bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: A Patient With Neuroleptic Malignant Syndrome, Water Intoxication and Hyponatremia Associated With Severe Cerebral Edema and Coma
Authors: Takenouchi Haruka , Anno Takatoshi , Kimura Yukiko , Kawasaki Fumiko , Shirai Ryo , Kaneto Hideaki , Kurokawa Katsumi , Tomoda Koichi 
Published: March 2022

BackgroundWater intoxication is typically caused by primary or psychogenic polydipsia that potentially may lead to fatal disturbance in brain functions. Neuroleptic malignant syndrome (NMS) is a serious complication induced by administration of antipsychotics and other psychotropic drugs. The combination of inappropriate secretion of antidiuretic hormone (SIDAH), NMS and rhabdomyolysis have been rarely reported. Our patient also developed severe water intoxication.Case presentationHerein we report a comatose case of NMS complicated with water intoxication, syndrome of SIADH and rhabdomyolysis. This patient had severe cerebral edema and hyponatremia that were improved rapidly by the correction of hyponatremia within a couple of days.ConclusionsMalignant neuroleptic syndrome water intoxication, SIADH and rhabdomyolysis can occur simultaneously. Comatose conditions induced by cerebral edema and hyponatremia can be successfully treated by meticulous fluid management and the correction of hyponatremia.
LYPD3, a New Biomarker and Therapeutic Target for Acute Myelogenous Leukemia
Authors: Hu Tingting , Zhang Yingjie , Yang Tianqing , He Qingnan , Zhao Mingyi 
Published: March 2022

Background: Acute myelogenous leukemia (AML) is nosocomial with the highest pediatric mortality rates and a relatively poor prognosis. C4.4A(LYPD3) is a tumorigenic and high-glycosylated cell surface protein that has been proven to be linked with the carcinogenic effects in solid tumors, but no hematologic tumors have been reported. We focus on exploring the molecular mechanism of LYPD3 in the regulation of the occurrence and development of AML to provide a research basis for the screening of markers related to the treatment and prognosis.Methods: Datasets on RNA Sequencing (RNA-seq) and mRNA expression profiles of 510 samples were obtained from The Cancer Genome Atlas Program/The Genotype-Tissue Expression (Tcga-gtex) on 10 March 2021, which included the information on 173 AML tumorous tissue samples and 337 normal blood samples. The differential expression, identification of prognostic genes based on the COX regression model, and LASSO regression were analyzed. In order to better verify, experiments including gene knockdown mediated by small interfering RNA (siRNA), cell proliferation assays, and Western blot were prefomed. We studied the possible associated pathways through which LYPD3 may have an impact on the pathogenesis and prognosis of AML by gene set enrichment analysis (GSEA).Results: A total of 11,490 differential expression genes (DEGs) were identified. Among them, 4,164 genes were upregulated, and 7,756 genes were downregulated. The univariate Cox regression analysis and LASSO regression analysis found that 28 genes including LYPD3, DNAJC8, and other genes were associated with overall survival (OS). After multivariate Cox analysis, a total of 10 genes were considered significantly correlated with OS in AML including LYPD3, which had a poor impact on AML (p &lt;0.05). The experiment results also supported the above conclusion. We identified 25 pathways, including the E2F signaling pathway, p53 signaling pathway, and PI3K_AKT signaling pathway, that were significantly upregulated in AML samples with high LYPD3 expression (p &lt; 0.05) by GSEA. Further, the results of the experiment suggested that LYPD3 participates in the development of AML through the p53 signaling pathway or/and PI3K/AKT signaling pathway.Conclusion: This study first proved that the expression of LYPD3 was elevated in AML, which was correlated with poor clinical characteristics and prognosis. In addition, LYPD3 participates in the development of AML through p53 or/and the PI3K/AKT signaling pathway.
Identification of Pathologic and Prognostic Genes in Prostate Cancer Based on Database Mining
Authors: Liu Kun , Chen Yijun , Feng Pengmian , Wang Yucheng , Sun Mengdi , Song Tao , Tan Jun , Li Chunyang , Liu Songpo , Kong Qinghong , Zhang Jidong 
Published: March 2022

Background: Prostate cancer (PCa) is an epithelial malignant tumor that occurs in the urinary system with high incidence and is the second most common cancer among men in the world. Thus, it is important to screen out potential key biomarkers for the pathogenesis and prognosis of PCa. The present study aimed to identify potential biomarkers to reveal the underlying molecular mechanisms.Methods: Differentially expressed genes (DEGs) between PCa tissues and matched normal tissues from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset were screened out by R software. Weighted gene co-expression network analysis was performed primarily to identify statistically significant genes for clinical manifestations. Protein–protein interaction (PPI) network analysis and network screening were performed based on the STRING database in conjunction with Cytoscape software. Hub genes were then screened out by Cytoscape in conjunction with stepwise algorithm and multivariate Cox regression analysis to construct a risk model. Gene expression in different clinical manifestations and survival analysis correlated with the expression of hub genes were performed. Moreover, the protein expression of hub genes was validated by the Human Protein Atlas database.Results: A total of 1,621 DEGs (870 downregulated genes and 751 upregulated genes) were identified from the TCGA-PRAD dataset. Eight prognostic genes [BUB1, KIF2C, CCNA2, CDC20, CCNB2, PBK, RRM2, and CDC45] and four hub genes (BUB1, KIF2C, CDC20, and PBK) potentially correlated with the pathogenesis of PCa were identified. A prognostic model with good predictive power for survival was constructed and was validated by the dataset in GSE21032. The survival analysis demonstrated that the expression of RRM2 was statistically significant to the prognosis of PCa, indicating that RRM2 may potentially play an important role in the PCa progression.Conclusion: The present study implied that RRM2 was associated with prognosis and could be used as a potential therapeutic target for PCa clinical treatment.
Long-Term Outcomes After Percutaneous Transluminal Pulmonary Angioplasty in Patients With Takayasu Arteritis and Pulmonary Hypertension
Authors: Huang Zhiwei , Wang Man , Hu Fenghuan , Liu Xiaoning 
Published: March 2022

ObjectiveTo investigate the long-term efficacy of percutaneous transluminal pulmonary angioplasty (PTPA) in patients with Takayasu arteritis (TA) and pulmonary artery stenosis and pulmonary hypertension (PH).MethodsData from 183 lesions from 79 surgeries performed on 32 patients with TA and PH were analyzed. Symptoms, laboratory investigation results, World Health Organization (WHO) functional class, 6-min walk distance (6 MWD), hemodynamic parameters, and prognosis were analyzed at baseline and follow-up.ResultsThe mean (± SD) age of the 32 patients (28 female, 4 male) was 42.8 ± 11.9 years, and the median follow-up was 49.5 months (interquartile range, 26–71 months). Compared with baseline, changes in total bilirubin, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, 6 MWD, and WHO score functional class demonstrated significant differences (P&lt;0.001). Echocardiography findings, right and left ventricular diameter, tricuspid annular plane systolic excursion, and estimated pulmonary artery systolic pressure were all improved (P=0.016, P&lt;0.001, P&lt;0.001, and P=0.005, respectively). Importantly, repeat right heart catheterization revealed that mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac index also improved significantly at follow-up (P&lt;0.001, P&lt;0.001, and P=0.011, respectively). Pulmonary angiography revealed post-procedure restenosis in 64 (35.0%) lesions underwent PTPA within three to six months. Among three patients who underwent stent implantation, one experienced restenosis. Two patients died during the follow-up period, one from aggravation of right heart failure after lung infection, and the other in a traffic accident.ConclusionsResults of this study indicated that PTPA significantly improved clinical symptoms, exercise tolerance, and hemodynamic parameters in patients with TA pulmonary artery stenosis and PH. More importantly, reperfusion pulmonary edema significantly decreased, and no patient died of PTPA-related complications with guidance from the pressure wire.
Harnessing Big Data, Smart and Digital Technologies and Artificial Intelligence for Preventing, Early Intercepting, Managing, and Treating Psoriatic Arthritis: Insights From a Systematic Review of the Literature
Authors: Bragazzi Nicola Luigi , Bridgewood Charlie , Watad Abdulla , Damiani Giovanni , Kong Jude Dzevela , McGonagle Dennis 
Published: March 2022

BackgroundRheumatological and dermatological disorders contribute to a significant portion of the global burden of disease. Big Data are increasingly having a more and more relevant role, being highly ubiquitous and pervasive in contemporary society and paving the way for new, unprecedented perspectives in biomedicine, including dermatology and rheumatology. Rheumatology and dermatology can potentially benefit from Big Data.MethodsA systematic review of the literature was conducted according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines, mining “Uno per tutti”, a highly integrated and automated tool/meta-database developed at the University of Genoa, Genoa, Italy, and consisting of 20 major scholarly electronic databases, including PubMed/MEDLINE. Big Data- or artificial intelligence-based studies were judged based on the modified Qiao’s critical appraisal tool for critical methodological quality assessment of Big Data/machine learning-based studies. Other studies designed as cross-sectional, longitudinal, or randomized investigations, reviews/overviews or expert opinions/commentaries were evaluated by means of the relevant “Joanna Briggs Institute” (JBI)’s critical appraisal tool for the critical methodological quality assessment.ResultsFourteen papers were included in the present systematic review of the literature. Most of the studies included concerned molecular applications of Big Data, especially in the fields of genomics and post-genomics. Other studies concerned epidemiological applications, with a practical dearth of studies assessing smart and digital applications for psoriatic arthritis patients.ConclusionsBig Data can be a real paradigm shift that revolutionizes rheumatological and dermatological practice and clinical research, helping to early intercept psoriatic arthritis patients. However, there are some methodological issues that should be properly addressed (like recording and association biases) and some ethical issues that should be considered (such as privacy). Therefore, further research in the field is warranted.Systematic Review RegistrationRegistration code 10.17605/OSF.IO/4KCU2.
The Impact of Total Variation Regularized Expectation Maximization Reconstruction on 68Ga-DOTA-TATE PET/CT Images in Patients With Neuroendocrine Tumor
Authors: Liu Lin , Liu Hanxiang , Xu Shijie , Zhang Shumao , Tao Yi , Mok Greta S. P. , Chen Yue 
Published: March 2022

ObjectiveThe aim of this study was to investigate the effects of the total variation regularized expectation maximization (TVREM) reconstruction on improving 68Ga-DOTA-TATE PET/CT images compared to the ordered subset expectation maximization (OSEM) reconstruction.MethodA total of 17 patients with neuroendocrine tumors who underwent clinical 68Ga-DOTA-TATE PET/CT were involved in this study retrospectively. The PET images were acquired with either 3 min-per-bed (min/bed) acquisition time and reconstructed with OSEM (2 iterations, 20 subsets, and a 3.2-mm Gaussian filter) and TVREM (seven penalization factors = 0.01, 0.07, 0.14, 0.21, 0.28, 0.35, and 0.42) for 2 and 3 min-per-bed (min/bed) acquisition time using list-mode. The SUVmean of the liver, background variability (BV), signal-to-noise ratios (SNR), SUVmax of the lesions and tumor-to-background ratios (TBR) were measured. The mean percentage difference in the SNR and TBR between TVREM with difference penalization factors and OSEM was calculated. Qualitative image quality was evaluated by two experienced radiologists using a 5-point score scale (5-excellent, 1-poor).ResultsIn total, 63 lesions were analyzed in this study. The SUVmean of the liver did not differ significantly between TVREM and OSEM. The BV of all TVREM groups was lower than OSEM groups (all p &lt; 0.05), and the BV of TVREM 2 min/bed group with penalization factor of 0.21 was considered comparable to OSEM 3 min/bed group (p = 0.010 and 0.006). The SNR, SUVmax and TBR were higher for all TVREM groups compared to OSEM groups (all p &lt; 0.05). The mean percentage difference in the SNR and TBR was larger for small lesions (&lt;10 mm) than that for medium (≥10 mm but &lt; 20 mm) and large lesions (≥20 mm). The highest image quality score was given to TVREM 2 min/bed group with penalization factor of 0.21 (3.77 ± 0.26) and TVREM 3 min/bed group with penalization factor of 0.35 (3.77 ± 0.26).ConclusionTVREM could reduce image noise, improve the SNR, SUVmax and TBR of the lesions, and has the potential to preserves the image quality with shorter acquisition time.
Transcranial Direct Current Stimulation May Reduce Prefrontal Recruitment During Dual Task Walking in Functionally Limited Older Adults – A Pilot Study
Authors: Jor’dan Azizah J. , Bernad-Elazari Hagar , Mirelman Anat , Gouskova Natalia A. , Lo On-Yee , Hausdorff Jeffrey M. , Manor Brad 
Published: March 2022

IntroductionTranscranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (dlPFC) improves dual task walking in older adults, when tested just after stimulation. The acute effects of tDCS on the cortical physiology of walking, however, remains unknown.MethodsIn a previous study, older adults with slow gait and executive dysfunction completed a dual task walking assessment before and after 20 min of tDCS targeting the left dlPFC or sham stimulation. In a subset of seven participants per group, functional near-infrared spectroscopy (fNIRS) was used to quantify left and right prefrontal recruitment defined as the oxygenated hemoglobin response to usual and dual task walking (ΔHbO2), as well as the absolute change in this metric from usual to dual task conditions (i.e., ΔHbO2cost). Paired t-tests examined pre- to post-stimulation differences in each fNIRS metric within each group.ResultsThe tDCS group exhibited pre- to post-stimulation reduction in left prefrontal ΔHbO2cost (p = 0.03). This mitigation of dual task “cost” to prefrontal recruitment was induced primarily by a reduction in left prefrontal ΔHbO2 specifically within the dual task condition (p = 0.001), an effect that was observed in all seven participants within this group. Sham stimulation did not influence ΔHbO2cost or ΔHbO2 in either walking condition (p &gt; 0.35), and neither tDCS nor sham substantially influenced right prefrontal recruitment (p &gt; 0.16).DiscussionThis preliminary fNIRS data suggests that tDCS over the left dlPFC may modulate prefrontal recruitment, as reflected by a relative reduction in the oxygen consumption of this brain region in response to dual task walking.
Pre-stroke Physical Inactivity and Stroke Severity in Male and Female Patients
Authors: Salmantabar Pegah , Abzhandadze Tamar , Viktorisson Adam , Reinholdsson Malin , Sunnerhagen Katharina S. 
Published: March 2022

IntroductionFemales experience more severe ischemic strokes than do males. A higher pre-stroke physical activity level is associated with less severe stroke. The primary aim of this study was to explore the association between pre-stroke physical inactivity and stroke severity in male and female patients.MethodsThis was a retrospective, registry-based study. The data were retrieved from two stroke registries from 2014 to 2019. The primary explanatory variable was physical activity level before the stroke, assessed using the Saltin-Grimby Physical Activity Level Scale. The outcome was moderate to severe stroke at hospital admission, assessed using the National Institutes of Health Stroke Scale (NIHSS). A moderate to severe stroke was defined as a NIHSS score of ≥6. Binary logistic regression analysis was performed to explore if physical inactivity before the stroke could explain stroke severity in male and female patients.ResultsIn total, we included 4,535 patients with ischemic stroke. Female patients (n = 2,145) had a mean age of 76 years, 35% had a moderate to severe stroke, and 64% were physically inactive pre-stroke. Male patients (n = 2,390) had a mean age of 72 years, 25% had a moderate to severe stroke, and 49% were physically inactive pre-stroke. Physical inactivity was associated with higher odds for moderate to severe stroke in both sexes (females' odds ratio [OR], 2.7, 95% confidence interval [CI]: 2.2–3.3, p &lt; 0.001 and males' OR, 2.06, 95% CI: 1.7–2.5, p &lt; 0.001). The association remained significant in the adjusted models.ConclusionsPhysically inactive females and males had higher odds of experiencing a moderate to severe stroke. However, the OR of female patients was somewhat higher than that of male patients.
Anomalous Levels of CD47/Signal Regulatory Protein Alpha in the Hippocampus Lead to Excess Microglial Engulfment in Mouse Model of Perioperative Neurocognitive Disorders
Authors: Shui Min , Sun Yi , Lin Dandan , Xue Ziyi , Liu Jianhui , Wu Anshi , Wei Changwei 
Published: March 2022

BackgroundPerioperative neurocognitive disorders (PNDs) are common complications of surgical patients, which can lead to prolonged hospitalization, increased complications, and decreased independence and quality of life. However, the underlying molecular mechanisms of PND remain largely obscure. Microglia activation and synapse loss were observed in PND. Cluster of differentiation 47 (CD47), which can bind to its receptor signal regulatory protein alpha (SIRPα) and generate “do not eat me” signal, protects synapses from excessive pruning. Therefore, we aimed to evaluate the potential role of CD47–SIRPα signaling in PND.MethodsThe tibial fracture surgery was performed in aged C57BL/6 mice for PND model establishment. The expression of CD47 and SIRPα in the hippocampus was assessed. Synaptic plasticity, dendritic spine density, microglial engulfment, and hippocampal-dependent memory function were evaluated after model establishment and intervention with SIRPα overexpression.ResultsCD47 and SIRPα expression in the hippocampus were both decreased after the surgery. SIRPα overexpression showed reduced engulfment within host microglia, but a total effect of excessive synapse engulfment decreased dendritic spine density and post-synaptic density protein 95 (PSD95) expression. SIRPα overexpression could not improve the synaptic dysfunction and cognitive impairment in PND. In addition, SIRPα overexpression led to increased CD47 and Iba1 expression.ConclusionAnesthesia and surgery affect CD47–SIRPα signaling. SIRPα overexpression could not ameliorate the cognitive impairment in PND mice. One reason may be that the increased Iba1 expression leads to a total effect of excessive synapse engulfment, which results in decreased dendritic spine density and PSD95 expression.
Tumor Treating Fields Suppression of Ciliogenesis Enhances Temozolomide Toxicity
Authors: Shi Ping , Tian Jia , Ulm Brittany S. , Mallinger Julianne C. , Khoshbouei Habibeh , Deleyrolle Loic P. , Sarkisian Matthew R. 
Published: March 2022

Tumor Treating Fields (TTFields) are low-intensity, alternating intermediate-frequency (200 kHz) electrical fields that extend survival of glioblastoma patients receiving maintenance temozolomide (TMZ) chemotherapy. How TTFields exert efficacy on cancer over normal cells or interact with TMZ is unclear. Primary cilia are microtubule-based organelles triggered by extracellular ligands, mechanical and electrical field stimulation and are capable of promoting cancer growth and TMZ chemoresistance. We found in both low- and high-grade patient glioma cell lines that TTFields ablated cilia within 24 h. Halting TTFields treatment led to recovered frequencies of elongated cilia. Cilia on normal primary astrocytes, neurons, and multiciliated/ependymal cells were less affected by TTFields. The TTFields-mediated loss of glioma cilia was partially rescued by chloroquine pretreatment, suggesting the effect is in part due to autophagy activation. We also observed death of ciliated cells during TTFields by live imaging. Notably, TMZ and TTFields have opposing effects on glioma ciliogenesis. TMZ-induced stimulation of ciliogenesis in both adherent cells and gliomaspheres was blocked by TTFields. Surprisingly, the inhibitory effects of TTFields and TMZ on tumor cell recurrence are linked to the relative timing of TMZ exposure to TTFields and ARL13B+ cilia. Finally, TTFields disrupted cilia in patient tumors treated ex vivo. Our findings suggest that the efficacy of TTFields may depend on the degree of tumor ciliogenesis and relative timing of TMZ treatment.
The Temporal Relationship Between Local School Closure and Increased Incidence of Pediatric Diabetic Ketoacidosis
Authors: McCluskey Casey K. , Zee-Cheng Janine E. , Klein Margaret J. , Scanlon Matthew C. , Rotta Alexandre T. , Remy Kenneth E. , Carroll Christopher L. , Shein Steven L. 
Published: March 2022

ImportanceThe incidence of pediatric diabetic ketoacidosis (DKA) increased early in the COVID-19 pandemic, but the relative contribution of behavioral changes and viral-related pathophysiology are unknown.ObjectiveTo evaluate the relationship between school closure date and onset of increased DKA to help clarify the etiology of the increased incidence.DesignA multi-center, quality-controlled Pediatric Intensive Care Unit (PICU) database was used to identify the number of admissions to a participating PICU with DKA on each calendar day from 60 days before local school closure to 90 days after, and compared to baseline data from the same periods in 2018–2019. Interrupted time series and multiple linear regression analyses were used to identify admission rates that differed significantly between 2020 and baseline.SettingEighty-one PICUs in the United StatesParticipants: Children ages 29 days to 17 years admitted to a PICU with DKAExposures: Statewide school closureMain outcome/measure: Rate of admission to the PICU for DKA.ResultsThere were 1936 admissions for children with DKA in 2020 and 1795 admissions/year to those same PICUs in 2018-2019. Demographics and clinical outcomes did not differ before school closure, but pandemic-era patients were less often white and had longer hospital length of stay in the post-school closure period. The difference between 2020 admissions and 2018-2019 admissions was not different than zero before school closure, and significantly higher than zero after school closure, but was significantly increased in 2020 at &gt;30 days after school closure (p = 0.039).Conclusions/RelevanceAn increase in pediatric DKA admissions began one month after school closures. Given that behavioral changes started near school closure dates and viral activity peaked weeks after, this suggests that behavioral factors may not be the primary etiology and it is possible that SARS-CoV-2 infection may have direct effects on pediatric DKA.