bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved electrochemical performance of bio-derived plasticized starch/ reduced graphene oxide/ molybdenum disulfide ternary nanocomposite for flexible energy storage applications
Authors: Mahmud Eashika , Islam Muhammad Rakibul
Published: September 2023

A ternary nanocomposite of plasticized starch (PS), reduced graphene oxide (rGO), and molybdenum disulfide (MoS2) was prepared via an aqueous casting process, with MoS2 concentrations ranging from 0.25 wt.% to 1.00 wt.%. The structural, surface morphological, optical, and electrochemical properties of the nanocomposites were studied. FTIR analysis reveals the formation of new chemical bonds between PS, rGO, and MoS2, indicating strong interactions among them. The XRD analysis showed a reduction in the crystallinity of the nanocomposite due to the incorporation of nanofiller. FESEM micrograph showed an increment of the surface roughness due to the incorporation of rGO-MoS2 layers. UV-vis spectroscopy demonstrated a reduction of optical bandgap from 4.71 eV to 2.90 eV, resulting from enhanced charge transfer between the layers and defect states due to the addition of nanofillers. The incorporation of MoS2 was found to increase the specific capacitance of the PS from 2.78 Fg− 1 to 124.98 Fg− 1 at a current density of 0.10 mAg− 1. The EIS analysis revealed that the nanofiller results in a significant reduction in charge transfer resistance from 4574 Ω to 0 Ω, facilitating the ion transportation between the layers. The PS/rGO/MoS2 nanocomposite also exhibited excellent stability, retaining about 85% of its capacitance up to 10,000 charging-discharging cycles. These biocompatible polymer-based nanocomposites with improved electrochemical performance synthesized from an easy and economical route may offer a promising direction to fabricate a nature-friendly electrode materials for energy storage applications.
Establishment and characterization of a patient-derived solitary fibrous tumor/hemangiopericytoma cell line model
Authors: Lee Jing Yi , Guan Peiyong , Lim Abner Ming Sun Herbert , Guo Zexi , Li Zhimei , Kok Jessica Sook Ting , Lee Elizabeth Chun Yong , Lim Boon Yee , Kannan Bavani , Loh Jui Wan , Ng Cedric Chuan-Young , Lim Kah Suan , Teh Bin Tean , Ko Tun Kiat , Chan Jason Yongsheng
Published: September 2023

Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma harboring NAB2-STAT6 gene fusions. Mechanistic studies and therapeutic development on SFT/HPC are impeded by scarcity and lack of system models. In this study, we established and characterized a novel SFT/HPC patient-derived cell line (PDC), SFT-S1, and screened for potential drug candidates that could be repurposed for the treatment of SFT/HPC. Immunohistochemistry profiles of the PDC was consistent with the patient’s tumor sample (CD99+/CD34+/desmin-). RNA sequencing followed by Sanger sequencing confirmed the pathognomonic NAB2exon3-STAT6exon18 fusion in both the PDC and the original tumor. Transcriptomic data showed strong enrichment for oncogenic pathways (epithelial-mesenchymal transition, FGF, EGR1 and TGFβ signalling pathways) in the tumor. Whole genome sequencing identified potentially pathogenic somatic variants such as MAGEA10 and ABCA2. Amongst a panel of 14 targeted agents screened, dasatinib was identified to be the most potent small molecule inhibitor against the PDC (IC50, 473 nM), followed by osimertinib (IC50, 730 nM) and sunitinib (IC50, 1765 nM). Methylation profiling of the tumor suggests that this specific variant of SFT/HPC could lead to genome-wide hypomethylation. In conclusion, we established a novel PDC model of SFT/HPC with comprehensive characterization of its genomic, epigenomic and transcriptomic landscape, which can facilitate future preclinical studies of SFT/HPC, such as in vitro drug screening and in vivo drug testing.
Knowledge and Perceptions on Sexual Reproductive Health and Rights Among University of Rwanda Students: A Mixed-Method Study
Authors: Muhayimana Alice , Ntalindwa Theoneste , Uwase Aline , Gerard Kaberuka , Niringiyumukiza Jean Damascene , Ingabire Allen JC , Nzabonimana Emmanuel , Kearns Irene Josephine , Laetitia Ishimwe Bazakare , Fulgence Maniriho , Dieu Habimana Jean , Mathias Nduwingoma
Published: September 2023

Background: Poor knowledge of sexual reproductive health and rights (SRHR) among university students has been constantly reported in low and middle-income countries. A study conducted on female students at the University of Rwanda (UR) about knowledge of emergency contraceptive method use revealed inadequate knowledge in family planning though they are sexually active. However, no study has assessed knowledge of SRHR in general among UR students. This study aims to explore the UR students’ knowledge and perspectives on SRHR.
Methodology: This was a mixed-method study. An online survey was conducted among a convenient sample of 441 UR students. After reviewing the survey results, 12 structured interviews were conducted among a sample of UR students from each of the six colleges.
In data collection, we used a validated questionnaire with 50 items on SRHR knowledge through Moodle online platform and physical in-depth interviews. SPSS version 25 was used for descriptive and logistic regression analysis, whereas N-vivo 12 was used for qualitative thematic analysis. A p-value <0.05 was considered significant.
Results: The majority had insufficient knowledge (57%).Prior exposure to the SRHR course through YouTube (aOR 3.66; [1.01-13.17]) and SRHR prior exposure through Radio (aOR: 5.58; [1.50-20.75]) were associated with SRHR knowledge. In qualitative analysis, five themes emerged: 1) Prevention of unplanned pregnancies, 2) Knowledge of SRHR Services, 3) Knowledge of contraceptive methods, 4) Perceptions of sexual intercourse among youths before marriage, 5) Perceptions of safe abortion. Participants reported that they use condoms, pills and abstinence, feel ashamed to ask for SRHR information or share their experiences in public, fear the use of long-acting contraceptive methods, and have limited condom access.
Conclusion and Recommendations: UR students do not have sufficient knowledge of SRHR. Every UR student should benefit from SRHR training from reliable sources to enable them to make effective choices regarding their reproductive health.
Urban Forestry and Urban Greening in Yenagoa, Bayelsa State, Nigeria: a Contribution to Climate Change Mitigation
Authors: Ezenwaka Jasper
Published: September 2023

This research was aimed at finding out the practices of urban forestry and urban greening in Yenagoa, Bayelsa State, Nigeria. Climate change issue has become a major topic of discussion among even the non-environmentalists because of its several effects on human and his environment. Types of plant species planted by homesteaders were appraised as well as reasons for the choices. Knowledge of climate change (causes, effects, and mitigations) were also appraised. Among the 30 participants that were involved in the Convenient sampling semi-structured survey, 43% had knowledge of climate change; 33% had knowledge of its causes; 40% were able to show some knowledge of role of vegetations in environmental purification, while all (100%) participants agreed that they would plant more vegetations if they had the knowledge of climate change and what role vegetations could play in curbing its effects. Various plant species were found around the homesteads including tree species, ornamental / horticultural, and agricultural species. The reasons for keeping the various species included economic, medicinal, and aesthetic values, in addition to others. More environmental education activities is recommended in order to increase people’s awareness to roles that greening of the environment can play in curbing the effects of climate change.
SHMT2 arginine methylation by PRMT1 facilitates esophageal cancer progression by enhancing glycolysis and one-carbon metabolism
Authors: Qiao Zhe , Li Yu , Cheng Yao , Liu Shiyuan , Li Shaomin
Published: September 2023

Background
Protein arginine methyltransferase 1 (PRMT1) is the main enzyme that directly responsible for the production of asymmetric dimethylarginine (ADMA), and upregulation of PRMT1 is observed in a variety of malignancies, including esophageal cancer (ESCA). Dysregulation of arginine methylation caused by PRMT1 overexpression is a driver of poor cancer progression, and the detailed mechanism of modulation is currently unknown.
Results
The present study confirmed a novel oncogenic mechanism of PRMT1 in ESCA. PRMT1 levels were significantly upregulated in ESCA, and its high expression correlated with TNM stage and poor patient prognosis. We continued to find the mechanisms by which PRMT1 expression was more relevant to ESCA progression. RNA-seq and KEGG enrichment analyses revealed that differentially expressed genes after PRMT1 silencing in ESCA might modulate serine/one-carbon metabolism. Knockdown of PRMT1 in vitro resulted in a significant reduction in ESCA cell growth, and indicators related to serine/one-carbon metabolism and glycolysis, whereas its overexpression showed opposite results. The catalytic activity of PRMT1 was crucial in mediating these biological processes. We found that PRMT1 mediated the ADMA modification of serine hydroxymethyltransferase 2 (SHMT2) at arginine 415 (R415), which activated SHMT2 activity and enhanced serine/one-carbon metabolism and glycolysis. The R415K mutation largely eliminated the arginine methylation of SHMT2 by PRMT1, and weakened PRMT1-induced glycolysis and serine/one-carbon metabolism.
Conclusion
Our study further confirmed the link between the two proteins, PRMT1 and SHMT2, as well as arginine methylation and glycolysis. The study of deeper molecular mechanisms will reveal a broader role of arginine methylation in the regulation of glycolysis.
Design and Fabrication of Multi-Material Pneumatic Soft Gripper Using Newly Developed High-Speed Multi-Material Vat Photopolymerization 3D Printer
Authors: Jiang Cho-Pei , Romario Yulius Shan , Bhat Chinmai , Hentihu M Fahrur Rozy , Zeng Xuan-Cheng , Ramezani Maziar
Published: September 2023

This study proposes a versatile, low-cost, shape-conforming soft gripper and fabricates it using the developed high-speed multi-material vat photopolymerization 3D printer for industrial applications. This additive manufacturing technology uses a rotary build plate that moves through 180° along the XY plane and multiple resin vats to accommodate different materials. A cleaning system uses pressurized air and alcohol to prevent contamination between layers and to increase the bond strength. The soft grippers are manufactured using soft (GC3D-ESK) and hard phase (AA-temp) materials to optimize the gripping force and prevent damage to the objects. Experimental results show that the tensile strength of the multi-material fabricated part (GC3D-HSK and AA-temp) is 5 times greater than that for the soft material GC3D-HSK. The multi-material specimen exhibits an elastic modulus of 89.28 MPa, which compares to only 2.08 MPa for the soft material. The multi-material fabricated specimen has high strength and high elastic modulus and is 65% more elongated than the hard material. In addition, the printing specimens that are cleaned with alcohol after successive printing of each layer have 4% greater tensile strength and 30% greater ductility. A shrinkage analysis determines the material compatibility. The percentage shrinkage for both GC3D-HSK and AA-temp is 0.1–0.2%. The printed pneumatic soft gripper is used to lift goods of less than 200g using a maximum pressure of 34.3 kPa. The printed gripper can lift objects of different weights and profiles without damaging the surface. The high-speed multi-material VP 3D printer can be used for additive manufacturing to optimize the design of pneumatic soft grippers.
The impact of skin involvement on the quality of life of breast cancer patients with chest wall recurrence and their caregivers
Authors: Zhou Danyang , Lin Qiulian , Cao Zhihui , Wu Wei , Nong Qiaohong , Hong Ruoxi , Wang Shusen
Published: September 2023

Purpose
To assess the impact of skin involvement on the quality of life (QoL) among breast cancer patients with chest wall recurrence and their caregivers.
Methods
We invited the female breast cancer patients with chest wall recurrence who received treatment at Sun Yat-sen University Cancer Center from November 2020 to July 2021 to complete EORTC QLQ-C30, EORTC QLQ-BR23, and HADS questionnaire. Their stable caregiver filled out SF-36 and HADS questionnaires. The assessment of the QoL was conducted once every two cycles of systemic treatment, with a total of three assessments. Survival analysis was performed using the Kaplan-Meier curves.
Results
A total of 42 participants and their family caregivers completed the QoL questionnaire for all three assessments. We found that in the skin involvement group, the breast symptoms worsened and the future perspectives decreased. The multiple functions and general health status of the patients in this group were also lower than those in the group without skin involvement. Skin involvement predicted the shorter disease progression of patients with chest wall recurrence. Compared to patients without skin involvement (5%), patients with skin involvement (29%) were more likely to experience the deterioration of arm symptoms. There were no differences in the family caregivers’ questionnaire between the two groups.
Conclusion
Chest wall recurrence patients with skin involvement had shorter disease progression intervals, more sever breast symptoms, and lower future prospects. This research further provided a reference for the application and promotion of QoL assessment tools in the management of recurrent breast cancer.
Psychometric evaluation of the Chinese Version of the Stimulant Relapse Risk Scale (C-SRRS) in Patients with Methamphetamine Use Disorder
Authors: Lin Jing-Shu , Ogai Yasukazu , Lin Chun , Chang Hu-Ming , Wu Yi-Chia , Huang Ming-Chyi , Fang Su-Chen
Published: September 2023

Background
Evaluating the risk of relapse is a pivotal step in the treatment of individuals with methamphetamine use disorder (MUD). The 30-item Stimulant Relapse Risk Scale (SRRS) was originally developed in Japan to meet the demand. This study examined the reliability, validity, and factor structure of the Chinese version of the SRRS (C-SRRS) for patients with MUD.
Methods
247 patients with MUD self-rated the C-SRRS. Cronbach’s alpha coefficients and inter-item correlation analysis were used to assess the internal consistency reliability. Construct validity was determined through confirmatory factor analysis (CFA), and concurrent validity was examined using the visual analogue scale (VAS) for drug craving and the severity of dependence scale (SDS). We followed the participants for 1 year and assessed the predictive validity based on the correlation of C-SRRS scores with the relapse rate within 3, 6, and 12 months of follow-up.
Results
CFA revealed satisfactory model fit estimates for 22 items of CRRS that consisted of four subscales. The four-factored 22-item C-SRRS had adequate internal consistency with Cronbach’s alphas ranging from 0.76 to 0.92. The 22-item C-SRRS scores were significantly correlated with the VAS and SDS scores as well as the relapse rate within 3, 6, and 12 months, indicating good concurrent and predictive validity of this scale. The receiver operating characteristic curve revealed a cutoff score of 40 could discriminate between high and low severity of methamphetamine dependence (area under the curve = 0.71, p < 0.01).
Conclusions
The 22-item C-SRRS that consists of four subscales is a valid and reliable instrument to assess the relapse risk in patients with MUD.
Framework for Personalized Prediction of Treatment Response in Relapsing-Remitting Multiple Sclerosis: A Replication Study in Independent Data
Authors: Sakr Anna Maria , Mansmann Ulrich , Havla Joachim , Ön Begum Irmak
Published: September 2023

Background
Individualizing and optimizing treatment of relapsing-remitting multiple sclerosis patients is a challenging problem, which would benefit from a clinically valid decision support. Stühler et al. presented black box models for this aim which were developed and internally evaluated in a German registry but lacked external validation.
Methods
In patients from the French OFSEP registry, we independently built and validated models predicting being free of relapse and free of confirmed disability progression (CDP), following the methodological roadmap and predictors reported by Stühler. Hierarchical Bayesian models were fit to predict the outcomes under 6 disease-modifying treatments given the individual disease course up to the moment of treatment change. Data was temporally split on 2017, and models were developed in patients treated earlier (n = 5517). Calibration curves, discrimination, and mean squared error (MSE) were assessed by external validation of models in more-recent patients (n = 3768). Standard count models were also applied and compared to the Bayesian ones.
Results
The performance of our temporally-validated relapse model (MSE: 0.326, C-Index: 0.639) is potentially superior to that of Stühler’s (MSE: 0.784, C-index: 0.608). Calibration plots revealed miscalibration. Our CDP model (MSE: 0.072, C-Index: 0.777) was also better than its counterpart (MSE: 0.131, C-index: 0.554). Results from standard count models were similar to the Bayesian ones.
Conclusions
The CDP model rebuilt and externally validated in independent data compared and strengthened the credibility of the Stühler models. Their model-building strategy was replicable.
Feasibility of Laparoscopic Surgery in Patients with Postoperative Adhesive Small Bowel Obstruction
Authors: Ochiai Hiroki , Ishii Yoshiyuki , Sako Hiroyuki , Yabe Nobushige , Watanabe Masahiko
Published: September 2023

Purpose Laparoscopic surgery for abdominopelvic disease is minimally invasive and associated with mild adhesion formation, resulting in a low incidence of small bowel obstruction after surgery. Theoretically, laparoscopic surgery may be a reasonable treatment modality for postoperative small bowel obstruction. This study aimed to evaluate the safety and effectiveness of laparoscopic surgery in the treatment of postoperative adhesive small bowel obstruction.
MethodsThis study included in 404 consecutive patients who underwent laparoscopic surgery for postoperative small bowel obstruction at Kitasato University Kitasato Institute Hospital, Tokyo, Japan, between 2012 and 2021.
ResultsThe median number of episodes of postoperative small bowel obstruction was 4 (range:1-26) times. The median duration of recurrent episodes of small bowel obstruction (hereinafter, duration of suffering) was 4 years (range:1-60). A transnasal decompression tube and ureteral stent were inserted before surgery in 34 (8.4%) and 14 (3.5%) patients, respectively. The median operation time and blood loss volume were 176 min (range:43-654) and 10 g (range:10-2335), respectively. Conversion to open surgery was required in 19 (4.5%) patients.
The following surgical procedures were performed: laparoscopic adhesiolysis (n=341; 84.4%), laparoscopic adhesiolysis with partial resection of the small bowel (n=56; 13.9%), and stricture plasty and/or bypass (n=7; 1.7%).
Postoperative complications occurred in 67 (16.8%) patients: paralytic ileus in 53 (13.1%) patients, small bowel injury in wight (1.9%) and postoperative bleeding in two (0.5%) patients. Operative mortality occurred in 1 (0.2%).
ConclusionsLaparoscopic surgery can be safely performed in patients with postoperative adhesive small bowel obstruction.
Full-Components Utilization of Cellulose Nanofibrils and Artificial Stone Wastes for Cement Enhancement
Authors: zhou bo , huang xin , yang xin , liu jize , huang zhuo , Yu Fei Fan , zhang xinxing
Published: September 2023

With the concept of carbon neutrality, the value-added utilization of biomass materials and solid wastes has become a cutting-edge topic. Cellulose nanofibrils (CNFs) have received much attention due to their excellent properties in terms of high aspect ratio, specific strength and specific surface area, but their large-scale preparation remains a great challenge. Here, we propose a facile aqueous solution method for the fabrication of CNFs through artificial stone wastes (ASWs)-assisted supramolecular interfacial interactions for the full-components utilization in cement mortar materials. The strong hydrogen bonding interaction between ASWs and CNFs can effectively prevent the intramolecular hydrogen bonding of CNFs and agglomeration of ASWs, while improving the stability of CNFs/ASWs suspensions. The resulted CNFs/ASWs with active hydroxyl or carboxyl group can improve the flexural and compressive strength of cement (30.8% and 37.8% higher than that of pristine cement, respectively) by embedding into the defects of cement mortar and promoting the hydration process of cement. This work not only provides a new idea for the large-scale preparation of biomass nanomaterials, but also opens up the full-components value-added utilization of biomass and solid wastes in cement materials.
Whole-body modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease
Authors: Martinelli Filippo , Heinken Almut , Henning Ann-Kristin , Wörheide Maria A. , Hensen Tim , González Antonio , Arnold Matthias , Asthana Sanjay , Budde Kathrin , Engelman Corinne D. , Estaki Mehrbod , Grabe Hans-Jörgen , Heston Margo , Johnson Sterling , Kastenmüller Gabi , Martino Cameron , McDonald Daniel , Rey Federico , Kilimann Ingo , Peters Olive , Wang Xiao , Spruth Eike Jakob , Schneider Anja , Fliessbach Klaus , Wiltfang Jens , Hansen Niels , Glanz Wenzel , Buerger Katharina , Janowitz Daniel , Laske Christoph , Munk Matthias H. , Spottke Annika , Roy Nina , Nauck Matthias , Teipel Stefan , Knight Rob , Kaddurah-Daouk Rima , Bendlin Barbara B. , Hertel Johannes , Thiele Ines
Published: September 2023

In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilized whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalized models. Notably, AD individuals displayed diminished formate microbial secretion in these models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.
Synthetic seeds of Acmella oleracea (Asteraceae) from micropropagated plants in different concentrations of 6-benzylaminopurine
Authors: Junior Jorge Braga Ribeiro , Dias Gabrielen de Maria Gomes , Guimarães Marcelo de Almeida , Nazareno Lailla Sabrina Queiroz , DoVale Júlio César , Zanuncio José Cola
Published: September 2023

Acmella oleracea, a leafy vegetable native to the Amazon region, has potential for the cosmetic, pharmaceutical and gastronomic industries. Hot environments and or low relative humidity accelerate losses of vigor and quality, making unfeasible to storage seeds of this plant. This makes necessary to develop new propagation and conservation techniques for A. oleracea. The objective was to evaluate the biometric characteristics, describe the stomata and to verify the presence or absence of epicuticular wax on the abaxial leaf epidermis of A. oleracea plantlet obtained from the conversion of synthetic seeds (SS) in vitro. The nodal segments of micropropagated plantlets, at different concentrations of 6-benzylaminopurine (BAP) (0.000; 0.025; 0.050; 0.100 and 0.200 mg l-1), were sectioned into explants of approximately 0.3 cm, encapsulated in alginate matrix to produce SS, inoculated in test tubes with Murashige & Skoog culture medium and kept in a growth room at a temperature of 25 ± 2 ºC and a photoperiod of 16 hours. The percentage of SS conversion, number of leaves and shoots, height and root dry mass were higher in the treatments with BAP. Shoot dry mass was 54.5% higher on plants originated from SS obtained with 0.100 mg l-1 of BAP than in the control. Anomocytic and ellipsoid-shaped stomata were well defined and epicuticular wax deposition was not observed on the abaxial epidermis of A. oleracea plantlets leaves. The stomata of A. oleracea and the absence of epicuticular wax on the leaf epidermis of this plant were similar between treatments.
Weak evidence of density dependent population regulation using predictive ability of models
Authors: Gebreyohannes Demissew , Houlahan Jeff
Published: September 2023

The relative importance of density dependence regulation in natural population fluctuations has long been debated1-3. The concept of density dependence implies that current abundance is determined by historical abundance. We have developed four models – two density dependent and two density independent - to predict population size one year beyond the training set and used predictive performance on more than 16,000 populations from 14 datasets to compare the understanding captured by those models. For 4 of 14 datasets the density dependent models make better predictions (i.e., density dependent regulated) than either of the density independent models. However, neither of the density dependent models is statistically significantly superior to density independent models for any of the 14 datasets. We conclude that the evidence for widespread density dependent population regulation is weak.
Autoimmune Disorders Reported Following COVID-19 Vaccination: A Disproportionality Analysis Using the WHO VigiBase
Authors: Kim Seohyun , Bea Sungho , Choe Seung-Ah , Choi Nam-Kyong , Shin Ju-Young
Published: September 2023

Purpose: Owing to autoimmune disorders (AIDs) and coronavirus disease (COVID-19) vaccines sharing common biological mechanisms, identifying the risk of AIDs associated with COVID-19 vaccines remains a critical unmet need. We aimed to assess the potential safety signals for 16 AIDs and explore co-reported adverse events (AEs) and drugs using the global database of the World Health Organization, VigiBase.
Methods: We assessed the occurrence of 16 AIDs following COVID-19 vaccination through the Standardised MedDRA Queries group “Immune-mediated/Autoimmune Disorders” from MedDRA and performed a disproportionality analysis using reporting odds ratio (ROR) and information component (IC) with 95% confidence intervals (CIs).
Results: We identified 25,219 AIDs associated with COVID-19 vaccines in VigiBase and detected four autoimmune safety signals following COVID-19 vaccination, including ankylosing spondylitis or psoriatic arthritis (ROR 1.86; 95% CI 1.53-2.27), inflammatory bowel disease (ROR 1.77; 95% CI 1.60-1.96), polymyalgia rheumatica (ROR 1.42; 95% CI 1.30-1.55), and thyroiditis (ROR 1.40; 95% CI 1.30-1.50), with positive IC025 values. The top co-reported AEs were musculoskeletal disorders, and immunosuppressants were the most representative co-reported drugs. Although rare, four AIDs showed disproportionality in reporting.
Conclusion: In response to the need to understand AID following COVID-19 vaccination using WHO-UMC VigiBase, four AIDs were identified in this study. Thus, our study highlights the need for active safety surveillance to detect potential AIDs and monitor the safety of the COVID-19 vaccination.
Associations between Estimation of Salt Intake and Salt-Restriction Spoons and Hypertension Status in Patients with Poorly Controlled Hypertension: A community-based Study from Huzhou City, Eastern China
Authors: Zhang Qi , Shen Yimei , Yu Meihua , Yang Zhongrong , Huang Zheng , Ding Jingying , Zhu Xinfeng
Published: September 2023

Background
As the prevalence of hypertension increases in China, it is advised to incorporate the use of salt-restriction spoons (SRS) as a lifestyle modification. This study aimed to examine the associations between estimated salt consumption, SRS usage, and the hypertension status in individuals with poorly controlled hypertension.
Methods
Data was collected in Huzhou City, Zhejiang Province, in 2021 using convenience sampling. The analysis involved univariate and multilevel ordinal logistic regression to assess the relevant factors.
Results
The study found that 73.34% of the 1215 patients had uncontrolled blood pressure. Urinary excretion was assessed through the utilization of the Kawasaki, INTERSALT, and Tanaka formulas. The outcomes of these three methodologies revealed average daily sodium excretion values of 208.70 (65.65), 154.78 (33.91), and 162.61 (40.87) mmol, respectively. The prevalence of utilizing SRS was found to be 37.78% in this study. Despite the acknowledgment among SAS users of the potential hazards associated with excessive salt consumption, there exists a contradictory pattern of attitudes and behaviors concerning salt reduction. Several risk factors, including being overweight or obese, alcohol consumption, and an increasing number of medications, were found to significantly impact blood pressure control (P < 0.05). A positive correlation was observed between salt restriction and hypertension status (Kawasaki adjusted OR = 0.58, 95% CI = 0.43–0.79; INTERSALT adjusted OR = 0.62, 95% CI = 0.41–0.92; Tanaka adjusted OR = 0.61, 95% CI = 0.45–0.92, p < 0.05) when controlling for other variables among individuals with varying levels of salt intake (quartiles 1–4, Q1 vs Q4). Our research also revealed that using or used SAS was a protective factor for blood pressure control (adjusted OR = 0.79, 95% CI = 0.64–0.99, P < 0.05).
Conclusions
Salt reduction campaigns are necessary in order to address the issue of hypertension. Patients with uncontrolled hypertension can effectively lower their blood pressure by reducing their sodium intake, preferably by utilizing SRS during home cooking in the region. In order to alleviate the burden of hypertension in China, further research is needed to develop interventions that can improve patient outcomes.
Advanced 123I-FP-CIT Serotonin Transporter Imaging: Specific Binding Ratio(SBR) Distribution Helps to Characterize MSA
Authors: Takahashi Kazuya , Ishiguro Masanobu , Inui Yoshitaka , Ichihara Takashi , Shou Sou , Nagao Ryunosuke , Mizutani Yasuaki , Ito Mizuki , Watanabe Hirohisa , Motomura Nobutoku , Toyama Hiroshi
Published: September 2023

Background
Sudden death in MSA is caused by a decrease in serotonergic innervation, but there is currently no method to test for this at the level of routine medical care. Therefore, we decided to investigate whether serotonergic nerve can be evaluated using dopamine transporter SPECT. 123I-FP-CIT can bind and accumulate not only dopamine transporters but also serotonin transporters (SERT). While the common method of SERT analysis by SPECT is considered unreliable in many respects, in this study we developed a more reliable SBR imaging technique to measure SERT in the brainstem.
Objective
Using a simple model, we derived a binding potential [1] to quantify the total quantity of 123I-FP-CIT specifically binding to its receptors in brain tissue. We then tried to establish a procedure for imaging that binding potential. Moreover, we investigated whether it was possible to observe differences in SERT distribution in the brainstem region using SBR images from healthy individuals and patients with MSA.
Subjects　A total of 17 healthy individuals and 11 patients with MSA were included in this study.
Methods
SPECT with TEW （Triple Energy Window） scatter correction and CT-AC and MR (T1) images were acquired. The MR images were aligned with the SPECT images. First, a reference site for the SBR calculation was set in the occipital lobe of each subject using the MR (T1) image and measurements were made from the SPECT image at the same position. For each pixel of the SPECT image, a pixel value (123I-FP-CIT accumulation) and accumulation ratio in comparison to the occipital lobe (reference site) were calculated, and a regional SBR distribution image (SBR image) was created. An image showing SERT accumulation was created from the SBR image using a constant threshold method, and the MR image of the same subject was aligned and fused with this image.
Results
The site of serotonin transporter accumulation was visualized as an SBR value on MRI images. Furthermore, SBR images revealed that the distribution of accumulation (distribution of SERT) was different between controls and MSA patients.
Conclusion
An apparent accumulation of SERT was noted in the brainstem region, suggesting that SBR imaging can be useful in determining and quantifying SERT accumulation.
Forced Degradation of an Anticancer Drug Apalutamide: Impurity Profiling and Structure Elucidation Study
Authors: Sapkal Rekha , Quadri Sadaf , Mahajan Rupali , Padhy Hara Prasad , Asthana Amit , Samanthula Gananadhamu , Dikundwar Amol G.
Published: September 2023

An anticancer drug apalutamide approved by USFDA in 2018 is one of the most commonly prescribed chemotherapeutic agents used for the treatment of prostate cancer. The present study aims at establishing the chemical structures of all the degradation products of the API formed under different stress conditions. Apalutamide degradation was studied under ICH-recommended conditions of hydrolysis (acidic, alkaline, neutral), oxidation, photolysis, and thermal stress. In total, seven degradation products (DP-1 to DP-7) were observed which were successfully separated on HPLC and further characterized using LC-MS/MS Q-TOF. The chromatographic separation was achieved using a Shimpack C18 column (4.6 mm × 250 mm, 5 µm) with 0.1% formic acid and acetonitrile as a mobile phase in a gradient elution mode. The injection volume, detection wavelength, and flow rate were set at 10 µL, 240 nm, and 1.0 mL/min, respectively. Degradation pathways for each of the observed DPs have been proposed based on the mass fragmentation pattern of API as well as DPs, identifying the underlying chemical transformations. Prediction of DPs was performed with Zeneth software tool and the results were compared with the experimental observations. In silico toxicity assessment carried out using Derek suite reveals toxic nature of some of these DPs.
Association of Serum and Hair Antioxidant Minerals with an Oxidative Stress Marker in Relation with Characteristics of Healthy Adults: A Cross-Sectional Study
Authors: Kang Yoo-Ree , Sung Mi-Kyung , Baik Hyun-Wook , Choi Mi-Kyeong
Published: September 2023

Excess oxidative stress generated in the body causes various types of cellular damage, including DNA damage. Certain trace minerals act as antioxidants by functioning as cofactors for antioxidant enzymes. This study was conducted to evaluate the serum and hair concentrations of major antioxidant trace minerals (zinc, manganese, selenium, and chromium) and to determine the association between the oxidative stress marker urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and serum or hair antioxidant trace mineral concentrations, according to the general characteristics of healthy adults. Study participants were selected after screening, and 108 participants aged 19–69 years were finally included. Serum and hair trace mineral concentrations were analyzed using inductively coupled plasma mass spectrometry, and urine 8-OHdG levels were quantified using an ELISA kit. Results showed that urinary 8-OHdG levels were significantly higher in exercisers than in those who did not exercise. Correlation analysis revealed that urinary 8-OHdG was negatively correlated with hair zinc in participants over 60 years of age and with poor health status, and positively correlated with hair chromium in participants with irregular dietary habits. In conclusion, these results suggest that urinary 8-OHdG is particularly correlated with hair zinc and chromium levels. Additional large-scale epidemiological studies are needed to generally confirm these findings.
Deafness DFNB110 associated with a human MAP3K1 recessive variant recapitulates hearing loss of Map3k1 kinase deficient mice
Authors: Faridi Rabia , Yousaf Rizwan , Inagaki Sayaka , Olszewski Rafal , Gu Shoujun , Morell Robert J. , Wilson Elizabeth , Xia Ying , Qaiser Tanveer Ahmed , Rashid Muhammad , Fenollar-Ferrer Cristina , Hoa Michael , Riazuddin Sheikh , Friedman Thomas B.
Published: September 2023

Deafness in vertebrates is associated with variants of hundreds of genes. Yet, many genes causing rare forms of deafness remain to be discovered. Microarrays and exome sequencing were used to study a consanguineous Pakistani family segregating nonsyndromic deafness in two sibships. A 1.2 Mb locus (DFNB110) on chromosome 5q11.2 encompassing six genes was identified. In one of the two sibships of this family, a novel homozygous recessive variant NM_005921.2:c.4460G>A p.(Arg1487His) in the kinase domain of MAP3K1 co-segregated with nonsyndromic deafness. MAP3K1 phosphorylates serine and threonine or tyrosine and functions in a signaling pathway where pathogenic variants of HGF, MET and GAB1 were previously reported to be associated with human deafness DFNB39, DFNB97 and DFNB26, respectively. Single-cell transcriptome data obtained from mouse cochlea mRNA show Map3k1 expression and its associated signaling partners necessary for hearing. Computational modeling of p.(Arg1487His) predicts a subtle structural alteration consistent with the limited DFNB110 phenotype in contrast to the pleiotropic phenotype of dominant MAP3K1 variants causing Disorders of Sex Development 46,XY sex-reversal and the reported syndromic deafness phenotype of two different protein truncating recessive variants of mouse Map3k1.
Cerebral large vessels vasculitis following Guillain-Barré syndrome as first clinical manifestations of primary Sjogren’s syndrome : a case report and review of the literature
Authors: saied zakaria , zouari rania , nabli fatma , rachdi amine , mohamed dina ben , sassi samia ben
Published: September 2023

Background :
Primary Sjogren’s syndrome (pSS) is an autoimmune exocrinopathy in which sicca syndrome of the exocrine glands represent the main clinical manifestation.
Severe extraglandular signs of pSS are determinant for the prognosis of this disease. Involvement of both peripheral and central nervous system (CNS) are known to be among the sites of high systemic activity in pSS.
Case presentation :
We, herein, report a case of a 57-year-old female patient with pSS presenting with typical Guillan-Barré syndrome (GBS), shortly followed by acute headaches accompanied by cortical blindness. Cerebral magnetic resonance imaging (MRI) demonstrated T2 signal abnormalities on the occipital region with narrowing and irregularities of the cerebral arteries, suggestive of CNS vasculitis.
Subtle sicca symptoms occurring prior to neurological symptoms by 8 months together with immunological disturbances (anti-SSA, anti-SSB antibodies positivity, type II cryoglobulins positivity, and C4 hypocomplementemia) allowed us to retain the diagnosis of pSS. Recovery of motor symptoms was possible under the combined use of immunoglobulins and corticotherapy during the initial phase. A three-years follow-up confirmed progressive motor recovery and disease stabilization under 6-months cyclophosphamide cycles relayed by azathioprine immunosuppressive therapy. However, severe residual visual loss persisted
Conclusions :
Neurological complications can be inaugural in pSS and they lead to urgent investigations and treatment. Peripheral and central neurological manifestations can coexist. The approach should integrate careful clinical assessment, as well as radiological and immunological findings.
Adverse Signals of Celecoxib Associated with Central Nervous System and Cancer: A Retrospective Analysis of the FDA Adverse Event Reporting System
Authors: Du Yikuan , Zhang Mengting , Chen Mianhai , Hu Mianda , Zeng Wenqi , Zhang Weichui , Zhu Jinfeng , Yang Chun
Published: September 2023

Purpose
Some of the COX-2 inhibitors are now clinically recognized as candidates for the treatment of various neurological disorders and cancers, especially celecoxib. We performed this pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) database to explore the mechanisms associated with Celecoxib in adverse events (AEs).
Methods
Mining data from the FAERS database of AEs in which the primary suspect drug was celecoxib. In this study, disproportionality analysis was used to detect potential positive signals between celecoxib and related adverse events. It includes proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN) and empirical Bayesian geometric mean (EBGM). Use software such as Microsoft Office Excel (EXCEL) and R Studio for processing and statistical analysis.
Results
A total of 111,59092 AE reports were extracted from FAERS and 32841 AE reports with celecoxib as the primary suspected drug were obtained. Celecoxib adverse reactions were mainly reported in cardiac disorders (n = 9602) and nervous system disorders (n = 4045). The number of reports of cerebrovascular accident (n = 3109, IC025 = 3.24) and cerebrovascular disorder (n = 265, IC025 = 5.06) and the signal strength of the two nervous system-related adverse reactions were inconsistent with the description in the labels. Discovery of 9 unexpected and serious AEs, such as Stevens-Johnson syndrome, male breast disease, and squamous cell carcinoma of the head and neck.
Conclusions
This study is consistent with clinical reports. In addition, unexpected AEs of celecoxib in neurological diseases and cancer were found, providing monitoring and risk identification for future clinical applications of celecoxib.
Impaired fasting glucose related to cumulative dose of prednisone in patients with leprosy reactions: a glucose monitoring and management protocol
Authors: Thomazelli Jaqueline Andreoli , Santos Diogo Fernandes , Leite Cassio Martins , Goulart Isabela Maria Bernardes , Antunes Douglas Eulálio
Published: September 2023

Purpose: Our aim was to analyze the effects of the cumulative prednisone dose on blood glucose levels in leprosy reaction (LR) participants without a pre-existing diagnosis of diabetes, using the fasting plasma glucose test, and to develop a protocol to assist in preventing hyperglycemia and glucocorticoid-induced diabetes mellitus (GIDM).
Method: A cross-sectional study enrolled 75 outpatients with LR who were attended at a Reference Center from 2018 to 2020. The binomial test was used to analyze the association among groups and demographic/epidemiological factors. The Mann-Whitney test was used for the median comparison within groups regarding hematologic/biochemical variables.
Results: The clinical forms of borderline-tuberculoid (41.9%; 13/31) and borderline-lepromatous (46.12%) were more prevalent in the groups with a cumulative prednisone dose of ≤4 and >12 months, respectively, compared to the other groups. The overall prevalence of impaired fasting glucose was 10.6% (8/75) when patients were assessed in the final phase of this study. A cumulative prednisone dose greater than 8 months, coupled with taking this corticosteroid during blood collection, was found to be associated with impaired fasting glucose. Furthermore, the comparison between patients taking prednisone (Prednisone+; Median:101mg/dL, Min.:74mg/dL, Max.:125mg/dL) and those without (Prednisone-; Median:76mg/dL, Min.:66mg/dL, Max.:99mg/dL) showed a significant difference (p=0.0176) after 12 months of cumulative dose.
Conclusion: Based on the findings, we established a glucose monitoring and management protocol for patients with LR who are taking prednisone, mainly for more than 8 months. The purpose of this protocol is to detect, manage, and prevent the development of hyperglycemia and GIDM.
Identification of Flood Extent Area and Flood Risk Zone Using Geospatial Technologies in Tahirpur Upazila
Authors: Meem Fatima Tabassum , Mahmud Md. Munir , Hossain Md. Jakir
Published: September 2023

The north-eastern part of Bangladesh, specifically Sunamganj, is located in one of the depressed or low-lying regions of the country, and the north-eastern haor (wetland) region of Bangladesh is highly prone to flash flooding, which destroys crops, property, and infrastructures. It is not feasible to remove flood danger, but geographic information system (GIS) and remote sensing-based technologies can greatly lessen its impact. Using geospatial technologies, this study attempts to identify the extent area of previous floods using Google Earth Engine (GEE) and land use/land cover (LULC) classes impacted by flooding in Tahirpur upazila, and to identify flood risk zone using an overlaying method by expert opinion. This study also attempts to identify flood-influencing characteristics include elevation, slope, TWI, NDVI, LULC, rainfall, distance from river, distance from road and drainage density. The flood extent area maps revealed that, in the study region, 61.21%, 62.29%, and 64.21% of the total area was flooded in 2018, 2020, and 2022, respectively. And the risk map reveals that 9.67%, 23.23%, 30.87%, 20.09% and10.14% of the total area are classified as very high risk, high risk, moderate risk, low risk and very low risk respectively. Thus, the findings could aid policymakers and planners in building a preparedness system that would prevent property loss and wealth in Tahirpur upazila.
Immune pressure on hematopoietic stem cells can drastically expand glycosylphosphatidylinositol-deficient clones in paroxysmal nocturnal hemoglobinuria
Authors: Shingai Naoki , Mizumaki Hiroki , Najima Yuho , Yamada Yuta , Dung Tran Cao , Haraguchi Kyoko , Toya Takashi , Okuyama Yoshiki , Doki Noriko , Nannya Yasuhito , Ogawa Seishi , Nakao Shinji
Published: September 2023

Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disease characterized by intravascular hemolysis, thrombosis, and bone marrow (BM) failure. Although PNH is caused by excessive proliferation of hematopoietic stem cell (HSC) clones with loss of function mutations in phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) gene, the factor that drives the expansion of PNH clones remains elusive.
Case presentation:
We present a 26-year-old female who presented with hemolytic anemia, thrombocytopenia, and leukopenia. Flow cytometry analysis of peripheral blood showed that 71.9% and 15.3% of the granulocytes and erythrocytes were glycosylphosphatidylinositol (GPI)(-). The patient was diagnosed with PNH with BM failure. Deep-targeted sequencing covering 369 different genes of sorted GPI(-) granulocytes revealed three different PIGA mutations (p.I69fs, variant allele frequency (VAF) 24.2%; p.T192P, VAF 5.8%; p.V300fs, VAF 5.1%) and no other mutations. She received six cycles of eculizumab and oral cyclosporine. Although the serum lactate dehydrogenase level decreased, the patient remained dependent on red blood cell transfusion. Six months after diagnosis, she received a syngeneic bone marrow transplant (BMT) from a genetically identical healthy twin, following an immune ablative conditioning regimen consisting of cyclophosphamide 200 mg/kg and rabbit anti-thymocyte globulin 10 mg/kg. After 4 years, the patient’s blood count remained normal without any signs of hemolysis. However, the peripheral blood contained 0.2% GPI(-) granulocytes, and the three PIGA mutations that had been detected before BMT persisted at proportions similar to those before transplantation (p.I69fs, VAF 36.1%; p.T192P, VAF 3.7%; p.V300fs, VAF 8.6%).
Conclusions
The PNH clones whose proportion had increased excessively before BMT decreased but persisted at low percentages for more than 4 years after the immunoablative conditioning regimen followed by syngeneic BMT. These findings indicate that immune pressure on HSCs, which caused BM failure before BMT, was sufficient for PIGA-mutated HSCs to clonally expand to cause PNH.