bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymorphism of virulence genes and biofilm associated with in vitro induced resistance to clarithromycin in Helicobacter pylori
Authors: Rosli Naim Asyraf , Al-Maleki Anis Rageh , Loke Mun Fai , Chua Eng Guan , Alhoot Mohammed Abdelfatah , Vadivelu Jamuna 
Published: October 2023

Abstract
Background
Clarithromycin-containing triple therapy is commonly used to treat Helicobacter pylori infections. Clarithromycin resistance is the leading cause of H. pylori treatment failure. Understanding the specific mutations that occur in H. pylori strains that have evolved antibiotic resistance can help create a more effective and individualised antibiotic treatment plan. However, little is understood about the genetic reprogramming linked to clarithromycin exposure and the emergence of antibiotic resistance in H. pylori. Therefore, this study aims to identify compensatory mutations and biofilm formation associated with the development of clarithromycin resistance in H. pylori. Clarithromycin-sensitive H. pylori clinical isolates were induced to develop clarithromycin resistance through in vitro exposure to incrementally increasing concentration of the antibiotic. The genomes of the origin sensitive isolates (S), isogenic breakpoint (B), and resistant isolates (R) were sequenced. Single nucleotide variations (SNVs), and insertions or deletions (InDels) associated with the development of clarithromycin resistance were identified. Growth and biofilm production were also assessed.

Results
The S isolates with A2143G mutation in the 23S rRNA gene were successfully induced to be resistant. According to the data, antibiotic exposure may alter the expression of certain genes, including those that code for the Cag4/Cag protein, the vacuolating cytotoxin domain-containing protein, the sel1 repeat family protein, and the rsmh gene, which may increase the risk of developing and enhances virulence in H. pylori. Enhanced biofilm formation was detected among R isolates compared to B and S isolates. Furthermore, high polymorphism was also detected among the genes associated with biofilm production.

Conclusions
Therefore, this study suggests that H. pylori may acquire virulence factors while also developing antibiotic resistance due to clarithromycin exposure.
Exploring the impact of professional soccer substitute players on physical and technical performance
Authors: Pan Pengyu , Li Fangbin , Han Bo , Yuan Bo , Liu Tianbiao 
Published: October 2023

Abstract
Background

Substitutions are generally used to promote the match performance of the whole team. This study aimed to analyze the performance of substitute players and explore the performance difference among substitute players, completed players, and replaced players across each position.

Methods
Chinese Super Soccer League (CSL) matches in the season 2018 including 5871 individual observation from 395 professional soccer players were analyzed by establishing linear mixed models to quantify the performance difference among substitute players (SP) (n = 1,071), entire match players (EMP) (n = 3,454), and replaced players (RP) (n = 1,346), and then separately for each position (central defenders, fullbacks, central midfielders, wide midfielders, and attackers).

Results
The results show SP display higher high intensity distance and sprint distance significantly (p < 0.05) relative to playing time than RP and EMP. SP in offensive positions (attackers, wide midfielders) showed significantly higher (p < 0.05) passing and organizing performance such as passes, ball control, short passes, and long passes than RP or EMP. The scoring performances of central midfielders of SP including goals, shots, and shots on target are significantly higher (p < 0.05) than RP or EMP. Central defenders of SP showed higher shot blocks and pass blocks (p < 0.05) while lower passing and organizing performance (p < 0.05).

Conclusion
Depending on different playing positions, substitute players could indeed improve physical and technical performance related to scoring, passing, and defending as offensive substitute players can boost organizing performance and substitute defenders enhance defending performance. These could help coaches better understand substitute players’ influence on match performance and optimize the substitution tactic.
Increased binding of anti-dsDNA antibodies to short oligonucleotides modified with topoisomerase I reveals a potential new enzyme function independent from DNA relaxation
Authors: Frese-Schaper Manuela , Voll Reinhard E. , Frese Steffen 
Published: October 2023

Abstract
Objective
Topoisomerase I (topo I) is a highly conserved enzyme which is known to reduce torsional stress at double-stranded (ds) DNA. Torsional stress induced by supercoiling of dsDNA requires either very long dsDNA existing in genomic DNA or circulation as presented in plasmid DNA. To enable DNA relaxation, topo I induce a transient single-strand break followed by stress-relieving rotation of the released DNA strand. Our group found by serendipity that the topo I inhibitor irinotecan is able to suppress murine systemic lupus erythematosus (SLE), an autoimmune disease which is characterized by the existence of pathogenic anti-dsDNA antibodies (abs). As a possible mechanism we demonstrated in the absence of immunosuppression an increased binding of anti-dsDNA abs to long genomic or circulated plasmid dsDNA modified with topo I.

Results
Here we show that this effect requires active site tyrosine of topo I which is known to facilitate DNA relaxation activity. Moreover, topo I enhanced anti-dsDNA abs binding to short linear oligonucleotides down to a size of 42 bp. Since oligonucleotides of such length are devoid of torsional stress and relaxation respectively, our results suggest a new and unknown function for the enzyme topo I.
Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer’s disease continuum
Authors: Goossens Julie , Cervantes González Alba , Dewit Nele , Lidón Laia , Fortea Juan , Alcolea Daniel , Lleó Alberto , Belbin Olivia , Vanmechelen Eugeen 
Published: October 2023

Abstract
Background
Synapse loss is an early event that precedes neuronal death and symptom onset and is considered the best neuropathological correlate of cognitive decline in Alzheimer’s disease (AD). Vesicle-associated membrane protein 2 (VAMP-2) has emerged as a promising biomarker of AD-related synapse degeneration in cerebrospinal fluid (CSF). The aim of this study was to explore the CSF profile of VAMP-2 across the AD continuum in relation to core AD biomarkers, other synaptic proteins, neurogranin (Ng) and synaptosomal-associated Protein-25 kDa (SNAP-25) and cognitive performance.

Methods
We developed a digital immunoassay on the Single Molecule Array platform to quantify VAMP-2 in CSF and used existing immunoassays to quantify Ng, SNAP-25 and core CSF AD biomarkers. The clinical study included 62 cognitively unimpaired AD biomarker-negative subjects and 152 participants across the AD continuum from the SPIN cohort (Sant Pau Initiative on Neurodegeneration). Cognitive measures of episodic, semantic, executive and visuospatial domains and global cognition were included. Statistical methods included χ2 tests, spearman correlation, and ANCOVA analyses.

Results
The VAMP-2 assay had a good analytical performance (repeatability 8.9%, intermediate precision 10.3%). Assay antibodies detected native VAMP-2 protein in human brain homogenates. CSF concentrations of VAMP-2, neurogranin and SNAP-25 were lower in preclinical AD stage 1 compared to controls and higher at later AD stages compared to AD stage 1 and were associated with core AD biomarkers, particularly total tau (adj. r2 = 0.62 to 0.78, p < 0.001). All three synaptic proteins were associated with all cognitive domains in individuals on the AD continuum (adj. r2 = 0.04 to 0.19, p < 0.05).

Conclusions
Our novel digital immunoassay accurately measures VAMP-2 changes in CSF, which reflect AD biomarkers and cognitive performance across multiple domains.
Osimertinib tolerance in a patient with Stevens Johnson syndrome during osimertinib therapy after treatment with pembrolizumab
Authors: Lopez Michael , Hagopian Garo , Doan Linda , Lee Benjamin J. , Rojek Nathan W. , Smith Janellen , Ou Sai-Hong Ignatius , Demirdag Yesim Yilmaz , Nagasaka Misako 
Published: October 2023

Abstract
Background
Osimertinib has emerged as an important tool in the treatment of non-small cell lung cancers (NSCLC) with certain activating mutations of epidermal growth factor receptor (EGFR). However, Osimertinib may cause adverse effects, including severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The risk of certain adverse effects may be increased in the setting of recent use of immune checkpoint inhibitor (ICI) therapy, although it is unclear whether recent use of ICI therapy is a risk factor for Osimertinib-induced SJS specifically.

Case presentation
We present a patient with EGFR L858R mutation-positive metastatic NSCLC who developed Osimertinib-induced SJS after recent administration of eight cycles of a pembrolizumab-containing chemotherapy regimen. Osimertinib, which was the best treatment targeting his lung cancer, was avoided due to history of SJS. Four years later, because of unresponsiveness or side effects of alternative treatments, he underwent Osimertinib challenge and tolerated it.

Conclusion
This case highlights the importance of multi-disciplinary care and supports the hypothesis that the risk of SJS to Osimertinib is significantly higher in the context of recent administration of ICI therapy and, patients may tolerate Osimertinib after certain time has elapsed after the last dose of ICI.
Durable effects of deep brain ultrasonic neuromodulation on major depression: a case report
Authors: Riis Thomas S. , Feldman Daniel A. , Vonesh Lily C. , Brown Jefferson R. , Solzbacher Daniela , Kubanek Jan , Mickey Brian J. 
Published: October 2023

Abstract
Background
Severe forms of depression have been linked to hyperactivity of the subcallosal cingulate cortex. The ability to stimulate the subcallosal cingulate cortex or associated circuits noninvasively and directly would maximize the number of patients who could receive treatment. To this end, we have developed an ultrasound-based device for effective noninvasive modulation of deep brain circuits. Here we describe an application of this tool to an individual with treatment-resistant depression.

Case presentation
A 30-year-old Caucasian woman with severe treatment-resistant non-psychotic depression was recruited into a clinical study approved by the Institutional Review Board of the University of Utah. The patient had a history of electroconvulsive therapy with full remission but without sustained benefit. Magnetic resonance imaging was used to coregister the ultrasound device to the subject’s brain anatomy and to evaluate neural responses to stimulation. Brief, 30-millisecond pulses of low-intensity ultrasound delivered into the subcallosal cingulate cortex target every 4 seconds caused a robust decrease in functional magnetic resonance imaging blood-oxygen-level-dependent activity within the target. Following repeated stimulation of three anterior cingulate targets, the patient’s depressive symptoms resolved within 24 hours of the stimulation. The patient remained in remission for at least 44 days afterwards.

Conclusions
This case illustrates the potential for ultrasonic neuromodulation to precisely engage deep neural circuits and to trigger a durable therapeutic reset of those circuits.
Trial registration ClinicalTrials.gov, NCT05301036. Registered 29 March 2022, https://clinicaltrials.gov/ct2/show/NCT05301036
Effects and mechanisms of Tai Chi on mild cognitive impairment and early-stage dementia: a scoping review
Authors: Jasim Nibras , Balakirishnan Darsiha , Zhang Han , Steiner-Lim Genevieve Z. , Karamacoska Diana , Yang Guo-Yan 
Published: October 2023

AbstractBackgroundDementia is associated with cognitive and functional decline that significantly impacts quality of life. There is currently no cure for dementia, thus, it is important to manage dementia in the early stages and delay deterioration. Previous studies have documented a range of health benefits of Tai Chi in people with early-stage dementia, however, none have systematically integrated these effects with their underlying mechanisms. The aims of this study were to (1) identify the neurocognitive, psychological, and physical health benefits of Tai Chi oi people with early-stage dementia, and (2) explore the underlying mechanisms of these effects.MethodsWe searched systematic reviews (SRs) and randomised control trials (RCTs) on Tai Chi for adults aged 50 years and older with mild cognitive impairment (MCI) or early-stage dementia in MEDLINE, PubMed, Cochrane Library, EMBASE, and major Chinese databases. No language or publication restrictions were applied. Risk of bias was assessed.ResultsEight SRs with meta-analyses and 6 additional published RCTs revealed inconsistent findings of Tai Chi on improving global cognitive function, attention and executive function, memory and language, and perceptual-motor function. There was no significant between-group difference in depressive symptoms. The results from the RCTs showed that Tai Chi can reduce arthritis pain and slow the progress of dementia. No studies on MCI or early-stage dementia investigating the underlying mechanisms of Tai Chi were identified. Instead, nine mechanistic studies on healthy adults were included. These suggested that Tai Chi may improve memory and cognition via increased regional brain activity, large-scale network functional connectivity, and regional grey matter volume.ConclusionThe effects of Tai Chi on neurocognitive outcomes in people with MCI and early-stage dementia are still inconclusive. Further high-quality clinical trials and mechanistic studies are needed to understand if and how Tai Chi may be applied as a successful intervention to delay deterioration and improve the quality of life in people with an increased risk of cognitive decline.
Evaluation of obesity prevention effect of black ginseng on serum, liver, and hypothalamus of mice on a high-fat diet using a metabolomics approach
Authors: Kim Ye Jin , Lee Dae Young , Yang Hye Rim , Im Kyung-Hoan , Park Sang Un , Kim Jae Geun , Kim Jae Kwang 
Published: October 2023

AbstractBlack ginseng is being studied to prevent obesity caused by a high-fat diet (HFD). The aim of this study was to evaluate the obesity-preventing effect of black ginseng extract (BGE) in the serum, liver, and hypothalamus of mice on an HFD using metabolomic techniques. Mice were divided into four groups which were respectively fed a normal diet (CTL), an HFD, an HFD with a low concentration of BGE (BGEL), and an HFD with a high concentration of BGE (BGEH) for 8 weeks. Metabolite profiling revealed a clear separation between the BGE diet and HFD groups. Lipid metabolism, including saturated fatty acids and cholesterol, was decreased in the BGEH mice. Specifically, neurotransmitters and intermediates of the tricarboxylic acid cycle were increased in the hypothalamus of BGEH mice. The results suggest the obesity prevention effect of black ginseng in that BGEH inhibits body fat accumulation and restores brain function damaged by HFD.
HOMA-IR is positively correlated with biological age and advanced aging in the US adult population
Authors: Yang Haifang , Gong Rongpeng , Liu Moli , Deng Ying , Zheng Xiaoyu , Hu Tianyang 
Published: October 2023

Abstract
Background
Insulin resistance (IR) had been reported to be associated with age; however, few studies have explored the association between IR and biological age (BA). The HOMA-IR value is a useful indicator of the extent of IR. This cross-sectional study is to explore the relationship between HOMA-IR and BA/advanced aging in the US population.

Methods
This study is a cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) data. The survey comprised 12,266 people from the NHANES, and their full HOMA-IR data as well as BA data were extracted. Four multiple linear regressions were performed to analyze the association between HOMA-IR and BA, and four multiple logistic regression models were performed to analyze the association between HOMA-IR and advanced aging. In addition, trend tests and stratified analysis were performed and smoothed fitted curves were plotted to test the robustness of the results.

Results
HOMA-IR was positively correlated with BA [β: 0.51 (0.39, 0.63)], and it was the same to advanced aging [OR: 1.05 (1.02, 1.07)], and both showed a monotonically increasing trend. The trend tests showed that the results were stable (all P for trend < 0.0001). The smoothed fitted curves showed that there were non-linear relationships between HOMA-IR and BA/advanced aging. And the stratified analysis indicated that the relationship between HOMA-IR and BA/advanced aging remained robust in all subgroups.

Conclusion
The study suggested that HOMA-IR is positively correlated with BA and advanced aging in the US adult population, with a monotonic upward trend. This is a new finding to reveal the relationship between HOMA-IR and age from new standpoint of BA rather than chronological age (CA). And it may contribute to a better understanding of human health aging and may aid future research in this field.
The firstly visited department affects the acceptance of CPAP in patients with obstructive sleep apnea: A cohort study
Authors: Wu Chung-Sheng , Chen David Hsin-Kuang , Ko Yuan-Chun , Bai Chyi-Huey , Chen Po-Yueh , Liu Wen-Te , Lin Yi-Chih 
Published: October 2023

Background Continuous positive airway pressure (CPAP) therapy is the first-line treatment for obstructive sleep apnea (OSA). However, the low acceptance rate of CPAP remains a challenging clinical issue. This study aimed to determine the factors that influence the acceptance rate of CPAP. Methods This retrospective cohort study was conducted at the sleep center of Shuang-Ho Hospital. Initially, 1186 OSA patients who received CPAP therapy between December 2013 and December 2017 were selected, and finally, 1016 patients were analyzed. All patients with OSA received CPAP therapy for at least 1 week, and their acceptance to treatment was subsequently recorded. Outcome measures included patients’ demographic and clinical characteristics (sex, age, BMI, comorbidities, history of smoking, and the medical specialist who prescribed CPAP treatment), polysomnography (PSG) results, and OSA surgical records. Results Patients with a lower CPAP acceptance rate were referred from otolaryngologists (acceptance rate of otolaryngology vs. others: 49.6% vs. 56.6%, p = .015), in addition to having a lower apnea–hypopnea index (AHI) (acceptance vs. non-acceptance: 55.83 vs. 40.79, p = .003), rapid eye movement AHI (REM-AHI) (acceptance vs. non-acceptance: 51.21 vs. 44.92, p = .014), and arousal index (acceptance vs. non-acceptance: 36.80 vs. 28.75, p = .011). The multiple logistic regression model showed that patients referred from otolaryngology had a lower CPAP acceptance rate (odds ratio 0.707, p = .0216) even after adjusting for age, sex, BMI, AHI, REM-AHI, arousal index, comorbidities, and smoking status. Conclusions Before their initial consultation, patients may already have their preferred treatment of choice, which is strongly linked to the type of medical specialists they visit, and consequently, affects their rate of acceptance to CPAP therapy. Therefore, physicians should provide personalized care to patients by exploring and abiding by their preferred treatment choices.
Optimization of tannase production by Aspergillus glaucus in solid-state fermentation of black tea waste
Authors: Saad Moataza Mahmoud , Saad Abdelnaby Mahmoud , Hassan Helmy Mohamed , Ibrahim Eman I. , Abdelraof Mohamed , Ali Basant A. 
Published: October 2023

AbstractTannases are valuable industrial enzymes used in food, pharmaceutical, cosmetic, leather manufacture and in environmental biotechnology. In this study, 15 fungal isolates were obtained from Egyptian cultivated soil and marine samples. The isolated fungi were qualitatively and quantitatively screened for their abilities to produce tannase. The selected fungal isolate NRC8 giving highest tannase activity was identified by molecular technique (18S rRNA) as Aspergillus glaucus. Among different tannin-containing wastes tested, the black tea waste was the best substrate for tannase production by Aspergillus glaucus in solid-state fermentation (SSF). Optimization of the different process parameters required for maximum enzyme production was carried out to design a suitable SSF process. Maximal tannase production was achieved with moisture content of 75%, an inoculums size of 6 × 108 spore/ml and sodium nitrate 0.2% (pH of 5.0) at 30 °C after 5 days of incubation. Box–Behnken experiment was designed to get a quadratic model for further optimization studies. Four-factor response-surface method with 27 runs was prepared using independent parameters including (moisture content %, initial pH, substrate concentration (g) and sodium nitrate concentration (g) for tannase model. The F- and P-values of the model were 4.30 and 0.002, respectively, which implied that the model is significant. In addition, the lack-of-fit was 1040.37 which indicates the same significance relative to the pure error. A. glaucus tannase was evaluated by the efficiency of conversion of tannic acid to gallic acid. Moreover, production of gallic acid from SSF process of A. glaucus using black tea waste was found to be 38.27 mg/ml. The best bioconversion efficiency was achieved at 40 °C with tannic acid concentration up to 200 g/L.
Graphical Abstract