bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA SNHG8 regulates the migration and angiogenesis of pHUVECs induced by high glucose via the TRPM7/ERK1/2 signaling axis
Authors: Fan Zongcheng , Chen Xin , Wang Laicheng , Yu Jianjian , Zhang Shunpeng , Xu Changsheng , Lin Jinxiu , Lin Yunchai , Peng Feng 
Published: December 2023

AbstractThis study aimed to evaluate the regulatory effect and molecular mechanism of long noncoding RNA small nucleolus RNA host gene 8 (LncRNA SNHG8) in the migration and angiogenesis of primary human umbilical vein endothelial cells (pHUVECs) under high-glucose (HG) conditions. The HG-induced endothelial injury model was established in vitro.The cell model of silencing SNHG8, overexpressing SNHG8, and silencing TRPM7 was established by transfecting SNHG8-siRNA, SNHG8 plasmid and TRPM7-siRNA into cells with liposomes.The SNHG8 level was determined through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of transient receptor potential melastatin 7 (TRPM7), endothelial nitric oxide synthase (eNOS), p-eNOS, extracellular signal-regulated kinase 1/2(ERK1/2), and p-ERK1/2 were assessed through western blot. Nitric oxide (NO) levels were measured with DAF-FM. pHUVEC migration was examined through wound healing and Transwell assay, and pHUVEC angiogenesis was observed through a tube formation assay. Results showed that HG promoted the expression of lncRNA SNHG8 and TRPM7 and decreased the ratio of p-eNOS/eNOS and p-ERK1/2/ERK1/2 in pHUVECs . NO production, migration , and angiogenesis were inhibited in pHUVECs under HG conditions. Silencing lncRNA SNHG8 and TRPM7 could significantly reverse the HG-induced decrease in eNOS activation, NO production , migration, and angiogenesis . SNHG8 and U0126 (ERK pathway inhibitor) overexpression enhanced the HG effects, whereas using U0126 did not affect the TRPM7 expression. In conclusion, lncRNA SNHG8 participates in HG-induced endothelial cell injury and likely regulates NO production, migration, and angiogenesis of pHUVECs via the TRPM7/ERK1/2 signaling axis.
Lymphocyte subsets and inflammatory factors as predictors of immunotherapy efficacy in patients with hepatocellular carcinoma
Authors: Shuyue Gao , Jiamin Cheng , Niansong Qian 
Published: December 2023

AbstractWe aimed to investigate the correlation between lymphocyte subpopulations expressing inhibitor receptors, IL-6 levels, and the efficacy of immunotherapy in patients with hepatocellular carcinoma. Blood samples were prospectively collected before and after immunotherapy from patients with intermediate and advanced hepatocellular carcinoma who were treated with immunotherapy at the Fifth Medical Center of the PLA General Hospital from August 2022 to October 2023. According to the efficacy of the patients, patients were divided into effective and ineffective groups, with 40 in the effective group and 44 in the ineffective group. We compared changes in lymphocyte subsets and IL-6 levels between the two groups. Optimal cut-off value was determined using ROC curves. Then, patients were categorized into high and low groups based on cut-off value, and the disease control rates and progression free survival were compared. Before immunotherapy, there were no significant differences in the baseline levels of lymphocyte subsets (PD1 + TIM3 + T/T, TIGIT + T/T, TIM3 + T/T, CTLA4 + T/T, LAG3 + T/T, PD1 + T/T) and IL-6 between the two groups (P > 0.05). After immunotherapy, the levels of PD1 + TIM3 + T/T, TIGIT + T/T, and IL-6 in the effective group were lower than those in the ineffective group and these differences were statistically significant (P = 0.001, P = 0.008, P = 0.000). However, the levels of other lymphocyte subsets showed no significant difference. Using the ROC curve to assess efficacy prediction, PD1 + TIM3 + T/T, TIGIT + T/T and IL-6 demonstrated high predictive ability (AUC = 0.79, AUC = 0.81, AUC = 0.78). The predictive value of efficacy was further improved when all three factors were combined (AUC = 0.92, P = 0.000). Based on the ROC curve, we identified optimal cut-off value for three factors. Notably, patients with values below the optimal cut-off value had higher disease control rate and progression free survival. The levels of PD1 + TIM3 + T/T, TIGIT + T/T, and IL-6 after 2 cycles of immunotherapy may serve as predictors of treatment efficacy in patients with hepatocellular carcinoma.
Temporal variation in environmental radioactivity and radiation exposure doses in the restricted areas around the Fukushima Daiichi Nuclear Power Plant
Authors: Liu Mengjie , Taira Yasuyuki , Matsuo Masahiko , Orita Makiko , Matsunaga Hitomi , Kashiwazaki Yuya , Xiao Xu , Takamura Noboru 
Published: December 2023

AbstractTemporal variation and fluctuation in environmental contamination in Futaba town and Okuma town, the location of the Fukushima Daiichi Nuclear Power Plant (FDNPP), were evaluated based on a car-borne survey conducted from October 2021 to November 2022. Although the environmental radioactivity in the interim storage facility area (ISF) was higher than that in open areas (i.e., the evacuation order lifted areas in Futaba town and the Specific Reconstruction and Regeneration Base area [SRRB] in Okuma town), only minor temporal changes were seen in the ambient dose and detection rate of radiocesium (the proportion of radiocesium detected points per all measuring points) in those areas, respectively. These findings suggest that the observed variations may result from physical decay and environmental remediation. Resuspension caused by human activities and weather could also affect the detection rate of radiocesium. The annual external effective doses in Futaba town and Okuma town were estimated to be at a limited level (< 1 mSv/year). Nevertheless, to help ensure the safety and future prosperity of residents and communities in the affected areas around the FDNPP, long-term follow-up monitoring of temporal exposure dose levels during the recovery and reconstruction phases is extremely important.
Machine learning models to predict the warfarin discharge dosage using clinical information of inpatients from South Korea
Authors: Choi Heejung , Kang Hee Jun , Ahn Imjin , Gwon Hansle , Kim Yunha , Seo Hyeram , Cho Ha Na , Han JiYe , Kim Minkyoung , Kee Gaeun , Park Seohyun , Kwon Osung , Roh Jae-Hyung , Kim Ah-Ram , Kim Ju Hyeon , Jun Tae Joon , Kim Young-Hak 
Published: December 2023

AbstractAs warfarin has a narrow therapeutic window and obvious response variability among individuals, it is difficult to rapidly determine personalized warfarin dosage. Adverse drug events(ADE) resulting from warfarin overdose can be critical, so that typically physicians adjust the warfarin dosage through the INR monitoring twice a week when starting warfarin. Our study aimed to develop machine learning (ML) models that predicts the discharge dosage of warfarin as the initial warfarin dosage using clinical data derived from electronic medical records within 2 days of hospitalization. During this retrospective study, adult patients who were prescribed warfarin at Asan Medical Center (AMC) between January 1, 2018, and October 31, 2020, were recruited as a model development cohort (n = 3168). Additionally, we created an external validation dataset (n = 891) from a Medical Information Mart for Intensive Care III (MIMIC-III). Variables for a model prediction were selected based on the clinical rationale that turned out to be associated with warfarin dosage, such as bleeding. The discharge dosage of warfarin was used the study outcome, because we assumed that patients achieved target INR at discharge. In this study, four ML models that predicted the warfarin discharge dosage were developed. We evaluated the model performance using the mean absolute error (MAE) and prediction accuracy. Finally, we compared the accuracy of the predictions of our models and the predictions of physicians for 40 data point to verify a clinical relevance of the models. The MAEs obtained using the internal validation set were as follows: XGBoost, 0.9; artificial neural network, 0.9; random forest, 1.0; linear regression, 1.0; and physicians, 1.3. As a result, our models had better prediction accuracy than the physicians, who have difficulty determining the warfarin discharge dosage using clinical information obtained within 2 days of hospitalization. We not only conducted the internal validation but also external validation. In conclusion, our ML model could help physicians predict the warfarin discharge dosage as the initial warfarin dosage from Korean population. However, conducting a successfully external validation in a further work is required for the application of the models.
Use of dipeptidyl peptidase-4 inhibitors was associated with a lower risk of Parkinson’s disease in diabetic patients
Authors: Lin Yu-Hsuan , Hsu Chih-Cheng , Liu Jia-Sin , Chang Kuo-Cheng , Huang Jin-An 
Published: December 2023

AbstractDiabetes mellitus is a risk factor for Parkinson's disease (PD). While animal studies have supported the benefits of incretin-based therapies, including dipeptidyl peptidase-4 (DPP4) inhibitors, in PD, clinical research has yielded controversial results. This cohort study aimed to assess the relationship between PD incidence and the utilization of DPP4 inhibitor in diabetic patients. Using Taiwan's National Health Insurance Research Database from 2009 to 2018, diabetic patients receiving metformin plus at least one second-line oral antidiabetic (OAD) were enrolled. The patients were categorized as DPP4 inhibitor users and non-users. Propensity score matching was employed to establish a 1:1 ratio between DPP4 inhibitor users and non-users. Among the 205,910 patients enrolled, 149 were diagnosed with PD during follow-up. The incidence rate was 0.29 per 1000 person-years for DPP4 inhibitor users and 0.55 per 1000 person-years for the non-users. DPP4 inhibitor users exhibited a significantly lower risk of PD (adjusted hazard ratio, 0.51; 95% CI 0.39–0.68). Among DPP4 inhibitor users, vildagliptin showed the strongest correlation with a reduction in the risk of PD. This study demonstrates that the use of DPP4 inhibitors along with metformin in diabetic patients is associated with a lower risk of PD compared to those using other OADs.
Recording the maxillomandibular relationship with the Aqualizer system prior to occlusal splint therapy for treating temporomandibular disorders: a randomized controlled trial
Authors: Huth Karin Christine , Bex Alexandra , Kollmuss Maximilian , Wuersching Sabina Noreen 
Published: December 2023

AbstractTemporomandibular disorders (TMD) present a public health issue and are one of the most common musculoskeletal conditions causing chronic pain. This study compares the outcomes of occlusal splint therapy in patients with TMD following two different maxillomandibular relationship (MMR) registration techniques. 40 TMD patients were randomly allocated to MMR registration with the Aqualizer system (AQU) or with chin point guidance (CPG) prior to fabricating occlusal splints. TMD symptoms, subjective pain intensity, and quality of life (QoL) were recorded at baseline and after 3 and 6 months. The treatment led to an overall reduction of TMD symptoms in both groups (Conover test, p < 0.00001). TMJ sounds, TMJ pain with palpation and muscle pain with palpation subsided regardless of the type of MMR registration method used (Cohen’s d > 0.8). AQU-based occlusal splints led to a better improvement of TMJ pain with maximum opening compared to CPG-based occlusal splints (Cohen’s d = 0.9; CPG d = 0.13). In both groups, occlusal splint treatment had little to no effect on correcting lateral mandible deviation or improving restricted jaw opening. After 6 months occlusal splints in both groups had a large effect on improving subjective pain intensity (Cohen’s d > 0.8), however, patients reported a higher QoL in the AQU group compared to the CPG group (Mann–Whitney-U-test, p < 0.05). The results of this study support the premise that occlusal splints are effective in relieving pain-related TMD symptoms. The Aqualizer can be considered for determining MMR in cases, where guided registration techniques are not possible.Trial registration: DRKS00031998.
Thrombopoietin-independent generation of platelet-like particles from megakaryoblastic cells
Authors: Nunthanasup Nuntiporn , Ketprasit Nutpakal , Noulsri Egarit , Palasuwan Attakorn , Combes Valery , Kulkeaw Kasem , Palasuwan Duangdao 
Published: December 2023

AbstractThe use of megakaryoblastic leukemia MEG-01 cells can help reveal the mechanisms of thrombopoiesis. However, conventional in vitro activation of platelet release from MEG-01 cells requires thrombopoietin, which is costly. Here, we aim to develop a more straightforward and affordable method. Synchronization of the MEG-01 cells was initially performed using serum-free culture, followed by spontaneous cell differentiation in the presence of serum. Different stages of megakaryoblast differentiation were classified based on cell morphology, DNA content, and cell cycle. The MEG-01 cells released platelet-like particles at a level comparable to that of the thrombopoietin-activated MEG-01 cells. The platelet-like particles were distinguishable from PLP-derived extracellular vesicles and could express P-selectin following ADP activation. Importantly, the platelet-like particles induced fibrin clotting in vitro using platelet-poor plasma. Therefore, this thrombopoietin-independent cell synchronization method is an effective and straightforward method for studying megakaryopoiesis and thrombopoiesis.
Tumor microenvironment remodeling plus immunotherapy could be used in mesenchymal-like tumor with high tumor residual and drug resistant rate
Authors: Shen Shuai , Liu Xing , Guo Qing , Liang Qingyu , Wu Jianqi , Guan Gefei , Zou Cunyi , Zhu Chen , Yan Zihao , Liu Tianqi , Chen Ling , Cheng Peng , Cheng Wen , Wu Anhua 
Published: December 2023

AbstractEpithelial-mesenchymal transition (EMT) is a common process during tumor progression and is always related to residual tumor, drug resistance and immune suppression. However, considering the heterogeneity in EMT process, there is still a need to establish robust EMT classification system with reasonable molecular, biological and clinical implications to investigate whether these unfavorable survival factors are common or unique in different individuals. In our work, we classify tumors with four EMT status, that is, EMTlow, EMTmid, EMThigh-NOS (Not Otherwise Specified), and EMThigh-AKT (AKT pathway overactivation) subtypes. We find that EMThigh-NOS subtype is driven by intrinsic somatic alterations. While, EMThigh-AKT subtype is maintained by extrinsic cellular interplay between tumor cells and macrophages in an AKT-dependent manner. EMThigh-AKT subtype is both unresectable and drug resistant while EMThigh-NOS subtype can be treated with cell cycle related drugs. Importantly, AKT activation in EMThigh-AKT not only enhances EMT process, but also contributes to the immunosuppressive microenvironment. By remodeling tumor immune-microenvironment by AKT inhibition, EMThigh-AKT can be treated by immune checkpoint blockade therapies. Meanwhile, we develop TumorMT website (http://tumormt.neuroscience.org.cn/) to apply this EMT classification and provide reasonable therapeutic guidance.
Neuronal gene expression in two generations of the marine parasitic worm, Cryptocotyle lingua
Authors: Tolstenkov Oleg , Chatzigeorgiou Marios , Gorbushin Alexander 
Published: December 2023

AbstractTrematodes, or flukes, undergo intricate anatomical and behavioral transformations during their life cycle, yet the functional changes in their nervous system remain poorly understood. We investigated the molecular basis of nervous system function in Cryptocotyle lingua, a species of relevance for fisheries. Transcriptomic analysis revealed a streamlined molecular toolkit with the absence of key signaling pathways and ion channels. Notably, we observed the loss of nitric oxide synthase across the Platyhelminthes. Furthermore, we identified upregulated neuronal genes in dispersal larvae, including those involved in aminergic pathways, synaptic vesicle trafficking, TRPA channels, and surprisingly nitric oxide receptors. Using neuronal markers and in situ hybridization, we hypothesized their functional relevance to larval adaptations and host-finding strategies. Additionally, employing a behavior quantification toolkit, we assessed cercaria motility, facilitating further investigations into the behavior and physiology of parasitic flatworms. This study enhances our understanding of trematode neurobiology and provides insights for targeted antiparasitic strategies.
Heat stress vulnerability and critical environmental limits for older adults
Authors: Tony Wolf S. , Cottle Rachel M. , Fisher Kat G. , Vecellio Daniel J. , Larry Kenney W. 
Published: December 2023

AbstractThe present study examined heat stress vulnerability of apparently healthy older vs. young adults and characterized critical environmental limits for older adults in an indoor setting at rest (Rest) and during minimal activity associated with activities of daily living. Critical environmental limits are combinations of ambient temperature and humidity above which heat balance cannot be maintained (i.e., becomes uncompensable) for a given metabolic heat production. Here we exposed fifty-one young (23 ± 4 yrs) and 49 older (71 ± 6 yrs) adults to progressive heat stress across a wide range of environments in an environmental chamber during Minimal Activity (young and older subjects) and Rest (older adults only). Heat compensability curves were shifted leftward for older adults indicating age-dependent heat vulnerablity (p < 0.01). During Minimal Activity, critical environmental limits were lower in older compared to young adults (p < 0.0001) and lower than those at Rest (p < 0.0001). These data document heat vulnerability of apparently healthy older adults and define critical environmental limits for indoor settings in older adults at rest and during activities of daily living, and can be used to develop evidence-based recommendations to minimize the deleterious impacts of extreme heat events in this population.
A cell-free strategy for host-specific profiling of intracellular antibiotic sensitivity and resistance
Authors: Chengan Kameshwari , Hind Charlotte , Stanley Maria , Wand Matthew E. , Nagappa Lakshmeesha K. , Howland Kevin , Hanson Tanith , Martín-Escolano Rubén , Tsaousis Anastasios D. , Bengoechea José A. , Mark Sutton J. , Smales Christopher M. , Moore Simon J. 
Published: December 2023

AbstractAntimicrobial resistance (AMR) is a pandemic spread across multiple infectious disease-causing microbes. To provide a host-specific tool to study antibiotic susceptibility and resistance, here we develop Klebsiella pneumoniae cell-free gene expression (CFE) systems from laboratory and clinical isolates. Using proteomics, we identify relative differences and unique proteins for these new CFE systems in comparison to an Escherichia coli MG1655 CFE model. Then we profile antimicrobial susceptibility in parallel with whole cells to quantify CFE antibiotic potency. Finally, we apply this native CFE tool to study AMR variants at a proof-of-concept level. Definably we show that RpoB H526L confers a 58-fold increase in CFE resistance to rifampicin—a genotype observed in rifampicin-resistant Mycobacterium tuberculosis clinical isolates. Overall, we provide a cell-free synthetic biology strategy for the profiling of antibiotic sensitivity and resistance from K. pneumoniae. While initial extract processing requires Biosafety Level 2, the CFE system is non-living, suitable for long-term storage and study in a Biosafety Level 1 lab. We anticipate the K. pneumoniae CFE bioassay is advantageous for host-specific antimicrobial testing, the characterisation of intracellular AMR variants and potentially structure-activity relationship studies.
Democrats are better than Republicans at discerning true and false news but do not have better metacognitive awareness
Authors: Dobbs Mitch , DeGutis Joseph , Morales Jorge , Joseph Kenneth , Swire-Thompson Briony 
Published: December 2023

AbstractInsight into one’s own cognitive abilities is one important aspect of metacognition. Whether this insight varies between groups when discerning true and false information has yet to be examined. We investigated whether demographics like political partisanship and age were associated with discernment ability, metacognitive efficiency, and response bias for true and false news. Participants rated the veracity of true and false news headlines and provided confidence ratings for each judgment. We found that Democrats and older adults were better at discerning true and false news than Republicans and younger adults. However, all demographic groups maintained good insight into their discernment ability. Although Republicans were less accurate than Democrats, they slightly outperformed Democrats in metacognitive efficiency when a politically equated item set was used. These results suggest that even when individuals mistake misinformation to be true, they are aware that they might be wrong.
Sport an der Hämodialyse
Authors: Haupt Franziska 
Published: December 2023

ZUSAMMENFASSUNGZiel dieser Forschungsarbeit war es festzustellen, ob Sport während der Hämodialyse (HD) Auswirkungen auf das Kt/V hat und wenn ja, welche dies sind. Es wurden 6 Patienten unabhängig von Alter, Geschlecht, Grunderkrankung, Dauer der Dialyse und Restdiurese ausgesucht. Alle Teilnehmer sollten für die Dauer von 3 Monaten während der HD für 30 Minuten mittels Betten ergometer trainieren. Es erfolgten vorab und im Anschluss des Projektes Kt/V-Kontrollen. Die Ergebnisse zeigten jedoch keine wesentlichen Veränderungen der Kt/V-Werte. Positive Effekte hatte der Sport auf den Phosphat- und HbA1c-Wert. Die Patienten fühlten sich durch den Sport fitter, hatten laut eigenen Aussagen eine bessere Laune und waren motivierter. Sie hatten in ihrer Freizeit mehr Energie als vor dem regelmäßigen Sport, wodurch sie allgemein aktiver waren.
tert-Butoxide-Mediated Protodeformylative Decarbonylation of α-Quaternary Homobenzaldehydes
Authors: Stokes Benjamin J. , Cai Xiao , Amsbaugh Ritter V. , Drake Lauren J. , Kotamraju Ravi M. A. , Licauco Nicholas Javier C. 
Published: December 2023

Abstract
tert-Butoxide mediates the Haller–Bauer-type (protodeformylative) decarbonylation of readily accessed α-quaternary homobenzaldehydes and related compounds at room temperature, generating cumene products. Both geminal dialkyl and geminal diaryl substituents are tolerated. gem-Dimethyls are sufficient for decarbonylation of polycyclic arenyl substrates whereas monocyclic aromatic homobenzaldehydes require cyclic gem-dialkyls or gem-diaryls for significant decarbonylation.