bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Mechanisms of the Ferroptosis-Related Gene TGFBR1 in Autoimmune Uveitis Based on Machine Learning Models
Authors: Zhang Danlei , Ren He , Xing Yiqiao , Chen Zhen
Published: October 2024

Autoimmune uveitis (AU) is a group of autoimmune-driven diseases characterized by intraocular inflammation, often leading to severe vision loss. Ferroptosis, a recently discovered form of programmed cell death, has not yet been fully explored in the pathogenesis of AU. This study aims to investigate the role of ferroptosis-related key genes in AU, providing a theoretical foundation for further mechanistic studies. We downloaded GSE198533 dataset from the Gene Expression Omnibus (GEO). Through differential gene expression (DEG) analysis, weighted gene co-expression network analysis (WGCNA), and two machine learning models, TGFBR1 and ZFAS1 were identified as critical hub genes. Additionally, we validated the expression of TGFBR1 in retinal inflammation in a mouse model of experimental autoimmune uveitis (EAU) and explored its functional role. The results showed that TGFBR1 expression was significantly downregulated in EAU. Moreover, TGFBR1 overexpression exacerbated retinal inflammation via the GPX4-mediated ferroptosis pathway, accompanied by decreased FOXP3 expression and elevated IL-17A levels, suggesting that TGFBR1 may aggravate the inflammatory response in Behçet's disease (BD) by influencing immune regulatory mechanisms. The correlation between TGFBR1 expression and disease severity highlights its potential as a therapeutic target for EAU and a biomarker for BD, offering promising avenues for molecular-targeted therapies in AU.
Stepwise leaching rare earth from weathered crust elution-deposited rare earth ores by the inhibition leaching of aluminum with HMTA
Authors: He Zhengyan , Zuo Qin , Tang Yuchen , Cui Wenqian , xu zhigao , Wu Ming , Qu Jun , Chi Ruan
Published: October 2024

In the leaching process of rare earth (RE) from weathered crust elution-deposited rare earth ores (WCE-DREO), the exchangeable impurity ions will also be exchanged and enter the RE leachate. Impurity removal must be treated before precipitating RE, which often causes the serious loss of RE and environmental pollution. Therefore, anti-impurity leaching of RE from WCE-DREO was investigated with hexamethylenetetramine (HMTA) as an impurity inhibitor and ammonium sulfate (AS) as a leaching agent. HMTA was first injected into the RE ores at a concentration of 0.8 wt.%, liquid/solid of 0.5:1 and natural pH. Then, the injection solution was replaced with 2 wt.% AS at liquid/solid of 0.5:1 and natural pH. The leaching efficiency of impurity Al could decrease to 5.99%. Without impurity removal, the RE leachate can be directly precipitated to obtain RE products with high quality. The leaching efficiency of RE was 92.95%, which was slightly higher than the traditional leaching technology with a single AS. The stepwise anti-impurity leaching technology simplifies the recovery process of RE, which benefits the green and high-efficiency exploitation of WCE-DREO. The physicochemical properties of RE ores and tailings were analyzed by modern analytical techniques to reveal the anti-impurity leaching mechanism. In the HMTA anti-impurity stage, HMTA can promote the conversion of exchangeable Al to adsorbed hydroxyl Al in RE ores. The adsorbed hydroxyl Al thinly attached to the surface of mineral particles is hard to be leached by leaching agent and retained in the RE ore in the AS leaching stage.
Viral IL-10 regulates nasopharyngeal carcinoma cell progression via the JAK1/STAT3 signalling pathway
Authors: Qiu Qin , Yang Xingyu , Li Xiaojiang , Ren Yanxin , Ning Huang
Published: October 2024

Purpose Nasopharyngeal carcinoma is a common clinical malignant tumour in the nasopharynx. The secretion of vIL-10 by EB virus can promote the development of nasopharyngeal carcinoma. The purpose of this study was to provide a theoretical basis for potential targets and mechanisms of vIL-10 in nasopharyngeal carcinoma.
Methods A total of 100 ng/mLvIL-10 was applied to the nasopharyngeal carcinoma CNE-2 cell line for 48 h,and then whole transcriptome sequencing analysis was performed to identifypotential targets and signalling pathways of vIL-10 innasopharyngeal carcinoma. The effects of vIL-10 on the proliferation, migration, invasion and apoptosis of human nasopharyngeal carcinoma cells were determined by ELISA, Ki67 immunofluorescence, colony formation, Transwell migration/invasion, Hoechst 33258 staining, flow cytometry and other experiments, and the potential effects of vIL-10 on nasopharyngeal carcinoma cells were verified at the cellular level. Western blotting was performed to measure the changes in key factors of the JAK1-STAT3 signalling pathway in nasopharyngeal carcinoma cells after vIL-10 treatment.
Results The whole transcriptome gene sequencing results showed that vIL-10 could effectively activate the JAK-STAT signalling pathway and upregulatethe expression of JAK1 and STAT3. Moreover, vIL-10 inhibited the apoptosis of nasopharyngeal carcinoma cells, enhanced their migration and invasion capabilities, and further promoted the proliferation of nasopharyngeal carcinoma cells.
Conclusion VIL-10 regulates the JAK1-STAT3 signalling pathway, promotes the proliferation of NPC cells, enhances their migration and invasion capabilities, inhibits tumour cell apoptosis, and participates in the progression of nasopharyngeal carcinoma.
Correlation of Suspicious And Pathological Cardiotocography (CTG) with Umbilical Cord Blood Gas Parameters: A Prospective Cohort Study
Authors: Paikaray Soumyashree , Jena Saubhagya Kumar , Balakrishnan Deepthy , Mohanty Pankaj Kumar
Published: October 2024

Introduction-Fetal blood sampling is considered the best option in overcoming the increased false positivity of CTG but is not used in many developing countries due to logistics difficulties. Hence, obstetricians highly rely on CTG for diagnosing fetal hypoxia. Studies of suspicious and pathological CTG correlating with umbilical blood parameters are limited. Lactate can be a reliable marker to assess intrapartum hypoxia. However, the correlation of suspicious and pathological CTG with lactate is least studied.
Methodology- A prospective observational cohort study was conducted to correlate suspicious and pathological CTG with umbilical cord arterial blood gas parameters in induced or laboring pregnant women and to compare the maternal and neonatal outcomes.
Results- Out of 2350 women subjected to continuous CTG, 104 and 101 participants had suspicious and pathological CTG, respectively. A statistically significant association of CTG was seen in women with preterm delivery and with the use of tramadol. The association of primary outcomes like pH, base excess, and lactate with CTG findings was significant.
Discussion- Other modalities to confirm acidosis should be used before an intervention in women with suspicious CTG. Drugs like tramadol and agents used for induction may play a role in abnormal CTG tracing in suspicious CTG. Cord blood lactate has a stronger association with CTG when compared with other umbilical cord parameters.
Conclusion- Pathological CTG should be taken cautiously as it carries a greater risk of perinatal distress, but suspicious CTG tracing needs to be supplemented with additional tests before any interventions.
DARS2 Promotes Bladder Cancer Progression by Enhancing PINK1-Mediated Mitophagy
Authors: Li Dongqing , Su Hang , Huang Yuan , Wang Zihuan , Zhang Jinge , Chen Chen , Hou Lina , Tan Wanlong , Li Fei
Published: October 2024

Background: Bladder cancer is the tenth most common cancer worldwide. Mitochondria, as central hubs of cellular metabolism, play a crucial role in various diseases and cancers. However, the role and underlying mechanisms of mitophagy, the key process governing mitochondrial quantity and quality control, remain unclear in bladder cancer.
Methods: 824 mitophagy-related genes were collected from the Genecards database. Construction and validation of the mitophagy-related genes prognostic model were completed by univariate Cox analysis, Lasso and SuperPC algorithms, Kaplan-Meier survival, univariate and multifactorial Cox regression. The screening and intervention of DARS2 were done by univariate Cox regression, Monocle3 pseudotime and DepMap analysis as wel as siRNA and shRNA. Mitophagy was detected by flow cytometry analysis, super-resolution microscopy, confocal microscopy and transmission electron microscopy.
Results: We screened 16 mitophagy-related genes to construct a prognostic model, which demonstrated strong predictive performance for overall survival, immune response, and chemotherapy outcomes in bladder cancer patients. Among these genes, DARS2 was identified as having a particularly significant impact on bladder cancer prognosis. Further investigation revealed that DARS2 promotes G1-to-S phase transition by upregulating CDK4 expression, thereby inhibiting cellular senescence and promoting cell proliferation. Additionally, DARS2 enhanced PINK1 expression in bladder cancer cells, leading to increased PINK1-mediated mitophagy. Importantly, both in vitro and in vivo experiments confirmed that DARS2 inhibits cellular senescence and promotes tumor progression by enhancing PINK1-mediated mitophagy.
Conclusions: DARS2 promotes PINK1-mediated mitophagy and facilitates G1-to-S phase transition, thereby delaying cellular senescence and promoting bladder cancer progression. Targeting DARS2 and mitophagy could be a promising therapeutic strategy to improve the prognosis of bladder cancer patients.
Importin 7 Mediated Nuclear Transport of MSI2 as a Therapeutic Target in Cervical Cancer
Authors: Qinyang Xu , zhou Wan-Zhen , Qiu Tian , Wang Juan , cheng jing , Jiang Rongzhen , Ai Zhihong , Teng Yincheng , Ma Li , Zhang Rui , Bai Yun
Published: October 2024

Cervical cancer (CC) remains a significant health threat to women worldwide, with a pressing need for novel therapeutic targets. Despite recent advances, the molecular mechanisms underlying CC progression are not fully understood. Nuclear transport proteins, key regulators of macromolecule movement between cellular compartments, have emerged as potential targets in cancer therapy. However, the specific role of Importin 7 (IPO7) in CC development and its clinical implications remain poorly characterized, indicating a significant gap in our current understanding. Here, we investigated IPO7's role in CC, leveraging clinical samples, bioinformatics analyses from TCGA and GEO databases, and experimental models. We found that IPO7 is upregulated in CC and associated with poor prognosis. IPO7 knockdown in cell lines and animal models revealed decreased cell proliferation, reduced colony formation, inhibited migration and invasion, and enhanced apoptosis. To uncover IPO7's molecular mechanisms, we performed mass spectrometry analysis, identifying MSI2, an RNA-binding protein, as a potential cargo. Further validation confirmed a direct interaction between IPO7 and MSI2, with IPO7 overexpression coupled with MSI2 knockdown abrogating oncogenic effects. Sequencing analysis of IPO7-knockdown cells indicated the MYC targets pathway and co-immunoprecipitation assays confirmed a direct interaction between MYC and MSI2, suggesting that IPO7 may facilitate the nuclear transport of MSI2 and MYC, thereby promoting cancer progression. Clinically, elevated MSI2 expression in CC patients, particularly in advanced stages, correlated with poorer outcomes. Our findings elucidate the role of IPO7 in CC, demonstrating its potential as a therapeutic target. The interaction between IPO7, MSI2, and MYC provides a novel avenue for developing targeted therapies. Importantly, our results underscore the importance of IPO7-mediated nuclear transport in CC progression, presenting a promising strategy for enhancing patient outcomes and advancing CC treatment.
On-treatment platelet reactivity at low shear stress and platelet activation status on aspirin or clopidogrel monotherapy in patients with TIA or ischaemic stroke
Authors: Lim Soon Tjin , Stephen Murphy , Smith Deirdre , Collins Ronan , Coughlan Tara , Murphy Sinead , McCarthy Alan , Egan Bridget , Lim Su-Yin , Cox Dermot , McCabe Dominick
Published: October 2024

Background
Simultaneously-collected data regarding platelet reactivity and activation status in ischaemic cerebrovascular disease (CVD) patients commencing commonly-prescribed antiplatelet agents are limited.
Methods
This prospective pilot observational study assessed TIA/ischaemic stroke patients before (baseline; N = 73), and 14 +/-7 days (14d; N = 59) and ≥ 90 days (90d; N = 38) after commencing aspirin or clopidogrel monotherapy. Platelet reactivity at low shear-stress in whole blood (Multiplate® Aspirin/ADP assays) and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. Prevalence of high on-treatment platelet reactivity (HTPR) was determined on the Multiplate analyser with ‘case-control definitions’ (Aspirin-HTPR: > 40U on Aspirin assay; Clopidogrel-HTPR: > 46 U on ADP assay), and innovative ‘longitudinal definitions’ of HTPR (failure to reduce aggregation on the relevant assay compared with the patient’s own baseline value by more than twice the co-efficient of variation of the assay).
Results
The case-control prevalence of aspirin-HTPR was 23.8% (5/21) at 14d, and 30.8% (4/13) at 90d, with corresponding values for longitudinal aspirin-HTPR of 4.8% (1/21) at 14d, and 0% at 90d. The case-control prevalence of clopidogrel-HTPR was 60.5% (23/38) at 14d, and 52% (13/25) at 90d, which was significantly higher than the prevalence of longitudinal clopidogrel-HTPR of 21% (8/38) at 14d, and 24% (6/25) at 90d (P ≤ 0.03), respectively. % Neutrophil-platelet complexes (P = 0.04) and % lymphocyte-platelet complexes (P = 0.002) were higher in patients with vs. those without case-control clopidogrel-HTPR at 14d, but not at 90d. The median % lymphocyte-platelet complexes significantly decreased between baseline and 14d (2.35% vs. 1.24%, P = 0.019), and median % monocyte-platelet complexes decreased between baseline and 90d (6.5% vs. 5.1%, P = 0.017) only in the clopidogrel-patient subgroup whose platelets were adequately inhibited by clopidogrel’. Two of four patients with recurrent vascular events had case-control clopidogrel-HTPR at 14d.
Conclusions
An important proportion of CVD patients had antiplatelet-HTPR at low shear-stress on the Multiplate assay. The prevalence of antiplatelet-HTPR is higher with case-control than with innovative longitudinal definitions. Quantification of % leucocyte-platelet complexes improves our understanding of the cellular mechanisms contributing to traditional case-control clopidogrel-HTPR in CVD patients.
Prevalence and antimicrobial susceptibility pattern of gram- negative bacteria contaminating the hands of patients’ visitors at regional referral hospitals in Dar-es-Salaam: A hospital based cross sectional study
Authors: Jonas Ninael , Mkenda Donath , Killel Erick , Henry Stanslaus , Magembe Emmanuel , Abednego Reuben , Urio Loveness , Lyamuya Eligius
Published: October 2024

Background
Hand contamination by bacteria is a significant source of infection transmission, especially in hospital settings. A healthcare-associated infection is one that a person contracts as a result of their interaction with a hospital. Health care workers’, patients’ and visitors’ hands are all transmission routes for infections, in particular bacterial infections. These infections elevate the economic burden on healthcare systems especially in low-income settings. The purpose of this study is to determine the prevalence of gram-negative bacteria hand contamination among patients’ visitors of referral hospitals in Dar es Salaam.
Results
Prevalence of gram-negative bacterial contamination on visitors’ hands was 91 (21.1%) on entry and 103 (30.2%) on exit. The most common bacteria contamination was from Klebsiella pneumoniae on both entry and exit points, 37 (41%) and 57 (43%) respectively. Resistance to cephalosporins (Cefotaxime and Ceftriaxone) were the most pronounced. Proportion of ESBL-producing bacteria was significantly higher at exit than at entry. Bacterial contamination was associated with not washing hands APR = 1.5 (95% CI:1.03–2.17), offering services to the patient APR = 1.9 (95% CI:1.21–2.87) and longer hospital stays (more than 7 days) APR = 1.5 (95% CI:1.1-2.0).
Conclusion
To prevent the transmission of bacteria, it is important to emphasize hand hygiene and exposure limits for visitors entering hospital environments.
Usefulness perinatal prognosis assessment using z-score over current low birth weight metric: a descriptive study
Authors: Murano Yayoi , Shoji Hiromichi , Sassa Miho , Sakamaki Ken , Shimizu Toshiaki , Gilmour Stuart , Yoneoka Daisuke
Published: October 2024

Background: A cut-off weight of 2500 g in infants, which is commonly referred as low birth weight infants, was established as an indicator of perinatal prognosis several decades ago.
However, perinatal medicine developed dramatically since then and theoutcomes are discussed using other factors including fetal growth nowadays.
This study was conducted to assess the present perinatal situation with recent assessment scales and reconsider the indicators used for perinatal outcome.
Methods: This is a retrospective descriptive study analyzing whole Japanese birth certificate data between 1992 and 2018. Trend in prenatal outcomes including birth weight, gestational age, presence of fetal growth restriction, preterm birth and birth weight-to-gestational age z-score were calculated. Fetal growth restriction was defined as birth weight-to-gestational age z-score less than 10 percentile.
Results: A total of 48,235,783 births in Japan were included. The proportion of infants with birth weight under 2500 g was constant while mean birth weight stopped declining and mean gestational age continued to fall. In contrast, the incidence of fetal growth restriction and the mean birth weight-to-gestational age z-score were improving. In detail, proportion of early term infants (between 37 weeks 0 day and 38 weeks 6 days of gestational age) was increasing while that of late preterm infants (between 34 weeks 0 day and 37 weeks 6 days of gestational age) was constant.
Conclusions: Over all perinatal outcome was improving. Shortened gestational age result from change in perinatal management policy due to progress in perinatal medicine that enabled smaller infants and/or infants born at shorter gestational age to survive. However, even if delivered with a shorter gestational period with an aim to achieve good outcomes, considering that the 10th percentile weight of a baby boy born to a primiparous mother at 37 weeks 0 days gestation, a full-term delivery, is 2203 g, for example, the infants would be classified as a low birthweight infant which is an indicator for poor prognosis. Therefore, low birth weight no longer reflects perinatal outcome appropriately and other factors like fetal growth should be considered as indicators for overall perinatal context.
Association of Chlamydia Trachomatis Sero-Positivity with Male Infertility in the Niger-Delta Region of Nigeria: A Case-Control Study
Authors: Asaboro Newton , Omo-Aghoja Lawrence Osuakpor , Adeyinka Ayotunde
Published: October 2024

Background
The role of Chlamydia infection in the causation of male infertility has not been conclusively evaluated, especially in the developing countries of sub-Sahara Africa that are worse affected by infertility. Understanding the relationship between the two will guide the deployment of preventive efforts and investigative approach more scientifically.
Methods
This was a case-control study of two groups of males – 68 male partners of infertile couples with abnormal semen parameters attending fertility clinic and 68 age-matched male partners (with normal semen parameters) of females attending the family planning clinic as controls at two tertiary hospitals in Delta state. The prevalence of chlamydial seropositivity, the sociodemographic characteristics, sexual & reproductive characteristics, and chlamydial serology of all the participants were determined and compared using appropriate statistical tools.
Results
Most (41.2%) of the participants were in the 35–39 years’ age category, were all married and were mostly (66.2%) skilled workers. The overall prevalence of Chlamydia seropositivity in this study was 11.8%. The prevalence of Chlamydia seropositivity was significantly higher among cases (19.1%) compared with controls (4.4%); (P < 001). Chlamydial seropositivity was significantly associated with oligospermia and teratozoospermia. On bivariate analysis, being in the infertile group (Crude OR 5.12, P = 0.008), history of a genital ulcer (Crude OR 0.124. P = 0.042), and history of dysuria (P = 0.008) were significantly associated with chlamydial trachomatis seropositivity. Upon multivariate logistic regression analysis, none of these covariates was found to be independent predictor of Chlamydia trachomatis seropositivity.
Conclusion
There was a significant association between Chlamydia trachomatis infection and abnormal semen parameters. There were no identified independent predictors of chlamydia trachomatis sero-positivity. Chlamydial screening should be incorporated as part of the basic male fertility investigations.
Analysis of the current situation and influencing factors of work family support for shared nurses in Shanxi Province：A cross-sectional study
Authors: wang xuan , xu YuHong , wu Jing , li JuanJuan , lili gao , Zhang NianNian , Wu ChunYan , Guo ShuMing , Zhang ZhiXia
Published: October 2024

Background
China is experiencing an aging population, resulting in a huge demand for "Internet plus + nursing services", a new service model. However, there are many risk problems in the process of shared nurse service. In order to improve the willingness of shared nurses to continue to participate, work family support scale is used to assess the problems shared nurses face in "Internet plus nursing service".
Aims
To assess the level of work-family support among shared nurses and to analyze the current situation and the factors that influence it.
Methods
A descriptive cross-sectional survey will be conducted from March to May 20234, using convenience sampling to select 360 shared nurses from Linfen City, Changzhi City, and Taiyuan City in Shanxi Province as survey subjects. Use the Work Family Support Questionnaire developed by Li Yongxin.
Results
The cumulative score of this study is (116.38 ± 26.81), and the average score of each item is (3.93 ± 0.87). Through multiple linear regression analysis, it was determined that hospital level, number of orders taken by online appointment nurses, and per capita annual household income have a significant impact on the work family support of online appointment nurses (P < 0.05).
Conclusion
The work-family support scores of shared nurses in China are high. Hospital level, the number of orders received by shared nurses, and per capita annual household income are the key factors affecting the work-family support scores of shared nurses. Hospitals and the government should improve the admission standards and audit mechanisms for shared nurses, establish a sound safety and security mechanism for shared nurses' travel, and strengthen the laws and systems about shared nurses.
Clinical trial number: not applicable.
Simulation and prediction of urban heat island effect driven by land use change: a case of Changsha-Zhuzhou-Xiangtan region
Authors: Xiong Liwei , Shan Xiaolan , Fang Xin , Li Shenxin
Published: October 2024

With the acceleration of urbanization, the rapid expansion of urban land use has led to an intensification and expansion of the urban heat island effect. This study focuses on the Changsha-Zhuzhou-Xiangtan region as the study area. Through geographical detectors, it analyzes the contribution intensity of land cover type data, DEM, GDP, and population density to the urban heat island. Using the CA-Markov model, it conducts a predictive analysis of land use conditions in the Changsha-Zhuzhou-Xiangtan region in 2025. Furthermore, based on the ANN-CA model, it predicts the intensity of the urban heat island in the Changsha-Zhuzhou-Xiangtan region for both 2025 and 2040. The results indicate that the proportion of construction land area, GDP, and DEM are the most influential factors contributing to the urban heat island. The prediction accuracy of the ANN-CA model for the urban heat island in 2015 and 2020, starting from 2000 and 2005, reached 86.12% and 94.8%, respectively, demonstrating the reliability of the ANN-CA model in predicting the urban heat island. Compared to 2020, the combined area proportion of strong and hot urban heat island regions in the Changsha-Zhuzhou-Xiangtan region increased by 1.04% in 2025 and 1.02% in 2040. During the period from 2020 to 2040, the heat island effect in the Changsha-Zhuzhou-Xiangtan region showed a slow increase, indicating that the heat island effect will be controlled to some extent overall.
A Robust and Data-Efficient Deep Learning Modelfor Cardiac Assessment without Segmentation
Authors: Artman Conor , Henao Ricardo
Published: October 2024

Video-based deep learning (DL) algorithms often rely on segmentation models to detect clinically important features in transthoracic echocardiograms (TTEs). While effective, these algorithms can be too data hungry for practice and may be sensitive to common data quality issues. To overcome these concerns, we present a data-efficient DL algorithm, Scaled Gumbel Softmax (SGS) EchoNet, that is robust to these common data quality issues and, importantly, requires no ventricular segmentation model. In lieu of a segmentation model, we decompose and transform the output of an R(2+1)D convolutional encoder to estimate frame-level weights associated with the cardiac cycle, that are then used to obtain a video representation that can be used for estimation. We find that our transformation obviates the need for a segmentation model while improving the ability of the predictive model to handle noisy inputs. We show that our model achieves comparable performance to the state of the art, while demonstrating robustness to noise on an independent (external) validation set.
Evaluation of degradation profile of selected space medicine after accelerated gamma irradiation and its comparison with photodegradation as per ICH Q1(B)
Authors: Patel Manali , Mehta Priti , Khan Saif , Singh Birendra
Published: October 2024

Long-duration space missions requires, the stability of pharmaceuticals for maintaining astronaut health. Pharmaceuticals are exposed to a unique space radiation environment that alters their stability and efficacy during prolonged missions. Gamma radiation is one of the major radiation present in space and it can penetrate spacecraft and affect the stability of pharmaceuticals by inducing physical or chemical changes. To evaluate the effect of gamma radiation on the physical and chemical stability, two drugs were selected namely ciprofloxacin and promethazine with its marketed liquid formulations. Both were exposed to gamma and photo radiation in the present study. Gamma irradiation was carried out at varying doses from 25 Gy to 800 Gy and photo irradiation was conducted over 1.2 million lux hours as per ICH Q1(B) guideline. The chemical stability of the exposed samples was analyzed using RP-HPLC analysis. Ciprofloxacin and Promethazine aqueous API solution and formulations exhibited dose-dependent degradation on gamma exposure. Comparative degradation profile of photo and gamma-irradiated aqueous solution of ciprofloxacin and promethazine indicates the difference in the degradation pathways leading to the formation of degradation products. Significant degradation was observed in the liquid formulation of ciprofloxacin with and without packing on gamma exposure. This is the first report to show that the primary packaging material used for ciprofloxacin eye/ear drops enables to control the degradation after irradiation with a low dose of gamma rays.
Identification of end stage renal disease associated loci in X chromosome: an X chromosome-wide association study
Authors: Zhou Xiaohong , Shi Dianchun , Li Ming , Liu Yibin , Ye Zhiming , Chen Wei , Wang Meng , Fu Dongying , Wang Yanna , Gan Hua , Fu Ping , Tan Xiaojun , Kong Yaozhong , Chen Jihong , Zhao Jinghong , Yu Xueqing , Liu Jianjun
Published: October 2024

Background
X-chromosomal genetic variants have been understudied in end stage renal disease (ESRD), which hold the promise to provide valuable insights into sexually dimorphic traits and diseases.
Methods
We performed a X chromosome-wide association study (XWAS) in a Chinese cohort (N = 2750), comprising 1489 cases with ESRD and 1261 controls, to identify locus associated with ESRD risk.
Results
One sex-shared loci, rs3138874 located in the promoter of COL4A5 were identified in the meta-analysis on the summary statistics from the sex-stratified XWAS. Additionally, 2 male-specific loci, comprising rs142591759 near MIR3202-2 and rs73250616 near SYTL4 were identified in the sex-stratified XWAS in males. Of the 3 ESRD associated loci, 2 were previously found to be associated with estimated Glomerular filtration rate (eGFR) in different populations. Finally, by integrating expression quantitative trait loci (eQTL) statistics from multiple tissues and conducting eQTL colocalization analysis, we found that SYTL4, TSPAN6, NOX1, CSTF2, PCDH19 and RPL36A are the target genes of ESRD associated locus Xq22.1.
Conclusion
Our finding revealed three X-chromosome loci linked to ESRD risk, which provided foundational knowledge for genetic risk prediction and advanced our understanding of the molecular underpinnings of ESRD.
Climate change induces rapid growth of dead ice in Asian glaciers
Authors: Wang Qiong , Wang Xin , Duan Keqin , Liu Shiyin , Yin Yongsheng , Liu Qiao , He Jinping , Zhang Yong , Wei Junfeng , Jiang Zongli
Published: October 2024

Dead ice in High Mountain Asia (HMA) varies responsive to dramatic glacier loss, profoundly impacting alpine water cycle patterns. We find significant dead ice increase over this century, additional area exceeds 3,000 km2, with mass 44.3 ± 2.0 ~ 64.1 ± 5.2 Gt. Debris coverage dominates dead ice spatial pattern. Dead ice expansion would significantly alter spatio-temporal patterns of glacier ablation and impact water supply sustainability in World's Water Towers.
Comparative analysis of mucosa-associated and luminal gut microbiota in pediatric ulcerative colitis
Authors: Kondo Takeo , Kondo Sonoko , Nakayama-Imaohji Haruyuki , Tada Ayano , Tabassum Nafisa , Emmanuel Munyeshyaka , Kusaka Takashi , Kuwahara Tomomi
Published: October 2024

Background
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease, are chronic disorders relating to gut microbiota dysbiosis. Despite severe pancolitis being more prevalent in pediatric UC than in adult cases, alterations in the colon mucosa-associated microbiota (MAM) and their association with disease severity remain to be elucidated. The present study aimed to compare the gut microbiota in colon lavage fluids (CLFs) and fecal samples from pediatric UC patients.
Results
A total of 140 CLFs and 23 fecal samples from 19 each of pediatric UC and non-IBD patients were analyzed. CLFs were collected by aspirating intestinal fluid after washing the colonic mucosa using an endoscope with a waterjet function. Microbiota profiles of each sample were analyzed by 16S rRNA gene amplicon sequencing. The community structure of MAM was similar throughout the colon in both pediatric UC and non-IBD. Bacterial compositions between MAM and feces were significantly different in non-IBD while no difference was observed in pediatric UC, indicating a compromised mucous layer that could not sufficiently separate the MAM and luminal microbiota in UC. In pediatric UC, homogenous distribution of MAM was gradually disordered with increases in disease activity or mucosal inflammation, and the bacterial groups that usually colonize the upper digestive tract or have environmental origin were more abundant in MAM. To potentially distinguish pediatric UC from non-IBD, we identified the key bacterial genera in MAM; they included Lactobacillus, Enterococcus, Blautia, Parabacteroides, Faecalibacterium and Fusobacterium.
Conclusion
Compared with feces, MAM is more enriched in specific bacterial groups in non-IBD pediatric patients, whereas the feces and MAM microbiota are similar in pediatric UC. Our results indicate that the fecal microbiota reflect the status of MAM in pediatric UC. Monitoring the key fecal bacteria that are specifically increased in MAM depending on disease activity might be useful for evaluation of patient prognosis in pediatric UC. Further studies on MAM are needed to elucidate the contribution of its community structure to the pathophysiology of pediatric UC.
Multi-object Detector with Double Task Network for Traffic Scenes
Authors: Wang Sheng-ye , Qu Zhong , Zheng Jian
Published: October 2024

Enhancing the precision of multi-object detection within traffic scenes is of paramount importance. Despite significant advancements in object detection algorithms based on deep neural networks, the persistent challenges of inaccuracies and low efficiency in multi-object detection demand innovative solutions. We introduce an efficient object detection method, referred to as DTNet, aimed at elevating accuracy in multi-object scenarios and extending its utility to diverse object recognition tasks, including object detection and instance segmentation. To address these challenges, we propose DTNet, which incorporates three key components: the OPSM, the PACT, and the B-NMS. Our study demonstrates substantial performance enhancements compared to state-of-the-art YOLO detectors. When compared to YOLOv7-segment, DTNet achieves an 1.7% improvement in P on the Cityscapes-trf dataset. Furthermore, on the COCOtrf 17 dataset, DTNet exhibits an 50.42% enhancement in mAP@0.5, underscoring its efficacy in multi-object detection. The experimental outcomes demonstrate that our strategies not only enhance performance related to presicion, maintaining an equivalent of 142 GFLOPs, but also achieve this with a mere addition of 0.02 (M) in Params.
Bridging the Gap:
Analyzing English Reading Proficiency Disparities Among Korean EFL Learners
Authors: Kim Eun Jung , Lee ByungMin
Published: October 2024

This study investigates the heterogeneity in English reading abilities among sixth-grade EFL learners in South Korea, focusing on their L2 reading profiles and the socio-educational factors predicting them. 598 students from mid- and low-income neighborhoods were assessed on five L2 literacy components: decoding, oral fluency, vocabulary knowledge, syntactic knowledge, and reading comprehension. Latent profile analysis identified distinct subgroups of learners, and multinomial logistic regression was used to analyze the key predictor variables influencing English reading proficiency. The results highlight a significant proficiency gap between students who began learning English in the third grade and those exposed earlier through private tutoring. Struggling readers showed deficits in decoding, while proficient readers excelled in fluency. The impact of early English education was limited compared to learning experiences in elementary school. The study suggests the need for targeted interventions to address reading disparities and provides pedagogical implications for improving English language instruction in Korean classrooms.
Multi-Drug Pharmacotyping improves Therapy Prediction in Pancreatic Cancer Organoids
Authors: Wansch Katharina , Pelzer Uwe , Schneider François , Dölvers Florian , Kühn Anna , Dragomir Mihnea P. , Ihlow Jana , Hilfenhaus Georg , Vecchione Loredana , Felsenstein Matthäus , Ma Dou , Lerchbaumer Markus , Jürgensen Christian , Bahra Marcus , Granada Adrian E. , Duwe Gregor , Stintzing Sebastian , Keilholz Ulrich , Neumann Christopher C.M.
Published: October 2024

Patient-Derived Organoids (PDOs) represent a promising technology for therapy prediction in pancreatic cancer, with the potential of enhancing treatment outcomes and allowing more effective, personalized treatment choices. However, classification approaches into sensitive and resistant models remain very variable and are based on single-agent testing only, neglecting synergistic effects of multi-drug combinations. Here, we established 13 PDOs and performed both combinatorial and single-agent drug testing. By comparing different clustering approaches of drug-response metrics and establishing a new classification approach based on pharmacokinetic modelling, we were able to evaluate which score best predicts the clinical response of patients. Our newly developed score considered the Area Under The Curve (AUC) of cell viability curves and reached a prediction accuracy of 85%. Our data supports previous findings for PDOs to constitute an effective platform for translational drug testing. Furthermore, our results suggest that the AUC is a more accurate drug-response metric than the half maximal inhibitory concentration (IC50), and that combinatorial drug testing yields a higher accuracy than single-agent testing. Based on our results, future PDO studies and PDO-based clinical trials should integrate combinatorial drug testing when performing pharmacotyping as it represents a more realistic translational approach towards drug testing and enhances the prediction accuracy of in-vitro drug testing. The methodology and outcomes presented in this study are of critical relevance for future PDO-based translational trials as they allow a new physiology-based approach towards multi-drug testing and classification of organoid response, which improves PDO prediction accuracy.
Agro-morphological characterization of Coffea canephora (Robusta) genotypes from the INERA Yangambi Coffee Collection, Democratic Republic of the Congo
Authors: Bollen Robrecht , Kambale Jean-Léon , Tas An-Sofie , Katshela Benjamin Ntumba , Tshimi Ebele Aaron , Wyffels Francis , Vandelook Filip , Honnay Olivier , Stoffelen Piet
Published: October 2024

Meeting rising quality standards while at the same time addressing climate challenges will make the commercial cultivation of Robusta coffee increasingly difficult. Whereas breeding new varieties may be an important part of the solution, such efforts for Robusta lag behind, with much of its genetic diversity still unexplored. By screening existing field genebanks to identify accessions with desirable traits, breeding programs can be significantly facilitated. This study quantifies the morphological diversity and agronomic potential of 70 genotypes from the INERA Coffee Collection in Yangambi, Democratic Republic of the Congo. We measured 29 traits, comprising vegetative, reproductive, tree architecture, and yield traits. Classification models were applied to establish whether these traits could accurately classify genotypes based on their background. Furthermore, the agronomic potential and green bean quality of the genotypes were studied. While significant variation in morphological traits was observed, no combination of traits could reliably predict the genetic background of different genotypes. Genotypes with promising traits for green beans were identified in both ‘Lula’ and ‘Lula’ – Wild hybrids, while promising yield traits were found in ‘Lula’ – Congolese subgroup A hybrids. Additionally, certain ‘Lula’ – Wild hybrids showed low specific leaf area and stomatal density, indicating potential fitness advantages in dry environments, warranting further study. Our findings highlight the agronomic potential of underexplored Robusta coffee genotypes from the Democratic Republic of the Congo and indicate the need for further screening to maximize their value.
Genetic analyses identify shared genetic components related to autoimmune and cardiovascular diseases
Authors: Pauklin Siim , Qiao Jun , Chang Min-Jing , Chen Miaoran , Zhao Yuhui , Hao Jiawei , Zhang Pengwei , Zhou Ruixin , Cai Liuyang , Liu Feng , Fan Xiaoping , Zou Rongjun , Li Zhixiu , Feng Yuliang
Published: October 2024

Objectives
Autoimmune diseases (ADs) play a significant and intricate role in the onset of cardiovascular diseases (CVDs). Our study aimed to elucidate the shared genetic etiology between Ads and CVDs.
Methods
We conducted genome-wide pleiotropy analyses to investigate the genetic foundation comprehensively and shared etiology of six ADs and six CVDs. We analyze the genetic architecture and genetic overlap between these traits. Then, SNP-level functional annotation identified significant genomic risk loci and potential causal variants. Gene-level analyses explored shared pleiotropic genes, followed by pathway enrichment analyses to elucidate underlying biological mechanisms. Finally, we assess potential causal pathways between ADs and CVDs.
Results
Despite negligible overall genetic connections, our results revealed a significant genetic overlap between ADs and CVDs, indicating a complex shared genetic architecture spread throughout the genome. The shared loci implicated several genes, including ATXN2, BRAP, SH2B3, ALDH2 (all located at 12q24.11-12), RNF123, MST1R, RBM6, and UBA7 (all located at 3p21.31), all of which are protein-coding genes. Top biological pathways enriched with these shared genes were related to the immune system and intracellular signal transduction.
Conclusions
The extensive genetic overlap with mixed effect directions between ADs and CVDs indicates a complex genetic relationship between these diseases. It suggests overlapping genetic risk may contribute to shared pathophysiological and clinical characteristics and may guide clinical treatment and management.
Partial Cystectomy as a Viable Alternative Treatment for an Intradiverticular Non Bilharzial Squamous Cell Carcinoma of Bladder with a 5-Year Follow-up: A Case Report.
Authors: TG Subash Kaushik , Daniel Benjith , Krishnamoorthy Sriram
Published: October 2024

Background: Squamous cell carcinoma (SCC) is a rare malignancy with poor prognosis, affecting the urinary bladder. Most of the SCC present as muscle invasive or locally advanced cancer. While majority of SCC of urinary bladder are of bilharzial origin, 2% to 5% of them can be of non-bilharzial origin. The uniqueness about this case is that patient had a good disease-free survival for 5 years after partial cystectomy performed for extravesical SCC bladder.
Summary: Though most of the SCC of urinary bladder are best treated by radical cystectomy, a 68-year-old male with painless hematuria, diagnosed with an intradiverticular SCC of the bladder on magnetic resonance imaging had a recurrence and metastases free survival on 5 years follow-up after partial cystectomy (PC).
Conclusion: This case report outlines the role and effectiveness of partial cystectomy as an alternative option in such patients with a follow-up of 5 years without any recurrence or metastases.
En bloc resection, inactivation and replantation combined with chemotherapy for tibial metastasis: a case report and literature review
Authors: Chu Dawei , Huang Rui , Zheng Jianping , Yang Zongqiang , Niu Ningkui , Shi Jiandang
Published: October 2024

Background
The extremities are the most common sites of bone metastasis of malignant tumors. Bone defect reconstruction after bone tumor resection has always been a great challenge in clinical treatment. At present, the most widely used method is individualized artificial prosthesis replacement, but it is expensive and difficult for patients with poor economic ability to bear. Therefore, choosing which reconstruction method can achieve good curative effect and economical affordability has become a problem of clinical thinking.
Case presentation:
We present here the case of a 43-year-old man who had been suffering from pain in his left calf for the past 2 years that had aggravated 6 months before the presentation. His tibia had osteolytic destruction on both X-ray and CT, while MRI showed malignant neoplastic lesions. Preoperative incision biopsy of the lesion revealed metastatic poorly differentiated adenocarcinoma, which required artificial prosthesis replacement. The patient came to our hospital considering that he could not afford the high cost of surgery. Based on the patient's medical history, physical manifestations, physical and auxiliary examinations, and disease characteristics, we diagnosed him as metastatic poorly differentiated adenocarcinoma of the left tibia and reconstructed with liquid nitrogen-inactivated autologous bone. The postoperative pathological results showed that the histopathology of the patient was a metastatic tumor of the left tibia from breast cancer. After multidisciplinary discussion, chemotherapy was followed. At present, the patient has been followed up for more than 26 months, and there is no tumor recurrence.
Conclusions
There are many methods for reconstruction of large bone defects after resection of bone tumors, but the choice of reconstruction method needs to be based on the different conditions of each patient. For patients in economically underdeveloped areas, liquid nitrogen-inactivated autologous bone replantation for bone metastasis may be an economical and safe choice.
Chip formation and morphology in cryogenic machining of Al-SiC composites
Authors: Mašek Petr , Alagan Nageswaran Tamil , Mára Vladimír , Awe Samuel A. , Nwabuisi Emeka , Zeman Pavel
Published: October 2024

Machining aluminium matrix composites is a challenging and costly endeavour, primarily owing to silicon carbide reinforce particles, which are abrasive and hard, resulting in excessive tool wear, suboptimal surface quality, and undesirable chip formation. This study investigates the influence of cryogenic cooling on the development and morphology of chips when aluminium-silicon carbide (Al-SiC) composites are turned with an uncoated tungsten carbide cutting tool. Compared with dry machining, cryogenic cooling significantly alters the chip formation process, producing shorter and less curled chips. Chip breakability is mainly caused by cracks at the aluminium reinforcement particle interface, and the particle distribution is more uniform in cryogenically cooled chips. Rake and dual (rake and flank) cooling strategies have proven to be more effective for cryogenic cooling. Chip breakability primarily depends on the chip curl diameter across the used conditions. Chip formation under cryogenic cooling indirectly indicated the significant temperature reduction in the cut.
Classification of ECG signals using CNN models
Authors: Chettaoui Hnia , Mouaddeb Rabeb , Moulahi Tarek , Bennaji Najoua
Published: October 2024

Electrical activity is essential for blood circulation, and any alteration in the orderly pattern of excitation waves propagating through the heart can lead to arrhythmias. The electrocardiogram (ECG) is a widely used tool for diagnosing arrhythmias, as it is rapid, affordable, and non-invasive. However, manual interpretation of ECG data is often time-consuming and subject to human error. With improved training, deep learning (DL) could provide a more effective alternative for rapid, automatic classification. This study presents a novel deep learning architecture, including a convolutional neural network (CNN), for classifying cardiac arrhythmias. Real ECG signals from the Heartbeat Categorization ECG dataset were used for training and validation. The models’ performance was evaluated using the confusion matrix, which determined precision, accuracy, recall, F1 score, mean, and AUC-ROC. Both models demonstrated exceptional performance, achieving accuracies of 0.995 and 0.996 on training and test datasets, outperforming existing methods in terms of accuracy and efficiency.