seven distinct time points between 0 hours and 12 days at incubation temperatures of 25°C and 37°C to represent a range of typical ambient temperatures during the summer. FMDV stability was quantified via virus titration.ResultsVirus decayed faster at higher ambient temperatures for all soils, but decay at 25°C was faster in some soils. Consequently, areas with high ambient temperatures may have lower between-farm transmission rates, slower outbreak spread, and simpler farm decontamination.DiscussionThis study provides a helpful exploration into understanding soil survival of the virus. Additional investigations into FMDV survival across different soil types will aid in developing better disinfection protocols and further refining regional viral transmission rate estimates.
Pathological study of a traumatic anthropogenic injury in the skeleton of a spiny butterfly ray (Gymnura altavela)
Authors: Montero-Hernández Gustavo , Caballero María José , Curros-Moreno Ángel , Suárez-Santana Cristian M. , Rivero Miguel A. , Caballero-Hernández Lucía , Encinoso Mario , Fernández Antonio , Castro-Alonso Ayoze 
Published: October 2024

IntroductionExternal injuries in elasmobranchs are frequent findings, either due to inter- or intraspecific interactions or as a result of interaction with human activities. However, the resilience of these species to traumatic injury remains poorly understood. This work provides an insight into the clinical presentation, diagnostic imaging, and pathological features of a severe traumatic injury to the cartilaginous skeleton of a spiny butterfly ray (Gymnura altavela).MethodsAn adult female was found lethargic in the bottom of the coast of Gran Canaria, with an external incised-contused traumatic lesion of 2 cm diameter in the scapulocoracoid cartilage. It was captured and transferred to the Poema del Mar Aquarium for its clinical evaluation and treatment. Despite these efforts, the animal eventually died and was transfer to the Institute of Animal Health and Food Safety (IUSA) for its pathological diagnosis, including a Computed Tomography (CT) study and necropsy.ResultsThe animal presented a marked reduction in hematocrit and hepatosomatic index due a chronic debilitation process. The CT scan revealed a destructive lesion with irregular margins at the level of the right scapulocoracoid cartilage. The main pathological findings were the disorganization of the tesserae layer, appearing as whitish square to rectangular geometric pieces separated from the cartilaginous core. Histologically, these pieces of tesserae were separated from the unmineralized cartilage core and displaced from the adjacent perichondrium, where inflammatory cells infiltrate. Edema and hemorrhages were also observed.ConclusionsThis study reports the first comprehensive description of skeleton trauma in a spiny butterfly ray, including the clinical presentation, diagnostic imaging and the anatomopathological features.