bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic value of whole-genome DNA methylation in response to Leflunomide in patients with Rheumatoid Arthritis
Authors: Chen Yulan , Wang Qiao , Liu Haina , Jin Lei , Feng Xin , Dai Bingbing , Chen Meng , Xin Fangran , Wei Tingting , Bai Bingqing , Fan Zhijun , Li Jiahui , Yao Yuxin , Liao Ruobing , Zhang Jintao , Jin Xiangnan , Fu Lingyu 
Published: September 2023

ObjectiveAlthough Leflunomide (LEF) is effective in treating rheumatoid arthritis (RA), there are still a considerable number of patients who respond poorly to LEF treatment. Till date, few LEF efficacy-predicting biomarkers have been identified. Herein, we explored and developed a DNA methylation-based predictive model for LEF-treated RA patient prognosis.MethodsTwo hundred forty-five RA patients were prospectively enrolled from four participating study centers. A whole-genome DNA methylation profiling was conducted to identify LEF-related response signatures via comparison of 40 samples using Illumina 850k methylation arrays. Furthermore, differentially methylated positions (DMPs) were validated in the 245 RA patients using a targeted bisulfite sequencing assay. Lastly, prognostic models were developed, which included clinical characteristics and DMPs scores, for the prediction of LEF treatment response using machine learning algorithms.ResultsWe recognized a seven-DMP signature consisting of cg17330251, cg19814518, cg20124410, cg21109666, cg22572476, cg23403192, and cg24432675, which was effective in predicting RA patient’s LEF response status. In the five machine learning algorithms, the support vector machine (SVM) algorithm provided the best predictive model, with the largest discriminative ability, accuracy, and stability. Lastly, the AUC of the complex model(the 7-DMP scores with the lymphocyte and the diagnostic age) was higher than the simple model (the seven-DMP signature, AUC:0.74 vs 0.73 in the test set).ConclusionIn conclusion, we constructed a prognostic model integrating a 7-DMP scores with the clinical patient profile to predict responses to LEF treatment. Our model will be able to effectively guide clinicians in determining whether a patient is LEF treatment sensitive or not.
Compensatory growth and production economics of Silver pompano, Trachinotus blochii (Lacepede, 1801), fingerlings stunted by feed and space deprivation
Authors: P. P. Suresh Babu , A. Anuraj , M. T. Shilta , Ebeneezar Sanal , P. Shinoj , K. Raghu Ramudu , N. D. Praveen , N. G. Vaidya , Pal Mahendra , I. Boby , K. K. Anikuttan , A. Gopalakrishnan 
Published: September 2023

The effect of stunting by feed and space deprivation on compensatory growth (CG) in Silver pompano,Trachinotus blochii, was investigated. A commercial pellet feed (45% protein and 10% fat) was fed two times a day, throughout the entire experiment. The 270-day experiment consisted of an initial 60-day stunting phase and a 60-day post-stunting phase carried out in 4 × 2 × 2 m3galvanized iron (GI) rectangular cages, and a 150-day grow-out phase carried out in 3-m diameter circular GI cages. During the stunting phase, the normal fish (in triplicates) were stocked at lower stocking density (17 fish/m3) and fed at 10% of body weight (BW), while stunted fish (one replication) were stocked at about three times higher stocking density (56 fish/m3) and fed at a three times lower feeding rate (3% of BW). The stunted and normal fish were reared in triplicates during the post-stunting phase, at uniform stocking density (15 fish/m3) with feeding at a higher rate (10% of BW) for stunted fish and normal feeding rate (8% of BW) was adopted for normal fish. During the grow-out stage, each replication from the post-stunting phase was shifted to 3-m circular cages with the same feeding rates. The lag in growth in stunted fish (5.56 g against 9.43 ± 0.13 g of normal) during the stunting phase was compensated during the post-stunting phase (36.88 ± 2.23 g against 38.13 ± 1.48 g of normal) by higher feeding rate. There were no significant (p&gt; 0.05) differences in final harvest, biometry, morphometry, dressing yield, carcass nutritional composition, and serum biochemical markers at the end of grow-out stage. Because of the significant difference (p&lt; 0.05) in the total feed provided (5.2 kg for stunted fish against 22.8 kg for normal fish) and the lesser unit cost for the production of stunted fingerling (USD 0.087 for stunted fish against USD 0.106 for normal), the farming of stunted fish brought about a higher net operational revenue and benefit:cost ratio.
Synthesis of novel acylated and esterified ciprofloxacin derivatives as efficient anticancer and antimicrobial agents
Authors: Alasadi Gheith M. , Al-Obaidi Zaid 
Published: September 2023

Nowadays, various factors enhance the resistance of some microbes to antibiotics. Irrational antibiotic use is considered an example of such factors. Therefore, the synthesis and reporting of heterocyclic compounds with multiple biological properties are of considerable value. Ciprofloxacin is an antibiotic used to treat infections. New amidification and esterification derivatives of ciprofloxacin were synthesized. Their structure was identified and confirmed using both proton and carbon-13 nuclear magnetic resonance, mass spectrometry, and elemental analysis. With the employment of MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-terazoliumbromide) methods, in vitro anticancer activity was evaluated. The utilization of clinical and laboratory standards institute (CLSI) instructions was involved in the in vitro antimicrobial activity evaluation of the newly synthesized derivatives. In terms of anticancer activity, cell proliferation, viability, and IC50, as well as antimicrobial activities, IZD (Inhibition Zone Diameter), MIC (Minimum Inhibitory Concentrations), MBC (Minimum Bactericidal Concentrations), and MFC (Minimum Fungicidal Concentration) were measured and reported. The lowest cell proliferation and viability and IC50 for 2,3-dihydroxypropyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate (compound 5) were observed to be 27.12% and 7.83 μg/mL. In antimicrobial activity, the lowest MIC for 2,3-dihydroxypropyl 7-(4-benzoylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (compound 6c) was observed to be 2 μg/mL (against Proteus mirabilis) and the lowest MIC for 1-cyclopropyl-6-fluoro-7-(4-(4-(methylthio)benzoyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (compound 3d) was observed to be 32 μg/mL (against Candida albicans, Aspergillus fumigatus). The effects were compared with commercially available drugs, and it was observed that some derivatives have the same efficacy as abemaciclib, which is used to treat breast cancer. Some derivatives were more effective than Cefazolin and Tolnaftate, well-known antibiotics and antifungals, respectively. Finally, a fairly clear relationship between the structure of the derivatives and their biological effectiveness was observed.
Bisphenol A exposure triggers endoplasmic reticulum stress pathway leading to ocular axial elongation in mice
Authors: Chen Junhan , Ikeda Shin-ichi , Kang Longdan , Negishi Kazuno , Tsubota Kazuo , Kurihara Toshihide 
Published: September 2023

BackgroundOcular axial elongation is one of the features of myopia progression. Endoplasmic reticulum (ER) stress-associated scleral remodeling plays an important role in ocular axial elongation. Bisphenol A (BPA) is one of the most common environmental pollutants and is known to affect various human organs through ER stress. However, whether BPA exerts an effect on scleral remodeling remains unknown. The purpose of this study was to determine the effect of BPA on the development of myopia and scleral ER stress.MethodsBPA was administered by intraperitoneal injection. 4-PBA was administered as an endoplasmic reticulum stress inhibitor by eye drops. Refraction and axial length were measured by refractometer and SD-OCT system. Western blot was performed to detect the expression level of ER stress-related proteins.ResultsBPA-administered mice exhibit axial elongation and myopic refractive shift with endoplasmic reticulum stress in the sclera. BPA administration activated scleral PERK and ATF6 pathways, and 4-PBA eye drops attenuated ER stress response and suppressed myopia progression.ConclusionBPA controlled axial elongation during myopia development in a mouse model by inducing scleral ER stress and activation of the PERK/ATF6 pathway. 4-PBA eye drops as ER stress inhibitor suppressed BPA-induced myopia development.
Microbiota and its antibiotic resistance profile in avocado Guatemalan fruits (Persea nubigena var. guatemalensis) sold at retail markets of Ibarra city, northern Ecuador
Authors: Angamarca Evelyn , Castillejo Pablo , Tenea Gabriela N. 
Published: September 2023

IntroductionAvocados are typically sold in unsanitary conditions at the retail markets in Ecuador, which can raise the risk of microbial contamination. These microorganisms could exhibit multi-antibiotic resistance (MAR), being a serious threat concern to human health. In this study, we aimed to evaluate the microbiota and its antibiotic resistance profile in avocado Guatemalan fruits (Persea nubigena var. guatemalensis), at ripe stage: immature, firm light green (ready to eat in 4 days), peel (AFPE) and pulp (AFPU), and mature intense green (ready to eat) peel (AMPE) and pulp (AMPU), to gain baseline information on the prevalence of MAR bacteria.MethodsCulture-independent (16S rRNA metagenomics) and culture-dependent approach (to detect specific indicator microorganisms) were used. Moreover, antibiotic susceptibility of selected target indicator bacteria was assessed providing information about the antibiotic resistance (AR) among the groups.ResultsBased on 16S rRNA gene metagenomic analysis, over 99.78% of reads were classified as bacteria in all samples. Shannon diversity index varies from 1.22 to 2.22, with the highest bacterial population assigned to AFPE samples (1327 species). The highest microbial counts of indicator Staphylococcus spp. (STAPHY), Enterobacter spp. (ENT), and Listeria spp. (LIST), were detected in AMPE samples. Thirty percent of the selected STAPHYs, and 20.91% of Enterobacter (ENT) clones were resistant to various classes of antibiotics. The MAR index varies between 0.25 to 0.88 and was clone-, and fruit ripe stage-dependent.ConclusionsThe results indicated that ready to eat avocados contained detectable levels of MAR bacteria, including methicillin resistant (MR)-STAPHY, which may act as a potential vector for the spread of antibiotic resistance. To achieve the increase of the production and marketing of Fuerte cultivar in Ecuador, it is vitally important to consider valuable strategies to protect the fruits at the early ripe stage in future. Thus, it is crucial to set up efficient control measures and develop coordinated strategies to guarantee the microbiological quality of the food.
Epigenetic regulation of Parkinson’s disease risk variant GPNMB cg17274742 methylation by sex and exercise from Taiwan Biobank
Authors: Chen Yen-Chung , Liaw Yi-Chia , Nfor Oswald Ndi , Hsiao Chih-Hsuan , Zhong Ji-Han , Wu Shey-Lin , Liaw Yung-Po 
Published: September 2023

BackgroundParkinson’s disease (PD) is a complex neurodegenerative disease with an elusive etiology that involves the interaction between genetic, behavioral, and environmental factors. Recently, epigenetic modifications, particularly DNA methylation, have been recognized to play an important role in the onset of PD. Glycoprotein non-metastatic melanoma protein B (GPNMB), a type I transmembrane protein crucial for immune cell activation and maturation, has emerged as a potential biomarker for the risk of PD. This research aims to investigate the influence of exercise and gender on the regulation of methylation levels of GPNMB cg17274742 in individuals.MethodsWe analyze data from 2,474 participants in the Taiwan Biobank, collected from 2008 and 2016. Methylation levels at the GPNMB cg17274742 CpG site were measured using Illumina Infinium MethylationEPIC beads. After excluding individuals with incomplete data or missing information on possible risk factors, our final analysis included 1,442 participants. We used multiple linear regression models to assess the association between sex and exercise with adjusted levels of GPNMB cg17274742 for age, BMI, smoking, drinking, coffee consumption, serum uric acid levels, and hypertension.ResultsOur results demonstrated that exercise significantly influenced the methylation levels of GPNMB cg17274742 in males (β = −0.00242; p = 0.0026), but not in females (β = −0.00002362; p = 0.9785). Furthermore, male participants who exercised showed significantly lower levels of methylation compared to the reference groups of the female and non-exercising reference groups (β = −0.00357; p = 0.0079). The effect of the interaction between gender and exercise on the methylation of GPNMB cg17274742 was statistically significant (p = 0.0078).ConclusionThis study suggests that gender and exercise can modulate GPNMB cg17274742, with hypomethylation observed in exercise men. More research is needed to understand the underlying mechanisms and implications of these epigenetic changes in the context of risk and prevention strategies.
Virtual reality in managing Complex Regional Pain Syndrome (CRPS): a scoping review
Authors: Arcos-Holzinger Mauricio , Biebl Johanna Theresia , Storz Claudia , Gutmann Marcus , Azad Shahnaz Christina , Holzapfel Boris Michael , Kraft Eduard 
Published: September 2023

BackgroundComplex Regional Pain Syndrome (CRPS) is a severe pain disorder that does not yet have a specific treatment. Patients with CRPS not only suffer from a wide range of symptoms that affect their quality of life but also present psychological affections to the way they see their body and specifically their affected limb. Virtual Reality (VR) modalities have become a targeted treatment for chronic pain and in the case of CRPS, may be a valuable approach to the mechanisms that affect these patients.ObjectivesUsing the PRISMA Scoping Review guidelines, we intend to uncover the key information from the studies available about VR modalities in the treatment of CRPS. We focus on the improvement of pain levels, body perception disturbances (BPD), and limb movement/daily function.ResultsOur search strategy resulted in 217 articles from PubMed. Twenty were assessed for eligibility and seven were included in the final qualitative synthesis. Of these seven articles, we included a clinical trial, three pilot studies, a blinded randomized controlled trial, a crossover double-blind trial, and a randomized controlled trial. These studies provide important subjective patient findings, along with some statistically significant results in the experiences of VR therapies modulating pain, BPD, and improving limb movement/daily function. However, not all the studies included statistical analysis, and there are contradicting data found from some patients that did not perceive any improvement from VR therapies.ConclusionsWe describe the results found in 7 articles that focus on the treatment of CRPS with VR modalities. Overall, the articles have various limitations, but the strategies related to immersive virtual reality, cardiac signaling, body switching and limb modulation have shown the most promising results for pain reduction and BPD improvement. These strategies reflect on pathophysiological mechanisms that are hypothesized to be affected in CRPS patients leading to the chronic pain and BPD that they experience. Not much evidence was found for improvement in limb movement and daily function. This review is a pathway for future studies on this topic and a more extensive data synthesis when more information is available.
Electroencephalography characteristics related to risk of sudden unexpected death in epilepsy in patients with Dravet syndrome
Authors: Kim Jeong-Youn , Shin Jeongyoon , Kim Laehyun , Kim Se Hee 
Published: September 2023

ObjectiveTo investigate the quantitative electroencephalography (EEG) features associated with a high risk of sudden unexpected death in epilepsy (SUDEP) in patients with Dravet syndrome (DS).MethodsPatients with DS and healthy controls (HCs) who underwent EEG were included in the study. EEG signals were recorded using a 21 channel digital EEG system, and pre-processed data were analyzed to identify quantitative EEG features associated with a high SUDEP risk. To assess the risk of SUDEP, SUDEP-7 scores were used.ResultsA total of 64 patients with DS [38 males and 26 females, aged: 128.51 ± 75.50 months (range: 23–380 months)], and 13 HCs [7 males and 6 females, aged: 95.46 ± 86.48 months (range: 13–263 months)] were included. For the absolute band power, the theta power was significantly higher in the high-SUDEP group than in the low-SUDEP group in the central brain region. For the relative band power, the theta power was also significantly higher in the high-SUDEP group than in the low-SUDEP group in the central and occipital brain regions. The alpha power was significantly lower in the high-SUDEP group than in the low-SUDEP group in the central and parietal brain regions.ConclusionPatients with high SUDEP-7 scores have different EEG features from those with low SUDEP-7 scores, suggesting that EEG may be used as a biomarker of SUDEP in DS.SignificanceEarly intervention in patients with DS at a high risk of SUDEP can reduce mortality and morbidity. Patients with high theta band powers warrant high-level supervision.
Predictive value of whole-brain CT perfusion combined with ABCD3 score for short-term secondary cerebral infarction after TIA
Authors: Liu Shushu , Chen Ting , Wu Wei 
Published: September 2023

ObjectiveTo investigate the predictive value of Whole Brain CT Perfusion (WB-CTP) combined with the ABCD3 score in patients with transient ischemic attack (TIA).MethodsA total of 336 TIA patients with TIA underwent WB-CTP and ABCD3 score assessment within 48 h of admission. Spearman correlation test was performed to analyze the relationship between the degree of vascular stenosis, relative perfusion values, and ABCD3 score. Logistic regression analysis was used to identify independent risk factors for secondary cerebral infarction. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of relative cerebral blood flow (rCBF), degree of vascular stenosis, ABCD3 score, and the WB-CTP-ABCD3 combined model for secondary cerebral infarction after TIA. Calibration curves and H-L tests were used to evaluate the predictive efficacy of the model.ResultsAmong the 336 TIA patients, 143 showed abnormal perfusion areas and 146 had responsible vessel stenosis. The degree of vascular stenosis, relative time-to-maximum (rTmax), and relative mean transit time (rMTT) were positively correlated with the ABCD3 score, while rCBF and relative cerebral blood volume (rCBV) were negatively correlated with the ABCD3 score. ROC curve analysis identified a cutoff value of 0.8205 for rCBF, with a sensitivity of 84.10% and specificity of 58.10% for distinguishing the cerebral infarction group from the non-cerebral infarction group. Furthermore, rCBF ≤ 0.8205, degree of vascular stenosis, and ABCD3 score &gt; 6 were identified as independent risk factors for secondary cerebral infarction in TIA patients within 90 days in TIA patients. The AUC of the WB-CTP-ABCD3 combined model for predicting secondary cerebral infarction within 90 days was 0.836. The model risk was assessed by plotting calibration curves. The value of p for the H-L goodness of fit test was 0.366 (p &gt; 0.05), which indicated that the difference between the obtained model and the perfect model were statistically insignificant.ConclusionThe combined model of WB-CTP-ABCD3 shows promise as a valuable method for predicting secondary cerebral infarction within 90 days following TIA.
COVID-19 lockdown related to decrease in premature birth rate and increase in birth weight in metropolitan France
Authors: Tessier Benoit , Annesi-Maesano Isabella , Cambonie Gilles , Molinari Nicolas , Kalfa Nicolas 
Published: September 2023

IntroductionThe worldwide rate of preterm birth (PTB) has been increasing over the last two decades. COVID-19 lockdowns provide a unique opportunity to assess the effects of socioenvironmental and lifestyle factors on premature birth and birth weight. We explored the effects of COVID-19 lockdowns on the PTB rate and birth weight at a nationwide scale in France until one year after their occurrence.Material and MethodsThis national retrospective observational study evaluated the rate of PTB and birth weight in France from January 2016 to December 2020. Data were obtained from the national Programme Médicalisé des Systèmes d'Information database. The rates of global and sub-categories of PTB were tested. The birth weight was studied before and after lockdown for all live births, for term and premature neonates, and for each category of low birth weight (LBW) by a stratified analysis.ResultsData from 2,949,372 births from January 2016 to December 2019, including 228,857 PTB, were compared to those of 699,344 births and 51,886 PTB from January to December 2020. The national rate of PTB decreased significantly from 7.7% to 7.3%, when compared with the 2016–2019 period. This decrease was persistent up to 9 months later. It was observed only for moderate PTB, whereas very PTB and extremely PTB remained stable. The national mean birth weight for full-term babies increased after the lockdown and was still observable up to 8 months later (+0.16%, p &lt; 0.0001). The proportion of children with LBW also decreased 2 months after lockdown (−0.15%; p = 0.02). For VLBW, the difference only appeared over the 6-month post-lockdown period (−0.06%; p = 0.006).ConclusionThis nationwide study shows a significant reduction in prematurity and a significant increase in birth weight in France after the lockdown for a period of time not limited to the lockdown itself. A more in-depth study of the factors determining these variations may help to drive PTB prevention policies.