bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single point mutations at the S129 residue of α-synuclein and their effect on structure, aggregation, and neurotoxicity
Authors: Pandit Esha , Das Lopamudra , Das Anoy Kumar , Dolui Sandip , Saha Saumen , Pal Uttam , Mondal Animesh , Chowdhury Joydeep , Biswas Subhas C. , Maiti Nakul C. 
Published: May 2023

Parkinson’s disease is an age-related neurological disorder, and the pathology of the disease is linked to different types of aggregates of α-synuclein or alpha-synuclein (aS), which is an intrinsically disordered protein. The C-terminal domain (residues 96–140) of the protein is highly fluctuating and possesses random/disordered coil conformation. Thus, the region plays a significant role in the protein’s solubility and stability by an interaction with other parts of the protein. In the current investigation, we examined the structure and aggregation behavior of two artificial single point mutations at a C-terminal residue at position 129 that represent a serine residue in the wild-type human aS (wt aS). Circular Dichroism (CD) and Raman spectroscopy were performed to analyse the secondary structure of the mutated proteins and compare it to the wt aS. Thioflavin T assay and atomic force microscopy imaging helped in understanding the aggregation kinetics and type of aggregates formed. Finally, the cytotoxicity assay gave an idea about the toxicity of the aggregates formed at different stages of incubation due to mutations. Compared to wt aS, the mutants S129A and S129W imparted structural stability and showed enhanced propensity toward the α-helical secondary structure. CD analysis showed proclivity of the mutant proteins toward α-helical conformation. The enhancement of α-helical propensity lengthened the lag phase of fibril formation. The growth rate of β-sheet-rich fibrillation was also reduced. Cytotoxicity tests on SH-SY5Y neuronal cell lines established that the S129A and S129W mutants and their aggregates were potentially less toxic than wt aS. The average survivability rate was ∼40% for cells treated with oligomers (presumably formed after 24 h of incubation of the freshly prepared monomeric protein solution) produced from wt aS and ∼80% for cells treated with oligomers obtained from mutant proteins. The relative structural stability with α-helical propensity of the mutants could be a plausible reason for their slow rate of oligomerization and fibrillation, and this was also the possible reason for reduced toxicity to neuronal cells.
Clinical features of Cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome and efficacy of the current therapy
Authors: Zhao Qing , Li Ning-ning , Chen You-xin , Zhao Xin-yu 
Published: May 2023

BackgroundCytomegalovirus retinitis (CMVR) is the most common and sight-threatening opportunistic retinal infection in patients with acquired immunodeficiency syndrome (AIDS) and several controversies remain to be settled. We aimed to summarize the current evidence and clarify the clinical features and prognosis of CMVR in AIDS patients.MethodsThe databases PubMed, EMBASE, and Ovid from inception to April 2022 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval (CI) were calculated using the Freeman-Tukey variant of arcsine square transformation.ResultsWe finally included 236 studies comprising 20,214 patients. CMVR in AIDS was male-dominated (88%, 95%CI 86%-89%), with 57% (95%CI 55%-60%) aged &lt;41 years and 44% (95%CI 41%-47%) being bilaterally involved. CMVR was preponderant in AIDS patients with the following characteristics: white and non-Hispanic, homosexual, HIV RNA load ≥ 400 copies/mL, and CD4+ T-cells &lt;50 cells/μL. The positivity of CMV-DNA in blood, aqueous humor, and vitreous humor was 66% (95%CI 52%-79%), 87% (95%CI 76%-96%), and 95% (95%CI 85%-100%), respectively. The most common symptoms were blurred vision (55%, 95%CI 46%-65%), followed by asymptomatic, visual field defect, and floaters. CMVR was first diagnosed and regarded as the clue to AIDS diagnosis in 9% (95%CI 6%-13%) of CMVR patients. Approximately 85% (95%CI 76%-93%) of the CMVR patients have received cART. CMVR remission was observed in 72%-92% of patients depending on the specific category of anti-CMV therapy. The general incidence of CMVR-related RD in the entire course was 24% (95%CI 18%-29%), of which most patients received PPV with SO or gas tamponade and the rate of anatomic success was 89% (95%CI 85%-93%).ConclusionCMVR is a common opportunistic infection with diverse clinical features in AIDS patients, preponderant in those who are male, homosexual, or with CD4+ T-cells &lt;50 cells/μL. Current therapies for CMVR and CMVR-related RD were shown to be effective. Early detection and routine ophthalmic screening should be promoted in AIDS patients.Systematic review registrationPROSPERO, identifier CRD42022363105.
Artificial intelligence for health message generation: an empirical study using a large language model (LLM) and prompt engineering
Authors: Lim Sue , Schmälzle Ralf 
Published: May 2023

IntroductionThis study introduces and examines the potential of an AI system to generate health awareness messages. The topic of folic acid, a vitamin that is critical during pregnancy, served as a test case.MethodWe used prompt engineering to generate awareness messages about folic acid and compared them to the most retweeted human-generated messages via human evaluation with an university sample and another sample comprising of young adult women. We also conducted computational text analysis to examine the similarities between the AI-generated messages and human generated tweets in terms of content and semantic structure.ResultsThe results showed that AI-generated messages ranked higher in message quality and clarity across both samples. The computational analyses revealed that the AI generated messages were on par with human-generated ones in terms of sentiment, reading ease, and semantic content.DiscussionOverall, these results demonstrate the potential of large language models for message generation. Theoretical, practical, and ethical implications are discussed.
Identification of mitophagy-related genes with potential clinical utility in myocardial infarction at transcriptional level
Authors: Yang Zhikai , Sun Liang , Wang Hua 
Published: May 2023

BackgroundMyocardial infarction (MI) ranks among the most prevalent cardiovascular diseases. Insufficient blood flow to the coronary arteries always leads to ischemic necrosis of the cardiac muscle. However, the mechanism of myocardial injury after MI remains unclear. This article aims to explore the potential common genes between mitophagy and MI and to construct a suitable prediction model.MethodsTwo Gene Expression Omnibus (GEO) datasets (GSE62646 and GSE59867) were used to screen the differential expression genes in peripheral blood. SVM, RF, and LASSO algorithm were employed to find MI and mitophagy-related genes. Moreover, DT, KNN, RF, SVM and LR were conducted to build the binary models, and screened the best model to further external validation (GSE61144) and internal validation (10-fold cross validation and Bootstrap), respectively. The performance of various machine learning models was compared. In addition, immune cell infiltration correlation analysis was conducted with MCP-Counter and CIBERSORT.ResultsWe finally identified ATG5, TOMM20, MFN2 transcriptionally differed between MI and stable coronary artery diseases. Both internal and external validation supported that these three genes could accurately predict MI withAUC = 0.914 and 0.930 by logistic regression, respectively. Additionally, functional analysis suggested that monocytes and neutrophils might be involved in mitochondrial autophagy after myocardial infarction.ConclusionThe data showed that the transcritional levels of ATG5, TOMM20 and MFN2 in patients with MI were significantly different from the control group, which might be helpful to further accurately diagnose diseases and have potential application value in clinical practice.
Primary hyperaldosteronism is associated with increased mortality and morbidity in patients with hypertension and diabetes
Authors: Pillai Krishnadev , Fares Ahmed , Dargham Soha , Al Suwaidi Jassim , Jayyousi Amin , Abi Khalil Charbel 
Published: May 2023

AimsPrimary hyperaldosteronism (PA) is a common cause of hypertension. It is more prevalent in patients with diabetes. We assessed the cardiovascular impact of PA in patients with established hypertension and diabetes.MethodsData from the National Inpatient Sample (2008-2016) was used to identify adults with PA with hypertension and diabetes comorbidities and then compared to non-PA patients. The primary outcome was in-hospital death. Secondary outcomes included ischemic stroke, hemorrhagic stroke, acute renal failure, atrial fibrillation, and acute heart failure.ResultsA total of 48,434,503 patients with hypertension and diabetes were included in the analysis, of whom 12,850 (0.03%) were diagnosed with primary hyperaldosteronism (PA). Compared to patients with hypertension and diabetes but no PA, those with PA were more likely to be younger [63(13) vs. 67 (14), male (57.1% vs. 48.3%), and African-Americans (32% vs. 18.5%) (p&lt;0.001 for all). PA was associated with a higher risk of mortality (adjusted OR 1.076 [1.076-1.077]), ischemic stroke [adjusted OR 1.049 (1.049-1.05)], hemorrhagic stroke [adjusted OR 1.05 (1.05-1.051)], acute renal failure [adjusted OR 1.058 (1.058-1.058)], acute heart failure [OR 1.104 (1.104-1.104)], and atrial fibrillation [adjusted OR 1.034 (1.033-1.034)]. As expected, older age and underlying cardiovascular disease were the strongest predictors of mortality. However, the female gender conferred protection [OR 0.889 (0.886-0.892].ConclusionPrimary hyperaldosteronism in patients with hypertension and diabetes is associated with increased mortality and morbidity.
Comparison of the adjuvant effect of conbercept intravitreal injection at different times before vitrectomy for proliferative diabetic retinopathy
Authors: Yang Zhikun , Di Yu , Ye Junjie , Yu Weihong , Guo Zijian 
Published: May 2023

PurposeTo assess the optimal time of intravitreal conbercept (IVC) treatment prior to pars plana vitrectomy (PPV) in patients with severe proliferative diabetic retinopathy (PDR).MethodThis study was exploratory in nature. Forty-eight consecutive patients (48 eyes) with PDR were divided into four groups according to different IVC times (0.5 mg/0.05 mL) before PPV: group A (3 days), group B (7 days), group C (14 days), and group D (non-IVC). Intraoperative and postoperative effectiveness were assessed, and vitreous VEGF concentrations were detected.ResultFor intraoperative effectiveness, groups A and D had a higher incidence of intraoperative bleeding than groups B and C (P = 0.041). Furthermore, groups A-C required less surgical time than group D (P &lt; 0.05). For postoperative effectiveness, group B had a significantly higher proportion of visual acuity that improved or remained unchanged than group D (P = 0.014), and groups A-C had lower proportions of postoperative bleeding than group D. The vitreous VEGF concentration of group B (67.04 ± 47.24 pg/mL) was significantly lower than that of group D (178.29 ± 110.50 pg/mL) (P = 0.005).ConclusionIVC treatment that was administered 7 days preoperatively was associated with better effectiveness and a lower vitreous VEGF concentration than its administration at other time points.
Effect of surgical treatment on patients with stage T3 or T4 triple-negative breast cancer: a SEER-based retrospective observational study
Authors: Hu Jie , Dai Changling , Zhang Yang , Chen Weijun , Sun Lihua , Zhang Xu , Duan Minjie , Fu Hao , Long Teng , Kang Wei , Yin Chengliang , Liu Xiaozhu , Yu Jie 
Published: May 2023

BackgroundThe use of surgery is controversial in patients with stage T3 or T4 triple-negative breast cancer (TNBC). We aimed to explore the effect of surgical treatment on overall survival (OS) of these patients.MethodsA total of 2,041 patients were selected and divided into the surgical and non-surgical groups based on the Surveillance, Epidemiology, and End Results database from 2010 to 2018. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to balance covariates between different groups. The OS of the two groups were assessed by Kaplan–Meier survival curves and Cox proportional hazards regression models.ResultsA total of 2,041 patients were included in the study. After PSM and IPTW, baseline characteristics of the matched variables were fully balanced. Kaplan–Meier survival curves showed that the median survival time and OS of TNBC patients with stage T3 or T4 in the surgical group were significantly improved compared with those in the non-surgical group. Multivariate Cox proportional hazards regression analysis showed that surgery was a protective factor for prognosis.ConclusionOur study found that surgery prolonged the median survival and improved OS compared with the non-surgical group of TNBC patients with stage T3 or T4.
Systematic analysis between inflammation-related index and sex hormones in American adults: cross-sectional research based NHANES 2013-2016
Authors: Wei Chengcheng , Zhang Wenting , Chen Jiabi , He Qingliu , Cao Li , Zhang Pu , Deng Changqi , Xiong Ming , Huang Yu , Guo Haixin , Wang Miao , Chen Zhaohui 
Published: May 2023

BackgroundA series of novel inflammation-related indexes has been confirmed to be efficient indicators of human immune and inflammatory status, with great potential as predictors for a variety of diseases. However, the association between inflammation-related indexes and sex hormones in the general population remained uncertain.MethodsWe incorporated data from the NHANES 2013-2016 survey of American adults. On the basis of distribution and comparison analysis, we chose to undertake separate analyses of men and women (including premenopausal and postmenopausal groups). Multivariable weighted linear regression models, eXtreme Gradient Boosting (XGBoost) models, generalized linear analysis, stratified models, logistic regression models and sensitivity analysis were utilized to assess the relationships between inflammation-related indexes and sex hormones.ResultsTotal 9372 participants out of 20146 were fitted into our research. We conducted separate gender analysis due to different distribution. Multivariable weighted linear regression indicated every component of the inflammation-related index was negatively correlated with at least one component of the male hormone indexes. However, SII, NLR, PPN, and NC were associated positively with female estradiol. XGBoost identify SII, PLR and NLR were the critical indexes on sex hormones. Inflammation-related indexes was associated with Testosterone deficiency in male and postmenstrual group and associated with Excessive Estradiol in premenstrual group. Finally, the subgroup analysis revealed that the association between sex hormones and inflammatory indicators was prominent in American adults over the age of 60 or those with BMI (&gt;28 kg/m2).ConclusionIn all, inflammation-related indexes act as independent risks associated with sex hormone alterations and metabolic disorder in both genders. Using multiple models, we revealed the relative importance of inflammation-related indexes. Subgroup analysis also identified the high-risk population. More prospective and experimental research should be conducted to validate the results.
Cluster and network analysis of non-headache symptoms in migraine patients reveals distinct subgroups based on onset age and vestibular-cochlear symptom interconnection
Authors: Li Hui , Xu Xiaonuo , Zhou Jiying , Dong Liang 
Published: May 2023

ObjectiveThe present study endeavors to identify natural subgroups of migraine patients based on the patterns of non-headache symptoms, utilizing cluster analysis. Subsequently, network analysis was performed to estimate the structure of symptoms and explore the potential pathophysiology of these findings.MethodA total of 475 patients who met the diagnostic criteria for migraine were surveyed face-to-face during the period of 2019 to 2022. The survey included collecting demographic and symptom data. Four different solutions were generated by the K-means for mixed large data (KAMILA) clustering algorithm, from which the final cluster solutions were selected based on a series of cluster metrics. Subsequently, we performed network analysis using Bayesian Gaussian graphical models (BGGM) to estimate the symptom structure across subgroups and conducted global and pairwise comparisons between structures.ResultCluster analysis identified two distinct patient groups, and the onset age of migraine proved to be an effective characteristic differentiating the two patient groups. Participants assigned to late-onset group showed a longer course of migraine, higher frequency of monthly headache attacks, and greater tendency toward medication overuse. In contrast, patients in early-onset group exhibited a higher frequency of nausea, vomiting, and phonophobia compared to their counterparts in the other group. The network analysis revealed a different symptom structure between the two groups globally, while the pairwise differences indicated an increasing connection between tinnitus and dizziness, and a decreasing connection between tinnitus and hearing loss in the early-onset group.ConclusionUtilizing clustering and network analysis, we have identified two distinct non-headache symptom structures of migraine patients with early-onset age and late-onset age. Our findings suggest that the vestibular-cochlear symptoms may differ in the context of different onset ages of migraine patients, which may contribute to a better understanding of the pathology of vestibular-cochlear symptoms in migraine.
The relationship between processing speed and remodeling spatial patterns of intrinsic brain activity in the elderly with different sleep duration
Authors: Pu Li , Zou Yao , Wang Yan , Lei Jia-Ling , Zhao Xiao-Nan , Zeng Xia , Yan Guo-Jian 
Published: May 2023

ObjectiveBrain neuroplasticity in which sleep affects the speed of information processing in the elderly population has not been reported. Therefore, this study was conducted to explore the effects of sleep on information processing speed and its central plasticity mechanism in the elderly.MethodsA total of 50 individuals aged 60 and older were enrolled in this case control study. All subjects were divided into two groups according to the sleep time: short sleep duration (&lt; 360 min) (6 men and 19 women; mean age: 66.96 ± 4.28 years old), and non-short sleep duration (&gt; 360 min) (13 men and 12 women). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated for each participant. Two-sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. Then, the relationships among clinical features, fMRI and cognitive function were analyzed using general linear model.ResultsShort sleep duration group showed significantly increased ALFF value in the bilateral middle frontal gyrus and right insula; significantly increased ReHo value in the left superior parietal gyrus, and decreased ReHo value in the right crebellum; significantly decreased DC value in the left inferior occipital gyrus, left superior parietal gyrus and right cerebellum (p &lt; 0.05, AlphaSim correction). The ALFF value of right insula is significantly associated with symbol digit modalities test (SDMT) score (β = −0.363, p = 0.033).ConclusionShort sleep duration and processing speed are significantly associated with remodeling spatial patterns of intrinsic brain activity in the elderly.
Case Report: The ultrasound features of acquired cystic disease-associated renal cell carcinoma: a case series
Authors: Yang Yanrong , Chen Hongyan , Li Yongzhong , Zhou Jiaojiao 
Published: May 2023

BackgroundAcquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a new subtype listed by the 2016 World Health Organization (WHO) classification, which occurred in end-stage renal disease (ESRD) patients. This study will present the imaging characteristics of the four cases diagnosed with ACD-RCC. Ultrasound is expected to help detect abnormalities early in the follow-up of patients on regular dialysis, allowing patients to receive early treatment.Case presentationWe searched the pathology database of our hospital for all inpatients diagnosed with ACD-RCC between January 2016 and May 2022. Pathology, ultrasound, and radiology readings are performed by experienced physicians with the title of attending physician or higher. Four cases were included in this study, all of whom were male, aged from 17 to 59. Two cases suffered from ACD-RCC in both kidneys, and kidney nephrectomies were performed. One case underwent renal transplantation, whose creatinine was back to normal, and the rest were on hemodialysis. On the pathological images, heteromorphic cells and oxalate crystals can be seen. Both ultrasound and enhanced CT showed an enhancement of the solid component of the occupancy. We followed up with outpatient and telephone visits.ConclusionIn clinical work, ACD-RCC should be considered when the mass appears in the background of multiple cysts in the kidney in patients with ESRD. A timely diagnosis will help with treatment and prognosis.