bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and usability of the system for assessment and intervention of frailty for community-dwelling pre-frail older adults: A pilot study
Authors: Tan Ren Siang , Goh Eileen Fabia , Wang Di , Chan Robin Chung Leung , Zeng Zhiwei , Yeo Audrey , Pek Kalene , Kua Joanne , Wong Wei Chin , Shen Zhiqi , Lim Wee Shiong 
Published: November 2022

BackgroundEffective multicomponent interventions in the community targeted at preventing frailty in at-risk older adults can promote healthy ageing. However, there is a lack of studies exploring the effectiveness of technology-enabled autonomous multi-domain community-based interventions for frailty. We developed a novel end-to-end System for Assessment and Intervention of Frailty (SAIF) with exercise, nutrition, and polypharmacy components. This pilot study aimed to explore SAIF’s effectiveness in improving frailty status, physical performance and strength, and its usability in pre-frail older adults.Materials and methodsThis is a single arm 8-week pilot study in 20 community-dwelling older adults who were pre-frail, defined using the Clinical Frailty Scale (CFS) as CFS 3 + (CFS 3 and FRAIL positive) or CFS 4. For outcomes, we assessed frailty status using the modified Fried Frailty Phenotype (FFP) and CFS; physical performance using Short Physical Performance Battery (SPPB); and Hand Grip Strength (HGS) at baseline and 8-week. User experience was explored using the System Usability Scale (SUS), interest-enjoyment subscale of the Intrinsic Motivation Inventory and open-ended questions. We analyzed effectiveness using repeated-measures tests on pre-post scores, and usability using a convergent mixed-method approach via thematic analysis of open-ended responses and descriptive statistics of usability/interest-enjoyment scales.ResultsSixteen participants (71.8 ± 5.5 years) completed the 8-week study. There was a significant improvement in FFP score (−0.5, p &lt; 0.05, effect size, r = 0.43), but not CFS (−1.0, p = 0.10, r = 0.29). Five (31.3%) improved in frailty status for both FFP and CFS. SPPB (+1.0, p &lt; 0.05, r = 0.42) and HGS (+3.5, p &lt; 0.05, r = 0.45) showed significant improvements. Three themes were identified: “Difficulty in module navigation” (barriers for SAIF interaction); “User engagement by gamification” (facilitators that encourage participation); and “Perceived benefits to physical health” (subjective improvements in physical well-being), which corroborated with SUS (68/100) and interest-enjoyment (3.9/5.0) scores. Taken together, user experience results cohere with the Senior Technology Acceptance and Adoption Model.ConclusionOur pilot study provides preliminary evidence of the effectiveness of SAIF in improving frailty status, physical performance and strength of pre-frail older adults, and offers user experience insights to plan the follow-up large-scale randomized controlled trial.
Changes of endophytic microbial community in Rhododendron simsii roots under heat stress and its correlation with leaf physiological indicators
Authors: Lin Wei , Liu Lei , Liang Jincheng , Tang Xuexiao , Shi Jie , Zhang Li , Wu Purui , Lan Siren , Wang Shusheng , Zhou Yan , Chen XiaoChou , Zhao Ying , Chen Xiang , Wu Binghua , Guo Lijin 
Published: November 2022

IntroductionThe response mechanism of Rhododendron simsii and its endophytic microorganism to heat stress is still unclear.MethodsThe light incubator was used to set the temperature gradients, and the control (CK) was (day/night: 14/10 h) 25/22°C, the moderate-heat-stress (MHS) was 35/30°C and the high-heat-stress (HHS) was 40/35°C.ResultsCompared with CK, MHS significantly increased the contents of malondialdehyde, hydrogen peroxide, proline, and soluble sugar, as well as the activities of catalase and peroxidase in leaf, while HHS increased the activities of ascorbate peroxidase, and decreased chlorophyll content. Compared with CK, MHS reduced soil available nitrogen (N) content. Both heat stress changed the endophytic microbial community structure in roots. MHS enriched Pezicula and Paracoccus, while HHS significantly enriched Acidothermus and Haliangium. The abundance of Pezicula positively correlated with the contents of chlorophyll a and proline in leaf, and negatively correlated with soil ammonium N content. The abundance of Pezicula and Haliangium positively correlated with soluble sugar and malondialdehyde contents, respectively.ConclusionsOur results suggest that root endophytic microorganisms play an important role in helping Rhododendron resisting heat stress, mainly by regulating soil N content and plant physiological characteristics.
Impact of early empirical antifungal therapy on prognosis of sepsis patients with positive yeast culture: A retrospective study from the MIMIC-IV database
Authors: Zou Zhi-ye , Sun Kai-jun , Fu Guang , Huang Jia-jia , Yang Zhen-jia , Zhou Zhi-peng , Ma Shao-lin , Zhu Feng , Wu Ming 
Published: November 2022

BackgroundMortality and other clinical outcomes of culture-negative and culture-positive among patients with fungal sepsis have not been documented, and whether antifungal therapy prior to fungal culture reports is related to decreased mortality among patients remains largely controversial. This study aimed to determine the mortality and other clinical outcomes of patients with positive yeast cultures and further investigate the effects of initial empiric antifungal therapy.MethodsA retrospective study was conducted among septic patients using the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients with sepsis were divided into two groups based on first fungal culture status during intensive care unit (ICU) stay, and initial empirical antifungal therapy was prescribed based on physician’s experience prior to fungal culture reports within 48 h. The primary outcome was in-hospital all-cause mortality. The secondary outcomes were 30-day all-cause mortality, 60-day all-cause mortality, length of ICU stay and length of hospital stay. Multivariate logistic regression, propensity score matching (PSM), subgroup analyses and survival curve analyses were performed.ResultsThis study included 18,496 sepsis patients, of whom 3,477 (18.8%) had positive yeast cultures. Patients with positive yeast cultures had higher in-hospital all-cause mortality, 60-day all-cause mortality, and longer lengths of ICU stay and hospital stay than those with negative yeast cultures after PSM (all p &lt; 0.01). Multivariate logistic regression analysis revealed that positive yeast culture was a risk factor for in-hospital mortality in the extended model. Subgroup analyses showed that the results were robust among the respiratory infection, urinary tract infection, gram-positive bacterial infection and bacteria-free culture subgroups. Interestingly, empiric antifungal therapy was not associated with lower in-hospital mortality among patients with positive yeast cultures, mainly manifested in stratification analysis, which showed that antifungal treatment did not improve outcomes in the bloodstream infection (odds ratio, OR 2.12, 95% CI: 1.16–3.91, p = 0.015) or urinary tract infection groups (OR 3.24, 95% CI: 1.48–7.11, p = 0.003).ConclusionCulture positivity for yeast among sepsis patients was associated with worse clinical outcomes, and empiric antifungal therapy did not lower in-hospital all-cause mortality in the bloodstream infection or urinary tract infection groups in the ICU.
Metabolomic exploration of the effects of habituation to livestock trailer and extended transportation in goats
Authors: Batchu Phaneendra , Naldurtiker Aditya , Kouakou Brou , Terrill Thomas H. , McCommon George W. , Kannan Govind 
Published: November 2022

Goats raised for meat production are often transported long distances. Twelve-month-old male Spanish goats were used to determine the effects of habituation to trailers on plasma metabolomic profiles when transported for extended periods. In a split-plot design, 168 goats were separated into two treatment (TRT; whole plot) groups and maintained on two different paddocks. Concentrate supplement was fed to one group inside two livestock trailers (habituated group, H), while the other group received the same quantity of concentrate, but not inside the trailers (non-habituated, NH). Goats were subjected to a 10-h transportation stress in 4 replicates (n = 21 goats/replicate/TRT) after 4 weeks of habituation period. Blood samples were collected prior to loading, 20 min after loading (0 h), and at 2, 4, 6, 8, and 10 h of transportation (Time; subplot). A targeted quantitative metabolomics approach was employed to analyze the samples. The data were analyzed using R software and MIXED procedures in SAS. Several amino acids (alanine, serine, glycine, histidine, glutamate, trans-hydroxyproline, asparagine, threonine, methylhistidine, ornithine, proline, leucine, tryptophan) were higher (p &lt; 0.05) in the H group compared to the NH group. Six long-chain acylcarnitines were higher (p &lt; 0.05), while free (C0) and short-chain (C3, C5) carnitines were lower (p &lt; 0.05) in the NH goats compared to the H goats. In general, amino acid concentrations decreased and long-chain acylcarnitine (&gt;C10) levels increased with transportation time (p &lt; 0.05). Butyric acid, α-ketoglutaric acid, and α-aminoadipic acid concentrations were lower (p &lt; 0.05) and β-hydroxybutyric acid concentrations were higher in the NH goats compared to the H goats. Plasma glucose, non-esterified fatty acid (NEFA) and urea nitrogen concentrations were significantly influenced by Time (p &lt; 0.01). Plasma NEFA concentrations were significantly lower (p &lt; 0.01) in the H group than the NH group. Habituation to trailers can be beneficial in enhancing stress coping abilities in goats due to higher concentrations of metabolites such as butyrate and certain amino acids that support antioxidant activities and immune function. Plasma long-chain acylcarnitines may be good indicators of stress during long-distance transportation in goats.
Computational study of nitro-benzylidene phenazine as dengue virus-2 NS2B-NS3 protease inhibitor
Authors: Salin Nurul Hanim , Hariono Maywan , Khalili Nur Sarah Dyana , Zakaria Iffah Izzati , Saqallah Fadi G. , Mohamad Taib Mohamad Nurul Azmi , Kamarulzaman Ezatul Ezleen , Wahab Habibah A. , Khawory Muhammad Hidhir 
Published: November 2022

According to the World Health Organisation (WHO), as of week 23 of 2022, there were more than 1,311 cases of dengue in Malaysia, with 13 deaths reported. Furthermore, there was an increase of 65.7% during the same period in 2021. Despite the increase in cumulative dengue incidence, there is no effective antiviral drug available for dengue treatment. This work aimed to evaluate several nitro-benzylidene phenazine compounds, especially those that contain 4-hydroxy-3,5-bis((2-(4-nitrophenyl)hydrazinylidene)-methyl)benzoate through pharmacophore queries selection method as potential dengue virus 2 (DENV2) NS2B-NS3 protease inhibitors. Herein, molecular docking was employed to correlate the energies of selected hits’ free binding and their binding affinities. Pan assay interference compounds (PAINS) filter was also adopted to identify and assess the drug-likeness, toxicity, mutagenicity potentials, and pharmacokinetic profiles to select hit compounds that can be considered as lead DENV2 NS2B-NS3 protease inhibitors. Molecular dynamics assessment of two nitro-benzylidene phenazine derivatives bearing dinitro and hydroxy groups at the benzylidene ring showed their stability at the main binding pocket of DENV2 protease, where their MM-PBSA binding energies were between -22.53 and -17.01 kcal/mol. This work reports those two nitro-benzylidene phenazine derivatives as hits with 52–55% efficiency as antiviral candidates. Therefore, further optimisation is required to minimise the lead compounds’ toxicity and mutagenicity.
Management of epilepsy in pregnancy in eastern China: A survey from the Zhejiang association against epilepsy
Authors: Xu Zheng-Yan-Ran , Qian Ping , Cai Meng-Ting , Ding Mei-ping , Guo Yi 
Published: November 2022

ObjectiveWe aimed to evaluate the knowledge of the board members of the Zhejiang Association Against Epilepsy (ZAAE) regarding pregnancy of women with epilepsy (WWE), as well as their clinical practice and obstacles in the management of WWE.MethodsA cross-sectional survey was conducted among the board members of the ZAAE using a questionnaire based on the management guidelines for WWE during pregnancy in China. We recorded the demographic characteristics of the surveyed practitioners, the coincidence rate of each question, clinical practice, and the barriers encountered in managing WWE.ResultsThis survey showed that the average knowledge score of the surveyed practitioners was 71.02%, and the knowledge score of neurologists was higher than that of neurosurgeons. Knowledge regarding the following three aspects was relatively poor: whether WWE is associated with an increased risk of cesarean section and preterm delivery, the preferred analgesic drugs for WWE during delivery, and the time of postpartum blood concentration monitoring. After multiple linear regression analysis, the score of neurologists was correlated to the number of pregnant WWE treated each year. In addition, the biggest difficulty in the management of WWE during pregnancy is the lack of patient education and doctors training on pregnant epilepsy management.ConclusionOur study revealed the ZAAE board members' knowledge and management status of pregnant WWE. In addition, our study identified the biggest obstacle to the management of WWE during pregnancy, and emphasized the importance of training and practice of epilepsy knowledge during pregnancy for practitioners and the significance of interdisciplinary communication.
Machine learning can predict mild cognitive impairment in Parkinson's disease
Authors: Amboni Marianna , Ricciardi Carlo , Adamo Sarah , Nicolai Emanuele , Volzone Antonio , Erro Roberto , Cuoco Sofia , Cesarelli Giuseppe , Basso Luca , D'Addio Giovanni , Salvatore Marco , Pace Leonardo , Barone Paolo 
Published: November 2022

BackgroundClinical markers of cognitive decline in Parkinson's disease (PD) encompass several mental non-motor symptoms such as hallucinations, apathy, anxiety, and depression. Furthermore, freezing of gait (FOG) and specific gait alterations have been associated with cognitive dysfunction in PD. Finally, although low cerebrospinal fluid levels of amyloid-β42 have been found to predict cognitive decline in PD, hitherto PET imaging of amyloid-β (Aβ) failed to consistently demonstrate the association between Aβ plaques deposition and mild cognitive impairment in PD (PD-MCI).AimFinding significant features associated with PD-MCI through a machine learning approach.Patients and methodsPatients were assessed with an extensive clinical and neuropsychological examination. Clinical evaluation included the assessment of mental non-motor symptoms and FOG using the specific items of the MDS-UPDRS I and II. Based on the neuropsychological examination, patients were classified as subjects without and with MCI (noPD-MCI, PD-MCI). All patients were evaluated using a motion analysis system. A subgroup of PD patients also underwent amyloid PET imaging. PD-MCI and noPD-MCI subjects were compared with a univariate statistical analysis on demographic data, clinical features, gait analysis variables, and amyloid PET data. Then, machine learning analysis was performed two times: Model 1 was implemented with age, clinical variables (hallucinations/psychosis, depression, anxiety, apathy, sleep problems, FOG), and gait features, while Model 2, including only the subgroup performing PET, was implemented with PET variables combined with the top five features of the former model.ResultsSeventy-five PD patients were enrolled (33 PD-MCI and 42 noPD-MCI). PD-MCI vs. noPD-MCI resulted in older and showed worse gait patterns, mainly characterized by increased dynamic instability and reduced step length; when comparing amyloid PET data, the two groups did not differ. Regarding the machine learning analyses, evaluation metrics were satisfactory for Model 1 overcoming 80% for accuracy and specificity, whereas they were disappointing for Model 2.ConclusionsThis study demonstrates that machine learning implemented with specific clinical features and gait variables exhibits high accuracy in predicting PD-MCI, whereas amyloid PET imaging is not able to increase prediction. Additionally, our results prompt that a data mining approach on certain gait parameters might represent a reliable surrogate biomarker of PD-MCI.
Segmentation and differentiation of periventricular and deep white matter hyperintensities in 2D T2-FLAIR MRI based on a cascade U-net
Authors: Gong Tan , Han Hualu , Tan Zheng , Ning Zihan , Qiao Huiyu , Yu Miaoxin , Zhao Xihai , Tang Xiaoying , Liu Gaifen , Shang Fei , Liu Shuai 
Published: November 2022

BackgroundWhite matter hyperintensities (WMHs) are a subtype of cerebral small vessel disease and can be divided into periventricular WMHs (pvWMHs) and deep WMHs (dWMHs). pvWMHs and dWMHs were proved to be determined by different etiologies. This study aimed to develop a 2D Cascade U-net (Cascade U) for the segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images.MethodsA total of 253 subjects were recruited in the present study. All subjects underwent 2D T2-FLAIR scan on a 3.0 Tesla MR scanner. Both contours of pvWMHs and dWMHs were manually delineated by the observers and considered as the gold standard. Fazekas scale was used to evaluate the burdens of pvWMHs and dWMHs, respectively. Cascade U consisted of a segmentation U-net and a differentiation U-net and was trained with a combined loss function. The performance of Cascade U was compared with two other U-net models (Pipeline U and Separate U). Dice similarity coefficient (DSC), Matthews correlation coefficient (MCC), precision, and recall were used to evaluate the performances of all models. The linear correlations between WMHs volume (WMHV) measured by all models and the gold standard were also conducted.ResultsCompared with other models, Cascade U exhibited a better performance on WMHs segmentation and pvWMHs identification. Cascade U achieved DSC values of 0.605 ± 0.135, 0.517 ± 0.263, and 0.510 ± 0.241 and MCC values of 0.617 ± 0.122, 0.526 ± 0.263, and 0.522 ± 0.243 on the segmentation of total WMHs, pvWMHs, and dWMHs, respectively. Cascade U exhibited strong correlations with the gold standard on measuring WMHV (R2 = 0.954, p &lt; 0.001), pvWMHV (R2 = 0.933, p &lt; 0.001), and dWMHV (R2 = 0.918, p &lt; 0.001). A significant correlation was found on lesion volume between Cascade U and gold standard (r &gt; 0.510, p &lt; 0.001).ConclusionCascade U showed competitive results in segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images, indicating potential feasibility in precisely evaluating the burdens of WMHs.
Effect of music intervention on subjective scores, heart rate variability, and prefrontal hemodynamics in patients with chronic pain
Authors: Du Jiahao , Shi Ping , Fang Fanfu , Yu Hongliu 
Published: November 2022

IntroductionMusic interventions have been proposed in recent years as a treatment for chronic pain. However, the mechanisms by which music relieves pain are unclear, and the effects of music intervention on physiological indicators in patients with chronic pain remain to be explored. This study aimed to explore whether a music intervention would have effects on subjective pain ratings, heart rate variability, and functional connectivity of the cerebral cortex in patients with chronic pain.MethodsA randomized controlled study was conducted on 37 pain patients aged 18–65 years, with the control group receiving usual care, and the intervention group receiving music intervention (8–150 Hz, 50–70 dB) for 30 min before bedtime for 7 days on top of usual care. Pain visual analog scale and heart rate variability were used as subjective and objective physiological indices before and after the music intervention, respectively. Changes in oxyhemoglobin and deoxyhemoglobin concentrations in the cerebral cortex were measured by functional near-infrared spectroscopy, and whole-brain correlation analysis was used to quantify the connectivity of prefrontal brain regions associated with the pain response.ResultsResults showed that patients with chronic pain in the intervention group had significantly lower visual assessment scale scores, as well as significantly lower overall voluntary mobility during pain episodes, resulting in relatively higher vagal innervation compared to the control group. In addition, connections between the bilateral dorsolateral prefrontal cortex (BA9, BA46) and frontal areas (BA10) were significantly higher in the intervention group.DiscussionThis study demonstrates the effectiveness of the combined application of music interventions with usual care in reducing pain levels in patients with chronic pain and provides insight into the pathological mechanisms of music interventions for analgesia, providing direction for new baseline indicators for quantitative clinical assessment of pain. The study was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100052993).Clinical trial registration[https://www.chictr.org.cn/showproj.aspx?proj=136268], identifier [ChiCTR2100052993].
Disrupted metabolic and spontaneous neuronal activity of hippocampus in sepsis associated encephalopathy rats: A study combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging
Authors: Li Haojia , Liao Hongsen , Zhang Chen , Xu Yajie , Xu Xiaomin , Chen Yuchen , Song Shaozheng , Li Qian , Si Yanna , Bao Hongguang 
Published: November 2022

BackgroundThe diagnosis of sepsis associated encephalopathy (SAE) remains challenging in clinical settings because of a lack of specific biomarkers. Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) can be used to aid in the diagnosis of cognition related diseases. This study investigated changes in functional activities and brain metabolites in the hippocampus in SAE rats by fMRI and 1H-MRS.Materials and methodsSepsis associated encephalopathy rats underwent cecal ligation and perforation (CLP) surgery. The Morris water maze (MWM) test was then used to evaluate cognitive function. Resting state-fMRI and 1H-MRS scanning were performed 7 and 14 days after CLP surgery to reveal spontaneous neuronal activity and metabolite changes in the hippocampus. The amplitude of low-frequency fluctuation (ALFF) was used to evaluate spontaneous neuronal activity in the hippocampus. Creatine (Cr), Myo-inositol (mI), and glutamine/glutamate (Glx) levels were measured with 1H-MRS scanning. Immunofluorescence and levels of interleukin (IL)-1β, interleukin (IL)-6, and C-reactive protein (CRP) in the hippocampus were additionally detected to evaluate microglial mediated inflammatory responses. Statistical analysis was performed to evaluate correlations between hippocampal metabolism and behavioral findings.ResultsCecal ligation and perforation treated rats exhibited impaired learning and memory function in the MWM test at days 7 and 14. Elevation of IL-1β in the hippocampus, as well as immunofluorescence results, confirmed severe neuro inflammation in the hippocampus in SAE rats. Compared with the sham group, the ALFF of the right CA-1 area of the hippocampus was higher at day 7after CLP surgery. The Glx/Cr and mI/Cr ratios were enhanced at day 7 after CLP surgery and slightly lower at day 14 after CLP surgery. The ALFF value, and Glx/Cr and mI/Cr ratios were negatively correlated with time spent in the target quadrant in the MWM test.ConclusionSpontaneous neuronal activity and metabolites showed significant alterations in SAE rats. The elevated ALFF value, Glx/Cr ratio, and mI/Cr ratio in the hippocampus were positively associated with cognitive deficits. Changes in ALFF and metabolites in hippocampus may serve as potential neuroimaging biomarkers of cognitive disorders in patients with SAE.