bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-acute phase Rac1/Pak1/p38/β-catenin signalling activation promotes ischemic recovery and facilitates migration of neural stem cells
Authors: Wu Fan , Xu Zihan , Zhang Luyuan , Li Ganglei , Lin Hongwei , Shen Jie , Zhou Lihui , Liu Zongchi , Shen Jian , Zhan Renya , Gong Jiangbiao , Zhu Yu
Published: January 2023

Ischemic stroke is one of the world's leading causes of death and disability. During ischemic stroke, neuronal death is caused by inflammation, oxidative stress, apoptosis, and excitatory toxicity. For a long time, there has been a lot of interest in various studies to promote the repair of nerve damage after stroke. However, the mechanisms underlying the complex pathophysiological processes remain to be fully elucidated. Cerebral Ras-related C3 botulinum toxin substrate (Rac) 1 was initially associated with poor prognosis after stroke. However, some recent studies suggest that Rac1 may contribute to the repair process of nerve injury after stroke and promote the recovery of nerve function. However, the current conflicting findings may be related to the timing of Rac1 interventions. Our study found that post-acute Rac1 activation contributes to ischemic recovery. Here, we first investigated the specific role of neuron Rac1 in neuroprotection and recovery of neurological function in the post-acute phase of stroke. We found that intraventricular injection of Rac1 activator beginning one week after MACO significantly improved brain atrophy and neurological function after MACO. Considering the important role of Rac1 in cell migration. In vitro experiments, we found that Rac1 induced NSCs migration after exogenous and endogenous activator stimulation. In vivo, the addition of Rac1 activator in the post-acute phase helped promote the migration of NSCs in SVC to the lesion area and differentiation into mature nerve cells. It is worth noting that Pak1 is an essential downstream protein of Rac1. Our results suggest that while Rac1 activates Pak1, Pak1 can promote the migration and differentiation of neural stem cells through the downstream p38/β-catenin signalling pathway. While promoting neurogenesis, we found that Rac1 promoted angiogenesis and axon remodelling, and enhanced the synaptic plasticity to support the process of nerve repair during the post-acute phase via downstream Pak1/p38/β-catenin signalling. It suggests that Rac1/Pak1/p38/β-catenin signalling may be a potential therapeutic target in the recovery stage of ischemic stroke.
Unusual magnetotransport and surface Dirac-cone state in single-crystalline Pt 3 Te 4 : a new candidate of Dirac semimetal
Authors: Hsu Kuan , Chen I Nan , Kuo Chia Nung , Lei Zhujialei , Lue Chin Shan , Wang Li-Min
Published: January 2023

Exotic magnetotransport and magnetization properties of Pt3Te4 single crystals were investigated to probe the topological properties of the Pt3Te4 semimetal. Pt3Te4 reveals a strongly correlated electronic feature as well as a non-trivial magnetoresistance (MR) characteristic. The signature of helical spin texture from the topological surface state and the chiral anomaly associated with a linear-like energy dispersion of electronic states were detected. At low temperatures, the negative longitudinal magnetoresistance in the low-field region could be explained with the transport formula containing the chiral-anomaly effect as well as the weak antilocalization transport. Moreover, the high-field transverse magnetoresistance at temperatures below 60 K showed a non-saturating linear-like behavior, which was examined with the theory of Abrikosov’s quantum MR, indicating a Dirac-cone-like dispersion in Pt3Te4 at low temperatures. This work reveals the drastic impact of the concept that the magnetotransport in Pt3Te4 can be dominated by the surface electrons in a Dirac fermion state, thus inferring that Pt3Te4 is a new candidate of Dirac semimetal.
Comparison of two high dose rate Intracavitary brachytherapy regimens in treatment of cervical cancer
Authors: Krishna Abhishek , AG Hasib , Fernandes Donald , MS Athiyamaan , Rao Sandesh , Shankar Sharaschandra , Ali Mohsina , Priyadarshini Hepsiba , Sophia Maria , CH Shridhar , George Seby , Babu Amrutha , Banerjee Sourjya , Sunny Johan , Srini Challapalli , Lobo Dilson
Published: January 2023

Background: To assess and compare the local control and toxicities between HDR Intracavitary Brachytherapy with 7.5 Gy and 9 Gy per fraction after EBRT in treatment of carcinoma cervix.
Methodology: A total of 180 patients were randomly assigned to 2 arms. Arm A received HDR intracavitary brachytherapy with a dose of 7.5 Gy per fraction, 1 fraction per week for 3 fractions and Arm B received 9 Gy per fraction, 1 fraction per week for 2 fractions. Patients were evaluated on follow up for assessment of local control and toxicities.
Results: The median follow up was 12 months (6-18 months). In arm A 89% of the patient had complete response and 11 % had recurrence or metastasis. In arm B 93% of the patient had complete response and 7 % had recurrence or metastasis. Grade 2/3 diarrhoea was seen in 4.4% of patients in Arm A and in 7.7% in Arm B. Grade 2/3 proctitis was seen in 3.3 % of patients in 7.5 Gy arm and in 6.6 % in 9 Gy arm. One patient in each arm had grade 1 haematuria. The overall duration of treatment was significant lower in Arm B compared to Arm A (59 days vs 68 days, p=0.01)
Conclusion: The result of this clinical study shows that Intracavitary brachytherapy with a dose of 9 Gy per fraction is non inferior to other schedules in term of local control and does not result in increased toxicity
Diaries as technologies for sense-making and self-transformation in times of vulnerability.
Authors: Marcos Marcos José Bernal , Zittoun Tania , Gillespie Alex
Published: January 2023

Diaries have been generally understood as “windows” on sense-making processes when studying life ruptures. In this article, we draw on Michel Foucault’s conceptualization of self-writing as a “technology of the self” and on sociocultural psychology to propose that diaries are not “windows,” but technologies that aid in the sense-making. Concretely, we analyzed three non-exhaustive and non-exclusive uses of diary writing in times of vulnerability: 1) imagination of the future and preparation to encounter difficulties; 2) distancing from one's own experience; and 3) creating personal commitments. Our longitudinal data comprised three public online diaries written over more than twenty years, belonging to three anonymous individuals selected from a database of more than 400 diaries. We analyzed these three diaries by iterating between qualitative and quantitative analysis. We conclude that: 1) beyond their expressive dimension, diaries are technologies that support the sense-making process, but not without difficulties; 2) diaries form a self-generated space for dialogue with oneself in which the diarist also becomes aware of the social nature of her life story; 3) diaries are not only technologies for the Socratic “know thyself” but also technologies to work on oneself, especially in terms of the personal perspective on the past or the future; and 4) the practice of diary writing goes beyond sense-making towards personal development and the desire to transform one's life trajectory.
VE-822 upregulates the deubiquitinase OTUD1 to stabilize FHL1 to inhibit the progression of lung adenocarcinoma
Authors: Zhang Qi , Li Jinglei , Chen Zihan , Jiang Ke , Yang Kunyu , Huang Fang , Huang Ai , Zhang Xiaodong , Zhang Jinxiang , Wang Hui
Published: January 2023

Background
The deubiquitinase ovarian tumor domain-containing 1 (OTUD1) has been considered as a tumor suppressor in many tumors, but there is minimal research on the role of OTUD1 in lung adenocarcinoma (LUAD) pathogenesis.
Methods
Bioinformatics analyses and western blot were applied for investigating OTUD1 expression in lung cancer and the drug that upregulated OTUD1. Kaplan–Meier analysis with log-rank test was used for survival analyses. IP-MS and co-IP were performed for identifying potential protein interactions with OTUD1. In vitro and in vivo assays were used for exploring the function of OTUD1 during the progression of LUAD.
Results
OTUD1 was dramatically downregulated in tumors and cell lines of human lung cancer. OTUD1 inhibited proliferation and migration of lung cancer cells in vitro. Moreover, OTUD1 inhibited growth of xenografts in nude mice and formation of primary lung tumors in urethane-induced lung cancer model. Mechanistically, we showed that OTUD1 deubiquitinated and stabilized FHL1. Furthermore, we listed and identified VE-822 as a candidate agonist for OTUD1. VE-822 inhibited proliferation of lung adenocarcinoma both in vitro and in vivo.
Conclusions
These results indicated that the deubiquitinase OTUD1, which was upregulated by VE-822, inhibited the progression of LUAD in vitro and in vivo by deubiquitinating and stabilizing FHL1.
Research of histological characteristics and single nucleotide polymorphisms in hereditary genes among Pakistani breast cancer patients
Authors: Nawaz Yasir , Khan Ali Zaib , Tanvir Fouzia , Ambreen Sadaf , Zafar Javaria , Umar Asma , Majeeed Imran , Iqbal Alia , Ayoub Ambar
Published: January 2023

Cancer is a type which involves irregular progression of cells with the capacity to enter and move to other portions of body. Breast cancer starts from breast tissues, mostly from inner coating of milk ducts. It is categorized into various methods by, grade, stage and receptors status. It is very common in females worldwide. Whole-exome sequencing (WES) was done in DNA removed from tumors of six breast cancer patients from Jinnah hospital Lahore, Pakistan. There were 19 patients from age 27 to 73 from which tissue sample were collected from 6 patients. The age distribution shows non-significant differences. The ER/PR status shows non-significant differences and odds ratio equals to 1. Somatic mutations were detected in three targeted genes ATM, TP53 and CDH (CDH5, CDH8, CDH10, CDH12, CDH16, CDH20, CDH23 and CDH24) in sample 1. Two genes with exonic variants were found in sample 2 containing TP53 and CDH (CDH5, CDH16, CDH19, and CDH23). Amino acid change and deletions were observed in different exonic sites of these genes. To conclude, more number of patients was observed having invasive ductal breast carcinoma. A number of novel somatic mutations for breast cancer were recognized. More studies are needed to define the functions of these mutated genes in breast cancer. Whole exome sequencing shows different type of mutations in different exonic regions of genes including TP53, ATM and CDH.
Self-pacing and multiple-attempt assessment to address student anxiety in pharmacy calculations
Authors: Bell Edward C.
Published: January 2023

Objective.

Pharmacy calculations is a course that can be challenging and is often associated with student anxiety about assessments and grades. This study was conducted to determine if student anxiety would be reduced in pharmacy calculations using self-paced, multiple-attempt assessments.

Materials and Methods.

Self-paced, multiple-attempt assessments were presented to students as graded practice modules and as examinations. Pre-post surveys were used to measure student anxiety in pharmacy calculations. Module performance indices and exam performance indices were correlated with course grade outcomes.

Results.

Fifty-four students participated in pre-surveys and forty-eight students participated in post-surveys. Westside Test Anxiety Scale survey results indicated use of self-paced, multiple-attempt assessments reduced students’ perceived anxiety about pharmacy calculations. Student comments about assessment methods were predominately positive. Course grades strongly correlated with module mean scores and high scores, and strongly correlated with mean exam scores. A negative correlation between course grades and belated module attempts alluded to harmful association between student procrastination and course performance in weaker students.

Conclusions.

Self-paced, multiple-attempt assessment was associated with improved perception of student test anxiety about pharmacy calculations. With care taken to limit student procrastination, use of these types of assessment could be an effective means of improving student comfort while promoting mastery of the subject.
Mechanistic insights into the anti-depressant effect of curcumin based on network pharmacology and experimental validation
Authors: Guo Jing , Fang Meng , Xiong Zhe , Zhou Ke , Zeng Peng
Published: January 2023

Growing evidence supports the involvement of neuroinflammation in the pathophysiology of depression. Administrating curcumin could revert the depressive-like symptoms and weakened microglial activation and increased the level of pro-inflammatory cytokine. This study aimed to identify potential anti-depression targets and mechanisms of curcumin (CUR) by an approach of network pharmacology. GSEA and KEGG pathways showed the most significantly enriched pathway of CUR against depression was the PI3K-Akt pathway. Moreover, 52 targets were significantly correlated with PI3K-Akt signaling pathway and CUR-related targets. In addition, among these top 50 targets which were ranked by degree in the PPI network, there were 23 targets involved in the 52 intersection targets. Thus, our findings suggest that CUR exerts its anti-depression effects through PI3K-Akt signaling pathway. Furthermore, we investigated the anti-depression effects of CUR using a mouse model of depression induced by lipopolysaccharide (LPS). Administration of LPS alone (2 mg/kg/day, i.p.) extended the immobility time in the open filed test (OFT) and tail suspension test (TST), decreased sucrose consumption in the sucrose preference test (SPT). Pretreatment with CUR (50 mg/kg/day, i.p.) for 7 consecutive days relieved LPS-induced changes in the behavior tests, the activity of PI3K-Akt signaling pathway, neuronal damage in the PFC and inflammatory response. Moreover, inhibition of the PI3K-Akt signaling pathway by LY294002 (7.5 mg/kg/day, i.p.) blocks the therapeutic effects of CUR. In conclusion, our study indicate that CUR may be an effective antidepressant agent for LPS-induced mouse model, in part because of its anti-inflammatory actin through PI3K-Akt signaling pathway.
Assessing and comparing crop evapotranspiration in different climatic regions of China using reanalysis products
Authors: Yu Xingjiao , Qian Long , Wang Wen’e , Hu Xiaotao , Huo Xuefei , Wang Yafei
Published: January 2023

This study aims to assess the accuracy of the crop reference evapotranspiration (ET0 CLDAS, ET0 ERA5) estimated by CLDAS, ERA5 reanalysis products, as well as the quality of reanalysis weather variables required to calculate PM-ET0, and to achieve the application of these reanalysis products to locations where weather data quality are low or (and) weather variables are missing. For this purpose, the applicability of surface meteorological elements such as daily maximum and minimum air temperatures, relative air humidity, 2m wind speed, and shortwave radiation from the ERA5 reanalysis datasets provided by the European Centre for Medium-Range Weather Forecasts (ECMWF), and the second-generation China Meteorological Administration Land Data Assimilation System (CLDASV2.0) datasets are evaluated in China by comparison with local observations from 689 stations reported by the Chinese Meteorological Administration (CMA). Statistical statistics including percent bias (PBias), coefficient of determination (R2), root mean square error (RMSE) and mean absolute error (MAE) are used to check the accuracy. The results show the highest correlation between reanalysis temperature and station observations, with a mean R2 of 0.96,0.90 for CLDAS reanalysis maximum and minimum air temperatures and 0.87,0.84 for ERA5. For the reanalysis of estimated solar radiation and relative humidity, an overestimation trend is shown for Rs, but to a lesser degree, an underestimation trend is shown for RH. Unlike the previous reanalysis variables, the reanalysis wind speed shows a lower accuracy, and average R2 = 0.25 (R2 = 0.18) for CLDAS reanalysis (ERA5 reanalysis) and site observations. In addition, the accuracy of ET0 estimated by the two reanalysis products is acceptable in China, but the spatial and temporal consistency between CLDAS estimates and site observations is higher, with mean RMSE, R2 of 0.91,0.82 for ET0 CLDAS and 1.42, 0.70 for ET0 ERA5, respectively, and the performance of describing the boundary details of the study area is better since CLDAS reanalysis products integrate terrain adjustment, the elevation of target location, wind speed, and other factors are taken into account.
Increased serum soluble interleukin-2 receptor levels in dermatomyositis are associated with Th17/Treg immune imbalance
Authors: Xie Yuhuan , Zhang Tingting , Su Rui , Liu Lu , Jiang Lei , Xue Hongwei , Gao Chong , Li Xiaofeng , Wang Caihong
Published: January 2023

Objective: In patients with dermatomyositis/polymyositis (DM/PM), especially DM patients with positive antibodies against melanoma differentiation-associated protein 5 (MDA5), the prognosis is very poor, acute progressive pulmonary interstitial disease is likely to occur, and the mortality rate is very high, while serum soluble interleukin-2 receptor (sIL-2R) is often used as a marker to assess T cell activation, it is still poorly understood. The aim of this study was to investigate the relationship between sIL-2R levels and disease activity, absolute number of peripheral blood lymphocyte subsets and related cytokines in DM patients.
Method: Sixty patients with DM (32 patients with inactive DM and 28 patients with active DM) were enrolled in this study and divided into inactive and active groups according to the Myositis Disease Activity Visual Analogue Scale (MYOACT), and the absolute numbers of peripheral lymphocyte subsets and CD4 + T cell subsets were measured by flow cytometry in each group, and serum cytokine levels were measured by flow cytometry bead array.
Results: Serum sIL-2R levels were positively correlated with independent visual analogue scale (VAS) in DM patients (p < 0.001), and the ratio of Th17/Treg cells was significantly higher in DM patients compared with the healthy group (P < 0.01), and there was a correlation between serum sIL-2 levels and Th17/Treg ratio. Multivariate logistic regression revealed that serum sIL-2R levels were an independent factor affecting disease activity. Serum IL-6 and IFN-γ levels were also increased in the active group compared with the inactive group (p = 0.011 and p = 0.034, respectively). In addition, receiver operating characteristic (ROC) curves showed that serum sIL-2R levels contributed to the discrimination of disease activity in DM patients, with an area under the ROC curve (AUC) of 0.757 (95% CI 0.630 – 0.884, P = 0.001).
Conclusion：In DM patients, serum sIL-2R levels are not only closely related to disease activity, but also involved in their Th17/Treg immune imbalance, which is an effective indicator for evaluating DM disease activity.
Neurobehavioral deficits, histoarchitectural alterations, parvalbumin neuronal damage and glial activation in the brain of male Wistar rat exposed Landfill leachate
Authors: Levi Usende Ifukibot , Bintu Mofio M. , Daniella Osinachi Chinonyerem , Oyenike Oyelowo-Abdulraheem Fatima , Agbonu Adikpe Oluwa , Adedamola Azeez Mariam , Ndidi Enefe , Mbagwu Smart , Edem Edem Ekpenyong , Olukayode Olopade James , James Connor , Sanni Fatimah Saka
Published: January 2023

Concerns about inappropriate disposal of waste into unsanitary municipal solid waste landfills around the world has been on the increase; and this pose a public health challenge due to leachate production. The neurotoxic effect of Gwagwalada landfill leachate (GLL) was investigated in male adult Wistar rats. Rats were exposed to 10% concentration of GLL for 21days. Control group received tap water for same period of experiment. Our results showed that neurobehavior, absolute body and brain weights and brain histomorphology as well as parvalbumin interneurons were severely altered, with consequent astrogliosis and microgliosis after 21 days of administrating GLL. Specifically, there was severe loss and shrinkage of purkinje cells, with their nucleus, and severe diffused vacuolations of the white matter tract of GLL exposed rat brains. There was severe cell loss in the granular layer of the cerebellum resulting to reduced thickness of the layer. Also. there was severe loss of dendritic arborization of the purkinje cells in GLL exposed rat brains, and damage as well of reduced populations of parvalbumin-containing fast-spiking GABAminergic interneurons in various regions of the brain. In conclusion, data from the present study demonstrated the detrimental effects of Gwagwalada landfill leachate on the brain which may be implicated in neuropsychological conditions.
Identifying the diagnostic value of inflammatory genes in intracranial aneurysms based on machine learning
Authors: Zhou Min , Fu Ya , Liang RiChu , Duan YongHong , Liu XiaoFei , Luo Jie , Jiang YuanDing , Liao Quan
Published: January 2023

Background Intracranial aneurysm (IA) is a cerebrovascular disease that can be caused by a variety of factors. Clinical trials have indicated that inflammation and inflammatory cells play critical roles in the pathophysiology of IA. Nonetheless, the roles of inflammation-related genes (IRGs) in IA remain unclear. Methods The GSE75436 and GSE54083 datasets were acquired from the Gene Expression Omnibus (GEO) database, and the IRGs were extracted from the MSigDB database. First, the two GEO datasets were combined, and the batch effects were removed. The differentially expressed inflammation-related genes (DEIRGs) were identified by overlapping the IRGs with the set of differentially expressed genes (DEGs) between IA and control samples. The functions of the DEIRGs were evaluated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Then, ROC curve analysis was used to verify the diagnostic ability of the DEIRGs, and diagnostic models were constructed with 7 machine learning methods. Furthermore, gene set enrichment analysis (GSEA) was performed to explore the potential biological functions of the biomarkers. Immune cell relevance was assessed by single-sample gene set enrichment analysis (ssGSEA). In addition, a TF–mRNA‒miRNA network was established, and potential biomarkers were predicted. Ultimately, the mRNA expression levels of the biomarkers were validated by quantitative real-time PCR (qRT‒PCR). Results In total, 35 DEIRGs were retrieved by overlapping the 964 DEGs and 200 IRGs. Functional enrichment analysis revealed that the DEIRGs were significantly enriched in the regulation of the inflammatory response, immune receptor activity, and lipid and atherosclerosis pathways. Moreover, 13 genes with an AUC greater than 0.85 were selected for diagnostic model construction by the RF algorithm, and 7 biomarkers were obtained in the final model. GSEA indicated that these 7 biomarkers were mainly associated with inflammation. The significantly differentially abundant immune cells exhibited positive correlations with the biomarkers. Subsequently, we proposed that SERPINE might be modulated by TBX3, MLX, and NR1I3 and that SLC11A2 might be modulated by hsa-miR-6838-5p, hsa-miR-4784, and hsa-miR-3663-5p. In addition, 22 drugs were predicted to interact with the biomarkers, including fluoxetine, aleplasinin, and orlistat. Finally, qRT‒PCR results showed that the expression levels of the 7 biomarkers were significantly higher in IA tissue than in superficial temporal artery tissue. Conclusion This research provides a new perspective for understanding the molecular mechanism of IA pathogenesis and valuable evidence for the pathological diagnosis of IRGs.
Fixation of Femoral Neck Fracture with Femoral Neck System : A retrospective cohort study of 43 patients
Authors: Yoon Jae Youn , Byun Seong-Eun , Cho Young-Ho
Published: January 2023

Introduction
This study aimed to analyze the clinical outcomes of femoral neck fractures (FNF) in patients treated with a femoral neck system (FNS, DePuy Synthes), which is a recently introduced device.
Methods
This study included 43 patients who underwent osteosynthesis using FNS for with a minimum follow-up of 6 months. The researchers examined the patients’ demographic factors and radiologically evaluated the fracture type and fixation status, bone union, and postoperative complications.
Results
Radiological bone union was confirmed in 39 patients (90.7%), and the mean time to union was 3.6 months. Two cases of nonunion, one case of lag screw cut-out, and one case of osteonecrosis were confirmed; all four cases later underwent arthroplasty. The mean time to reoperation was 4.5 months. Meanwhile, five patients underwent implant removal after the bone union, and distal locking screw stripping was noted in three patients. All three patients required metal plate cutting to remove the implants.
Conclusion
Osteosynthesis of FNF using the newly introduced FNS showed satisfactory outcomes and excellent mechanical stability without any postoperative complications. However, distal locking screw failure during implant removal should also be considered.
Long-term treatment with gadopentetic acid or gadodiamide increases TRPC5 expression and decreases adriamycin nuclear accumulation in breast cancer cells
Authors: Zhang Weiheng , Wang Mengyuan , Lv Weizhen , White Fletcher , Chen Xingjuan , Obukhov Alexander
Published: January 2023

Gadopentetic acid and gadodiamide are paramagnetic gadolinium-based contrast agents (GBCAs) that are routinely used for dynamic contrast-enhanced magnetic resonance imaging (MRI) to monitor disease progression in cancer patients. However, growing evidence indicates that repeated administration of GBCAs may lead to gadolinium (III) cation accumulation in the cortical bone tissue, skin, basal ganglia, and cerebellum, potentially leading to a subsequent slow long-term discharge of Gd3+. Gd3+ is a known activator of the TRPC5 channel which is implicated in breast cancer resistance to chemotherapy. Here we found that gadopentetic acid (Gd-DTPA, 1 mM) enhanced the inward and outward currents through TRPC5 exogenously expressed in HEK293 cells. Gd-DTPA (1 mM) also activated the Gd3+ sensitive R593A mutant of TRPC5, which exhibits a reduced sensitivity to GPCR-Gq/11-PLC dependent gating. Conversely, Gd-DTPA had no effect on TRPC5-E543Q, a Gd3+ insensitive TRPC5 mutant. Long-term treatment (28 days) of human breast cancer cells (MCF-7) and adriamycin-resistant MCF-7 cells (MCF-7/ADM) with Gd-DTPA (1 mM) or gadodiamide (GDD, 1 mM) did not affect cell survival in the presence of ADM. However, the treatment with Gd-DTPA or GDD significantly increased TRPC5 expression and decreased the accumulation of ADM in the nuclei of MCF-7 cells, increasing the risk of the breast cancer cell chemoresistance. The antagonist of TRPC5, AC1903 (1 µM), reversed the Gd-DTPA-treatment mediated changes in ADM nuclear accumulation. We propose that clinically, repeated administration of GBCAs should be minimized in breast cancer patients to reduce the risk of drug resistance.
Religion and Persecution
Authors: Khalil Umair , Panza Laura
Published: January 2023

This paper investigates the relationship between local religiosity and episodes of persecutions in Europe between 1100-1850. We introduce a novel proxy for measuring local religion: the cult of saints in early Western Christianity. Our findings show that cities with an established cult of a saint are associated with an 8 percentage points (pp) increase in the likelihood of Jewish persecutions and a 12 pp increased likelihood of witch trials. However, cities with more progressive gender norms, measured by the presence of a female saint cult, are less likely to persecute witches compared to male-only saint cities. Our baseline relationship persists after controlling for a range of city-level economic, geographic and institutional characteristics and after accounting for other major confounders. Suggestive evidence points towards two mechanisms behind the saints-persecution relationship: (i) changes in norms induced by longer exposure to Christianity; and (ii) proximity of religious groups due to congruence of religious festivities.
JEL Codes: D74; N33; N43; N93; Z12
Computational design of Checkpoint Kinase-1 (CHK-1) inhibitors for cancer therapy
Authors: Chandrasekaran Jaikanth , Kanekar Saptami , Dagamajalu Shobha , Modi Prashanth , Gopinathan Kirthika , Raju Rajesh , Prasad T. S. Keshav , Balaya Rex Devasahayam Arokia
Published: January 2023

CHK-1 kinase belongs to the serine/threonine family of kinases, which play a vital role in cell cycle arrest and proved to be a promising therapeutic target to control cancer development and progression. Many potent and selective CHK-1 inhibitors have been reported, but only a few are currently in clinical trial. In this era, drug re-profiling has proved to be a major step in drug discovery and development that is cost and time beneficial. In this study, we have incorporated a combined in silico computational approach to widen the chemical range of CHK-1 inhibitors from the existing FDA approved drugs. An e-pharmacophore model was created from 3D crystal coordinates of CHK-1 protein complex with the clinical trial inhibitor (CCT245737). The hypothesis with seven molecular features was screened with FDA drugs and the obtained drugs were subjected into Glide XP molecular docking. The top 10% scored ligands were visualized and Procaterol was best identified which showed similar interaction patterns with enzyme active sites as the clinical trial inhibitor. Furthermore, total binding free energy, pharmacokinetic properties and molecular dynamics were also evaluated. The results consolidated showed better binding affinity, acceptable kinetic profile and significant stability of Procaterol binding with CHK-1 kinase. In conclusion, we highlight that Procaterol is a re-provable potent CHK-1 inhibitor and appears as a new structural scaffold for further optimisation.
Scalp Acupuncture Alleviates Cerebral Ischemic Stroke-induced Motor Dysfunction in Rats via regulating Endoplasmic Reticulum Stress and ER-phagy
Authors: Zhang Yuxin , Lou Huijuan , Lu Jing , Tang Xiaolei , Pang Tingting , Lei Siyuan , Wang Yufeng , Sun Liwei
Published: January 2023

Cerebral ischemic stroke is a high-risk disease and imposes heavy burdens on patients in china. Acupuncture has been used for thousands of years to treat motor dysfunction, cognitive disorder and language barrier caused by cerebral ischemic stroke. Acupoint lines, vertex middle line and anterior oblique line of vertex temple, are always employed to treat cerebral ischemic stroke. However, the mechanism of the two acupoint lines in relieving cerebral ischemic stroke needs further exploration. In the present study, scalp acupuncture treatment alleviated the motor dysfunction, brain damage, and cell death induced by middle cerebral artery occlusion (MCAO) in rats. Proteomics analysis and ultrastructure observation indicated that endoplasmic reticulum and lysosomes might involve in the mechanism of the scalp acupuncture treatment in suppressing MCAO-triggered neural deficits. Effect of the scalp acupuncture treatment on ER stress was then investigated and found that the activation of ER stress mediators, including PERK, IRE1, and ATF6, was downregulated after the scalp acupuncture treatment. Co-localization analysis of KDEL and CD63 showed that the engulfment of ER fragments by lysosomes was accelerated by the scalp acupuncture treatment, indicating that the scalp acupuncture treatment alleviated ER stress via enhancing micro-ER-phagy. Moreover, expression of pro-apoptotic protein CHOP, phosphorylated-JNK, cleaved capases-3 and − 9 also decreased after the scalp acupuncture. In conclusion, the present study showed that scalp acupuncture of vertex middle line and anterior oblique line of vertex temple may alleviate cerebral ischemic stroke by inhibiting ER stress-accelerated apoptosis.
Menstrual characteristics and dysmenorrhea among Palestinian adolescent refugee camp dwellers in the West Bank and Jordan: a cross-sectional study
Authors: Ghandour Rula , Hammoudeh Weeam , Stigum Hein , Giacaman Rita , Fjeld Heidi , Holmboe-Ottesen Gerd
Published: January 2023

Background: Women and girls experience menstruation throughout their reproductive years. Normal adolescent menstrual cycles gauge current and future reproductive health. Dysmenorrhea (painful menstruation) is the most prevalent menstrual disturbance in adolescents that can be debilitating. This study examines the menstrual characteristics of adolescents living in Palestinian refugee camps in the West Bank of the Israeli-occupied Palestinian territory and Jordan, including estimates of dysmenorrhea levels and associated factors.Methods:We conducted a household survey of 15 to 18-year-old adolescents. Field workers collected data on menstrual characteristics, dysmenorrhea (using the WaLIDD scale), demographic, socio-economic, and health variables. A linear regression model was used to examine the link between dysmenorrhea and other participant characteristics.Results: 2737 girls participated in the study. Mean age was 16.8±1.1 years. Mean age-at-menarche was 13.1±1.2; mean bleeding duration was 5.3±1.5 days, and mean cycle length was 28.1±6.2 days. Around 6% of participating girls reported heavy menstrual bleeding. High dysmenorrhea levels were reported (96%), with 41% reporting severe symptoms. Higher dysmenorrhea levels were associated with older age, earlier age-at-menarche, longer bleeding durations, heavier menstrual flow, skipping breakfast regularly, and limited physical activity patterns. Eighty-nine percent used non-pharmacological approaches to ease menstrual pain, whereas 25% used medications.Conclusion:The study indicates regular menstrual patterns and a slightly higher age-at-menarche than the global average. However, an alarmingly high prevalence of dysmenorrhea among participants was found. This research emphasizes the need for integrated efforts to assist adolescents with menstrual challenges such as dysmenorrhea and irregular periods to achieve informed recommendations and effective actions.
Overvoltage Mitigation in LVDC Distribution System Caused by DC Circuit Breaker Connected with Constant Power Load
Authors: Hussain Adil , Javid Zahid , Mujeeb Asad , Hassan Rizwan UL , Ahmed Rizwan
Published: January 2023

The operation of a high-speed DC circuit breaker can cause overvoltage transients in the Low Voltage Direct Current (LVDC) distribution system especially when the load is driving constant power. If adequate damping is not provided, then the destabilizing effect of constant power load (CPL) can drive the system towards instability. This paper presents a new method to mitigate the over-voltage transients caused by the operation of a DC circuit breaker in an LVDC system. The proposed method is based on utilizing the existing Energy Storage System (ESS) in the DC grid to limit the switching over-voltage within the safe limits. In this study, supercapacitor sizing is performed, while considering the instability problems of the CPLs. First, an analytical expression is built to determine the required value of the supercapacitor, for a basic LVDC distribution system is first considered, state-space modeling methodology is then provided to extend the suggested method for a detailed LVDC distribution system. The Control System Toolbox of the MATLAB program is used for simulations. MATLAB/Simulink time-domain models are also developed to triangulate the theoretical findings. The effectiveness of the proposed model is validated by simulation results.
Analysis of trace elements (Zn and Cu) levels in COVID-19 patients with ICU and Non-ICU hospitalization
Authors: Ram Sant , Saini Neha , Saini Ram Krishan , Kaur Sandeep , Pathak Piyush , Jassal Ravjit , Chidananda Mohana Kumari , Zohmangaihi Deepy , Soni Shiv lal , Suri Vikas
Published: January 2023

Background: The persistence of the COVID-19 pandemic besides its current resurgence and continuously increasing fatalities indicates a vital need for severity assessment at its early stages. Recent studies have already ascribed mortality to chronic inflammation. But the part of trace elements, especially zinc and copper that have been known to possess antiviral roles for a long time is least studied in COVID-19.
Methods: The study comprised 122 COVID-19-positive participants admitted to the tertiary care hospital. Among them, eighty-one (~66%) were admitted to ICU under high severity. Levels of Zn and Cu along with CRP were analyzed and compared among ICU and non-ICU admitted patients. Using ROC analysis, the potential and precise levels for defining severity were determined.
Results: We found a significant reduction in Zn levels (p=0.001) in ICU-admitted patients compared to the non-ICU group which was more pronounced in females and patients aged above 50 years. Reduction in the levels of Zn is accompanied by elevated CRP levels (p<0.001) in ICU patients with no effect on Cu levels. Upon ROC analysis, Zn and CRP were found to have significant AUC (p<0.0001). Further, CRP to Zn ratio displayed improved AUC with 90% sensitivity indicating their applicability to predict ICU requirements.
Conclusions: The present study was primarily aimed to predict the status of zinc and copper in COVID-19 patients and their utility as a prognostic tool for deciding the severity. Our findings indicate that CRP to Zn ratio might feasibly be used to predict the progression of COVID-19 toward severity. Keywords: COVID-19, Severity, Zinc, Copper, CRP
Empirical Analysis of Public Revenue, Development Expenditure and Economic Growth in India Using Vector Autoregressive Model
Authors: Sumandeep Sumandeep , Ravi Ravi Kiran , Sharma Rakesh Kumar
Published: January 2023

The current research scrutinizes the empirical relationship among pubic revenue, govt. expenditures & economic growth in India. This research factually investigates India’s economic growth experience during the period 1990–2017. Multivariate vector auto-regression with focus on generalized Impulse Response Function has been applied for analyzing yearly data of public revenue, developmental expenditure & Gross Domestic Product from 1990–2017. The study used unrestricted VAR & Granger Causality using data from 1990–2017. The outcome of co-integration reflects that the development expenditure doesn’t show significant impact on GDP. The public revenue (PR) is found to be significant at lag time. GDP & development expenditure (DE) have a significant impact on public revenue. A positive association of tax revenue with GDP has been found. Similar association has also been found between tax revenues & development expenditure. The findings enrich the research literature and it can be inferred that to enhance GDP and growth, there is need to accelerate development expenditures on capital projects. Public revenue receipts emerge as a major route for financing public expenditure. This also supports a growth nexus.
A12, C23, I1, I2.
Self-supplying Cu2+ and oxidative stress synergistically enhanced disulfiram-mediated melanoma chemotherapy
Authors: Gao Yingqian , Cai Xiaojun , Zou Weijuan , Tang Xiuzhen , Jiang Lixian , Hao Junnian , Zheng Yuanyi , Ye Xinhua , Ying Tao , Li Ao
Published: January 2023

Background
Disulfiram (DSF) combined Cu2+ ions can target and kill cancer cells by disrupting cellular degradation of extruded proteins, and has therefore received particular attention for its tumor chemotherapeutic potential. However, the Cu2+/DSF ratio and oxidative environment can affect the efficacy of DSF-mediated chemotherapy. Herein, self-supplying Cu2+ and oxidative stress synergistically enhanced DSF-mediated chemotherapy is proposed for melanoma based on PVP-coated CuO2 nanodots (CPNDs).
Results
Once ingested, DSF is broken down to diethyldithiocarbamate (DTC), which is delivered into the tumor via circulation. Under the acidic tumor microenvironment, CPNDs produce sufficient Cu2+ and H2O2. DTC readily chelates Cu2+ ions to generate CuET, which shows antitumor efficacy. CuET-mediated chemotherapy can be enhanced by H2O2. Sufficient Cu2+ generation can guarantee maximum efficacy of DSF-mediated chemotherapy. Furthermore, Cu2+ can react with H2O2 to generate toxic hydroxyl radicals (•OH) via a Fenton-like reaction, promoting the efficacy of CuET. As a result, accompanied with oral uptaking of DSF and intratumoral injection of CPNDs strategy, the treatment achieves remarkable antitumor activity, which has been systematically verified both in vivo and in vitro assays.
Conclusion
This study hypothesizes that employing CPNDs instead of Cu2+ ions could generate H2O2 for Cu2+ and oxidative stress synergistically enhanced DSF-mediated melanoma chemotherapy, providing a simple but efficient strategy for achieving chemotherapeutic effeicacy.
Grow Newtonian rigid inertia into parameter repetitiveness memory equivalent bio-inertia by degenerating eigenstates on a surface tension region to define quantum growth gravity for turnover selection inheritance
Authors: Lai Yi Yu
Published: January 2023

Note: Please see pdf for full abstract with equations.
Inversion energy is parameter-against-gravity-internal-fluctuation, the non-simultaneousness in correlated internal fluctuations is quantizing time. Modified Newtonian Laws are, first: 𝑑/𝑑𝑥 cosx =−𝑠𝑖𝑛𝑥, 𝑑/𝑑𝑥 sinx = 𝑐𝑜𝑠𝑥; second: 𝐹⃗=𝑚∙𝑎⃗+|𝑚𝑔⃗∫𝑡𝑔𝜃⋅𝑑𝜃 ⟩↿⇂ third: Wavelength =2/𝑛 L, frequency = n𝑓0. Bio-systems are topological spaces that can process input objects into inversion energy for entropy-control by repetitiveness memory, the capability of equivalent procured inversion energy with memorized trigonometric repetitiveness by quantizing time is bio-inertia. Evolution grows the trigonometric condensate equivalent capacity of a topological space. Schrödinger equation has only quantized energy but hasn’t quantized time thus inducing quantum collapse, we then write down equation 𝑯̂𝜓=𝑬𝜓 + Σn|cos(1/𝑛 𝑥)⟩ to grow eigenstates on certain surface tension regions to define quantum growth gravity for lifespan. Originating from elastic quantum scale differences between Planck regions and surface tension regions, bio quantum duality grows in vivo cross folded-surface tension region flow. Life relies on trigonometric negentropy procured from elastic entropy generation ground condensates and physically inherit by bio quantum growth turnover selection.
Based on machine learning 316 stainless steel low-cycle fatigue life prediction method
Authors: Duan Hongyan , Cao Mengjie , Liu Lin , Yue Shunqiang , He Hong , Zhao Yingjian , Zhang Zengwang , liu Yang
Published: January 2023

The low cycle fatigue life of 316 stainless steel is a significant basis for safety assessment. Usually, many factors affect the low-cycle fatigue life of stainless steel, and the relationship between the influencing factors and fatigue life is complicated and nonlinear. Therefore, it is hard to predict fatigue life by the traditional empirical formula. Based on this, a machine learning algorithm is proposed. In this paper, based on the existing large amount of experimental data, machine learning methods are used to predict the low circumferential fatigue life of 316 stainless steel. The results show that the prediction accuracy of nu-SVR and ELM models is high and can meet engineering needs.
Sleep problems associated with exposure to or use of psychoactive substances among residents in a slum setting in Uganda
Authors: Wafula Solomon T. , Namakula Lydia N , Isunju John Bosco , Mugambe Richard K , Ssekamatte Tonny , Musoke David , Wanyenze Rhoda K.
Published: January 2023

BackgroundAdult substance use may be a significant predictor of sleeping problems, according to extant research. Children exposed to secondhand (SHS) also have a high likelihood of sleep problems. There is limited information on the relationships between exposure to psychoactive substances and subsequent sleep issues in adults and children, particularly in Uganda. We set out to assess the links between exposure to psychoactive substances and sleep problems in adults and children.Methods:This was a cross-sectional study among 284 adults in a slum setting in Kampala, Uganda. We assessed self-reported sleeping problems among adults (sleep duration, insomnia, sleep dissatisfaction) and sleep-disordered breathing disorder (SBD) among children. We also assessed children's early-life SHS exposure (during pregnancy and the first six months of life) using questionnaires. Using a generalized linear model of the Poisson family, we estimated the association between sleeping problems and psychoactive substance use (adults) and SHS exposure (children).ResultsOn working days, 59.2% of adults reported sleeping less than 7 hours, and 28.3% expressed dissatisfaction with their sleep patterns and durations. Approximately 39.6% of the children were reported to have sleep-disordered breathing problems. Among adults, sleep dissatisfaction was associated with alcohol use (PR = 1.78(1.20 - 2.64)). Compared to unexposed counterparts, children, exposed to both prenatal SHS and within the first six months of life had a higher risk of SBD (PR= 1.81, 95%CI 1.23 – 2.67).ConclusionsAlcohol was linked to sleep dissatisfaction among adults while earlier life exposure to SHS was associated with an increased risk of SBD problems in children. This emphasizes the need to support ongoing public health initiatives and maintain a smoke-free environment, particularly for children in their early life.
Deep Reinforcement Learning Based on Balanced Stratified Prioritized Experience Replay for Customer Credit Scoring in Peer-to-Peer Lending
Authors: Wang Yadong , Jia Yanlin , Fan Sha , Xiao Jin
Published: January 2023

In recent years, deep reinforcement learning (DRL) models have been successfully utilised to solve various classification problems. However, these models have never been applied to customer credit scoring in peer-to-peer (P2P) lending. Moreover, the imbalanced class distribution in experience replay, which may affect the performance of DRL models, has rarely been considered. Therefore, this article proposes a novel DRL model, namely a deep Q-network based on a balanced stratified prioritized experience replay (DQN-BSPER) model, for customer credit scoring in P2P lending. Firstly, customer credit scoring is formulated as a discrete-time finite-Markov decision process. Subsequently, a balanced stratified prioritized experience replay technology is presented to optimize the loss function of the deep Q-network model. This technology can not only balance the numbers of minority and majority experience samples in the mini-batch by using stratified sampling technology but also select more important experience samples for replay based on the priority principle. To verify the model performance, four evaluation measures are introduced for the empirical analysis of two real-world customer credit scoring datasets in P2P lending. The experimental results show that the DQN-BSPER model can outperform four benchmark DRL models and seven traditional benchmark classification models. In addition, the DQN-BSPER model with a discount factor γ of 0.1 has excellent credit scoring performance.