bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of key genes and imbalance of immune cell infiltration in immunoglobulin A associated vasculitis nephritis by integrated bioinformatic analysis
Authors: Jia Xianxian , Zhu Hua , Jiang Qinglian , Gu Jia , Yu Shihan , Chi Xuyang , Wang Rui , Shan Yu , Jiang Hong , Ma Xiaoxue 
Published: March 2023

BackgroundIgAV, the most common systemic vasculitis in childhood, is an immunoglobulin A-associated immune complex-mediated disease and its underlying molecular mechanisms are not fully understood. This study attempted to identify differentially expressed genes (DEGs) and find dysregulated immune cell types in IgAV to find the underlying pathogenesis for IgAVN.MethodsGSE102114 datasets were obtained from the Gene Expression Omnibus (GEO) database to identify DEGs. Then, the protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database. And key hub genes were identified by cytoHubba plug-in, performed functional enrichment analyses and followed by verification using PCR based on patient samples. Finally, the abundance of 24 immune cells were detected by Immune Cell Abundance Identifier (ImmuCellAI) to estimate the proportions and dysregulation of immune cell types within IgAVN.ResultA total of 4200 DEGs were screened in IgAVN patients compared to Health Donor, including 2004 upregulated and 2196 downregulated genes. Of the top 10 hub genes from PPI network, STAT1, TLR4, PTEN, UBB, HSPA8, ATP5B, UBA52, and CDC42 were verified significantly upregulated in more patients. Enrichment analyses indicated that hub genes were primarily enriched in Toll-like receptor (TLR) signaling pathway, nucleotide oligomerization domain (NOD)-like receptor signaling pathway, and Th17 signaling pathways. Moreover, we found a diversity of immune cells in IgAVN, consisting mainly of T cells. Finally, this study suggests that the overdifferentiation of Th2 cells, Th17 cells and Tfh cells may be involved in the occurrence and development of IgAVN.ConclusionWe screened out the key genes, pathways and maladjusted immune cells and associated with the pathogenesis of IgAVN. The unique characteristics of IgAV-infiltrating immune cell subsets were confirmed, providing new insights for future molecular targeted therapy and a direction for immunological research on IgAVN.
Laboratory evaluation of broflanilide (TENEBENAL™) against Anopheles gambiae in Moshi, Tanzania – delayed mortality, cross-resistance, and residual efficacy
Authors: Snetselaar Janneke , Rowland Mark W. , Azizi Salum , Mawa Benson , Malone David J. , Kirby Matthew J. 
Published: March 2023

IntroductionBroflanilide is a novel meta-diamide insecticide, which has a distinct mode of action compared to other active ingredients used for Indoor Residual Spraying (IRS). This study details a laboratory evaluation of broflanilide, of putative discriminating concentrations, potential cross-resistance, and residual efficacy on two substrates.MethodsMosquitoes were exposed to broflanilide in bottle bioassays to determine lethal concentrations (LC50 and LC95). These were used to calculate resistance ratios between the susceptible Kisumu and the pyrethroid-resistant Muleba-Kis strains of Anopheles gambiae s.s. Prototype wettable powder formulations of broflanilide were applied to mud and concrete to determine the optimal observation period for determining delayed mortality, and a Cox proportional hazards model was fitted to determine a potential dose response effect. Subsequently, residual efficacy of application rates ranging between 25 mg/m2 and 300 mg/m2 were monitored monthly.ResultsLC values of tested strains were not significantly different; therefore, the polyfactorial resistance mechanisms possessed by the resistant strain did not confer resistance to broflanilide. A significant effect of concentration and time since spraying was found on mosquito survival, indicating that higher broflanilide concentrations are more effective and that this effect was strongest immediately after spraying. Knockdown at 60min post exposure was negligible, with on average only 1% of all mosquitoes knocked down. On the mud surface, but not on concrete, there was a delayed killing effect, with mortality increasing until 72 hours after exposure. The residual efficacy test indicated that on concrete the 100 mg/m2 and 200 mg/m2 concentrations of both broflanilide 50WP formulations remained efficacious for 9 months post spraying. On mud, there were large variations in mosquito mortality from month to month. Generally, higher concentrations resulted in higher mortality, despite variation over time.DiscussionCross-resistance to broflanilide was not detected in mosquitoes with multiple resistance mechanisms. This opens up the possibility for wide-scale use of broflanilide, especially in areas with established pyrethroid resistance. Like some other insecticide classes, delayed mortality up to 72 hours post exposure was found for broflanilide. Promising residual efficacy was found with broflanilide 50WP formulations on concrete. On mud, efficacy varied and further testing with a refined formulation is recommended.
Face expression recognition based on NGO-BILSTM model
Authors: Zhong Jiarui , Chen Tangxian , Yi Liuhan 
Published: March 2023

IntroductionFacial expression recognition has always been a hot topic in computer vision and artificial intelligence. In recent years, deep learning models have achieved good results in accurately recognizing facial expressions. BILSTM network is such a model. However, the BILSTM network's performance depends largely on its hyperparameters, which is a challenge for optimization.MethodsIn this paper, a Northern Goshawk optimization (NGO) algorithm is proposed to optimize the hyperparameters of BILSTM network for facial expression recognition. The proposed methods were evaluated and compared with other methods on the FER2013, FERplus and RAF-DB datasets, taking into account factors such as cultural background, race and gender.ResultsThe results show that the recognition accuracy of the model on FER2013 and FERPlus data sets is much higher than that of the traditional VGG16 network. The recognition accuracy is 89.72% on the RAF-DB dataset, which is 5.45, 9.63, 7.36, and 3.18% higher than that of the proposed facial expression recognition algorithms DLP-CNN, gACNN, pACNN, and LDL-ALSG in recent 2 years, respectively.DiscussionIn conclusion, NGO algorithm effectively optimized the hyperparameters of BILSTM network, improved the performance of facial expression recognition, and provided a new method for the hyperparameter optimization of BILSTM network for facial expression recognition.
Elevated IL-6 plasma levels are associated with GAD antibodies-associated autoimmune epilepsy
Authors: Basnyat Pabitra , Peltola Maria , Raitanen Jani , Liimatainen Suvi , Rainesalo Sirpa , Pesu Marko , Peltola Jukka 
Published: March 2023

BackgroundAntibodies against glutamic acid decarboxylase (GADA) are present in multiple neurological manifestations, such as stiff-person syndrome, cerebellar ataxia, limbic encephalitis, and epilepsy. Increasing data support the clinical significance of GADA as an autoimmune etiology of epilepsy, however, there is not yet definitive evidence to confirm the pathogenic link between GADA and epilepsy.ObjectiveInterleukin-6 (IL-6), a pro-convulsive and neurotoxic cytokine, and interleukin-10 (IL-10), an anti-inflammatory and neuroprotective cytokine, are crucial inflammatory mediators in the brain. Increased production of IL-6 and its association with epileptic disease profiles are well established, suggesting the presence of chronic systemic inflammation in epilepsy. Therefore, in this study, we investigated the association of plasma cytokine concentrations of IL-6 and IL-10 and their ratio with GADA in patients with drug-resistant epilepsy.MethodsInterleukin-6 and IL-10 concentrations were measured by ELISA in plasma, and the IL-6/IL-10 ratio was calculated in a cross-sectional cohort of 247 patients with epilepsy who had their GADA titers measured previously for their clinical significance in epilepsy. Based on GADA titers, patients were grouped as GADA negative (n = 238), GADA low positive (antibody titers &lt; 1,000 RU/mL, n = 5), and GADA high positive (antibody titers ≥ 1,000 RU/mL, n = 4).ResultsMedian IL-6 concentrations were significantly higher in patients with high GADA positivity [2.86 pg/mL, interquartile range (IQR) = 1.90–5.34 pg/mL] than in GADA-negative patients [1.18 pg/mL, interquartile range (IQR) = 0.54–2.32 pg/mL; p = 0.039]. Similarly, IL-10 concentrations were also higher in GADA high-positive patients [1.45 pg/mL, interquartile range (IQR) = 0.53–14.32 pg/mL] than in GADA-negative patients [0.50 pg/mL, interquartile range (IQR) = 0.24–1.00 pg/mL], however, the difference was not statistically significant (p = 0.110). Neither IL-6 nor IL-10 concentrations were different between GADA-negative and GADA low-positive patients (p &gt; 0.05) or between GADA low-positive or GADA high-positive patients (p &gt; 0.05). The IL-6/IL-10 ratio was also similar among all the study groups.ConclusionIncreased circulatory concentrations of IL-6 are associated with high GADA titers in patients with epilepsy. These data provide additional pathophysiological significance of IL-6 and help to further describe the immune mechanisms involved in the pathogenesis of GADA-associated autoimmune epilepsy.
Single and repeated high-level blast, low-level blast, and new-onset self-reported health conditions in the U.S. Millennium Cohort Study: An exploratory investigation
Authors: Belding Jennifer N. , Kolaja Claire A. , Rull Rudolph P. , Trone Daniel W. 
Published: March 2023

IntroductionAlthough previous research suggests that overpressure exposure from either high-level blast (HLB) or low-level blast (LLB) are harmful to health, to date no large-scale studies with representative samples of military personnel have utilized prospective designs and self-reported measures to examine the relationships between blast exposure and health conditions. To address these limitations, this analysis of data from the Millennium Cohort Study (MCS), the largest and longest running study of U.S. service members and veterans, examined (1) whether single or repeated HLB exposure is associated with self-reported diagnoses of illness and injury, (2) whether repeated HLB is associated with greater risk than single HLB, (3) potential adverse consequences of LLB exposure using military occupation as a proxy, and (4) the combined effects of single or repeated HLB and LLB exposure.MethodMCS participants who completed the 2011–2013 survey (N = 138,949) were classified as having been exposed to “no,” “single,” or “repeated” HLB exposure, and into low or high risk of exposure to LLB based on occupation. Participants self-reported diagnosis of 45 medical conditions; newly reported diagnoses were regressed on single and repeated (vs. no) HLB, occupational risk of LLB, and relevant interactions using logistic regression.ResultsSingle and repeated HLB were associated with new onset of 25 and 29 diagnoses, respectively; repeated HLB exposure was associated with greater risk than single HLB exposure for five diagnoses (e.g., PTSD, depression). Occupational risk of LLB was associated with 11 diagnoses (e.g., PTSD, significant hearing loss). Additionally, 14 significant interactions were detected across 11 diagnoses.DiscussionFindings suggest that overpressure exposure (including single HLB, repeated HLB, and occupational risk of LLB) may increase the risks of self-reporting clinical diagnoses of PTSD, hearing loss, chronic fatigue syndrome, neuropathy-caused reduced sensation in the hands and feet, depression, vision loss, sinusitis, reflux, and anemia. Furthermore, the combination of HLB and LLB exposure may be associated with greater risk of migraines, PTSD, and impaired fecundity. These findings provide further evidence of the potential adverse consequences associated with overpressure exposure and underscore the necessity of public health surveillance initiatives for blast exposure and/or safety recommendations for training and operational environments.
Physiological concentration of protocatechuic acid directly protects vascular endothelial function against inflammation in diabetes through Akt/eNOS pathway
Authors: Chook Chui Yiu Bamboo , Cheung Yiu Ming , Ma Ka Ying , Leung Fung Ping , Zhu Hanyue , Niu Qingshan Jason , Wong Wing Tak , Chen Zhen-Yu 
Published: March 2023

BackgroundCardiovascular diseases (CVDs) have been the major cause of mortality in type 2 diabetes. However, new approaches are still warranted since current diabetic medications, which focus mainly on glycemic control, do not effectively lower cardiovascular mortality rate in diabetic patients. Protocatechuic acid (PCA) is a phenolic acid widely distributed in garlic, onion, cauliflower and other plant-based foods. Given the anti-oxidative effects of PCA in vitro, we hypothesized that PCA would also have direct beneficial effects on endothelial function in addition to the systemic effects on vascular health demonstrated by previous studies.Methods and resultsSince IL-1β is the major pathological contributor to endothelial dysfunction in diabetes, the anti-inflammatory effects of PCA specific on endothelial cells were further verified by the use of IL-1β-induced inflammation model. Direct incubation of db/db mouse aortas with physiological concentration of PCA significantly ameliorated endothelium-dependent relaxation impairment, as well as reactive oxygen species overproduction mediated by diabetes. In addition to the well-studied anti-oxidative activity, PCA demonstrated strong anti-inflammatory effects by suppressing the pro-inflammatory cytokines MCP1, VCAM1 and ICAM1, as well as increasing the phosphorylation of eNOS and Akt in the inflammatory endothelial cell model induced by the key player in diabetic endothelial dysfunction IL-1β. Upon blocking of Akt phosphorylation, p-eNOS/eNOS remained low and the inhibition of pro-inflammatory cytokines by PCA ceased.ConclusionPCA exerts protection on vascular endothelial function against inflammation through Akt/eNOS pathway, suggesting daily acquisition of PCA may be encouraged for diabetic patients.
Lung aeration reduces blood pressure surges caused by umbilical cord milking in preterm lambs
Authors: Blank Douglas A. , Crossley Kelly J. , Thiel Alison , Rodgers Karyn A. , Zahra Valerie , Kluckow Martin , Gill Andrew W. , Polglase Graeme R. , Hooper Stuart B. 
Published: March 2023

BackgroundUmbilical cord milking (UCM) at birth causes surges in arterial blood pressure and blood flow to the brain, which may explain the high risk of intraventricular haemorrhage (IVH) in extremely preterm infants receiving UCM. This high risk of IVH has not been reported in older infants.ObjectiveWe hypothesized that lung aeration before UCM, reduces the surge in blood pressure and blood flow induced by UCM.MethodsAt 126 days' gestation, fetal lambs (N = 8) were exteriorised, intubated and instrumented to measure umbilical, pulmonary, cerebral blood flows, and arterial pressures. Prior to ventilation onset, the umbilical cord was briefly (2–3 s) occluded (8 times), which was followed by 8 consecutive UCMs when all physiological parameters had returned to baseline. Lambs were then ventilated. After diastolic pulmonary blood flow markedly increased in response to ventilation, the lambs received a further 8 consecutive UCMs. Ovine umbilical cord is shorter than the human umbilical cord, with ∼10 cm available for UCMs. Therefore, 8 UCMs/occlusions were done to match the volume reported in the human studies. Umbilical cord clamping occurred after the final milk.ResultsBoth umbilical cord occlusions and UCM caused significant increases in carotid arterial blood flow and pressure. However, the increases in systolic and mean arterial blood pressure (10 ± 3 mmHg vs. 3 ± 2 mmHg, p = 0.01 and 10 ± 4 mmHg vs. 6 ± 2 mmHg, p = 0.048, respectively) and carotid artery blood flow (17 ± 6 ml/min vs. 10 ± 6 ml/min, p = 0.02) were significantly greater when UCM occurred before ventilation onset compared with UCM after ventilation.ConclusionsUCM after ventilation onset significantly reduces the increases in carotid blood flow and blood pressure caused by UCM.
Multimodal imaging of congenital pyriform fossa fistula in children
Authors: Zhai Aiguo , Peng Xuehua , Guo Yu , Li Jian , Shao Jianbo 
Published: March 2023

ObjectiveOur aim was to explore the clinical value of multimodal imaging examinations in the diagnosis of congenital pyriform fossa fistula in children, so as to provide clues for the early diagnosis and treatment of congenital pyriform fossa fistula.MethodsThe clinical and imaging data of 55 children with pyriform fossa fistula diagnosed surgically in our hospital from 2015 to 2018 were analyzed retrospectively. All 55 patients underwent a CT scan. Of those patients, contrast enhancement CT was performed in 47 cases, MRI was performed in 2 cases, and barium esophagography was performed in 41 cases.ResultsAmong the 55 cases, there were 24 male patients and 31 female patients. The age ranged from 11 months to 13 years old, and the median age was 3.8 years old. The lesions of 49 cases (89.1%) were located on the left side, and the imaging of CT showed soft tissue mass in the anterior cervical region blurred boundary. There was ipsilateral thyroid involvement in 50 cases (90.9%), trachea and/or carotid sheath extension in 43 cases (78.2%), abscess formation in 39 cases (70.9%), and pneumatosis in 25 cases (45.5%). The CT examination of 22 children after treatment showed a linear or tubular low-density shadow in the thyroid gland, gas accumulation in the anterior cervical region or thyroid, and residual contrast medium, partly. A total of 24 cases underwent barium esophagography during the acute phase, and 15 cases (62.5%) showed sinus formation from the pyriform fossa downward or punctate high-density shadow in the anterior cervical region. The 2 cases where MRI was performed showed abscess formation in one side of the neck and thyroid involvement.ConclusionPyriform fossa fistula is most common in the left anterior cervical region, and it is closely related to the thyroid gland. The plain and enhanced-contrast CT scan can be used as the first choice during the infection stage. It helps to understand the location, extent, and structure of the surrounding tissue. The preliminary diagnosis of pyriform sinus fistula was according to the imaging features. It provided an important basis for clinical diagnosis and reduced the pain caused by repeated infection or surgical incision and drainage.
Glomerular capillary C3 deposition as a risk factor for unfavorable renal outcome in pediatric primary focal segmental glomerular sclerosis
Authors: Peng Yingchao , Li Banghai , Li Xiaojie , Ju Tao , Zhang Zhiqiang , Wang Peipei , Sun Tao , Shu Jiaping , Wang Meiqiu , Sun Xiaoyi , Chen Huangyu , Gao Chunlin , Xia Zhengkun 
Published: March 2023

IntroductionSome patients with primary focal segmental sclerosis (FSGS) demonstrate complement 3 (C3) deposition in glomerular capillary loops (Cap-C3) and/or mesangial area (Mes-C3). The clinicopathological and prognostic significance of C3 deposition remains incompletely investigated, especially in the pediatric cohort.MethodsWe retrospectively analyzed 264 children of biopsy-proven primary FSGS between January 2003 and December 2020. The correlation between Cap-C3 and renal outcome was evaluated by the Kaplan-Meier method and Cox multivariate regression analysis. Renal end-point event was defined as the development of end-stage renal disease, death for renal disease, or an estimated glomerular filtration rate reduction by at least 50% from baseline.ResultsAmong the 264 patients, 30 (11.4%) had Cap-C3. Kaplan-Meier analysis showed that patients with Cap-C3 had significantly lower renal survival rates than patients without Cap-C3 (60.17% vs. 84.71% at 5 years, 39.49% vs. 65.55% at 10 years, P &lt; 0.01). Cox multivariate regression analysis showed that Cap-C3 was an independent risk factor for poor renal outcome (HR 3.53, 95% CI 1.22–10.19, P = 0.02).ConclusionGlomerular capillary C3 deposition was an independent risk factor for unfavorable renal outcome in children with primary FSGS.
The early life course-related traits with three psychiatric disorders: A two-sample Mendelian randomization study
Authors: He Renke , Mo Jiaying , Zhu Kejing , Luo Qinyu , Liu Xueying , Huang Hefeng , Sheng Jianzhong 
Published: March 2023

Objectives:Several studies have indicated a potential association between early life course-related traits and neurological and psychiatric disorders in adulthood, but the causal link remains unclear.Methods:Instrumental variables (IVs) that have been shown to be strongly associated with exposure were obtained from summary data of genome-wide association studies (GWASs). Four early life course-related traits [i.e., birthweight (BW), childhood body mass index (BMI), early body size, and age at first birth (AFB)] were used as exposure IVs to estimate their causal associations with three neurological and psychiatric diseases [i.e., Alzheimer’s disease (AD), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD)]. Four different statistical methods, i.e., inverse-variance weighting (IVW), MR–Egger (MRE), weighted median (WM), and weighted mode (Wm), were performed in our MR analysis. Sensitivity analysis was performed by using the leave-one-out method, and horizontal pleiotropy was assessed using the MR-PRESSO package.Results:There was evidence suggesting that BW has a causal effect on AD (ORMR-PRESSO = 1.05, p = 1.14E-03), but this association was not confirmed via multivariable Mendelian randomization (MVMR) (ORMVMR = 0.97, 95% CI 0.92–1.02, p = 3.00E-01). A strong relationship was observed between childhood BMI and ADHD among both sexes; a 1-SD increase in BMI significantly predicted a 1.46-fold increase in the OR for ADHD (p = 9.13E-06). In addition, a similar relationship was found between early life body size and ADHD (ORMR-PRESSO = 1.47, p = 9.62E-05), and this effect was mainly driven by male participants (ORMR-PRESSO = 1.50, p = 1.28E-3). Earlier AFB could significantly predict a higher risk of MDD (ORMR-PRESSO = 1.19, p = 1.96E-10) and ADHD (ORMR-PRESSO = 1.45, p = 1.47E-15). No significant causal associations were observed between the remaining exposures and outcomes.Conclusion:Our results reveal the adverse effects of childhood obesity and preterm birth on the risk of ADHD later in life. The results of MVMR also show that lower BW may have no direct relationship with AD after adjusting for BMI. Furthermore, AFB may predict a higher risk of MDD.