bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of human probiotics on memory, psychological and biological measures in elderly: A study protocol of bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge Biota)
Authors: Bartos Ales , Weinerova Josefina , Diondet Sofia , Vales Karel 
Published: November 2022

BackgroundGut microbiota may influence brain functions. Therefore, we prepared a study protocol for a double-blind, crossover, randomized clinical trial to determine the complex effects of human probiotics on memory, psychological, and biological measures in the elderly.MethodsWe selected eligible participants using an effective electronic questionnaire containing the inclusion and exclusion criteria and a brief electronic cognitive test. One-third of the respondents with the worst cognitive scores on the electronic test are randomized to group A, starting with a 3-month probiotic intervention, and to group B, starting with a placebo. In a crossover design, both groups change their intervention/placebo status after 3 months for the next 3 months. Participants refusing longer personal assessments due to the COVID-19 pandemic were randomly allocated to one of two subgroups assessed online. Participants in both groups are matched in age, education, gender, and cognitive scores on electronic testing at baseline. At three time points, participants are assessed using a neuropsychological battery, self-report measures of mood, a physical fitness test, blood, urine, and stool samples, and actigraphy. A subset of participants also provided their biological samples and underwent the neuropsychological battery in an extended testing phase 3 months after study termination to find out the long-term effect of the intervention.DiscussionThis is the first trial to address the comprehensive effects of human probiotics on memory and many other measures in the elderly. We assume that the probiotic group will have better outcomes than the placebo group after the first and second trimesters. We expect that the probiotic effect will persist for the next 3 months. These study’s findings will contribute to an interesting area of how to improve memory, psychological and biological and other factors naturally and will examine the importance of probiotics for overall health in the elderly.Clinical trial registration[clinicaltrials.gov], identifier [NCT05051501].
Case report and review of literature: Isolated intramedullary spinal neurocysticercosis
Authors: Andino Diana , Tsiang John T. , Pecoraro Nathan C. , Jani Ronak , Iordanou Jordan C. , Zakaria Jehad , Borys Ewa , Pasquale David D. , Nockels Russ P. , Schneck Michael J. 
Published: November 2022

BackgroundCases of isolated intramedullary spinal neurocysticercosis are extremely rare. Only 25 cases have been reported before 2022. Due to its rarity, the diagnosis of spinal neurocysticercosis may be missed.Case presentationWe describe a 37-year-old female patient who developed back pain and lower extremity weakness and was found to have an intramedullary thoracic spine cystic lesion. She was taken to the operating room for resection of the lesion. Pathology revealed a larval cyst wall consistent with neurocysticercosis. The patient was started on albendazole and dexamethasone. Her exam improved post-operatively, and she was able to ambulate with minimal difficulty at the time of follow up.ConclusionThe case provides insights on the diagnosis and treatment of isolated intramedullary spinal neurocysticercosis. Review of the literature suggests that combined surgical and medical intervention results in significant improvement in the patient's neurological exam, and decreases morbidity associated with the disease. We propose a treatment paradigm for this rare manifestation of neurocysticercosis.
Response to subsequent antiseizure medications after first antiseizure medication failure in newly diagnosed epilepsy
Authors: Hersi Hire , Saarinen Jukka T. , Raitanen Jani , Peltola Jukka 
Published: November 2022

ObjectiveThere is a lack of studies using the International League Against Epilepsy (ILAE) recommendation to define drug-resistant epilepsy (DRE). This study evaluated the seizure freedom rates of substitution or add-on and subsequent antiseizure medication (ASM) therapies using different proposed definitions of DRE or ASM trials in patients with a failed first ASM. We also identified prognostic factors for 1-year seizure freedom.MethodsThis study included 459 patients with epilepsy of whom 151 were not seizure-free after the first ASM. Multilevel mixed-effects logistic regression was used to examine the correlation between observations from the same patient.ResultsThe overall seizure freedom rate with the first and subsequent ASMs was 88.0% (404/459). The rate of DRE when defined as the failure of two ASMs for any reason was 20.0%, and according to the ILAE definition of DRE, it was 16.3%. After failing the first ASM, 63.6% of patients (96/151) became seizure free with subsequent ASMs and tried an average of 1.9 ASMs (range 1–5). Of the patients who achieved 1-year seizure freedom, 10.1% (41/404) were taking polytherapy and there was no difference between substitution and add-on. All the patients with generalized epilepsy were seizure-free. A favorable prognostic factor was age &gt;60 years and an EEG without epileptiform activity. The efficacies of the different ASMs were largely similar, but drugs that enhanced GABA-mediated inhibitory neurotransmission had the lowest seizure freedom rate.SignificanceIn adults with newly-diagnosed epilepsy, 1-year seizure freedom was achieved for almost 90% of the patients. After failing the first ASM, two-thirds of the patients responded to subsequent ASM regimens. Our results support the feasibility and applicability of the ILAE concept of an adequate ASM trial and the failure of two ASMs as a definition of DRE.
The effect of interictal epileptic discharges and following spindles on motor sequence learning in epilepsy patients
Authors: Okadome Toshiki , Yamaguchi Takahiro , Mukaino Takahiko , Sakata Ayumi , Ogata Katsuya , Shigeto Hiroshi , Isobe Noriko , Uehara Taira 
Published: November 2022

PurposeInterictal epileptic discharges (IEDs) are known to affect cognitive function in patients with epilepsy, but the mechanism has not been elucidated. Sleep spindles appearing in synchronization with IEDs were recently demonstrated to impair memory consolidation in rat, but this has not been investigated in humans. On the other hand, the increase of sleep spindles at night after learning is positively correlated with amplified learning effects during sleep for motor sequence learning. In this study, we examined the effects of IEDs and IED-coupled spindles on motor sequence learning in patients with epilepsy, and clarified their pathological significance.Materials and methodsPatients undergoing long-term video-electroencephalography (LT-VEEG) at our hospital from June 2019 to November 2021 and age-matched healthy subjects were recruited. Motor sequence learning consisting of a finger-tapping task was performed before bedtime and the next morning, and the improvement rate of performance was defined as the sleep-dependent learning effect. We searched for factors associated with the changes in learning effect observed between the periods of when antiseizure medications (ASMs) were withdrawn for LT-VEEG and when they were returned to usual doses after LT-VEEG.ResultsExcluding six patients who had epileptic seizures at night after learning, nine patients and 11 healthy subjects were included in the study. In the patient group, there was no significant learning effect when ASMs were withdrawn. The changes in learning effect of the patient group during ASM withdrawal were not correlated with changes in sleep duration or IED density; however, they were significantly negatively correlated with changes in IED-coupled spindle density.ConclusionWe found that the increase of IED-coupled spindles correlated with the decrease of sleep-dependent learning effects of procedural memory. Pathological IED-coupled sleep spindles could hinder memory consolidation, that is dependent on physiological sleep spindles, resulting in cognitive dysfunction in patients with epilepsy.
Inflammatory rheumatic diseases and the risk of Parkinson's disease: A systematic review and meta-analysis
Authors: He Lili , Zhao Hecong , Wang Fuli , Guo Xiaoyan 
Published: November 2022

BackgroundSeveral studies showed inconsistencies in the relationships between inflammatory rheumatic diseases (IRDs) and the risk of Parkinson's disease (PD). Therefore, we carried out a meta-analysis to investigate the associations between different IRDs and PD risk.MethodsA comprehensive search was undertaken on PubMed, Embase, Cochrane Library, and Web of Science databases up to June 2022. Studies reporting the relationships between IRDs and PD risk were included. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated by using random-effects models.ResultsTwenty-two publications covering seven IRDs containing data from 833,004 patients were identified for quantitative analysis. The pooled results indicated that ankylosing spondylitis (RR = 1.55, 95% CI: 1.31–1.83, I2 = 32.1%, P &lt; 0.001), Sjögren's syndrome (RR = 1.34, 95% CI: 1.22–1.47, I2 = 58.5%, P &lt; 0.001), and Behcet's disease (RR = 1.93, 95% CI: 1.07–3.49, I2 = 57.6%, P = 0.030) were associated with an increased PD risk. However, no significant associations were observed between gout, rheumatoid arthritis, systemic lupus erythematosus, as well as polymyalgia rheumatica and the subsequent development of PD.ConclusionAnkylosing spondylitis, Sjögren's syndrome, and Behcet's disease may increase PD risk.
Inverse association of a traditional Korean diet composed of a multigrain rice-containing meal with fruits and nuts with metabolic syndrome risk: The KoGES
Authors: Kim Min Jung , Hur Haeng Jeon , Jang Dai Ja , Kim Myung-Sunny , Park Sunmin , Yang Hye Jeong 
Published: November 2022

BackgroundHansik, a traditional Korean diet, may have a beneficial impact on metabolic syndrome (MetS) risk as dietary westernization increases its prevalence. We examined the hypothesis that adherence to the hansik diet may be inversely associated with the risk of MetS and its components and sought to understand the gender differences in 58,701 men and women aged over 40.Materials and methodsHansik was defined using 14 components from which the Korean dietary pattern index (Kdiet-index) was generated by summing their scores. Low-hansik intake was defined as the Kdiet-index with &lt;8. MetS was categorized based on the 2005 revised NCEP-ATP III criteria modified for Asians.ResultsThe Kdiet-index score was negatively associated with the dietary inflammation index and showed that the high intake of a meal with multigrain rice, fruits, and their products, and nuts, and low intake of fried foods were inversely associated with MetS by 0.707, 0.864, 0.769, and 0.918 times, respectively, after adjusting for covariates. More women and participants with more educated and lower income belonged to the high-hansik group, and participants with high self-rated health scores consumed more hansik. All participants on a high-hansik diet were associated with a 0.87 time lower risk of MetS. Specifically, the association between hansik intake and MetS risk was not significant among men following stratification by gender. Body composition, including the body mass index, waist circumference, and fat mass, was inversely associated with hansik intake, while the skeletal muscle mass index was positively associated with the hansik intake in each gender and all participants. In all the participants in the high-hansik group, no significant changes were seen in the serum glucose and HDL concentration. However, a high-hansik intake showed lower blood pressure and serum LDL and triglyceride concentrations only in men and a higher glomerular filtration rate in both genders.ConclusionsHansik intake might improve MetS risk, with its primary beneficial effects on body composition, dyslipidemia, and blood pressure gender-dependently.
Mapping global epidemiology of thyroid nodules among general population: A systematic review and meta-analysis
Authors: Mu Chunyang , Ming Xin , Tian Ye , Liu Yang , Yao Menglin , Ni Yinyun , Liu Yong , Li Zhihui 
Published: November 2022

IntroductionAn emerging public health issue is brought on by the worldwide increase of thyroid nodules (TNs). The goal of the current study is to determine the global prevalence of TNs among the general population.MethodsWe screened articles published from January 2000 to May 2022. TN prevalence was calculated with the DerSimonian–Laird random effects model with arcsine transformation.ResultsA total of 20,358 entries were found in our research, and 102 of them met our inclusion criteria. A total of 9,276,178 individuals have been diagnosed as TNs; the overall prevalence was 24.83% (95% CI 21.44–28.55), regardless of the diagnostic techniques. TNs have become more prevalent during 2012–2022 (29.29%) compared with 2000–2011 (21.53%, p = 0.02). In addition, we discovered that women (36.51%) were more likely to have TNs than men (23.47%, p &lt; 0.01). Interestingly, we found that obesity was correlated with the prevalence of TNs. Additionally, age-specific-stratified TN prevalence was found in our results.DiscussionThis meta-analysis shows that, regardless of country development and economic status, TNs are spreading more widely over the world. Our findings showed a strong correlation between rising TN prevalence and older age, female sex, and elevated weight. To stop the TN epidemic from spreading over the world, increased awareness, the understanding of the disease, and quick action are required.
Circulating tumor cells as a preoperative risk marker for occult metastases in patients with resectable cholangiocarcinoma
Authors: Fründt Thorben , von Felden Johann , Krause Jenny , Heumann Asmus , Li Jun , Riethdorf Sabine , Pantel Klaus , Huber Samuel , Lohse Ansgar W. , Wege Henning , Schulze Kornelius 
Published: November 2022

Cholangiocarcinoma (CCA) is an aggressive tumor associated with a high rate of recurrence after resection. An important risk factor for recurrence is the presence of occult metasta-ses, which are not radiologically detectable at the time of diagnosis. There are currently no biomarkers for the preoperative assessment of micrometastases. A previous study demonstrated the prognostic relevance of circulating tumor cells (CTC) in patients with advanced CCA but the potential of CTCs as a preoperative marker for detecting occult metastases has not been investigated so far. In this two-phase study, we first recruited a cohort of 27 patients with histologically proven, metastatic CCA or gallbladder cancer (GBCA) to assess feasibility (feasibility cohort, FC). CTCs were measured in the peripheral blood using the CellSearch System (CSS) between October 2012 and January 2017. Subsequently, in 11 patients undergoing curative-intended resection for CCA (intrahepatic CCA: n =4; extrahepatic CCA n= 6; gallbladder cancer: n=1), peripheral and central venous blood specimens were obtained to improve detection rate by simultaneous measurement and to elucidate distribution of CTCs in different venous compartments. Presence of CTCs detection was correlated with postoperative TNM-status.In the FC, CTCs (range 1-3 cells, median: 1) were detected in 40% (11/27) patients and were signifi-cantly associated with worse overall survival (hazard ratio: 3.59; 95% CI: 1.79- 7.1; p = 0.04). By combined peripheral and central measurement, CTC detection was increased to 54% (6/11) in the resection cohort (RC) and was associated with metastases that were only identified during the surgical procedure (peritoneal carcinoma: n = 1; infiltration of the duodenum: n = 1) or immediately after surgery (evidence of pulmonary metastases by CT scan two days after resection, not evident on initial tumor staging prior resection). Taken together, in this single center pilot study, we demonstrated that CTCs are detectable in CCA patients and are associated with significantly impaired survival in patients at metastatic stage. Detection rate prior to surgery was improved to &gt;50% by combined peripheral and central measurement. Moreover, preoperative CTC detection may indicate existing metastases and could help to stratify patients more accurately.
2,4-Disubstituted pyridine derivatives are effective against intracellular and biofilm-forming tubercle bacilli
Authors: Korycka-Machała M. , Kawka M. , Lach J. , Płocińska R. , Bekier A. , Dziadek B. , Brzostek A. , Płociński P. , Strapagiel D. , Szczesio M. , Gobis K. , Dziadek J. 
Published: November 2022

It was recently reported that 4-substituted picolinohydrazonamides carrying hydrophilic cyclic amines, such as morpholine and pyrrolidine, at the end of their thiosemicarbazide chain have potent antimycobacterial activity in vitro at concentrations below 1 μg/ml. Here, two selected compounds, 2,4-disubstituted pyridine derivatives 11 and 15, revealed significant bactericidal activity against Mycobacterium tuberculosis localized intracellularly within human macrophages, as well as against biofilm-forming tubercle bacilli. Mutants were selected that were resistant to the investigated compounds at an efficiency similar to that identified in the presence of the first line antituberculosis drug rifampicin. The resistant mutants were viable in the presence of the tested compounds exclusively on solid media. Genome-wide sequencing of the mutants selected in the presence of compound 11 revealed the accumulation of nonsynonymous mutations in the mmpR5 gene encoding a transcriptional repressor of the MmpS5-MmpL5 efflux pump, whose upregulation has been associated with bedaquiline resistance. The depletion of MmpR5 in wild-type M. tuberculosis using CRISPR–Cas9 technology increased the resistance of this strain to compound 11. Mass spectrometry-based proteomics (LC–MS/MS) of wild-type tubercle bacilli growing in subinhibitory concentrations of compounds 11 or 15 revealed 15 overproduced proteins not detectable in the control cells, including virulence-related proteins.
Exploring a four-gene risk model based on doxorubicin resistance-associated lncRNAs in hepatocellular carcinoma
Authors: Zhang Zunyi , Chen Weixun , Luo Chu , Zhang Wei 
Published: November 2022

Background: Liver cancer is a lethal cancer type among which hepatocellular carcinoma (HCC) is the most common manifestation globally. Drug resistance is a central problem impeding the efficiency of HCC treatment. Long non-coding RNAs reportedly result in drug resistance. This study aimed to identify key lncRNAs associated with doxorubicin resistance and HCC prognosis.Materials and Methods: HCC samples with gene expression profiles and clinical data were accessed from public databases. We applied differential analysis to identify key lncRNAs that differed between HCC and normal samples and between drug-fast and control samples. We also used univariate Cox regression analysis to screen lncRNAs or genes associated with HCC prognosis. The least absolute shrinkage and selection operator (LASSO) was used to identify the key prognostic genes. Finally, we used receiver operating characteristic analysis to validate the effectiveness of the risk model.Results: The results of this study revealed RNF157-AS1 as a key lncRNA associated with both doxorubicin resistance and HCC prognosis. Metabolic pathways such as fatty acid metabolism and oxidative phosphorylation were enriched in RNF157-AS1-related genes. LASSO identified four protein-coding genes—CENPP, TSGA10, MRPL53, and BFSP1—to construct a risk model. The four-gene risk model effectively classified HCC samples into two risk groups with different overall survival. Finally, we established a nomogram, which showed superior performance in predicting the long-term prognosis of HCC.Conclusion: RNF157-AS1 may be involved in doxorubicin resistance and may serve as a potential therapeutic target. The four-gene risk model showed potential for the prediction of HCC prognosis.
Formulation of water-soluble Buddleja globosa Hope extracts and characterization of their antimicrobial properties against Pseudomonas aeruginosa
Authors: Araya Nicolas , Leiva-Soto Martín A. , Bruna Maria V. , Castro-Munoz Almendra , Behrend-Keim Beatriz , Moraga-Espinoza Daniel , Bahamondez-Canas Tania F. 
Published: November 2022

Buddleja globosa Hope (BG) extracts are traditionally used to treat skin and gastric ulcers due to their healing properties. Non-aqueous solvents such as ethanol and DMSO are usually used to extract naturally occurring compounds. However, the cytotoxicity of these solvents and the low water solubility of the extracted compounds can hinder their biomedical applications. To overcome the limited solubility of the BG extracts, we aimed to enhance the solubility by processing a standardized hydroalcoholic extract (BG-126) through spray drying (SD), with and without two solubility enhancers. Spray-dried BG (BG-SD) extracts and spray-dried BG extracts plus polyvinylpyrrolidone (BG-SD PVP) and Soluplus® (BG-SD SP) were developed starting from BG-126 (containing 53% ethanol). These four formulations were characterized by total phenolic content, water solubility at 25°C and 37°C, and antimicrobial properties against Pseudomonas aeruginosa. All the SD formulations presented a solubility that allowed them to reach maximum concentrations of 1,024 μg/ml catechin for BG-SD and 2,048 μg/ml catechin for BG-SD PVP and BG-SD SP for antimicrobial testing. BG-SD showed the highest antimicrobial potency with a minimum inhibitory concentration (MIC) of 512 μg/ml catechin, followed by BG-126 with a MIC of 1,024 μg/ml catechin and SP. BG-126 was also shown to inhibit biofilm formation, as well as the excipients PVP and SP. The spray-dried BG (BG-SD) extract represents a promising natural active component with enhanced antimicrobial properties against P. aeruginosa for further research and the development of novel phytopharmaceuticals.