bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase III, randomized, double-blind, placebo-controlled clinical study: a study on the safety and clinical efficacy of AZVUDINE in moderate COVID-19 patients
Authors: de Souza Sávio Bastos , Cabral Paula Gebe Abreu , da Silva Renato Martins , Arruda Raul Ferraz , Cabral Sheila Passos de Figueiredo , de Assis Arícia Leone Evangelista Monteiro , Viana Junior Antônio Brazil , Degrave Wim Maurits Sylvain , Moreira Aline dos Santos , Silva Cléber Glória , Chang Junbiao , Lei Pingsheng
Published: October 2023

Background

In 2019, a highly pathogenic coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surfaced and resulted in the outbreak of coronavirus disease 2019 (COVID-19). With the aim of finding effective drugs to fight against the disease, several trials have been conducted since COVID-19 can only be considered a treatable disease, from a clinical point of view, after the availability of specific and effective antivirals. AZVUDINE (FNC), initially developed for treating HIV, is a potential treatment for COVID-19 as it has the capability to lower the patient’s viral load and promote recovery.

Methods

Volunteers infected with SARS-CoV-2 confirmed by reverse transcription polymerase chain reaction (RT-PCR), with good kidney and liver function, who were not using other antivirals or monoclonal antibodies were eligible. Samples from patients were assessed for viral load every 48 h during treatment using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and droplet digital polymerase chain reaction (ddPCR).

Results

The study’s primary outcome measure was the percentage of participants showing an improvement in clinical scores, while the secondary outcome measure was the percentage of participants with a clinical outcome of cure. These measures were used to assess the safety and efficacy of FNC for treating COVID-19. In the analysis of sociodemographic variables, no significant differences were detected between patients in the FNC and the placebo group for race, age group, or sex. The results showed a potential benefit to participants who received FNC during the study, as observed in the shorter hospital stay, shorter negative conversion time of SARS-CoV-2, and a significant reduction in viral load. Furthermore, the reduction in fever and chills were significant at D1, D2, and D3. In this study, a total of 112 adverse events cases were noted, with 105 cases being categorized as non-serious and only 7 cases as serious adverse events.

Conclusion

The pandemic is not being effectively controlled and is causing multiple waves of infection that require extensive medical resources. However, FNC has demonstrated potential to reduce the treatment duration of moderate COVID-19 cases, thereby saving significant medical resources. This makes FNC a promising candidate for COVID-19 treatment.

Clinical trial registration: [clinicaltrials.gov], identifier [NCT04668235].
High-flow arteriovenous fistula in X-linked Alport syndrome: a case report
Authors: Takahashi Daisuke , Katayama Kan , Iyoda Yoshinobu , Fukumori Ayumi , Tsujimoto Kayo , Yamawaki Masahiro , Tanaka Fumika , Saiki Ryosuke , Oda Keiko , Suzuki Yasuo , Murata Tomohiro , Okugawa Yoshinaga , Dohi Kaoru
Published: October 2023

Most male X-linked Alport syndrome patients with COL4A5 nonsense mutations experience end-stage kidney failure by 30 years old. Although there is no definition of high-flow arteriovenous fistula, access blood flows greater than 2000 mL/min might predict the occurrence of high-output heart failure. A 50-year-old Japanese man had suffered from proteinuria at 4 years old and sensorineural hearing loss and a lenticular lens at 20 years old. He had started to receive hemodialysis treatment due to end-stage kidney disease at 22 years old. A genetic test confirmed a novel hemizygous nonsense variant COL4A5 c.2980G > T (p.Gly994Ter), and he was diagnosed with X-linked Alport syndrome. COL4A5 c.2980G > T was considered “pathogenic” according to the American College of Medical Genetics and Genomics guidelines and in vitro experiments. Shortness of breath on exertion was exaggerated, his brachial artery blood flow was over 4,236–4,353 mL/min, his cardiac output was 5,874 mL/min, and he needed radial artery banding at 51 years old. After radial artery banding surgery, the brachial artery blood flow decreased to 987–1,236 mL/min, and echocardiography showed a cardiac output at 5100 mL/min with improved E’ and E/E’. His shortness of breath on exertion improved gradually. Although rare, high-output heart failure due to high-flow arteriovenous fistula should be kept in mind as a complication in X-linked Alport syndrome patients, and our patient was successfully treated with radial artery banding surgery.
Prevalence of and prognosis for poor immunological recovery by virally suppressed and aged HIV-infected patients
Authors: Fan Lina , Li Penghui , Yu Aiping , Liu Dan , Wang Ziyu , Wu Yue , Zhang Defa , Zou Meiyin , Ma Ping
Published: October 2023

Background

Antiretroviral therapy (ART) prolongs lifespan and decreases mortality of HIV infected patients. However, many patients do not achieve optimal immune reconstitution. The influence of non-optimal immune recovery on non-AIDS related diseases is not well defined in aged HIV-infected patients receiving ART.

Methods

A retrospective study was conducted at Tianjin Second People’s Hospital, China to evaluate the association of an inadequate immunological response and non-AIDS diseases in HIV infected patients ≥60 years of age and virally suppressed for at least 2 years by ART.

Results

The study included patients (n = 666) who initiated ART between August 2009 and December 2020. The prevalence of patients with an inadequate immunological response was 29.6%. The percentage of non-AIDS diseases such as hypertension, cardiovascular disease (CVD), diabetes, tumor, and chronic kidney disease (CKD) was 32.9, 9.9, 31, 4.1, and 13%, respectively. In addition to baseline CD4+ T cell counts, CVD and tumor were associated with poor immune reconstitution in aged Chinese HIV-1 infected patients. The adjusted odds ratios (95% confidence interval) were AOR 2.45 (95% CI: 1.22–4.93) and 3.06 (95% CI: 1.09–8.56, p = 0.03). Inadequate immunological response was associated with greater mortality (AOR: 2.83, 95% CI: 1.42–5.67, p = 0.003) in this cohort.

Conclusion

These results tend to demonstrate appropriate drug selection at ART initiation and prevention of non-AIDS complications during ART decreased mortality of and an inadequate immunological response in aged HIV infected patients.
Early application of awake extracorporeal membrane oxygenation in pneumocystis jirovecii pneumonia complicated with severe acute respiratory distress syndrome: a case report
Authors: Wu Qinglin , Cen Fulan , Wang Guowei , Huang Jia
Published: October 2023

Introduction

Patients suffering from severe acute respiratory distress syndrome (ARDS) are usually treated with mechanical ventilation. Extracorporeal membrane oxygenation (ECMO) has traditionally been considered a life-saving therapy and was reserved as a last resort when other treatment options were exhausted. However, this report outlines our successful initial experience with early implementation of awake venovenous extracorporeal membrane oxygenation (VV-ECMO) in a case of pneumocystis jirovecii pneumonia complicated by severe acute respiratory distress syndrome (ARDS), offering a promising new approach for recovery.

Case presentation

We present a case report of the effective application of awake VV-ECMO in a 29 years-old man with severe ARDS caused by pneumocystis jirovecii pneumonia. The patient initially received antibiotic treatment and non-invasive ventilation (NIV) for respiratory distress, but these interventions failed to improve the worsening dyspnea that occurred in the patient. Following the combined antifungal therapy, high-flow nasal cannula (HFNC) oxygen therapy, and VV-ECMO for a duration of 7 days, the patient’s symptoms improved, showing relief.

Conclusion

Awake VV-ECMO proved to be an effective treatment for critically ill patients with ARDS, avoiding the need for invasive mechanical ventilation. However, increased clinical evidence is needed to verify whether awake ECMO could be widely used in severe ARDS caused by other diseases or conditions.
Calpain-2 protein influences chikungunya virus replication and regulates vimentin rearrangement caused by chikungunya virus infection
Authors: Li Jia , Zheng Kang , Shen Huilong , Wu Hua , Wan Chengsong , Zhang Renli , Liu Zhimin
Published: October 2023

Chikungunya fever (CHIF), a vector-borne disease transmitted mainly by Aedes albopictus and Aedes aegypti, is caused by Chikungunya virus (CHIKV) infection. To date, it is estimated that 39% of the world’s population is at risk of infection for living in countries and regions where CHIKV is endemic. However, at present, the cellular receptors of CHIKV remains not clear, and there are no specific drugs and vaccines for CHIF. Here, the cytotoxicity of calpain-2 protein activity inhibitor III and specific siRNA was detected by MTT assays. The replication of CHIKV was detected by qPCR amplification and plaque assay. Western blot was used to determine the level of the calpain-2 protein and vimentin protein. Immunofluorescence was also operated for detecting the rearrangement of vimentin protein. Our results indicated that calpain-2 protein activity inhibitor III and specific siRNA might suppress CHIKV replication. Furthermore, CHIKV infection led to vimentin remodeling and formation of cage-like structures, which could be inhibited by the inhibitor III. In summary, we confirmed that calpain-2 protein influenced chikungunya virus replication and regulated vimentin rearrangement caused by chikungunya virus infection, which could be important for understanding the biological significance of CHIKV replication and the future development of antiviral strategies.
Characterization and fungicide sensitivity of Trichoderma species causing green mold of Ganoderma sichuanense in China
Authors: Li Xuefei , Sossah Frederick Leo , Tuo Yonglan , Hu Jiajun , Wei Qian , Li Shiyu , Rong Na , Wiafe-Kwagyan Michael , Li Changtian , Zhang Bo , Li Xiao , Li Yu
Published: October 2023

Green mold disease, caused by Trichoderma spp., is one of the most devastating diseases of mushrooms in China. The application of fungicides remains one of the important control methods among the integrated pest management tools for disease management in mushroom farms. This study aimed to identify Trichoderma spp., isolated from G. sichuanense fruiting bodies displaying green mold symptoms collected from mushroom farms in Zhejiang, Hubei, and Jilin Province, China, and evaluate their in vitro sensitivity to six fungicides. A total of 47 isolates were obtained and classified into nine Trichoderma spp. namely, T. asperellum, T. citrinoviride, T. ganodermatiderum, T. guizhouense, T. hamatum, T. harzianum, T. koningiopsis, T. paratroviride, and T. virens, through morphological characteristics and phylogenetic analysis of concatenated sequences of translation elongation factor 1-alpha (TEF) and DNA-dependent RNA polymerase II subunit (RPB2) genes. The pathogenicity test was repeated two times, and re-isolation of the nine Trichoderma spp. from the fruiting bodies of G. sichuanense fulfilled Koch’s postulates. Prochloraz manganese showed the best performance against most species. This research contributes to our understanding of green mold disease, reveals the phylogenetic relationships among Trichoderma species, and expands our knowledge of Trichoderma species diversity associated with green mold disease in G. sichuanense.
Alzheimer’s disease: an axonal injury disease?
Authors: Dan Liang , Zhang Zhaohui
Published: October 2023

Alzheimer’s disease (AD) is the primary cause of dementia and is anticipated to impose a substantial economic burden in the future. Over a significant period, the widely accepted amyloid cascade hypothesis has guided research efforts, and the recent FDA approval of an anti- amyloid-beta (Aβ) protofibrils antibody, believed to decelerate AD progression, has further solidified its significance. However, the excessive emphasis placed on the amyloid cascade hypothesis has overshadowed the physiological nature of Aβ and tau proteins within axons. Axons, specialized neuronal structures, sustain damage during the early stages of AD, exerting a pivotal influence on disease progression. In this review, we present a comprehensive summary of the relationship between axonal damage and AD pathology, amalgamating the physiological roles of Aβ and tau proteins, along with the impact of AD risk genes such as APOE and TREM2. Furthermore, we underscore the exceptional significance of axonal damage in the context of AD.
Role of microRNA-34a in blood–brain barrier permeability and mitochondrial function in ischemic stroke
Authors: Payne Cole T. , Tabassum Sidra , Wu Silin , Hu Heng , Gusdon Aaron M. , Choi Huimahn A. , Ren Xuefang S.
Published: October 2023

Over the past decade, there has been an uptick in the number of studies conducting research on the role of microRNA (miRNA) molecules in stroke. Among these molecules, miR-34a has emerged as a significant player, as its levels have been observed to exhibit a substantial rise following ischemic events. Elevated levels of miR-34a have been found to have multiple effects, including the modulation of inflammatory molecules involved in the post-stroke recovery process, as well as negative effects on the blood–brain barrier (BBB) permeability. Interestingly, the increase of miR-34a appears to increase BBB permeability post stroke, through the negative effect on mitochondrial function. The strength of mitochondrial function is crucial for limiting para-cellular permeability and maintaining the structural integrity of the BBB. Furthermore, the activation of ischemic repair mechanisms and the reduction of ischemic event damage depend on healthy mitochondrial activity. This review aims to emphasize the involvement of miR-34a in ischemic stroke, specifically its interaction with mitochondrial genes in cerebrovascular endothelial cells, the effect on mitochondrial function, and lastly its regulatory role in BBB permeability. A comprehensive understanding of the role of miR-34a in maintaining BBB integrity and its contribution to the pathogenesis of stroke holds significant value in establishing a foundation for the development of future therapeutics and diagnostic markers.
Analyzing physiological signals recorded with a wearable sensor across the menstrual cycle using circular statistics
Authors: Sides Krystal , Kilungeja Grentina , Tapia Matthew , Kreidl Patrick , Brinkmann Benjamin H. , Nasseri Mona
Published: October 2023

This study aims to identify the most significant features in physiological signals representing a biphasic pattern in the menstrual cycle using circular statistics which is an appropriate analytic method for the interpretation of data with a periodic nature. The results can be used empirically to determine menstrual phases. A non-uniform pattern was observed in ovulating subjects, with a significant periodicity (p<0.05) in mean temperature, heart rate (HR), Inter-beat Interval (IBI), mean tonic component of Electrodermal Activity (EDA), and signal magnitude area (SMA) of the EDA phasic component in the frequency domain. In contrast, non-ovulating cycles displayed a more uniform distribution (p>0.05). There was a significant difference between ovulating and non-ovulating cycles (p<0.05) in temperature, IBI, and EDA but not in mean HR. Selected features were used in training an Autoregressive Integrated Moving Average (ARIMA) model, using data from at least one cycle of a subject, to predict the behavior of the signal in the last cycle. By iteratively retraining the algorithm on a per-day basis, the mean temperature, HR, IBI and EDA tonic values of the next day were predicted with root mean square error (RMSE) of 0.13 ± 0.07 (C°), 1.31 ± 0.34 (bpm), 0.016 ± 0.005 (s) and 0.17 ± 0.17 (μS), respectively.
Frameless robot-assisted stereoelectroencephalography-guided radiofrequency: methodology, results, complications and stereotactic application accuracy in pediatric hypothalamic hamartomas
Authors: Li Ping , Zhou Yuanfeng , Zhang Qin , Yang Yuantao , Wang Min , Zhu Renqing , Li Hao , Gu Shuo , Zhao Rui
Published: October 2023

Objective

We aimed to investigate the methodology, results, complications and stereotactic application accuracy of electrode implantation and its explanatory variables in stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) for pediatric hypothalamic hamartoma.

Methods

Children with hypothalamic hamartoma who underwent robot-assisted SEEG-RFTC between December 2017 and November 2021 were retrospectively analyzed. The methodology, seizure outcome, complications, in vivo accuracy of electrode implantation and its explanatory variables were analyzed.

Results

A total of 161 electrodes were implanted in 28 patients with 30 surgeries. Nine electrodes not following the planned trajectories due to intraoperative replanning were excluded, and the entry point and target point errors of 152 electrodes were statistically analyzed. The median entry point error was 0.87 mm (interquartile range, 0.50–1.41 mm), and the median target point error was 2.74 mm (interquartile range, 2.01–3.63 mm). Multifactor analysis showed that whether the electrode was bent (b = 2.16, p < 0.001), the length of the intracranial electrode (b = 0.02, p = 0.049), and the entry point error (b = 0.337, p = 0.017) had statistically significant effects on the target error. During follow-up (mean duration 31 months), 27 of 30 (90%) procedures were seizure-free. The implantation-related complication rate was 2.6% (4/152), and the major complication rate in all procedures was 6.7% (2/30).

Conclusion

Robot-assisted SEEG-RFTC is a safe, effective and accurate procedure for pediatric hypothalamic hamartoma. Explanatory variables significantly associated with the target point localization error at multivariate analysis include whether the intracranial electrode is bent, the intracranial electrode length and the entry point error.
In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments
Authors: Mom Robin , Réty Stéphane , Mocquet Vincent , Auguin Daniel
Published: October 2023

Ménière’s disease (MD) is characterized by an abnormal dilatation of the endolymphatic compartment called endolymphatic hydrops and is associated with fluctuating hearing losses and vertigo. Corticosteroid treatment is typically administered for its anti-inflammatory effects to MD patients. However, we recently described for the first time a direct interaction of two corticosteroids (dexamethasone and cortisol) with human AQP2 which strongly inhibited water fluxes. From these initial studies, we proposed an AQPs Corticosteroids Binding Site (ACBS). In the present work, we tested the interaction of 10 molecules associated to the steroid family for this putative ACBS. We observed a wide diversity of affinity and inhibitory potential of these molecules toward AQP2 and discussed the implications for inner ear physiology. Among the tested compounds, cholecalciferol, calcitriol and oestradiol were the most efficient AQP2 water permeability inhibitors.
Mechanisms and effects of metformin on skeletal muscle disorders
Authors: Shang Ren , Miao Jing
Published: October 2023

Skeletal muscle disorders are mostly genetic and include several rare diseases. With disease progression, muscle fibrosis and adiposis occur, resulting in limited mobility. The long course of these diseases combined with limited treatment options affect patients both psychologically and economically, hence the development of novel treatments for neuromuscular diseases is crucial to obtain a better quality of life. As a widely used hypoglycemic drug in clinical practice, metformin not only has anti-inflammatory, autophagy-regulating, and mitochondrial biogenesis-regulating effects, but it has also been reported to improve the symptoms of neuromuscular diseases, delay hypokinesia, and regulate skeletal muscle mass. However, metformin’s specific mechanism of action in neuromuscular diseases requires further elucidation. This review summarizes the evidence showing that metformin can regulate inflammation, autophagy, and mitochondrial biogenesis through different pathways, and further explores its mechanism of action in Duchenne muscular dystrophy, statin-associated muscle disorders, and age-related sarcopenia. This review clarifies the directions of future research on therapy for neuromuscular diseases.
Novel utilization of deep brain stimulation in the pedunculopontine nucleus with globus pallidus internus for treatment of childhood-onset dystonia
Authors: MacLean Jennifer A. , Nataraj Jaya , Davies Jordan , Zakharova Aleksandra , Kurtz Joshua , Liker Mark A. , Olaya Joffre , Sanger Terence D.
Published: October 2023

Introduction

Deep brain stimulation (DBS) is a well-documented therapy for dystonia utilized in many adult and pediatric movement disorders. Pedunculopontine nucleus (PPN) has been investigated as a DBS target primarily in adult patients with dystonia or dyskinesias from Parkinson’s disease, showing improvement in postural instability and gait dysfunction. Due to the difficulty in targeting PPN using standard techniques, it is not commonly chosen as a target for adult or pediatric pathology. There is no current literature describing the targeting of PPN in DBS for childhood-onset dystonia.

Methods

Two pediatric and one young adult patient with childhood-onset dystonia who underwent DBS implantation at our institution were identified. Patient 1 has Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN) syndrome. Patient 2 has Glutaric Aciduria Type 1 (GA1). Patient 3 has atypical pantothenate kinase-associated neurodegeneration (PKAN). PPN was identified as a potential target for these patients due to axial or orofacial dystonia. Pre- and post-operative videos taken as part of routine clinical assessments were evaluated and scored on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS). All patients had permanent electrodes placed bilaterally in PPN and globus pallidus internus (GPi). A Likert scale on quality of life was also obtained from the patient/parents as applicable.

Results

Significant programming was necessary over the first 3–12 months to optimize patients’ response to stimulation. All patients experienced at least a 34% improvement in the BFMDRS score. Patients 2 and 3 also experienced an over 30% improvement in BADS score. All patients/parents appreciated improvement in quality of life postoperatively.

Discussion

Deep brain stimulation in PPN was safely and successfully used in two pediatric patients and one young adult patient with childhood-onset dystonia. These patients showed clinically significant improvements in BFMDRS scoring post operatively. This represents the first reported DBS targeting of PPN in pediatric patients, and suggests that PPN is a possible target for pediatric-onset dystonia with axial and orofacial symptoms that may be refractory to traditional pallidal stimulation alone.
Nerve regeneration using decellularized tissues: challenges and opportunities
Authors: Mahdian Maryam , Tabatabai Tayebeh Sadat , Abpeikar Zahra , Rezakhani Leila , Khazaei Mozafar
Published: October 2023

In tissue engineering, the decellularization of organs and tissues as a biological scaffold plays a critical role in the repair of neurodegenerative diseases. Various protocols for cell removal can distinguish the effects of treatment ability, tissue structure, and extracellular matrix (ECM) ability. Despite considerable progress in nerve regeneration and functional recovery, the slow regeneration and recovery potential of the central nervous system (CNS) remains a challenge. The success of neural tissue engineering is primarily influenced by composition, microstructure, and mechanical properties. The primary objective of restorative techniques is to guide existing axons properly toward the distal end of the damaged nerve and the target organs. However, due to the limitations of nerve autografts, researchers are seeking alternative methods with high therapeutic efficiency and without the limitations of autograft transplantation. Decellularization scaffolds, due to their lack of immunogenicity and the preservation of essential factors in the ECM and high angiogenic ability, provide a suitable three-dimensional (3D) substrate for the adhesion and growth of axons being repaired toward the target organs. This study focuses on mentioning the types of scaffolds used in nerve regeneration, and the methods of tissue decellularization, and specifically explores the use of decellularized nerve tissues (DNT) for nerve transplantation.
The impact of early life stress and schizophrenia on motor and cognitive functioning: an experimental study
Authors: Oginga Fredrick Otieno , Mpofana Thabisile
Published: October 2023

Background

Early life stress (ELS) and parental psychopathology, such as schizophrenia (SZ), have been associated with altered neurobiological and behavioral outcomes later in life. Previous studies have investigated the effects of ELS and parental SZ on various aspects of behavior, however, we have studied the combined effects of these stressors and how they interact, as individuals in real-life situations may experience multiple stressors simultaneously.

Objective

The aim of this study was to investigate the impact of ELS and schizophrenia on locomotor activity, anxiety-like behavior, exploratory tendencies, and spatial memory in Sprague Dawley (SD) rats.

Methods

Male and female SD pups were randomly assigned to eight groups: control, ELS, schizophrenia, and ELS + schizophrenia. ELS was induced by prenatal stress (maternal stress) and maternal separation (MS) during the first 2 weeks of life, while SZ was induced by subcutaneous administration of ketamine. Behavioral tests included an open field test (OFT) for motor abilities and a Morris water maze (MWM) for cognitive abilities. ANOVA and post hoc Tukey tests were utilized to analyze the data.

Results

Our results show that ELS and parental psychopathology had enduring effects on SZ symptoms, particularly psychomotor retardation (p < 0.05). The OFT revealed increased anxiety-like behavior in the ELS group (p = 0.023) and the parental psychopathology group (p = 0.017) compared to controls. The combined ELS and parental psychopathology group exhibited the highest anxiety-like behavior (p = 0.006). The MWM analysis indicated impaired spatial memory in the ELS group (p = 0.012) and the combined ELS and parental psychopathology group (p = 0.003) compared to controls. Significantly, the exposure to ELS resulted in a decrease in the population of glial fibrillary acidic protein-positive (GFAP+) astrocytes. However, this effect was reversed by positive parental mental health.

Conclusion

Our findings highlight the interactive effects of ELS and parental psychopathology on anxiety-like behavior and spatial memory in rats. ELS was linked to increased anxiety-like behavior, while SZ was associated with anhedonia-like behavior. Positive parenting augments neuroplasticity, synaptic function, and overall cognitive capacities.
Relationship between three dietary indices and health-related quality of life among rural elderly in China: a cross-sectional study
Authors: Yang Chen , Liu Peijun , Huang Wenjing , Zhou Ying , Liu Cuiping , Gao Tianlin , Zhong Feng
Published: October 2023

Purpose

This study aimed to explore the association between health-related quality of life (HRQOL) and diet quality using three evidence-based dietary indices among older people in rural China.

Methods

This cross-sectional study included 1,258 rural older people (mean age 72.32 years; 55.6% female). HRQOL was assessed using the European Five Dimension Health Scale (EQ-5D), and dietary intake was assessed using a Food Frequency Questionnaire. Three dietary scoring indices, including the Alternate Healthy Eating Index, Dietary Approaches to Stop Hypertension, and Dietary Diversity Score (DDS), were calculated to assess and analyze the relationship between these dietary indices and quality of life.

Results

The EQ-5D score was 0.95 ± 0.10, and the EQ-Visual Analog Scale (VAS) score was 76.76 ± 14.44. All three groups with higher dietary indices had higher quality of life scores. After controlling for covariates in multivariate adjusted binary logistic regression analyzes, participants in the top tertile of DDS had higher quality of life scores than those in the bottom tertile. DDS was consistently associated with EQ-5D (Model 2: OR = 1.567, p = 0.001; Model3: OR = 1.351, p = 0.044) and EQ-VAS (Model 2: OR = 1.830, p < 0.001; Model 3: OR = 1.383, p = 0.047), significantly different from the other groups.

Conclusion

Older people in rural China who adhere to various foods experience a better quality of healthy life.
Temporal trends and barriers for inpatient palliative care referral in metastatic gynecologic cancer patients receiving specific critical care therapies
Authors: Shen Li , Chen Longpei , Zhou Yun , Chen Tianran , Han Hedong , Xia Qiuyan , Liu Zhanguo
Published: October 2023

Objective

Existing evidence suggests that palliative care (PC) is highly underutilized in metastatic gynecologic cancer (mGCa). This study aims to explore temporal trends and predictors for inpatient PC referral in mGCa patients who received specific critical care therapies (CCT).

Methods

The National Inpatient Sample from 2003 to 2015 was used to identify mGCa patients receiving CCT. Basic characteristics were compared between patients with and without PC. Annual percentage change (APC) was estimated to reflect the temporal trend in the entire cohort and subgroups. Multivariable logistic regression was employed to explore potential predictors of inpatient PC referral.

Results

In total, 122,981 mGCa patients were identified, of whom 10,380 received CCT. Among these, 1,208 (11.64%) received inpatient PC. Overall, the rate of PC referral increased from 1.81% in 2003 to 26.30% in 2015 (APC: 29.08%). A higher increase in PC usage was found in white patients (APC: 30.81%), medium-sized hospitals (APC: 31.43%), the Midwest region (APC: 33.84%), and among patients with ovarian cancer (APC: 31.35%). Multivariable analysis suggested that medium bedsize, large bedsize, Midwest region, West region, uterine cancer and cervical cancer were related to increased PC use, while metastatic sites from lymph nodes and genital organs were related to lower PC referral.

Conclusion

Further studies are warranted to better illustrate the barriers for PC and finally improve the delivery of optimal end-of-life care for mGCa patients who receive inpatient CCT, especially for those diagnosed with ovarian cancer or admitted to small scale and Northeast hospitals.
Development of a predictive nomogram for switching immunosuppressive drugs in pediatric liver transplant recipients
Authors: Gu Guangxiang , Zhou Tao , Zong Zhipeng , Zhang Jianjun
Published: October 2023

Background

Tacrolimus (TAC) is the preferred calcineurin inhibitor (CNI) for pediatric liver transplant recipients. However, some recipients may not achieve the desired therapeutic window concentration of TAC, leading to poor prognosis. This study aimed to develop a clinical model that can predict the effectiveness of TAC in pediatric liver transplant recipients and help clinicians quickly identify cyclosporin as an alternative.

Methods

We retrospectively analyzed data from 2,032 pediatric liver transplant recipients who underwent surgery at Renji Hospital, Shanghai Jiaotong University School of Medicine between 2006 and 2019. Demographic, comorbidity and pre-operative laboratory data were collected, and a nomogram was constructed using multivariate logistic regression analysis to estimate the risk of poor therapeutic outcomes for TAC-based immunosuppression.

Results

The constructed nomogram included seven parameters, namely recipient CYP3A4 genotype, pre-transplant cholangitis, GRWR, spleen long diameter, serum albumin, graft volume reduction, and donor CYP genotype. The nomogram showed good discriminative ability with an area under the receiver operating characteristic curve (AUC) of 74.5% and good calibration. Decision curve analysis indicated a high potential clinical application of the model.

Conclusion

This simple clinical model effectively predicts the risk of poor therapeutic outcomes in pediatric liver transplant recipients who receive TAC-based immunosuppression. Clinicians can use the model to identify cyclosporin as an alternative quickly, potentially improving patient prognosis.
Overcoming barriers: a review on innovations in drug delivery to the middle and inner ear
Authors: Delaney Derek S. , Liew Lawrence J. , Lye Joey , Atlas Marcus D. , Wong Elaine Y. M.
Published: October 2023

Despite significant advances in the development of therapeutics for hearing loss, drug delivery to the middle and inner ear remains a challenge. As conventional oral or intravascular administration are ineffective due to poor bioavailability and impermeability of the blood-labyrinth-barrier, localized delivery is becoming a preferable approach for certain drugs. Even then, localized delivery to the ear precludes continual drug delivery due to the invasive and potentially traumatic procedures required to access the middle and inner ear. To address this, the preclinical development of controlled release therapeutics and drug delivery devices have greatly advanced, with some now showing promise clinically. This review will discuss the existing challenges in drug development for treating the most prevalent and damaging hearing disorders, in particular otitis media, perforation of the tympanic membrane, cholesteatoma and sensorineural hearing loss. We will then address novel developments in drug delivery that address these including novel controlled release therapeutics such as hydrogel and nanotechnology and finally, novel device delivery approaches such as microfluidic systems and cochlear prosthesis-mediated delivery. The aim of this review is to investigate how drugs can reach the middle and inner ear more efficiently and how recent innovations could be applied in aiding drug delivery in certain pathologic contexts.
Traditional Chinese Medicine in the treatment of hemorrhoids—a review of preparations used and their mechanism of action
Authors: Zhou Meng’en , Jin Wenqi , Li Peng , Wang Ruolin , Guo Xiutian
Published: October 2023

Hemorrhoids are a proctological disease primarily characterized by bleeding, prolapse, edema, and pain, severely affecting the quality of life. Surgery is an effective treatment for hemorrhoids, but the cost is relatively high, and complications such as difficulty in defecation, persistent pain, and heavy bleeding may occur postoperatively. Traditional Chinese Medicine (TCM) has a distinctive advantage in alleviating the clinical symptoms of hemorrhoid patients, reducing pain, and improving the quality of life. However, there are few summary literature about the mechanism of TCM in the prevention and treatment of hemorrhoids. Based on the etiology of hemorrhoids in both traditional Chinese and Western medicine, this paper reviews the recent research on the mechanism of TCM in the treatment of hemorrhoids, hoping to provide a basis for the better application of TCM in clinical and experimental research.
Chronic exposure to mercury increases arrhythmia and mortality post-acute myocardial infarction in rats
Authors: Bello Keren A. S. , Wilke Maria Clara B. , Simões Rakel P. , Landim-Vieira Maicon , Langa Paulina , Stefanon Ivanita , Vassallo Dalton Valentim , Fernandes Aurélia Araújo
Published: October 2023

Introduction: Mercury (Hg) is a heavy metal that causes a variety of toxic effects in eukaryotic cells. Previous studies have reported detrimental effects of mercury toxicity in the cardiovascular system. Given the importance of understanding the relationship between Hg and cardiovascular disease, we sought to investigate if the Hg could worsen the myocardial repercussions following ischemic injury. We demonstrated that once mercury toxicity is established, it can influence the outcome of myocardial infarction (MI).

Methods: Male Wistar rats received intramuscular injections of either saline (NaCl 0.9%) or mercuric chloride (HgCl2, first dose of 4.6 μg/kg, and subsequent doses of 0.07 μg/kg/day) for 4 weeks. Three weeks post-exposure, we induced transmural infarction in the left ventricle free wall through coronary artery occlusion surgery. Results: ECG recordings obtained from MI groups demonstrated alterations in the rhythm of the heartbeat/heart electrical activity, as expected, including ventricular extrasystoles and ventricular tachycardia. However, the MI group exposed to Hg (MI-Hg) exhibited augmented ventricular extrasystoles and ventricular tachycardia compared to the MI group. Also, Basckó coefficient revealed that the arrhythmic events—after MI—were aggravated by Hg exposure.

Discussion: Our results indicate that the significantly increased mortality in MI-Hg groups when compared to MI (21%, MI vs 32%, MI-Hg) is correlated with greater occurrence of arrhythmias. In conclusion, this study further supports the idea that exposure to mercury (Hg) should be recognized as a significant risk factor that exacerbates the impact of cardiac ischemic injury, potentially leading to an increased mortality rate among patients experiencing acute MI.
Assessing the suitability and dynamics of three medicinal Sambucus species in China under current and future climate scenarios
Authors: Luo Weixue , Han Shunxin , Yu Ting , Wang Peng , Ma Yuxuan , Wan Maji , Liu Jinchun , Li Zongfeng , Tao Jianping
Published: October 2023

Climate change exerts profound influences on the ecological environments on a global scale, leading to habitat destruction and altering distribution patterns for numerous plant species. Traditional Chinese medicinal plants, such as those belonging to the Sambucus genus, have been extensively utilized for several centuries to treat fractures, rheumatism, and inflammation. However, our understanding of their geographic distribution and climatic adaptation within China still needs to be improved. In this study, we screened the optimal predictive model (random forest model) to predict the potential suitable distribution of three Sambucus species (Sambucus adnata, Sambucus javanica, and Sambucus williamsii) across China under both current and future climate scenarios. Moreover, we identified key climate factors that influence their potential distributions. Our findings revealed that S. adnata and S. javanica are predominantly shaped by temperature seasonality and mean diurnal range, respectively, whereas S. williamsii is significantly affected by the precipitation of the wettest month. Currently, S. williamsii is primarily distributed in north and central south China (covering 9.57 × 105 km2), S. javanica is prevalent in the south and east regions (covering 6.41×105 km2), and S. adnata predominantly thrives in the southwest China (covering 1.99×105 km2). Under future climate change scenarios, it is anticipated that S. adnata may migrate to higher latitudes while S. javanica may shift to lower latitudes. However, potentially suitable areas for S. williamsii may contract under certain scenarios for the years 2050 and 2090, with an expansion trend under the SSP585 scenario for the year 2090. Our study emphasizes the importance of climatic variables in influencing the potential geographic distribution of Sambucus species. These findings provide valuable theoretical insights for the preservation, cultivation, and utilization of Sambucus medicinal plant resources in the context of ongoing climate change.
Temperature differences between sites lead to altered phenylpropanoid metabolism in a varietal dependent manner
Authors: Gashu Kelem , Verma Pankaj Kumar , Acuña Tania , Agam Nurit , Bustan Amnon , Fait Aaron
Published: October 2023

Elevated temperature has already caused a significant loss of wine growing areas and resulted in inferior fruit quality, particularly in arid and semi-arid regions. The existence of broad genetic diversity in V. vinifera is key in adapting viticulture to climate change; however, a lack of understanding on the variability in berry metabolic response to climate change remains a major challenge to build ad-hoc strategies for quality fruit production. In the present study, we examined the impact of a consistent temperature difference between two vineyards on polyphenol metabolism in the berries of 20 red V. vinifera cultivars across three consecutive seasons (2017–2019). The results emphasize a varietal specific response in the content of several phenylpropanoid metabolites; the interaction factor between the variety and the vineyard location was also found significant. Higher seasonal temperatures were coupled with lower flavonol and anthocyanin contents, but such reductions were not related with the level of expression of phenylpropanoid related genes. Hierarchical clustering analyses of the metabolic data revealed varieties with a location specific response, exceptional among them was Tempranillo, suggesting a greater susceptibility to temperature of this cultivar. In conclusion, our results indicate that the extensive genetic capacity of V. vinifera bears a significant potential to withstand temperature increase associated with climate change.
Unraveling dyadic psycho-physiology of social presence between strangers during an audio drama – a signal-analysis approach
Authors: Kauttonen Janne , Paekivi Sander , Kauramäki Jaakko , Tikka Pia
Published: October 2023

A mere co-presence of an unfamiliar person may modulate an individual’s attentive engagement with specific events or situations to a significant degree. To understand better how such social presence affects experiences, we recorded a set of parallel multimodal facial and psychophysiological data with subjects (N = 36) who listened to dramatic audio scenes alone or when facing an unfamiliar person. Both a selection of 6 s affective sound clips (IADS-2) followed by a 27 min soundtrack extracted from a Finnish episode film depicted familiar and often intense social situations familiar from the everyday world. Considering the systemic complexity of both the chosen naturalistic stimuli and expected variations in the experimental social situation, we applied a novel combination of signal analysis methods using inter-subject correlation (ISC) analysis, Representational Similarity Analysis (RSA) and Recurrence Quantification Analysis (RQA) followed by gradient boosting classification. We report our findings concerning three facial signals, gaze, eyebrow and smile that can be linked to socially motivated facial movements. We found that ISC values of pairs, whether calculated on true pairs or any two individuals who had a partner, were lower than the group with single individuals. Thus, audio stimuli induced more unique responses in those subjects who were listening to it in the presence of another person, while individual listeners tended to yield a more uniform response as it was driven by dramatized audio stimulus alone. Furthermore, our classifiers models trained using recurrence properties of gaze, eyebrows and smile signals demonstrated distinctive differences in the recurrence dynamics of signals from paired subjects and revealed the impact of individual differences on the latter. We showed that the presence of an unfamiliar co-listener that modifies social dynamics of dyadic listening tasks can be detected reliably from visible facial modalities. By applying our analysis framework to a broader range of psycho-physiological data, together with annotations of the content, and subjective reports of participants, we expected more detailed dyadic dependencies to be revealed. Our work contributes towards modeling and predicting human social behaviors to specific types of audio-visually mediated, virtual, and live social situations.
Identifying the communication of burnout syndrome on the Twitter platform from the individual, organizational, and environmental perspective
Authors: Ježková Petrů Gabriela , Zychová Kristýna , Drahotová Kateřina , Kuralová Kateřina , Kvasničková Stanislavská Lucie , Pilař Ladislav
Published: October 2023

Addressing the escalating prevalence of burnout syndrome, which affects individuals across various professions and domains, is becoming increasingly imperative due to its profound impact on personal and professional aspects of employees’ lives. This paper explores the intersection of burnout syndrome and human resource management, recognizing employees as the primary assets of organizations. It emphasizes the growing importance of nurturing employee well-being, care, and work-life balance from a human resource management standpoint. Employing social media analysis, this study delves into Twitter-based discourse on burnout syndrome, categorizing communication into three distinct dimensions: individual, organizational, and environmental. This innovative approach provides fresh insights into interpreting burnout syndrome discourse through big data analysis within social network analysis. The methodology deployed in this study was predicated upon the enhanced Social Media Analysis based on Hashtag Research framework and frequency, topic and visual analysis were conducted. The investigation encompasses Twitter communication from January 1st, 2019, to July 31st, 2022, comprising a dataset of 190,770 tweets. Notably, the study identifies the most frequently used hashtags related to burnout syndrome, with #stress and #mentalhealth leading the discussion, followed closely by #selfcare, #wellbeing, and #healthcare. Moreover, a comprehensive analysis unveils seven predominant topics within the discourse on burnout syndrome: organization, healthcare, communication, stress and therapy, time, symptoms, and leadership. This study underscores the evolving landscape of burnout syndrome communication and its multifaceted implications for individuals, organizations, and the broader environment, shedding light on the pressing need for proactive interventions. In organizations at all levels of management, the concept of burnout should be included in the value philosophy of organizations and should focus on organizational aspects, working hours and work-life balance for a healthier working environment and well-being of employees at all levels of management.
Fluctuations and individual differences in empathy interact with stress to predict mental health, parenting, and relationship outcomes
Authors: Shalev Ido , Eran Alal , Uzefovsky Florina
Published: October 2023

Introduction

Empathy is a complex, multifaceted ability allowing for the most basic forms of social communication and plays a prominent role in multiple aspects of everyday lives. In this intensive longitudinal study, we assessed how empathy interacts with stress to predict central domains of psychosocial functioning: mental health, romantic relationships, and parenting.

Methods

Fluctuations and individual differences in empathy were assessed across eight time points, where participants from the general population (N = 566) self-reported their empathy, stress, depressive symptoms, romantic satisfaction, and parental functioning.

Results

Both trait and state aspects of empathy were associated with all psychosocial outcomes, with state empathy showing a stronger effect. Additionally, empathy components interacted with stress—emotional empathy better-predicted outcomes under high stress, while cognitive empathy under low stress.

Discussion

Our findings advance the theoretical understanding of empathy, emphasizing the effects of state-dependent empathy fluctuations on our everyday mental and social lives.