bluuebunny/crossref_metadata_2025 huggingface dataset:
Head-shaking-induced nystagmus reflects dynamic vestibular compensation: A 2-year follow-up study
Authors: Striteska Maja , Valis Martin , Chrobok Viktor , Profant Oliver , Califano Luigi , Syba Jaroslav , Trnkova Katerina , Kremlacek Jan , Chovanec Martin
Published: September 2022

Purpose

We aimed to assess the ability of a head-shaking test (HST) to reflect vestibular compensation in patients after unilateral peripheral vestibular loss and to provide missing evidence and new insights into the features of head-shaking-induced nystagmus (HSN) over a 2-year follow-up.

Background

HSN may occur after a prolonged sinusoidal oscillation of the head. HSN is frequently observed in subjects with vestibular function asymmetry; it usually beats toward the functionally intact or “stronger” ear and can be followed by a reversal of its direction.

Study design

A prospective observational case-control study.

Settings

A tertiary academic referral center.

Methods

A total of 38 patients after acute unilateral vestibular loss (22 patients with vestibular neuronitis and 16 patients after vestibular neurectomy) and 28 healthy controls were followed for four consecutive visits over a 2-year period. A complex vestibular assessment was performed on all participants, which included spontaneous nystagmus (SPN), the caloric test, the head-shaking test (HST), the video head impulse test (vHIT), the Timed Up and Go (TUG) test, and the Dizziness Handicap Inventory (DHI) questionnaire. We established the criteria for the poorly compensated group to assess different compensatory behaviors and results.

Results

We found a time-related decrease in HSN (ρ < −0.84, p < 0.001) after unilateral vestibular loss. After 2 years of follow-up, HSN intensity in compensated patients reached the level of the control group; TUG and DHI also improved to normal; however, the caloric and vHIT tests remained abnormal throughout all follow-ups, indicating a chronic vestibular deficit. Besides, poorly compensated patients had a well-detectable HSN throughout all follow-ups; TUG remained abnormal, and DHI showed at least a moderate deficit.

Conclusions

Our study showed that, after a unilateral peripheral vestibular loss, the intensity of HSN decreased exponentially over time, reflecting an improvement in dynamic ability and self-perceived deficit. HSN tended to decline to the value of the control group once vestibular compensation was satisfactory and sufficient for a patient's everyday life. In contrast, well-detectable HSN in poorly compensated patients with insufficient clinical recovery confirmed the potential of HSN to reflect and distinguish between adequate and insufficient dynamic compensation. HSN could serve as an objective indicator of stable unilateral vestibular loss.
Impact of type of oral anticoagulants in patients with cerebral microbleeds after atrial fibrillation-related ischemic stroke or TIA: Results of the NOACISP-LONGTERM registry
Authors: Wagner Benjamin , Hert Lisa , Polymeris Alexandros A. , Schaedelin Sabine , Lieb Johanna M. , Seiffge David J. , Traenka Christopher , Thilemann Sebastian , Fladt Joachim , Altersberger Valerian L. , Zietz Annaelle , Dittrich Tolga D. , Fisch Urs , Gensicke Henrik , De Marchis Gian Marco , Bonati Leo H. , Lyrer Philippe A. , Engelter Stefan T. , Peters Nils
Published: September 2022

Background

Cerebral microbleeds (CMBs) may have a differential impact on clinical outcome in stroke patients with atrial fibrillation (AF) treated with different types of oral anticoagulation (OAC).

Methods

Observational single-center study on AF-stroke-patients treated with OAC. Magnetic-resonance-imaging was performed to assess CMBs. Outcome measures consisted of recurrent ischemic stroke (IS), intracranial hemorrhage (ICH), death, and their combined analysis. Functional disability was assessed by mRS. Using adjusted logistic regression and Cox proportional-hazards models, we assessed the association of the presence of CMBs and OAC type (vitamin K antagonists [VKAs] vs. direct oral anticoagulants [DOACs]) with clinical outcome.

Results

Of 310 AF-stroke patients treated with OAC [DOACs: n = 234 (75%); VKAs: n = 76 (25%)], CMBs were present in 86 (28%) patients; of these, 66 (77%) received DOACs. In both groups, CMBs were associated with an increased risk for the composite outcome: VKAs: HR 3.654 [1.614; 8.277]; p = 0.002; DOACs: HR 2.230 [1.233; 4.034]; p = 0.008. Patients with CMBs had ~50% higher absolute rates of the composite outcome compared to the overall cohort, with a comparable ratio between treatment groups [VKAs 13/20(65%) vs. DOACs 19/66(29%); p < 0.01]. The VKA-group had a 2-fold higher IS [VKAs:4 (20%) vs. DOACs:6 (9%); p = 0.35] and a 10-fold higher ICH rate [VKAs: 3 (15%) vs. DOACs: 1 (1.5%); p = 0.038]. No significant interaction was observed between type of OAC and presence of CMBs. DOAC-patients showed a significantly better functional outcome (OR 0.40 [0.17; 0.94]; p = 0.04).

Conclusions

In AF-stroke patients treated with OAC, the presence of CMBs was associated with an unfavorable composite outcome for both VKAs and DOACs, with a higher risk for recurrent IS than for ICH. Strokes were numerically higher under VKAs and increased in the presence of CMBs.

Clinical trial registration

http://www.clinicaltrials.gov, Unique identifier: NCT03826927.
Incidence of stroke in the first year after diagnosis of cancer—A systematic review and meta-analysis
Authors: Lun Ronda , Roy Danielle Carole , Hao Yu , Deka Rishi , Huang Wen-Kuan , Navi Babak B. , Siegal Deborah M. , Ramsay Tim , Fergusson Dean , Shorr Risa , Dowlatshahi Dar
Published: September 2022

Background

Patients newly diagnosed with cancer represent a population at highest risk for stroke. The objective of this systematic review and meta-analysis was to estimate the incidence of stroke in the first year following a new diagnosis of cancer.

Methods

We searched MEDLINE and EMBASE from January 1980 to June 2021 for observational studies that enrolled adults with a new diagnosis of all cancers excluding non-melanoma skin cancer, and that reported the incidence of stroke at 1 year. PRISMA guidelines for meta-analyses were followed. Two reviewers independently extracted data and appraised risk of bias. We used the Dersimonian and Laird random effects method to pool cumulative incidences after logit transformation, and reported pooled proportions as percentages. Statistical heterogeneity was assessed using the I2 statistic.

Results

A total of 12,083 studies were screened; 41 studies were included for analysis. Data from 2,552,121 subjects with cancer were analyzed. The cumulative incidence of total stroke at 1 year was 1.4% (95% CI 0.9–2.2%), while the pooled incidence of ischemic stroke was 1.3% (95% CI 1.0–1.8%) and 0.3% (95% CI 0.1–0.9%) for spontaneous intracerebral hemorrhage (ICH), with consistently high statistical heterogeneity (>99% I2).

Conclusion

The estimated incidence of stroke during the first year after a new diagnosis of cancer is 1.4%, with a higher risk for ischemic stroke than ICH. Cancer patients should be educated on the risk of stroke at the time of diagnosis. Future studies should evaluate optimal primary prevention strategies in this high-risk group of patients.

Systematic review registration

https://osf.io/ucwy9/.
Disrupted topological properties of the structural brain network in patients with cerebellar infarction on different sides are associated with cognitive impairment
Authors: Wang Duohao , Yao Qun , Lin Xingjian , Hu Jun , Shi Jingping
Published: September 2022

Purpose

To explore changes in the brain structural network in patients with cerebellar infarction on different sides and their correlations with changes in cognitive function.

Methods

Nineteen patients with acute left posterior cerebellar infarction and 18 patients with acute right posterior cerebellar infarction seen from July 2016 to September 2019 in the Department of Neurology, Affiliated Brain Hospital of Nanjing Medical University, were selected. A total of 27 healthy controls matched for sex, age, and years of education were recruited. The subjects underwent head diffusion magnetic resonance imaging examination and neuropsychological cognitive scale evaluation, and we analyzed changes in brain structural network properties in patients with cerebellar infarction and their correlation with changes in patients' cognitive function.

Results

The Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MOCA) and the Rey auditory verbal learning test (RAVLT) scores in the left and right cerebellar infarction groups were significantly lower than those in the healthy control group (p < 0.05). In addition, the digit span test (DST) scores were lower in the left cerebellar infarction group (p < 0.05); the trail-making test (TMT) times in the right cerebellar infarction group were significantly higher than those in the left cerebellar infarction group (p < 0.05). Meanwhile, the left and right cerebellar infarction groups had abnormal brain topological properties, including clustering coefficient, shortest path length, global efficiency, local efficiency and nodal efficiency. After unilateral cerebellar infarction, bilateral cerebral nodal efficiency was abnormal. Correlation analysis showed that there was a close correlation between decreased processing speed in patients with left cerebellar infarction and decreased efficiency of right cerebral nodes (p < 0.05), and there was a close relationship between executive dysfunction and decreased efficiency of left cerebral nodes in patients with right cerebellar infarction (p < 0.05).

Conclusion

Patients with cerebellar infarction have cognitive impairment. Unilateral cerebellar infarction can reduce the network efficiency of key regions in the bilateral cerebral hemispheres, and these abnormal changes are closely related to patient cognitive impairment. The results of this study provide evidence for understanding the underlying neural mechanisms of cerebellar cognitive impairment and suggest that brain topological network properties may be markers of cerebellar cognitive impairment.
Photobiomodulation for the treatment of neuroinflammation: A systematic review of controlled laboratory animal studies
Authors: Cardoso Fabrízio dos Santos , Salehpour Farzad , Coimbra Norberto Cysne , Gonzalez-Lima Francisco , Gomes da Silva Sérgio
Published: September 2022

Background

Neuroinflammation is a response that involves different cell lineages of the central nervous system, such as neurons and glial cells. Among the non-pharmacological interventions for neuroinflammation, photobiomodulation (PBM) is gaining prominence because of its beneficial effects found in experimental brain research. We systematically reviewed the effects of PBM on laboratory animal models, specially to investigate potential benefits of PBM as an efficient anti-inflammatory therapy.

Methods

We conducted a systematic search on the bibliographic databases (PubMed and ScienceDirect) with the keywords based on MeSH terms: photobiomodulation, low-level laser therapy, brain, neuroinflammation, inflammation, cytokine, and microglia. Data search was limited from 2009 to June 2022. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The initial systematic search identified 140 articles. Among them, 54 articles were removed for duplication and 59 articles by screening. Therefore, 27 studies met the inclusion criteria.

Results

The studies showed that PBM has anti-inflammatory properties in several conditions, such as traumatic brain injury, edema formation and hyperalgesia, ischemia, neurodegenerative conditions, aging, epilepsy, depression, and spinal cord injury.

Conclusion

Taken together, these results indicate that transcranial PBM therapy is a promising strategy to treat brain pathological conditions induced by neuroinflammation.
Genetic influence on brain volume alterations related to self-reported childhood abuse
Authors: Tian Tian , Li Yuanhao , Li Jia , Zhang Guiling , Wang Jian , Wan Changhua , Fang Jicheng , Wu Di , Zhou Yiran , Qin Yuanyuan , Zhu Hongquan , Liu Dong , Zhu Wenzhen
Published: September 2022

As an important predictor of adulthood psychopathology, self-reported childhood abuse appears heritable and is associated with brain abnormalities. However, the specific genetic mechanisms behind these brain alterations remain largely unknown. This study recruited young adults who reported different degrees of childhood abuse from the community. In order to fully understand the influence of genes on brain changes related to self-reported childhood abuse, various experiments were conducted in this study. Firstly, volume changes of gray matter and white matter related to childhood abuse were investigated by using advanced magnetic resonance imaging techniques. After sequencing the whole exons, we further investigated the relationship between polygenic risk score, brain volume alterations, and childhood abuse score. Furthermore, transcription-neuroimaging association analysis was used to identify risk genes whose expressions were associated with brain volume alterations. The gray matter volumes of left caudate and superior parietal lobule, and white matter volumes of left cerebellum and right temporal lobe-basal ganglia region were significantly correlated with the childhood abuse score. More importantly, brain volume changes mediated the influence of polygenic risk on self-reported childhood abuse. Additionally, transcription-neuroimaging association analysis reported 63 risk genes whose expression levels were significantly associated with childhood abuse-related brain volume changes. These genes are involved in multiple biological processes, such as nerve development, synaptic transmission, and cell construction. Combining data from multiple perspectives, our work provides evidence of brain abnormalities associated with childhood abuse, and further indicates that polygene genetic risk and risk gene expression may affect the occurrence of childhood abuse by brain regulation, which provides insights into the molecularpathology and neuromechanism of childhood adversity. Paying attention to the physical and mental health of high-risk children may be a fundamental way to prevent childhood abuse and promote lifelong mental health.
Influence of denaturants on amyloid β42 aggregation kinetics
Authors: Weiffert Tanja , Meisl Georg , Curk Samo , Cukalevski Risto , Šarić Anđela , Knowles Tuomas P. J. , Linse Sara
Published: September 2022

Amyloid formation is linked to devastating neurodegenerative diseases, motivating detailed studies of the mechanisms of amyloid formation. For Aβ, the peptide associated with Alzheimer’s disease, the mechanism and rate of aggregation have been established for a range of variants and conditionsin vitroand in bodily fluids. A key outstanding question is how the relative stabilities of monomers, fibrils and intermediates affect each step in the fibril formation process. By monitoring the kinetics of aggregation of Aβ42, in the presence of urea or guanidinium hydrochloride (GuHCl), we here determine the rates of the underlying microscopic steps and establish the importance of changes in relative stability induced by the presence of denaturant for each individual step. Denaturants shift the equilibrium towards the unfolded state of each species. We find that a non-ionic denaturant, urea, reduces the overall aggregation rate, and that the effect on nucleation is stronger than the effect on elongation. Urea reduces the rate of secondary nucleation by decreasing the coverage of fibril surfaces and the rate of nucleus formation. It also reduces the rate of primary nucleation, increasing its reaction order. The ionic denaturant, GuHCl, accelerates the aggregation at low denaturant concentrations and decelerates the aggregation at high denaturant concentrations. Below approximately 0.25 M GuHCl, the screening of repulsive electrostatic interactions between peptides by the charged denaturant dominates, leading to an increased aggregation rate. At higher GuHCl concentrations, the electrostatic repulsion is completely screened, and the denaturing effect dominates. The results illustrate how the differential effects of denaturants on stability of monomer, oligomer and fibril translate to differential effects on microscopic steps, with the rate of nucleation being most strongly reduced.
Fermented foods and cardiometabolic health: Definitions, current evidence, and future perspectives
Authors: Li Katherine J. , Burton-Pimentel Kathryn J. , Vergères Guy , Feskens Edith J. M. , Brouwer-Brolsma Elske M.
Published: September 2022

Unhealthy diets contribute to the increasing burden of non-communicable diseases. Annually, over 11 million deaths worldwide are attributed to dietary risk factors, with the vast majority of deaths resulting from cardiometabolic diseases (CMDs) including cardiovascular disease (∼10 million) and type II diabetes (∼339,000). As such, defining diets and dietary patterns that mitigate CMD risk is of great public health importance. Recently, the consumption of fermented foods has emerged as an important dietary strategy for improving cardiometabolic health. Fermented foods have been present in the human diet for over 10,000 years, but knowledge on whether their consumption benefits human health, and the molecular and microbiological mechanisms underpinning their purported health benefits, is relatively nascent. This review provides an overview of the definitions of fermented foods, types and qualities of fermented foods consumed in Europe and globally, possible mechanisms between the consumption of fermented foods and cardiometabolic health, as well as the current state of the epidemiological evidence on fermented food intake and cardiometabolic health. Finally, we outline future perspectives and opportunities for improving the role of fermented foods in human diets.
Timed restricted feeding cycles drive daily rhythms in female rats maintained in constant light but only partially restore the estrous cycle
Authors: Guerrero-Vargas Natalí N. , Espitia-Bautista Estefania , Escalona Rene , Lugo-Martínez Haydée , Gutiérrez-Pérez Mariana , Navarro-Espíndola Raful , Setién María Fernanda , Boy-Waxman Sebastián , Retana-Flores Elizabeth Angélica , Ortega Berenice , Buijs Ruud M. , Escobar Carolina
Published: September 2022

Light at night is an emergent problem for modern society. Rodents exposed to light at night develop a loss of circadian rhythms, which leads to increased adiposity, altered immune response, and increased growth of tumors. In female rats, constant light (LL) eliminates the estrous cycle leading to a state of persistent estrus. The suprachiasmatic nucleus (SCN) drives circadian rhythms, and it interacts with the neuroendocrine network necessary for reproductive function. Timed restricted feeding (RF) exerts a powerful entraining influence on the circadian system, and it can influence the SCN activity and can restore rhythmicity or accelerate re-entrainment in experimental conditions of shift work or jet lag. The present study explored RF in female rats exposed to LL, with the hypothesis that this cyclic condition can rescue or prevent the loss of daily rhythms and benefit the expression of the estrous cycle. Two different feeding schedules were explored: 1. A 12-h food/12-h fasting schedule applied to arrhythmic rats after 3 weeks in LL, visualized as a rescue strategy (LL + RFR, 3 weeks), or applied simultaneously with the first day of LL as a preventive strategy (LL + RFP, 6 weeks). 2. A 12-h window of food intake with food given in four distributed pulses (every 3 h), applied after 3 weeks in LL, as a rescue strategy (LL + PR, 3 weeks) or applied simultaneously with the first day of LL as a preventive strategy (LL + PP, 6 weeks). Here, we present evidence that scheduled feeding can drive daily rhythms of activity and temperature in rats exposed to LL. However, the protocol of distributed feeding pulses was more efficient to restore the day–night activity and core temperature as well as the c-Fos day–night change in the SCN. Likewise, the distributed feeding partially restored the estrous cycle and the ovary morphology under LL condition. Data here provided indicate that the 12-h feeding/12-h fasting window determines the rest-activity cycle and can benefit directly the circadian and reproductive function. Moreover, this effect is stronger when food is distributed along the 12 h of subjective night.
The impact of the COVID-19 pandemic on diagnosis and treatment of patients with soft tissue and bone sarcomas or aggressive benign musculoskeletal diseases: A single-center retrospective study (SarCorD study)
Authors: Onesti Concetta Elisa , Vari Sabrina , Nardozza Francesca , Maggi Gabriella , Minghelli Denise , Rossi Barbara , Sperati Francesca , Checcucci Elisa , Faltyn Wioletta , Cercato Maria Cecilia , Cosimati Antonella , Biagini Roberto , Ciliberto Gennaro , Ferraresi Virginia
Published: September 2022

Background

The COVID-19 pandemic led to a rapid reorganization of healthcare activities, leading to reduced access to clinics, interruption of screenings, and treatment schedule modifications in several cancer types. Few data are available on sarcomas. We analyzed COVID-19-related diagnostic delay in a sarcoma referral center in Italy.

Methods

We retrospectively enrolled in this study patients with histological diagnosis of soft tissue or bone sarcoma and aggressive benign musculoskeletal diseases obtained during the first year of the pandemic (Covid group) or the year before (Control group) and followed at the Regina Elena National Cancer Institute in Rome. The primary endpoint was the time from the first symptom to histological diagnosis.

Results

We evaluated 372 patients, 185 of whom were eligible for primary endpoint analysis (92 patients in the Control group and 93 patients in the Covid group). The patients were affected by soft tissue sarcoma in most cases (63.0% and 66.7% in Covid and Control groups, respectively). We observed a diagnostic delay in the Covid group with a median time from the first symptom to the definitive histological diagnosis of 103.00 days (95% CI 92.77–113.23) vs. 90.00 days (95% CI 69.49–110.51) in the Control group (p = 0.024), but not a delay in treatment beginning (151 days, 95% CI 132.9–169.1 vs. 144 days, 95% CI 120.3–167.7, respectively, p = 0.208). No differences in stage at diagnosis were observed (12% vs. 16.5% of patients with metastatic disease at diagnosis in the Covid and Control groups, respectively, p = 0.380). Progression-free survival (p = 0.897) and overall survival (p = 0.725) were comparable in the subgroup of patients affected by soft tissue sarcoma.

Conclusions

A delay in sarcoma diagnosis but not in starting treatment has been observed during the first year of the COVID-19 pandemic. Nevertheless, no difference in stage at diagnosis or in terms of survival has been observed.
Association of body composition with clinical outcome in Chinese women diagnosed with breast cancer
Authors: Liu Xinyi , Zhang Enming , Wang Suxing , Shen Yixiao , Xi Kaiwen , Fang Qiong
Published: September 2022

Objective

This study aims to explore the association of body composition with clinical outcomes in Chinese women diagnosed with breast cancer.

Method

A total of 2,948 Chinese female patients with breast cancer have been included in this retrospective study. Body composition mainly includes the measurements of adiposity and muscle mass. Visceral fat area (VFA) is used to measure visceral obesity, while appendicular skeletal muscle mass index (ASMI) is utilized to evaluate sarcopenia. The endpoints of this study are disease-free survival (DFS) and overall survival (OS). The association of the body composition parameters with DFS and OS was statistically analyzed.

Result

The median follow-up time for survivors was 42 months (range, 3 to 70 months). In total, 194 patients (6.9%) had breast cancer recurrence, and 32 patients passed away (1.1%). Among the 2,948 patients included, 1,226 (41.6%) patients were viscerally obese, and 511 (17.3%) patients were sarcopenic. We found that visceral obesity had a significant prognostic impact on DFS (HR, 1.46; 95% CI, 1.10–1.95; p = 0.010) but not on OS (P = 0.173). Multivariate analysis revealed sarcopenia as an independent prognostic factor for DFS (HR, 1.44; 95% CI, 1.02–2.03; p = 0.038) and OS (HR, 2.13; 95% CI, 1.00–4.51; p = 0.049). Body mass index was not significantly associated with both DFS (P = 0.224) and OS (P = 0.544).

Conclusion

Visceral obesity is associated with a higher risk of disease recurrence, and sarcopenia is significantly associated with increased recurrence and overall mortality among Chinese women with breast cancer. Body composition assessment could be a simple and useful approach in breast cancer management. Further studies can focus on decreasing visceral fat and increasing skeletal muscle mass to improve prognosis in breast cancer survivors.
APOBEC3B: Future direction of liver cancer research
Authors: Yang Xingyue , Dai Jing , Yao Shun , An Jiaxing , Wen Guorong , Jin Hai , Zhang Li , Zheng Liming , Chen Xingyue , Yi Zhiqiang , Tuo Biguang
Published: September 2022

Liver cancer is one of the most common cancers in the world, and the rate of liver cancer is high due to the of its illness. The main risk factor for liver cancer is infection with the hepatitis B virus (HBV), but a considerable number of genetic and epigenetic factors are also directly or indirectly involved in the underlying pathogenesis of liver cancer. In particular, the apolipoprotein B mRNA editing enzyme, catalytic peptide-like protein (APOBEC) family (DNA or mRNA editor family), which has been the focus of virology research for more than a decade, has been found to play a significant role in the occurrence and development of various cancers, providing a new direction for the research of liver cancer. APOBEC3B is a cytosine deaminase that controls a variety of biological processes, such as protein expression, innate immunity, and embryonic development, by participating in the process of cytidine deamination to uridine in DNA and RNA. In humans, APOBEC3B has long been known as a DNA editor for limiting viral replication and transcription. APOBEC3B is widely expressed at low levels in a variety of normal tissues and organs, but it is significantly upregulated in different types of tumor tissues and tumor lines. Thus, APOBEC3B has received increasing attention in various cancers, but the role of APOBEC3B in the occurrence and development of liver cancer due to infection with HBV remains unclear. This review provides a brief introduction to the pathogenesis of hepatocellular carcinoma induced by HBV, and it further explores the latest results of APOBEC3B research in the development of HBV and liver cancer, thereby providing new directions and strategies for the treatment and prevention of liver cancer.
Screening for Wilson’s disease in acute liver failure: A new scoring system in children
Authors: Feng Cai-Xia , Chen Xiu-Qi , He Xiao-Li , Lan Lian-Cheng , Tang Qing , Huang Li , Shan Qing-Wen
Published: September 2022

Background

Wilson’s disease (WD) is a rare cause of acute liver failure (ALF) and has a high fatality rate. Rapid and accurate diagnosis is important for ALF because of WD (ALF-WD). Our objective was to establish a simple, rapid, and accurate diagnostic test to distinguish ALF-WD from non-WD ALF (NWDALF) in children.

Materials and methods

The data from all cases with pediatric ALF were retrospectively collected and analyzed. We performed receiver operator characteristics curve (ROC) analysis and confirmed the optimum cut-off points.

Results

Fifty-eight patients with pediatric ALF (12 with WD, 46 with other etiologies) were included. Older age was observed in ALF-WD compared to NWDALF (11.16 ± 2.51 years vs. 3.34 ± 3.81 years, p < 0.001). An analysis based on routine biochemical testings revealed that total bilirubin (TBil), direct bilirubin, indirect bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST:ALT ratio, alkaline phosphatase (ALP), ALP:TBil ratio, serum albumin, gamma-glutamyl transferase, cholinesterase, hemoglobin, and platelet were statistically significant between the ALF-WD and NWDALF groups. The optimum cut-off points were obtained through ROC analysis. A scoring system was formed by assigning a score of 1 or 0 to patients who met the 13 cut-off points. Using ROC analysis, we determined a cut-off point of ≥ 6.5 for ALF-WD with 91.7% sensitivity and 97.8% specificity (p < 0.0001). In addition, a best cut-off point of ≥ 1.5 based on only five variables (ALT, AST, AST:ALT ratio, ALP, and ALP:TBil ratio), had 100% sensitivity and 91.3% specificity for ALF-WD (p < 0.0001). Based on this, when age was calculated as the sixth indicator, the best cut-off value of ≥ 2.5 had 100% sensitivity and 97.8% specificity (p < 00.0001).

Conclusion

Our study developed a new scoring system that consists of simple laboratory tests with good sensitivity and specificity and can be used by clinicians to quickly distinguish ALF-WD from NWDALF in children.
Short-term effectiveness of baricitinib in children with refractory and/or severe juvenile dermatomyositis
Authors: Wang Zhaoling , Zheng Qi , Xuan Wenjie , Xu Xisheng , Lu Meiping , Wu Jianqiang , Zou Lixia , Xu Yiping , Xu Xuefeng
Published: September 2022

Objective

To determine the short-term effectiveness safety of baricitinib in children with refractory and/or severe juvenile dermatomyositis (rsJDM) in a real-world setting.

Methods

This was a single-center retrospective study, including 20 children with rsJDM. They were all treated using baricitinib combined with steroids and other immunosuppressive agents. The childhood myositis assessment scale (CMAS) and PRINTO remission criteria were used to evaluate the disease severity and treatment outcome at 0, 4, 12, and 24 weeks after initiation of baricitinib.

Results

The skin rash improved in 95% of patients (19/20) at week 24, with a significant decrease of skin-DAS at weeks 12 (6.0 vs. 2.0, p < 0.05] and week 24 [6.0 vs. 1.0, p < 0.05) by median statistics. The CMAS score increased significantly at week 12 (41.0 [29.0, 44.0] vs. 46.0 [42.0, 52.0], p < 0.05) and week 24 (41.0 [29.0, 44.0] vs. 50.0 [45.0, 52.0], p < 0.05), as did the manual muscle testing (MMT)-8 score at week 24 (73.0 [610, 76.0] vs. 79.0 [77.0, 80.0], p < 0.05). At 24 weeks, the complete response (CR) and partial response (PR) were achieved in 75% (15/20) and 15% (3/20), respectively. The dose of corticosteroids (CS) decreased by 37% from the baseline (0.53 [0.42, 1.00] mg/kg) to week 12 (0.33 [0.18, 0.40] mg/kg) (p < 0.05), and by 49% at week 24 (p < 0.05). No serious side effects were observed.

Conclusion

Baricitinib combined with traditional immunosuppressants treatment was efficacious in rsJDM. Add-on therapy of baricitinib was helpful for tapering CS dose. No serious side effects were observed in this study.
The Cao-Xiang-Wei-Kang formula attenuates the progression of experimental colitis by restoring the homeostasis of the microbiome and suppressing inflammation
Authors: Yu Wei , Li Qi , Shao Changlei , Zhang Yijia , Kang Cai , Zheng Yang , Liu Xihao , Liu Xincheng , Yan Jing
Published: September 2022

Inflammatory bowel disease (IBD) is pathologically characterized by an immune response accommodative insufficiency and dysbiosis accompanied by persistent epithelial barrier dysfunction. The Cao-Xiang-Wei-Kang (CW) formula has been utilized to treat gastrointestinal disorders in the clinic. The present study was designed to delineate the pharmacological mechanisms of this formula from different aspects of the etiology of ulcerative colitis (UC), a major subtype of IBD. Dextran sodium sulfate (DSS) was given to mice for a week at a concentration of 2%, and the CW solution was administered for 3 weeks. 16S rRNA gene sequencing and untargeted metabolomics were conducted to examine the changes in the microbiome profile, and biochemical experiments were performed to confirm the therapeutic functions predicted by system pharmacology analysis. The CW treatment hampered DSS-induced experimental colitis progression, and the targets were enriched in inflammation, infection, and tumorigenesis, which was corroborated by suppressed caspase 3 (Casp3) and interleukin-1b (IL-1b) and increased cleaved caspase 3 expression and casp-3 activity in the colon samples from colitis mice subjected to the CW therapy. Moreover, the CW therapy rescued the decreased richness and diversity, suppressed the potentially pathogenic phenotype of the gut microorganisms, and reversed the altered linoleic acid metabolism and cytochrome P450 activity in murine colitis models. In our in vitro experiments, the CW administration increased the alternative activation of macrophages (Mφs) and inhibited the tumor necrosis factor-α (TNFα)-induced reactive oxygen species (ROS) level and subsequent death in intestinal organoids (IOs). We propose that the CW formula alleviates the progression of murine colitis by suppressing inflammation, promoting mucosal healing, and re-establishing a microbiome profile that favors re-epithelization.
Potential safety signals for antibacterial agents from the Brazilian national pharmacovigilance database (Vigimed/VigiFlow)
Authors: Barbosa Luiza Hoehl Loureiro Alves , Silva Alice Ramos Oliveira , Carvalho-Assef Ana Paula D’Alincourt , Lima Elisangela Costa , da Silva Fabricio Alves Barbosa
Published: September 2022

Antibacterial drugs are a widely used drug class due to the frequency of infectious diseases globally. Risks knowledge should ground these medicines’ selection. Data mining in large databases is essential to identify early safety signals and to support pharmacovigilance systems. We conducted a cross-sectional study to assess adverse drug events related to antibiotics reporting between December 2018 and December 2021 in the Brazilian database (Vigimed/VigiFlow). We used the Reporting Odds Ratio (ROR) disproportionality analysis method to identify disproportionate reporting signals (SDR), referring to statistical combinations between drugs and adverse events. Vancomycin was the most reported antibiotic (n = 1,733), followed by ceftriaxone (n = 1,277) and piperacillin and tazobactam (n = 1,024). We detected 294 safety signals related to antibacterials. We identified azithromycin leading in the number of safety signals (n = 49), followed by polymyxin B (n = 25). Of these, 95 were not provided for in the drug label and had little or no reports in the medical literature. Three serious events are associated with ceftazidime and avibactam, a new drug in the Brazilian market. We also found suicide attempts as a sign associated with amoxicillin/clavulanate. Gait disturbance, a worrying event, especially in the elderly, was associated with azithromycin. Our findings may help guide further pharmacoepidemiologic studies and monitoring safety signals in pharmacovigilance.
The neuroprotective effect of dexmedetomidine and its mechanism
Authors: Hu Yijun , Zhou Hong , Zhang Huanxin , Sui Yunlong , Zhang Zhen , Zou Yuntao , Li Kunquan , Zhao Yunyi , Xie Jiangbo , Zhang Lunzhong
Published: September 2022

Dexmedetomidine (DEX) is a highly selective α2 receptor agonist that is routinely used in the clinic for sedation and anesthesia. Recently, an increasing number of studies have shown that DEX has a protective effect against brain injury caused by traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), cerebral ischemia and ischemia–reperfusion (I/R), suggesting its potential as a neuroprotective agent. Here, we summarized the neuroprotective effects of DEX in several models of neurological damage and examined its mechanism based on the current literature. Ultimately, we found that the neuroprotective effect of DEX mainly involved inhibition of inflammatory reactions, reduction of apoptosis and autophagy, and protection of the blood–brain barrier and enhancement of stable cell structures in five way. Therefore, DEX can provide a crucial advantage in neurological recovery for patients with brain injury. The purpose of this study was to further clarify the neuroprotective mechanisms of DEX therefore suggesting its potential in the clinical management of the neurological injuries.
AZD6738 Inhibits fibrotic response of conjunctival fibroblasts by regulating checkpoint kinase 1/P53 and PI3K/AKT pathways
Authors: Huang Longxiang , Ye Qin , Lan Chunlin , Wang Xiaohui , Zhu Yihua
Published: September 2022

Trabeculectomy can effectively reduce intraocular pressure (IOP) in glaucoma patients, the long-term surgical failure is due to the excessive proliferation and fibrotic response of conjunctival fibroblasts which causes the subconjunctival scar and non-functional filtering bleb. In this study, we demonstrated that AZD6738 (Ceralasertib), a novel potent ataxia telangiectasia and Rad3-related (ATR) kinase inhibitor, can inhibit the fibrotic response of conjunctival fibroblasts for the first time. Our in vitro study demonstrated that AZD6738 inhibited the level and the phosphorylation of checkpoint kinase 1 (CHK1), reduced TGF-β1-induced cell proliferation and migration, and induced apoptosis of human conjunctival fibroblasts (HConFs) in the high-dose group (5 μM). Low-dose AZD6738 (0.1 μM) inhibited the phosphorylation of CHK1 and reduce fibrotic response but did not promote apoptosis of HConFs. Further molecular research indicated that AZD6738 regulates survival and apoptosis of HConFs by balancing the CHK1/P53 and PI3K/AKT pathways, and inhibiting TGF-β1-induced fibrotic response including myofibroblast activation and relative extracellular matrix (ECM) protein synthesis such as fibronectin (FN), collagen Ⅰ (COL1) and collagen Ⅳ (COL4) through a dual pharmacological mechanism. Hence, our results show that AZD6738 inhibits fibrotic responses in cultured HConFs in vitro and may become a potential therapeutic option for anti-subconjunctival scarring after trabeculectomy.
Anti-depression effectiveness of essential oil from the fruits of Zanthoxylum bungeanum maxim. on chronic unpredictable mild stress-induced depression behavior in mice
Authors: Tang Dandan , Liang Qi , Zhang Mengmeng , Li Meiyan , Zhang Qing , Zhang Siyuan , Ai Li , Wu Chunjie
Published: September 2022

The fruits of Zanthoxylum bungeanum Maxim. Was a popular traditional Chinese herbal medicine for pain relief, itching prevention, and diarrhea relief. The fruits of Zanthoxylum bungeanum Maxim. Essential oil (HEO) had an effect of improving anxiety and other emotional disorders. In this paper, we aim to systematically research the antidepressant effects of HEO on Chronic Mild Unpredictable Stimulation (CUMS) mice and explore the relevant molecular mechanisms. Experimental mice were exposed to CUMS for 8 weeks. Meanwhile, for 8 weeks, Sertraline hydrochloride (20 mg/kg/day) and HEO (50, 100, and 150 mg/kg/day) were administered by gavage. HEO treatment increased residence time of central zone in OFT and open-arm in EPM test but decreased immobility times in FST and TST. Moreover, HEO treatment improved the levels of 5-HT, DA, NE, and BDNF, but reduced CRF and CORT levels of the HPA axis in the hippocampus. Network pharmacology predicted the possible mechanisms for the antidepressant effects of HEO by regulation of PI3K/Akt signaling pathway. The mRNA expression of PI3K and Akt were increased, and immunofluorescence results in the hippocampus indicated that HEO treatment could increase the phosphorylation of PI3K and Akt. Besides, the viability of CORT-treated PC12 cells was significantly improved by HEO treatment. The AO-EB staining, MOMP analysis, and flow cytometry analysis results showed HEO inhibiting the CORT-induced apoptosis in PC12 cells significantly. Besides, the phosphorylation of PI3K and Akt in COTR-induced PC12 cells could increase by HEO treatment. In conclusion, HEO ameliorated depression behavior induced by CUMS, potentially via regulating HPA axis and activating PI3K/Akt signaling pathway to reduce neuronal apoptosis.
Non-coding RNAs as potential biomarkers and therapeutic targets in polycystic kidney disease
Authors: Zheng Qi , Reid Glen , Eccles Michael R. , Stayner Cherie
Published: September 2022

Polycystic kidney disease (PKD) is a significant cause of end-stage kidney failure and there are few effective drugs for treating this inherited condition. Numerous aberrantly expressed non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), may contribute to PKD pathogenesis by participating in multiple intracellular and intercellular functions through post-transcriptional regulation of protein-encoding genes. Insights into the mechanisms of miRNAs and other ncRNAs in the development of PKD may provide novel therapeutic strategies. In this review, we discuss the current knowledge about the roles of dysregulated miRNAs and other ncRNAs in PKD. These roles involve multiple aspects of cellular function including mitochondrial metabolism, proliferation, cell death, fibrosis and cell-to-cell communication. We also summarize the potential application of miRNAs as biomarkers or therapeutic targets in PKD, and briefly describe strategies to overcome the challenges of delivering RNA to the kidney, providing a better understanding of the fundamental advances in utilizing miRNAs and other non-coding RNAs to treat PKD.
The potential of glucagon-like peptide-1 receptor agonists in heart failure
Authors: Kreiner Frederik Flindt , Hovingh G. Kees Kornelis , von Scholten Bernt Johan
Published: September 2022

Heart failure (HF) remains one of the cardiovascular diseases (CVDs) associated with a high unmet medical need due to high morbidity and mortality rates and lack of efficacious interventions. HF is closely related to cardiometabolic diseases such as diabetes, obesity and chronic kidney disease, and strategies that address most or all these intertwined conditions are desirable. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved for type 2 diabetes (T2D), and some are also indicated for reduction of the risk of atherosclerotic CVD in T2D and for weight management. As we summarise in this concise review, preliminary evidence suggests that the cardioprotective benefits of GLP-1 RAs may also extend to HF. The most robust clinical evidence arguably originates from the large cardiovascular outcomes trials (CVOTs) completed for most GLP-1 RAs, of which the latest showed a significant relative risk reduction (RRR) of 39% (HR) with once-weekly efpeglenatide on HF requiring hospitalisation, corroborating a meta-analysis which found a significant RRR across eight GLP-1 RA CVOTs of 11%. Further, although incompletely described, multiple studies are available to provide insights into the mechanistic underpinnings, which appear to be associated mostly with indirect cardioprotective benefits owing to the ability of GLP-1 RAs to address hyperglycaemia, and reduce body weight, and, amongst others, inflammation. In sum, current evidence positions GLP-1 RAs as a potential cardioprotective strategy in HF, with HF with preserved ejection fraction emerging as the clinically most relevant phenotype for the drug class, especially when occurring in people with obesity with and without diabetes.
How negative out-party affect influenced public attitudes about the coronavirus crisis in Norway
Authors: Ryan Alexander
Published: September 2022

Research on affective polarization and negative partisanship toward disliked out-parties has increased significantly in recent years. However, there are surprisingly few studies that actually examine its political consequences, especially outside of the US. This study relies on two survey experiments to examine how dislike toward out-parties affected how Norwegian citizens evaluated the country's response to the coronavirus crisis. The first experiment follows the example of previous research on the US case and tests how out-party dislike measured before the coronavirus outbreak affected subsequent attitudes about how Norway and the conservative government had managed the crisis. The second experiment then randomly assigns party cues to a policy proposal included in the country's economic rescue package and tests whether like-dislike party evaluations moderate the effect of receiving the party cues. Overall, the results show that out-party dislike predicted attitudes to the government's response, but, contrary to studies focusing on the US case, this effect was either nonexistent or weaker for those who rated the country's response. Additionally, while out-party cues polarized opinions to the proposal, the moderating effect of out-party dislike was only more consistently found for those who received party cues from the populist-right party.
How to stimulate employees’ innovative behavior: Internal social capital, workplace friendship and innovative identity
Authors: Zhao Xiaoyang , Yi Changjun , Chen Chusheng
Published: September 2022

With the digital transformation of the economy and the rise of community innovation, how stimulating employees’ innovative behavior (EIB) becomes the basis for building sustainable competitive advantage in organizations. However, research has yet to systematically investigate the effect of internal social capital (ISC) on EIB. Based on social identity theory and resource conservation theory, this paper constructs a model to explain the mediating role of II between ISC and EIB and the moderating role of workplace friendship (WF). Using SPSS 27 and Amos 24 to analyze the data of 284 questionnaires, the results show that (1) ISC has a positive effect on EIB, (2) II plays a partial mediating effect in the relationship between ISC and EIB, and (3) WF has a positive moderating effect on the relationship between ISC and EIB. The conclusion provides management insight and practical guidance for creating an internal organizational climate to promote EIBs.
Effects of extended reality on language learning: A meta-analysis
Authors: Chen Jingying , Dai Jian , Zhu Keke , Xu Liujie
Published: September 2022

In recent years, there has been increasing use of extended reality (XR) in language learning. Many scholars have conducted empirical research on the relationship between the two, but conclusions have been inconsistent, which calls for an organization and reanalysis of relevant literature. Articles published between 2000 and 2022 on the impact of XR on language learning were retrieved from the Web of Science and Scopus databases, and 17 of them (including 21 independent samples and 993 subjects) were included in this meta-analysis. The findings indicate that XR could promote language learning (effect size = 0.825). The moderating effects of education level, target language, and technology type were also tested, and the results indicate that the target language type significantly moderated the effect of XR technology on language learning (Q = 30.563,p < 0.001). Moreover, based on the subgroup analysis, several research questions worthy of further exploration in this field are discussed. Some suggestions are provided, noting that these technologies should be personally designed for learners and learning objects when applied in order to improve the effects of language learning.
The assessment method of foreign language communication ability of intelligent emotional network based on artificial emotion
Authors: Li Chen
Published: September 2022

The traditional evaluation methods of foreign language communication skills cannot deal with emotional information in the process of communication. Psychologists believe that a real personalized evaluation system should be smart. Based on the emotion network technology of artificial emotion intelligence, aiming at the shortcomings of the traditional evaluation system, this paper puts forward a new language ability evaluation system with certain emotion judgment function. The system can easily obtain and identify emotions in foreign communication, and can also carry out individual learning at the cognitive and emotional levels on the basis of comprehensive analysis of emotions and communication effects.