bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and durability of AGT103-T autologous T cell therapy for HIV infection in a Phase 1 trial
Authors: Muvarak Nidal , Li Haishan , Lahusen Tyler , Galvin Jeffrey A. , Kumar Princy N. , Pauza C. David , Bordon José 
Published: November 2022

The cell and gene therapy product AGT103-T was designed to restore the Gag-specific CD4+ T cell response in persons with chronic HIV disease who are receiving antiretroviral therapy. This autologous, genetically engineered cell product is under investigation in a Phase 1 clinical trial (NCT03215004). Trial participants were conditioned with cyclophosphamide approximately 1 week before receiving a one-time low (&lt; 109 genetically modified CD4+ T cells) or high (≥109 genetically modified CD4+ T cells) dose of AGT103-T, delivering between 2 and 21 million genetically modified cells per kilogram (kg) body weight. There were no serious adverse events (SAEs) and all adverse events (AEs) were mild. Genetically modified AGT103-T cells were detected in most of the participant blood samples collected 6 months after infusion, which was the last scheduled monitoring visit. Peripheral blood mononuclear cells (PBMC) collected after cell product infusion were tested to determine the abundance of Gag-specific T cells as a measure of objective responses to therapy. Gag-specific CD4+ T cells were detected in all treated individuals and were substantially increased by 9 to 300-fold compared to baseline, by 14 days after cell product infusion. Gag-specific CD8+ T cells were increased by 1.7 to 10-fold relative to baseline, by 28 days after cell product infusion. Levels of Gag-specific CD4+ T cells remained high (~2 to 70-fold higher relative to baseline) throughout 3–6 months after infusion. AGT103-T at low or high doses was safe and effective for improving host T cell immunity to HIV. Further studies, including antiretroviral treatment interruption, are warranted to evaluate the product's efficacy in HIV disease.Clinical trial registrationwww.clinicaltrials.gov, identifier: NCT03215004.
Lack of direct association between viral hepatitis and sleep disturbances
Authors: Lin Sheng-Jie , Tang Shang-Ching Joy , Lee Yu-Chia , Liu Ting-Yu , Huang Ting-Chun , Yu Rwei-Ling , Tan Chun-Hsiang 
Published: November 2022

BackgroundIndividuals with chronic viral hepatitis are at increased risk of experiencing poor sleep quality and sleep disturbances. However, it remains unclear whether the sleep disorders associated with viral hepatitis are secondary to the comorbidities related to viral hepatitis or the direct effect of hepatitis viruses on sleep. This study investigated the direct impact of viral hepatitis B and C on sleep quality.MethodsIndividuals with viral hepatitis B or C and their healthy counterparts were recruited for the present study, and they were evaluated with the Parkinson's Disease Sleep Scale-2, the Epworth Sleepiness Scale, and the Pittsburgh Sleep Quality Index in the absence of common comorbidities associated with viral hepatitis.ResultsNeither hepatitis B nor hepatitis C was found to cause significant differences in insomnia symptoms or excessive daytime sleepiness. However, individuals with hepatitis C, but not hepatitis B, tended to be less likely to experience restlessness of the legs or arms at night.ConclusionsThis study suggests that hepatitis viruses B and C may not cause a significant impact on sleep quality and related disorders directly. Sleep disturbances in individuals with chronic viral hepatitis may instead be attributable to hepatic decompensation or the comorbid factors associated with viral hepatitis.
Effect of hearing aids on cognitive functions in middle-aged and older adults with hearing loss: A systematic review and meta-analysis
Authors: Yang Zhizhong , Ni Jingnian , Teng Yuou , Su Mingwan , Wei Mingqing , Li Ting , Fan Dongsheng , Lu Tao , Xie Hengge , Zhang Wei , Shi Jing , Tian Jinzhou 
Published: November 2022

ObjectiveThe study aimed to examine the effects of hearing aids on cognitive function in middle-aged and older adults with hearing loss.Data sources and study selectionPubMed, Cochrane Library, and Embase were searched for studies published before 30 March 2022. Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) were included in the search. Restriction was set on neither types, severity, or the time of onset of hearing impairment nor cognitive or psychiatric statuses.Data extraction and synthesisTwo independent reviewers extracted data and assessed the study quality of RCTs. Cognitive function outcomes were descriptively summarized and converted to standardized mean difference (SMD) in the meta-analysis. Meta-analysis was conducted in RCTs. Sub-group analyses were conducted by cognitive statuses, psychiatric disorders, and cognitive domains.ResultsA total of 15 studies met the inclusion criteria, including five RCTs (n = 339) and 10 NRSIs (n = 507). Groups were classified as subjects without dementia or with normal global cognition, subjects with AD or dementia, and subjects with depressive symptoms. For subjects without dementia, improvements were found in global cognition, executive function, and episodic memory. For subjects with depressive symptoms, improvements were found in immediate memory, global cognition, and executive function. No improvement was found in subjects with AD or dementia. In total, four RCTs were included in the meta-analysis. For subjects without dementia (SMD = 0.11, 95% confidence interval [CI]: −0.15–0.37) and those with AD, no significant effect was found (SMD = −0.19, 95% CI: −0.65–0.28). For subjects without dementia, no significant effect was found in language (SMD = 0.14, 95% CI: −0.30–0.59) or general executive function (SMD = −0.04, 95% CI: −0.46–0.38). Further sub-group analysis found no significant effect in executive function (SMD = −0.27, 95% CI: −0.72–0.18) or processing speed (SMD = −0.02, 95% CI: −0.49–0.44).ConclusionHearing aids might improve cognitive performance in domains such as executive function in subjects without dementia. The effects on subjects with depressive symptoms remained unclear. No improvement was found in subjects with AD or dementia. Long-term RCTs and well-matched comparison-group studies with large sample sizes are warranted.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022349057.
A multi-frame network model for predicting seizure based on sEEG and iEEG data
Authors: Lu Liangfu , Zhang Feng , Wu Yubo , Ma Songnan , Zhang Xin , Ni Guangjian 
Published: November 2022

IntroductionAnalysis and prediction of seizures by processing the EEG signals could assist doctors in accurate diagnosis and improve the quality of the patient's life with epilepsy. Nowadays, seizure prediction models based on deep learning have become one of the most popular topics in seizure studies, and many models have been presented. However, the prediction results are strongly related to the various complicated pre-processing strategies of models, and cannot be directly applied to raw data in real-time applications. Moreover, due to the inherent deficiencies in single-frame models and the non-stationary nature of EEG signals, the generalization ability of the existing model frameworks is generally poor.MethodsTherefore, we proposed an end-to-end seizure prediction model in this paper, where we designed a multi-frame network for automatic feature extraction and classification. Instance and sequence-based frames are proposed in our approach, which can help us simultaneously extract features of different modes for further classification. Moreover, complicated pre-processing steps are not included in our model, and the novel frames can be directly applied to the raw data. It should be noted that the approaches proposed in the paper can be easily used as the general model which has been validated and compared with existing model frames.ResultsThe experimental results showed that the multi-frame network proposed in this paper was superior to the existing model frame in accuracy, sensitivity, specificity, F1-score, and AUC in the classification performance of EEG signals.DiscussionOur results provided a new research idea for this field. Researchers can further integrate the idea of the multi-frame network into the state-of-the-art single-frame seizure prediction models and then achieve better results.
A novel tDCS control condition using optimized anesthetic gel to block peripheral nerve input
Authors: Kerstens Silke , Orban de Xivry Jean-Jacques , Mc Laughlin Myles 
Published: November 2022

BackgroundRecent studies indicate that some transcranial direct current stimulation (tDCS) effects may be caused by indirect stimulation of peripheral nerves in the scalp rather than the electric field in the brain. To address this, we developed a novel tDCS control condition in which peripheral input is blocked using topical anesthetics. We developed a compounded anesthetic gel containing benzocaine and lidocaine (BL10) that blocks peripheral input during tDCS.MethodsIn a blinded randomized cross-over study of 18 healthy volunteers (M/F), we compared the gel's efficacy to EMLA and an inert placebo gel. Subjects used a visual analog scale (VAS) to rate the stimulation sensation in the scalp produced by 10 s of 2 mA tDCS every 2 min during 1 h. In an additional in-vitro experiment, the effect of a DC current on gel resistivity and temperature was investigated.ResultsBoth the BL10 and EMLA gel, lowered the stimulation sensations compared to the placebo gel. The BL10 gel showed a tendency to work faster than the EMLA gel with reported sensations for the BL10 gel being lower than for EMLA for the first 30 min. The DC current caused a drastic increase in gel resistivity for the EMLA gel, while it did not affect gel resistivity for the BL10 and placebo gel, nor did it affect gel temperature.ConclusionsTopical anesthetics reduce stimulation sensations by blocking peripheral nerve input during tDCS. The BL10 gel tends to work faster and is more electrically stable than EMLA gel.Clinical trial registrationThe study is registered at ClinicalTrials.gov with name “Understanding the Neural Mechanisms Behind tDCS” and number NCT04577677.
Efficacy and mechanism of intermittent fasting in metabolic associated fatty liver disease based on ultraperformance liquid chromatography-tandem mass spectrometry
Authors: Deng Jiang , Feng Dandan , Jia Xiaoli , Zhai Song , Liu Yixin , Gao Ning , Zhang Xin , Li Mei , Lu Mengnan , Liu Chenrui , Dang Shuangsuo , Shi Juanjuan 
Published: November 2022

ObjectivesDrug treatment of metabolic associated fatty liver disease (MAFLD) remains lacking. This study analyzes the efficacy and mechanism underlying intermittent fasting combined with lipidomics.MethodsThirty-two male rats were randomly divided into three groups: Normal group, administered a standard diet; MAFLD group, administered a 60% high-fat diet; time-restricted feeding (TRF) group, administered a 60% high-fat diet. Eating was allowed for 6 h per day (16:00–22:00). After 15 weeks, liver lipidomics and other indicators were compared.ResultsA total of 1,062 metabolites were detected. Compared with the Normal group, the weight, body fat ratio, aspartate aminotransferase, total cholesterol, low-density cholesterol, fasting blood glucose, uric acid, and levels of 317 lipids including triglycerides (TG) (17:0−18:1−20:4) were upregulated, whereas the levels of 265 lipids including phosphatidyl ethanolamine (PE) (17:0−20:5) were downregulated in the MAFLD group (P &lt; 0.05). Compared with the MAFLD group, the weight, body fat ratio, daily food intake, and levels of 253 lipids including TG (17:0−18:1−22:5) were lower in the TRF group. Furthermore, the levels of 82 lipids including phosphatidylcholine (PC) (20:4−22:6) were upregulated in the TRF group (P &lt; 0.05), while serum TG level was increased; however, the increase was not significant (P &gt; 0.05). Enrichment analysis of differential metabolites showed that the pathways associated with the observed changes mainly included metabolic pathways, regulation of lipolysis in adipocytes, and fat digestion and absorption, while reverse-transcription polymerase chain reaction showed that TRF improved the abnormal expression of FAS and PPARα genes in the MAFLD group (P &lt; 0.05).ConclusionOur results suggest that 6 h of TRF can improve MAFLD via reducing food intake by 13% and improving the expression of genes in the PPARα/FAS pathway, thereby providing insights into the prevention and treatment of MAFLD.
Cervical squamous cell carcinoma of unknown primary: Oncological outcomes and prognostic factors
Authors: Meulemans Jeroen , Voortmans Jens , Nuyts Sandra , Daisne Jean-François , Clement Paul , Laenen Annouschka , Delaere Pierre , Van Lierde Charlotte , Poorten Vincent Vander 
Published: November 2022

Background/ObjectivesCervical squamous cell carcinoma of unknown primary (SCCUP) is a rare entity within head and neck cancer and both treatment regimens as well as identified potential predictors for oncological outcomes vary between published series. In this study, we evaluated oncological outcomes and identified potential prognostic factors for outcome.Patients and methodsThis retrospective monocentric cohort study includes 82 SCCUP patients diagnosed and treated between January 2000 and June 2021. Overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and locoregional recurrence-free survival (LRFS) were evaluated. The Cox proportional hazards model was used to analyze the prognostic effect of patient and tumor characteristics on oncological outcomes.ResultsFive year OS, DSS, DFS and LRFS were respectively 53.9%, 72.2%, 68.9% and 67.3%. The p16 status was evaluated in 55 patients with 40% being p16 positive. On univariable analysis, p16 negative SCCUPs had significantly worse survival and recurrence rates in the presence of clinical extranodal extension (cENE) (OS: p=0.0013, DSS: p=0.0099, DFS: p=0.0164, LRFS: p=0.0099) and radiological extranodal extension (rENE) (OS: p=0.0034, DSS: p=0.0137, DFS: p=0.0167, LRFS: p=0.0100). In p16 positive SCCUP patients, rENE had a significantly negative prognostic effect on DFS (p=0.0345) and LRFS (p=0.0367). Total group multivariate analysis identified rENE as an independent negative predictor for all oncological outcomes. The “number of positive lymph nodes” was a second independent predictor for DSS (p=0.0257) and DFS (p=0.0435).ConclusionsWe report favorable oncological outcomes, comparable to previously published results. Although the presence of rENE seems associated with poor oncological outcomes, the differential effect of clinical, radiological and pathological ENE in both p16 positive and negative subgroups remain to be elucidated by further prospective research.
Effect of perioperative seizures on mortality and recurrence in patients with brain metastases
Authors: Zheng Yilong , Yang Yuxiu , Ng Min Hui , Chew Adrienne Yu Hsiang , Goh Chun Peng , Chua Christopher Yuan Kit , Rathakrishnan Rahul , Ang Yvonne , Wong Andrea Li Ann , Vellayappan Balamurugan , Teo Kejia , Nga Vincent Diong Weng , Yeo Tseng Tsai , Lim Mervyn Jun Rui 
Published: November 2022

ObjectiveTo identify the independent risk factors for 30-day perioperative seizures, as well as to evaluate the effect of perioperative seizures on overall mortality and tumor recurrence among patients who underwent surgical resection of brain metastases.MethodsPatients who underwent surgical resection of brain metastases at our institution between 2011 and 2019 were included. 30-day perioperative seizures were defined as the presence of any preoperative or postoperative seizures diagnosed by a neurosurgeon or neurologist within 30 days of metastases resection. Independent risk factors for 30-day perioperative seizures were evaluated using multivariate logistic regression models. Kaplan-Meier plots and Cox regression models were constructed to evaluate the effects of 30-day perioperative seizures on overall mortality and tumor recurrence. Subgroup analyses were conducted for 30-day preoperative and 30-day postoperative seizures.ResultsA total of 158 patients were included in the analysis. The mean (SD) age was 59.3 (12.0) years, and 20 (12.7%) patients had 30-day perioperative seizures. The presence of 30-day preoperative seizures (OR=41.4; 95% CI=4.76, 924; p=0.002) was an independent risk factor for 30-day postoperative seizures. Multivariate Cox regression revealed that any 30-day perioperative seizure (HR=3.25; 95% CI=1.60, 6.62; p=0.001) was independently and significantly associated with overall mortality but not tumor recurrence (HR=1.95; 95% CI=0.78, 4.91; p=0.154).ConclusionsAmong patients with resected brain metastases, the presence of any 30-day perioperative seizure was independently associated with overall mortality. This suggests that 30-day perioperative seizures may be a prognostic marker of poor outcome. Further research evaluating this association as well as the effect of perioperative antiepileptic drugs in patients with resected brain metastases may be warranted.
Is the six-minute walk test still reliable compared to cardiopulmonary exercise test for exercise capacity in children with congenital heart disease?
Authors: Qu Jiangbo , Shi Hui , Guo Yugong , Chen Xinxin , Xiao Xuwen , Zheng Xiaojuan , Cui Yanqin 
Published: November 2022

ObjectivesWe aimed to assess the validity of the six-minute walk test (6MWT) to reflect the functional capacity of children with congenital heart disease (CHD), evaluate a possible correlation between the 6MWT distance with cardiopulmonary exercise test (CPET) variables, as well as to find a cutoff value to stratification the physical fitness in this population.MethodsWe enrolled 459 children with CHD, 6–18 years old, who performed a complete CPET and 6MWT on the same day in a cross-sectional observational study. Correlations between variables of CPET and six-minute walking distance (6MWD) were analyzed and cutoff values of 6MWD were identified for the classification of the physical fitness in the population.ResultsThe mean distance ambulated during the 6MWT was 578 ± 65 m, 590 ± 65 m for boys, and 562 ± 62 m for girls (p &lt; 0.001). Both VO2max and %predicted VO2max showed a correlation with the 6MWT distance (r = 0.35, p &lt; 0.001 and r = 0.51, p &lt; 0.001, respectively), and an inverse correlation was found between VE/VCO2 slope and the 6MWT distance (r = −0.31; p &lt; 0.001). There appeared to be a linear association between 6MWD and VO2max up to a 6MWD of approximately 600 m. We divided the population into 4 subgroups (boys &lt;130 cm; boys ≥130 cm; girls &lt;130 cm; girls ≥130 cm), and get the cutoff values (554 m, 617 m, 549 m, 587 m) respectively equivalent to 80% of predicted VO2max. The 6MWT distances of another 102 patients were applied for external verification of the cutoff values.ConclusionsOur study provided evidence on when a 6MWT should be considered as a convincing complementary test in the pediatric population with CHD and explored the classification of exercise tolerance using a 6MWD value. The cut-off values for 6MWD may be qualified as an intervention target for exercise rehabilitation.
Pharmacodynamic evaluation of lefamulin in the treatment of gonorrhea using a hollow fiber infection model simulating Neisseria gonorrhoeae infections
Authors: Jacobsson Susanne , Golparian Daniel , Oxelbark Joakim , Wicha Wolfgang W. , da Costa Renata Maria Augusto , Franceschi Francois , Brown David , Louie Arnold , Gelone Steven P. , Drusano George , Unemo Magnus 
Published: November 2022

The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is seriously threatening the treatment and control of gonorrhea globally. Novel treatment options are essential, coupled with appropriate methods to pharmacodynamically examine the efficacy and resistance emergence of these novel drugs. Herein, we used our dynamic in vitro hollow fiber infection model (HFIM) to evaluate protein-unbound lefamulin, a semisynthetic pleuromutilin, against N. gonorrhoeae. Dose–range and dose–fractionation experiments with N. gonorrhoeae reference strains: WHO F (susceptible to all relevant antimicrobials), WHO X (extensively drug-resistant, including ceftriaxone resistance), and WHO V (high-level azithromycin resistant, and highest gonococcal MIC of lefamulin (2 mg/l) reported), were performed to examine lefamulin gonococcal killing and resistance development during treatment. The dose–range experiments, simulating a single oral dose of lefamulin based on human plasma concentrations, indicated that ≥1.2 g, ≥2.8 g, and ≥9.6 g of lefamulin were required to eradicate WHO F, X, and V, respectively. Dose–fractionation experiments, based on human lefamulin plasma concentrations, showed that WHO X was eradicated with ≥2.8 g per day when administered as q12 h (1.4 g twice a day) and with ≥3.6 g per day when administered as q8 h (1.2 g thrice a day), both for 7 days. However, when simulating the treatment with 5–10 times higher concentrations of free lefamulin in relevant gonorrhea tissues (based on urogenital tissues in a rat model), 600 mg every 12 h for 5 days (approved oral treatment for community-acquired bacterial pneumonia) eradicated all strains, and no lefamulin resistance emerged in the successful treatment arms. In many arms failing single or multiple dose treatments for WHO X, lefamulin-resistant mutants (MIC = 2 mg/l), containing an A132V amino acid substitution in ribosomal protein L3, were selected. Nevertheless, these lefamulin-resistant mutants demonstrated an impaired biofitness. In conclusion, a clinical study is warranted to elucidate the clinical potential of lefamulin as a treatment option for uncomplicated gonorrhea (as well as several other bacterial STIs).
Managingtomato bacterial wilt by suppressing Ralstonia solanacearum population in soil and enhancing host resistance through fungus-derived furoic acid compound
Authors: Ye Meijin , Feng Hong , Hu Jianghong , Yu Qing , Liu Songqing 
Published: November 2022

Synthetic chemical pesticides are primarily used to manage plant pests and diseases, but their widespread and unregulated use has resulted in major health and environmental hazards. Using biocontrol microbes and their bioactive compounds is a safe and sustainable approach in plant protection. In this study, a furoic acid (FA) compound having strong antibacterial activity against soil-borne phytopathogenic bacterium Ralstonia solanacearum [causal agent of bacterial wilt (BW) disease] was isolated from Aspergillus niger and identified as 5-(hydroxymethyl)-2-furoic acid compound through spectroscopic analyses (liquid chromatography–mass spectrometry (MS), electron ionization MS, and NMR). The SEM study of bacterial cells indicated the severe morphological destructions by the FA compound. The FA was further evaluated to check its potential in enhancing host resistance and managing tomato BW disease in a greenhouse experiment and field tests. The results showed that FA significantly enhanced the expression of resistance-related genes (PAL, LOX, PR1, and PR2) in tomato and caused a significant reduction (11.2 log10 colony-forming units/g) of the R. solanacearum population in soil, resulting in the reduction of bacterial wilt disease severity on tomato plants and increase in plant length (58 ± 2.7 cm), plant biomass (28 ± 1.7 g), and root length (13 ± 1.2 cm). The findings of this study suggested that the fungus-derived FA compound can be a potential natural compound of biological source for the soil-borne BW disease in tomato.