bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Auditory Characteristics to Select Hearing Aid Compression Speeds for Presbycusic Patients
Authors: Zhang Yi , Chen Jing , Zhang Yanmei , Sun Baoxuan , Liu Yuhe 
Published: July 2022

ObjectivesThis study aimed to select the optimal hearing aid compression speeds (fast-acting and slow-acting) for presbycusic patients by using auditory characteristics including temporal modulation and speech-in-noise performance.MethodsIn total, 24 patients with unilateral or bilateral moderate sensorineural hearing loss who scored higher than 21 on the Montreal Cognitive Assessment (MoCA) test participated in this study. The electrocochleogram (ECochG) results, including summating potentials (SP) and action potentials (AP), were recorded. Subjects' temporal modulation thresholds and speech recognition at 4 individualized signal-to-noise ratios were measured under three conditions, namely, unaided, aided with fast-acting compression (FAC), and aided with slow-acting compression (SAC).ResultsThe results of this study showed that modulation discrimination thresholds in the unaided (−8.14 dB) and aided SAC (−8.19 dB) conditions were better than the modulation thresholds in the FAC (−4.67 dB) conditions. The speech recognition threshold (SRT75%) for FAC (5.21 dB) did not differ significantly from SAC (3.39 dB) (p = 0.12). A decision tree analysis showed that the inclusion of the AP, unaided modulation thresholds, and unaided SRT75% may correctly identify the optimal compression speeds (FAC vs. SAC) for individual presbycusic patients with up to 90% accuracy.ConclusionBoth modes of compression speeds improved a presbycusic patient's speech recognition ability in noise. The SAC hearing aids may better preserve the modulation thresholds than the FAC hearing aids. The measurement of AP, along with the unaided modulation thresholds and unaided SRT75%, may help guide the selection of optimal compression speeds for individual presbycusic patients.
Liuwei Dihuang Decoction Alleviates Cognitive Dysfunction in Mice With D-Galactose-Induced Aging by Regulating Lipid Metabolism and Oxidative Stress via the Microbiota-Gut-Brain Axis
Authors: Liu Baiyan , Chen Bowei , Yi Jian , Long Hongping , Wen Huiqiao , Tian Fengming , Liu Yingfei , Xiao Lan , Li Lisong 
Published: July 2022

BackgroundAging is an important cause of cognitive dysfunction. Liuwei Dihuang decoction (LW), a commonly applied Chinese medicine formula, is widely used for the treatment of aging-related diseases in China. Previously, LW was confirmed to be effective in prolonging life span and reducing oxidative stress in aged mice. Unfortunately, the underlying mechanism of LW remains unclear. The aim of this study was to interpret the mechanism by which LW alleviates cognitive dysfunction related to aging from the perspective of the microbiota-gut-brain axis.MethodAll C57BL/6 mice (n = 60) were randomly divided into five groups: the control, model, vitamin E (positive control group), low-dose LW and high-dose LW groups (n = 12 in each group). Except for those in the control group, D-galactose was subcutaneously injected into mice in the other groups to induce the aging model. The antiaging effect of LW was evaluated by the water maze test, electron microscopy, 16S rRNA sequencing, combined LC–MS and GC–MS metabolomics, and ELISA.ResultsLiuwei Dihuang decoction ameliorated cognitive dysfunction and hippocampal synaptic ultrastructure damage in aging mice. Moreover, LW decreased Proteobacteria abundance and increased gut microbiota diversity in aging mice. Metabolomic analysis showed that LW treatment was associated with the significantly differential abundance of 14 metabolites, which were mainly enriched in apelin signaling, sphingolipid metabolism, glycerophospholipid and other metabolic pathways. Additionally, LW affected lipid metabolism and oxidative stress in aging mice. Finally, we also found that LW-regulated microbial species such as Proteobacteria and Fibrobacterota had potential relationships with lipid metabolism, oxidative stress and hippocampal metabolites.ConclusionIn brief, LW improved cognitive function in aging mice by regulating lipid metabolism and oxidative stress through restoration of the homeostasis of the microbiota-gut-brain axis.
Excessive Sodium Intake Leads to Cardiovascular Disease by Promoting Sex-Specific Dysfunction of Murine Heart
Authors: Chen Xiuli , Wu Haiying , Huang Shenzhen 
Published: July 2022

BackgroundGlobally, a high-salt diet (HSD) has become a threat to human health as it can lead to a high risk of cardiac damage. Although some studies investigating HSD have been carried out, the majority has been conducted in males, and there are few female-specific studies, thereby ignoring any effects of sex-specific damage on the heart. In this study, we determined how HSD induces different pathways of cardiovascular diseases through sex-specific effects on cardiac damage in mice.MethodsAn HSD murine model of male and female C57BL/6J mice was fed with sodium-rich chow (4% NaCl). After 8 weeks, cardiac tissues were collected, and the whole gene transcriptome of the hearts of male and female mice was characterized and analyzed using high-throughput RNA sequencing. Immunohistochemistry staining was used to further assess the harmful effects of HSD on protein expression of genes associated with immunity, fibrosis, and apoptosis in male and female mice.ResultsHSD drastically altered the cardiac transcriptome compared to that of the normal heart in both male and female mice and had a sex-specific effect on the cardiac composition in the transcriptome. HSD produced various differentially expressed genes and affected different KEGG pathways of the transcriptome in male and female mice. Furthermore, we found that HSD induced different pathways of cardiovascular disease in the male mice and female mice. The pathway of hypertrophic cardiomyopathy is significantly enriched in HSD-treated male mice, while the pathway of dilated cardiomyopathy is significantly enriched in HSD-treated female mice. Finally, metabolism, immunity, fibrosis, and apoptosis in the mouse heart showed sex-specific changes predicting cardiac damage.ConclusionOur results demonstrate that HSD adversely impacts cardiac structure and function by affecting the metabolism, immunity, fibrosis, and apoptosis in the murine heart and induces the mouse to suffer from sex-specific cardiovascular disease. This study provides a new perspective and basis for the differences in the pharmacology and interventional treatment of sex-specific cardiovascular diseases induced by HSD in men and women.
Resistance Training Attenuates Activation of STAT3 and Muscle Atrophy in Tumor-Bearing Mice
Authors: Testa Mayra Tardelli de Jesus , Cella Paola Sanches , Marinello Poliana Camila , Frajacomo Fernando Tadeu Trevisan , Padilha Camila de Souza , Perandini Patricia Chimin , Moura Felipe Arruda , Duarte José Alberto , Cecchini Rubens , Guarnier Flavia Alessandra , Deminice Rafael 
Published: July 2022

PurposeAlthough the role of signal transducers and activators of transcription (STAT3) in cachexia due to the association of circulating IL-6 and muscle wasting has been extensively demonstrated, the effect of resistance training on STAT3 in mediating muscle atrophy in tumor-bearing mice is unknown. The aim of this study is to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice.MethodsMale Swiss mice were inoculated with Ehrlich tumor cells and exposed or not exposed to resistance exercise protocol of ladder climbing. Skeletal muscle STAT3 protein content was measured, compared between groups, and tested for possible association with plasma interleukins and local oxidative stress markers. Components of the ubiquitin-proteasome and autophagy pathways were assessed by real-time PCR or immunoblotting.ResultsResistance training prevented STAT3 excessive activation in skeletal muscle mediated by the overabundance of plasma IL-6 and muscle oxidative stress. These mechanisms contributed to preventing the increased key genes and proteins of ubiquitin-proteasome and autophagy pathways in tumor-bearing mice, such as Atrogin-1, LC3B-II, and Beclin-1. Beyond preventing muscle atrophy, RT also prevented strength loss and impaired locomotor capacity, hallmarks of sarcopenia.ConclusionOur results suggest that STAT3 inhibition is central in resistance exercise protective effects against cancer-induced muscle atrophy and strength loss.
Mutant-Allele Tumor Heterogeneity, a Favorable Biomarker to Assess Intra-Tumor Heterogeneity, in Advanced Lung Adenocarcinoma
Authors: Wu Xiaoxuan , Song Peng , Guo Lei , Ying Jianming , Li Wenbin 
Published: July 2022

BackgroundIntra-tumor heterogeneity (ITH) plays a vital role in drug resistance and recurrence of lung cancer. We used a mutant-allele tumor heterogeneity (MATH) algorithm to assess ITH and investigated its association with clinical and molecular features in advanced lung adenocarcinoma.MethodsTissues from 63 patients with advanced lung adenocarcinoma were analyzed by next-generation sequencing (NGS) using a panel targeting 520 cancer-relevant genes. We calculated the MATH values from NGS data and further investigated their correlation with clinical and molecular characteristics.ResultsAmong the 63 patients with advanced lung adenocarcinoma, the median value of MATH was 33.06. Patients with EGFR mutation had higher level of MATH score than those with wild-type EGFR status (P = 0.008). Patients with stage IV disease showed a trend to have a higher MATH score than those with stage III (P = 0.052). MATH was higher in patients with disruptive TP53 mutations than in those with non-disruptive mutations (P = 0.036) or wild-type sequence (P = 0.023), but did not differ between tumors with non-disruptive mutations and wild-type TP53 (P = 0.867). High MATH is associated with mutations in mismatch repair (MMR) pathway (P = 0.026) and base excision repair (BER) pathway (P = 0.008). In addition, MATH was found to have a positive correlation with tumor mutational burden (TMB) (Spearman ρ = 0.354; P = 0.004). In 26 patients harboring EGFR mutation treated with first generation EGFR TKI as single-agent therapy, the objective response rate was higher in the Low-MATH group than in the High-MATH group (75% vs. 21%; P = 0.016) and Low-MATH group showed a significantly longer progression-free survival than High-MATH group (median PFS: 13.7 months vs. 10.1 months; P = 0.024).ConclusionsFor patients with advanced lung adenocarcinoma, MATH may serve as a clinically practical biomarker to assess intratumor heterogeneity.
Causes of Death Among Prostate Cancer Patients Aged 40 Years and Older in the United States
Authors: Ye Yuzhong , Zheng Yongqiang , Miao Qi , Ruan Hailong , Zhang Xiaoping 
Published: July 2022

PurposeLittle is known about the detailed spectrum of the cause of death associated with prostate cancer (PCa). This study systematically characterized the cause of death among patients with PCa.MethodsPatients aged 40 years and older with primary PCa were identified from the Surveillance, Epidemiology, and End Results program. Mortality rates were estimated. Standardized mortality ratios (SMRs) of non-cancer deaths were calculated to evaluate the risk of death and to compare with the cancer-free population.ResultsThis study included 1,170,489 patients with PCa. There were 501,262 deaths, of which 27.4% were due to PCa and 57.0% were due to non-cancer causes. Non-cancer deaths increased over time from 1975 to 2016, and index cancer death decreased continually. The risk of non-cancer deaths was 1.45 times (SMR, 1.45; 95% confidence interval [CI], 1.45–1.46) that of the general population. Cardiovascular disease was the most common non-cancer cause of death, accounting for 30.2% of all deaths among PCa patients. Alzheimer’s disease (SMR, 3.92; 95% CI, 3.85–4.00) had the highest risk of death. The mortality rate and SMR of non-cancer deaths increased with increased follow-up after diagnosis.ConclusionInstead of the index cancer, non-cancer comorbidities were the leading cause of death among patients with PCa, and the risk of non-cancer deaths was much higher than among the general population. Clinicians and researchers should be aware of this trend to conduct timely and targeted interventions.
Studies on Jackfruit–Okra Mucilage-Based Curcumin Mucoadhesive Tablet for Colon Targeted Delivery
Authors: Kurra Pallavi , Narra Kishore , Orfali Raha , Puttugunta Srinivasa Babu , Khan Shah Alam , Meenakshi Dhanalekshmi Unnikrishnan , Francis Arul Prakash , Asdaq Syed Mohammed Basheeruddin , Imran Mohd. 
Published: July 2022

The present work investigates a blend of jack fruit mucilage (JFM) and okra mucilage (OKM) as promising mucoadhesive carriers for colon-specific delivery of a curcumin (CMN)-loaded mucoadhesive tablet (CMT) formulation. Formulation optimization was performed using central composite design (CCD) to further decipher the effect of varying proportions of the mucoadhesive carriers JFM and OKG on response factors such as drug release (% DR) and mucoadhesive strength (MA). The optimized formulation CMT (F14) demonstrated a favorable 54.35% in vitro release of CMN in 12 h with release kinetics resulting from a zero-order anomalous diffusion mechanism and MA of 34.1733 ± 1.26 g. Accelerated stability testing of CMT (F14) confirmed a shelf life of about 4.7 years. In vivo drug targeting studies performed using rabbit models in order to observe transit behavior (colon-specific delivery) of the dosage form were assessed by fluoroscopic images of the GI tract. Taking the results together, the results confirm that the combination of JFM and OKM could be exploited as an ideal mucoadhesive carrier for effective delivery of macromolecules to the colon.
Non-Antimicrobial Adjuvant Therapy Using Ticagrelor Reduced Biofilm-Related Staphylococcus aureus Prosthetic Joint Infection
Authors: Pant Narayan , Miranda-Hernandez Socorro , Rush Catherine , Warner Jeffrey , Eisen Damon P. 
Published: July 2022

Background: Prosthetic joint infection (PJI), frequently caused by Staphylococcus aureus, leads to a significant arthroplasty failure rate. Biofilm is a crucial virulence factor of S. aureus that is intrinsic to the pathogenesis of PJI. Biofilm-related infections are recalcitrant to antibiotic treatment. Surgical and antibiotic therapy could be combined with non-antibacterial adjuvants to improve overall treatment success. Ticagrelor, a P2Y12 receptor inhibitor antiplatelet drug, is known to have anti-staphylococcal antibacterial and antibiofilm activity. However, the molecular mechanism for ticagrelor’s antibiofilm activity and its efficacy in the treatment of S. aureus PJI are unknown.Methods: To study the in vitro antibacterial and antibiofilm activity of ticagrelor, broth microdilution and crystal violet staining method were used. Ticagrelor’s effect on the expression of S. aureus biofilm genes (icaA, icaD, ebps, fib, eno, and agr) was studied using the relative quantification method. To test ticagrelor’s in vivo efficacy to treat S. aureus PJI, mice were randomized into five groups (n = 8/group): infected femoral implants treated with ticagrelor alone; infected implants treated with cefazolin alone; infected implants treated with ticagrelor and cefazolin; infected implants treated with phosphate buffer solution (PBS)-positive controls, and sterile implants-negative controls. Ticagrelor was administered orally from day 4 to day 7 post-surgery, while cefazolin was injected intravenously on day 7.Results: Ticagrelor, alone and with selected antibiotics, showed in vitro antibacterial and antibiofilm activity against S. aureus. Strain-specific downregulation of biofilm-related genes, fib, icaD, ebps, and eno, was shown. In an animal model of biofilm-related S. aureus PJI, ticagrelor alone and combined with cefazolin significantly reduced bacterial concentrations on the implants compared with the positive control group. Ticagrelor significantly reduced bacterial dissemination to periprosthetic tissue compared with the positive controls.Conclusion: Ticagrelor adjuvant therapy reduced S. aureus PJI in an animal model. However, this study is very preliminary to make a conclusion on the clinical implication of the findings. Based on the current results, more studies are recommended to better understand its implication.
Moderating Role of Resilience Between Depression and Stress Response of Vocational Middle School Students During the COVID-19 Pandemic
Authors: Jin Mingqi , Ding Lingling , Fan Jiali , Sheng Xin , Luo Bingqing , Hang Ronghua , Feng Linpu , Huang Long 
Published: July 2022

ObjectIn this study, we aimed to explore the influences of stress responses and psychological resilience on depression of vocational middle school students during the initial COVID-19 outbreak in China.MethodsAn online questionnaire survey on the students of a medical school in Jiangxi Province, China, and obtained 3,532 valid questionnaires. A self-compiled general situation questionnaire, Stress Response of COVID-19 Questionnaire, the Resilience Scale for Chinese Adolescents and Center for Epidemiological Studies Depression Scale (CES-D) were used. Hierarchical regression analysis was used to explore the regulatory role of psychological resilience between stress response and depression.Results(1) There were significant differences in gender between vocational middle school students' evaluation (t = 3.07, P = 0.002) and defense (t = 3.28, P = 0.001) of the pandemic. Males had higher cognitive evaluation of the pandemic than females, and females had more defense against the pandemic than males. (2) There is a significant difference between vocational middle school students from different grades in depression level (F = 3.62, P = 0.03), pneumonia defense (F = 13.65, P &lt; 0.001) and pneumonia panic (F = 3.10, P = 0.045). (3) Depression level (F = 7.17, P &lt; 0.001), pneumonia evaluation (F = 2.78, P = 0.04) and pneumonia panic (F = 3.32, P = 0.02) of the students concerning the spatial distance of the pandemic. (4) The severity of urban pandemic affects the evaluation of pneumonia among vocational middle school students. (5) Depression was negatively correlated with psychological resilience and pneumonia evaluation, and positively correlated with pneumonia panic. Psychological resilience was positively correlated with pneumonia evaluation and pneumonia defense, and negatively correlated with pneumonia panic. (6) Psychological resilience could reduce the level of depression caused by pneumonia evaluation and pneumonia panic.ConclusionThere were significant differences in depression level and stress responses in grades, gender and spatial distance of pandemic. Resilience has a significant negative moderator effect on the relationship between pandemic panic and depression. Resilience has a significant positive moderator effect on the relationship between pandemic evaluation and depression.
Impact of the National Reimbursement Drug List Negotiation Policy on Accessibility of Anticancer Drugs in China: An Interrupted Time Series Study
Authors: Zhu Hong , Zhu Jingmin , Zhou Yingyu , Shan Linghan , Li Cui , Cui Yu , Kang Zheng , Jiao Mingli , Liu Huan , Gao Lijun , Wu Qunhong , Hao Yanhua 
Published: July 2022

ObjectiveSince 2016, the Chinese government has been regularly implementing the National Reimbursement Drug List Negotiation (NRDLN) to improve the accessibility of drugs. In the second round of NRDLN in July 2017, 18 anticancer drugs were included. This study analyzed the impact of the NRDLN on the accessibility of these 18 anticancer drugs in China.MethodsNational hospital procurement data were collected from 2015 to 2019. As measurements of drug accessibility, monthly average of drug availability or defined daily dose cost (DDDc) was calculated. Interrupted time series (ITS) analysis was employed to evaluate the impact of NRDLN on drug accessibility. Multilevel growth curve models were estimated for different drug categories, regions or levels of hospitals.ResultsThe overall availability of 18 anticancer drugs increased from about 10.5% in 2015 to slightly over 30% in 2019. The average DDDc dropped from 527.93 CNY in 2015 to 401.87 CNY in 2019, with a reduction of 23.88%. The implementation of NRDLN was associated with higher availability and lower costs for all 18 anticancer drugs. We found an increasing level in monthly drug availability (β2 = 2.1126), which ascended more sharply after the implementation of NRDLN (β3 = 0.3656). There was a decreasing level in DDDc before July 2017 (β2 = −108.7213), together with a significant decline in the slope associated with the implementation of NRDLN (β3 = −4.8332). Compared to Traditional Chinese Medicines, the availability of Western Medicines was higher and increased at a higher rate (β3 = 0.4165 vs. 0.1108). Drug availability experienced a larger instant and slope increase in western China compared to other regions, and in secondary hospitals than tertiary hospitals. Nevertheless, regional and hospital-level difference in the effect of NRDLN on DDDc were less evident.ConclusionThe implementation of NRDLN improves the availability and reduces the cost of some anticancer drugs in China. It contributes to promoting accessibility of anticancer drugs, as well as relieving regional or hospital-level disparities. However, there are still challenges to benefit more patients sufficiently and equally. It requires more policy efforts and collaborative policy combination.
Management of Long COVID—The CoviMouv' Pilot Study: Importance of Adapted Physical Activity for Prolonged Symptoms Following SARS-CoV2 Infection
Authors: Colas Claire , Bayle Manon , Labeix Pierre , Botelho-Nevers Elisabeth , Gagneux-Brunon Amandine , Cazorla Céline , Schein Flora , Breugnon Emma , Garcin Arnauld , Feasson Léonard , Roche Frédéric , Hupin David 
Published: July 2022

ContextAfter a COVID-19 infection, some patients have persistent symptoms, the most common is fatigue. To prevent it from becoming chronic (post-COVID-19 syndrome), early management before 3 months could be useful. Exercise and education are recommended.ObjectiveTo assess fatigue in patients with prolonged symptoms after COVID-19 infection and who received a mixed program of remote adapted physical activity and therapeutic education. The secondary objective was to evaluate the efficacy and safety of this training method thanks to aerobic and anaerobic parameters.Methods“CoviMouv': From Coaching in Visual to Mouv in real” is a nonrandomized controlled pilot study. Patients in telerehabilitation followed 12 remote exercise sessions and 3 therapeutic education workshops. Patients on traditional rehabilitation followed their program with a community-based physiotherapist.ResultsFatigue was reduced after the one-month intervention in both groups (p = 0.010). The majority of aerobic parameters were significantly improved, e.g., maximal oxygen uptake (p = 0.005), walking distance (p = 0.019) or hyperventilation values (p = 0.035). The anaerobic parameter was not improved (p = 0.400). No adverse event was declared.DiscussionTelerehabilitation is a good alternative when a face-to-face program is not possible. This care at an early stage of the disease could help prevent the chronicity of post-COVID-19 symptoms and the installation of vicious circles of physical deconditioning. A larger study would be necessary.