bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychometric properties of the Japanese version of the Kansas City Cardiomyopathy Questionnaire in Japanese patients with chronic heart failure
Authors: Watanabe-Fujinuma Emi , Origasa Hideki , Bamber Luke , Roessig Lothar , Toyoda Tetsumi , Haga Yuri , Gwaltney Chad , Pieske Burkert 
Published: July 2020

Abstract
Background
Heart failure is a worldwide health problem that significantly affects patients’ physical function and health state. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcome measure commonly used for the assessment of health states of patients with heart failure. This study aimed to evaluate the psychometric properties of the Japanese version of the KCCQ.

Methods
Using pooled data of 141 Japanese patients with chronic heart failure from three clinical trials, the Japanese version of the KCCQ was evaluated for validity and reliability, with a focus on the clinical summary score (CSS) and its component domains. For construct validity, the associations of baseline KCCQ scores with New York Heart Association (NYHA) class and the EuroQol five-dimension, three-level (EQ-5D-3L) scores at baseline were analyzed. For reliability, internal consistency was assessed using Cronbach’s α, and test–retest reliability (reproducibility) was assessed among stable patients. Responsiveness to changes in patients’ clinical status was assessed by analyzing score changes between two timepoints among patients whose health states improved.

Results
Among 141 patients (mean age, 73.7 ± 10.9 years), 76.6% were NYHA class II at baseline. For CSS and its component domains (physical limitations, symptom frequency, and symptom severity), baseline scores were all significantly lower in patients with a higher NYHA class (p <  0.001 for all, Jonckheere-Terpstra test). The physical limitations domain and CSS showed a moderate correlation (Spearman’s ρ = − 0.40 to − 0.54) with three functional status-related EQ-5D dimensions (mobility, self-care, and usual activities). The Cronbach’s standardized α was high (> 0.70) for all KCCQ domain/summary scores. In the test–retest analysis among 58 stable patients, all domain/summary scores minimally changed by 0.3–4.2 points with intraclass correlation coefficients of 0.65–0.84, demonstrating moderate to good reproducibility, except for the symptom stability domain. Among 44 patients with improved health states, all domain/summary scores except for the symptom stability and self-efficacy domains substantially improved from baseline with a medium to large effect size of 0.62–0.88.

Conclusions
The Japanese version of the KCCQ was demonstrated to be a valid and reliable tool for the assessment of symptoms and physical function of Japanese patients with chronic heart failure.
Outcomes from Indo–United States–Egypt tri-national psychiatric research training programmes
Authors: Malavia Tulsi A. , Nimgaonkar Vishwajit , Bhatia Triptish , Ibrahim Ibtihal M. A. , Mansour Hader , Wesesky Maribeth , Wood Joel , Deshpande Smita N. , Hawk Mary 
Published: July 2020

Abstract
Background
The prevalence of mental health disorders is increasing globally. Countries in South Asia, Southeast Asia and the Middle East regions carry high burdens of mental health need; however, there are relatively few mental health research publications from this region, suggesting inadequate research funds and a paucity of qualified research personnel. To increase and strengthen the pool of mental health researchers in India and Egypt, we conducted three psychiatric research programmes in these countries: the Training Program for Psychiatric Genetics in India (2002–2011), the Tri-National Training Program for Psychiatric Genetics (2009–2014) and the Cross-Fertilized Research Training for New Investigators in Egypt and India (2014–2019). A total of 66 trainees, including psychiatrists, psychiatric social workers, clinical psychologists and research psychologists, were supported in research development, which included didactic training, proposal development, hands-on research and manuscript preparation.

Methods
The aim of this study is to evaluate these three training programmes using the four-level Kirkpatrick Model of Training Evaluation that assesses reaction, learning, behaviour and outcomes. A descriptive analysis was used to explore the data collected throughout the duration of the three training programmes. Online surveys were crafted and sent to the mentors and trainees of the three programmes to supplement objective training data.

Results
In addition to positive changes in the areas of reaction, learning and behaviour, significant outcomes were demonstrated. As of the writing of this manuscript, the trainees published a total of 130 papers, 59 as first author. In addition, 26 trainees have co-authored papers with one or more trainees or mentors, which demonstrates successful research networking and collaboration.

Conclusion
Our findings suggest that our training approach is a successful model for building independent mental health researchers. This is a critical step in the development of effective mental health interventions in low- and middle-income countries.
ERK and Akt exhibit distinct signaling responses following stimulation by pro-angiogenic factors
Authors: Song Min , Finley Stacey D. 
Published: July 2020

AbstractBackgroundAngiogenesis plays an important role in the survival of tissues, as blood vessels provide oxygen and nutrients required by the resident cells. Thus, targeting angiogenesis is a prominent strategy in many different settings, including both tissue engineering and cancer treatment. However, not all of the approaches that modulate angiogenesis lead to successful outcomes. Angiogenesis-based therapies primarily target pro-angiogenic factors such as vascular endothelial growth factor-A (VEGF) or fibroblast growth factor (FGF) in isolation, and there is a limited understanding of how these promoters combine together to stimulate angiogenesis. Targeting one pathway could be insufficient, as alternative pathways may compensate, diminishing the overall effect of the treatment strategy.MethodsTo gain mechanistic insight and identify novel therapeutic strategies, we have developed a detailed mathematical model to quantitatively characterize the crosstalk of FGF and VEGF intracellular signaling. The model focuses on FGF- and VEGF-induced mitogen-activated protein kinase (MAPK) signaling to promote cell proliferation and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway, which promotes cell survival and migration. We fit the model to published experimental datasets that measure phosphorylated extracellular regulated kinase (pERK) and Akt (pAkt) upon FGF or VEGF stimulation. We validate the model with separate sets of data.ResultsWe apply the trained and validated mathematical model to characterize the dynamics of pERK and pAkt in response to the mono- and co-stimulation by FGF and VEGF. The model predicts that for certain ranges of ligand concentrations, the maximum pERK level is more responsive to changes in ligand concentration compared to the maximum pAkt level. Also, the combination of FGF and VEGF indicates a greater effect in increasing the maximum pERK compared to the summation of individual effects, which is not seen for maximum pAkt levels. In addition, our model identifies the influential species and kinetic parameters that specifically modulate the pERK and pAkt responses, which represent potential targets for angiogenesis-based therapies.ConclusionsOverall, the model predicts the combination effects of FGF and VEGF stimulation on ERK and Akt quantitatively and provides a framework to mechanistically explain experimental results and guide experimental design. Thus, this model can be utilized to study the effects of pro- and anti-angiogenic therapies that particularly target ERK and/or Akt activation upon stimulation with FGF and VEGF.
Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models
Authors: Iba Michiyo , Kim Changyoun , Sallin Michelle , Kwon Somin , Verma Anjali , Overk Cassia , Rissman Robert A. , Sen Ranjan , Sen Jyoti Misra , Masliah Eliezer 
Published: July 2020

Abstract
Background
α-Synuclein (α-syn) is a pre-synaptic protein which progressively accumulates in neuronal and non-neuronal cells in neurodegenerative diseases such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Recent evidence suggests that aberrant immune activation may be involved in neurodegeneration in PD/DLB. While previous studies have often focused on the microglial responses, less is known about the role of the peripheral immune system in these disorders.

Methods
To understand the involvement of the peripheral immune system in PD/DLB, we evaluated T cell populations in the brains of α-syn transgenic (tg) mice (e.g., Thy1 promoter line 61) and DLB patients.

Results
Immunohistochemical analysis showed perivascular and parenchymal infiltration by CD3+/CD4+ helper T cells, but not cytotoxic T cells (CD3+/CD8+) or B cells (CD20+), in the neocortex, hippocampus, and striatum of α-syn tg mice. CD3+ cells were found in close proximity to the processes of activated astroglia, particularly in areas of the brain with significant astrogliosis, microgliosis, and expression of pro-inflammatory cytokines. In addition, a subset of CD3+ cells co-expressed interferon γ. Flow cytometric analysis of immune cells in the brains of α-syn tg mice revealed that CD1d-tet+ T cells were also increased in the brains of α-syn tg mice suggestive of natural killer T cells. In post-mortem DLB brains, we similarly detected increased numbers of infiltrating CD3+/CD4+ T cells in close proximity with blood vessels.

Conclusion
These results suggest that infiltrating adaptive immune cells play an important role in neuroinflammation and neurodegeneration in synucleinopathies and that modulating peripheral T cells may be a viable therapeutic strategy for PD/DLB.
Nuclear factor kappa B activation appears weaker in schizophrenia patients with high brain cytokines than in non-schizophrenic controls with high brain cytokines
Authors: Murphy Caitlin E. , Lawther Adam J. , Webster Maree J. , Asai Makoto , Kondo Yuji , Matsumoto Mitsuyuki , Walker Adam K. , Weickert Cynthia Shannon 
Published: July 2020

Abstract
Background
High inflammation status despite an absence of known infection characterizes a subpopulation of people with schizophrenia who suffer from more severe cognitive deficits, less cortical grey matter, and worse neuropathology. Transcripts encoding factors upstream of nuclear factor kappa B (NF-κB), a major transcriptional activator for the synthesis of pro-inflammatory cytokines, are increased in the frontal cortex in schizophrenia compared to controls. However, the extent to which these changes are disease-specific, restricted to those with schizophrenia and high-neuroinflammatory status, or caused by loss of a key NF-κB inhibitor (HIVEP2) found in schizophrenia brain, has not been tested.

Methods
Post-mortem prefrontal cortex samples were assessed in 141 human brains (69 controls and 72 schizophrenia) and 13 brains of wild-type mice and mice lacking HIVEP2 (6 wild-type, 7 knockout mice). Gene expression of pro-inflammatory cytokines and acute phase protein SERPINA3 was used to categorize high and low neuroinflammation biotype groups in human samples via cluster analysis. Expression of 18 canonical and non-canonical NF-κB pathway genes was assessed by qPCR in human and mouse tissue.

Results
In humans, we found non-canonical upstream activators of NF-κB were generally elevated in individuals with neuroinflammation regardless of diagnosis, supporting NF-κB activation in both controls and people with schizophrenia when cytokine mRNAs are high. However, high neuroinflammation schizophrenia patients had weaker (or absent) transcriptional increases of several canonical upstream activators of NF-κB as compared to the high neuroinflammation controls. HIVEP2 mRNA reduction was specific to patients with schizophrenia who also had high neuroinflammatory status, and we also found decreases in NF-κB transcripts typically induced by activated microglia in mice lacking HIVEP2.

Conclusions
Collectively, our results show that high cortical expression of pro-inflammatory cytokines and low cortical expression of HIVEP2 in a subset of people with schizophrenia is associated with a relatively weak NF-κB transcriptional signature compared to non-schizophrenic controls with high cytokine expression. We speculate that this comparatively milder NF-κB induction may reflect schizophrenia-specific suppression possibly related to HIVEP2 deficiency in the cortex.
Effect of AIDS-defining events at initiation of antiretroviral therapy on long-term mortality of HIV/AIDS patients in Southwestern China: a retrospective cohort study
Authors: Huang Yunxuan , Zhou Oulu , Zheng Zhigang , Xu Yuexiang , Shao Yi , Qin Chunwei , Qin Fengxiang , Lai Jingzhen , Liu Huifang , Chen Rongfeng , Ye Li , Liang Hao , Qin Xionglin , Jiang Junjun 
Published: July 2020

Abstract
Objective
To evaluate the impact of AIDS-defining events (ADE) on long-term mortality of HIV positive individuals on antiretroviral therapy (ART), a retrospective HIV/AIDS treatment cohort study performed in Southwestern China.

Methods
The retrospective cohort was conducted among 6757 HIV/AIDS patients on ART (2NRTIs + 1NNRTI, 2NRTIs + 1PI and Single or two drugs) recruited in Guigang city, Guangxi, China, from January 2004 to December 2018. Participants were divided into ADE and non-ADE groups, and were followed-up every six months to observe treatment outcomes. Comparison of mortality between groups was performed using the log-rank test and Kaplan–Meier analysis. Cox proportional hazard regression was used to explore the risk factors of mortality. 1:1 propensity score matching (PSM) was used to balance confounding factors and adjust the mortality risk.

Results
Of 6757 participants with 29,096.06 person-years of follow-up, 16.86% (1139/6757) belonged to ADE group while the others (83.14%) belonged to the non-ADE group. The most common cause of death by ADE was disseminated mycosis (31.65%), followed by recurrent severe bacterial pneumonia (28.48%), herpes zoster (17.72%), and extra-pulmonary tuberculosis (8.86%). The mortality of the ADE group was significantly higher than that of the non-ADE group [3.45/100 person-years (95% CI 2.92–3.97) vs. 2.34/100 person-years (95% CI 2.15–2.52), P<0.001]. The death risk of the ADE group was also higher than that of the non- ADE group [adjusted hazard ratio (aHR) = 1.291, 95% CI 1.061–1.571, P = 0.011], which was confirmed by PSM analysis (aHR = 1.581, 95% CI 1.192–2.099, P = 0.002). Cox analysis indicated that ADE, older age, male gender, previous non-use of cotrimoxazole, advanced WHO clinical stage, and low baseline CD4+ cell count were the risk factors for death.

Conclusions
Even on ART, the mortality risk of HIV positive individuals with ADE was higher than those without ADE. Active testing, earlier diagnosis, and timely therapy with ART may reduce the death risk of ADE.
Gut transcriptomic changes during hibernation in the greater horseshoe bat (Rhinolophus ferrumequinum)
Authors: Sun Haijian , Wang Jiaying , Xing Yutong , Pan Yi-Hsuan , Mao Xiuguang 
Published: July 2020

Abstract
Background
The gut is the major organ for nutrient absorption and immune response in the body of animals. Although effects of fasting on the gut functions have been extensively studied in model animals (e.g. mice), little is known about the response of the gut to fasting in a natural condition (e.g. hibernation). During hibernation, animals endure the long term of fasting and hypothermia.

Results
Here we generated the first gut transcriptome in a wild hibernating bat (Rhinolophus ferrumequinum). We identified 1614 differentially expressed genes (DEGs) during four physiological states (Torpor, Arousal, Winter Active and Summer Active). Gene co-expression network analysis assigns 926 DEGs into six modules associated with Torpor and Arousal. Our results reveal that in response to the stress of luminal nutrient deficiency during hibernation, the gut helps to reduce food intake by overexpressing genes (e.g. CCK and GPR17) that regulate the sensitivity to insulin and leptin. At the same time, the gut contributes energy supply by overexpressing genes that increase capacity for ketogenesis (HMGCS2) and selective autophagy (TEX264). Furthermore, we identified separate sets of multiple DEGs upregulated in Torpor and Arousal whose functions are involved in innate immunity.

Conclusion
This is the first gut transcriptome of a hibernating mammal. Our study identified candidate genes associated with regulation of food intake and enhance of innate immunity in the gut during hibernation. By comparing with previous studies, we found that two DEGs (CPE and HSPA8) were also significantly elevated during torpor in liver and brain of R. ferrumequinum and several DEGs (e.g. TXNIP and PDK1/4) were commonly upregulated during torpor in multiple tissues of different mammals. Our results support that shared expression changes may underlie the hibernation phenotype by most mammals.
Seroprevalence of anti-hepatitis E antibodies and antigens among HIV-infected patients in Fars Province, southern Iran
Authors: Shahriarirad Reza , Erfani Amirhossein , Rastegarian Mohammad , Zeighami Ali , Arefkhah Nasir , Ghorbani Fariba , Sarvari Jamal , Sarkari Bahador 
Published: July 2020

AbstractObjectiveHIV-infected patients have immunological and clinical features that might affect the pathogenesis, as well as the outcome of the HIV/HEV co-infection. The current study aimed to determine the seroprevalence of anti-HEV antibodies and HEV antigens among HIV-infected patients in Fars Province, Southwest Iran.MethodsBlood samples (5 mL) were collected from 251 HIV-confirmed patients. Respective data, including patients’ demographic information, were obtained for each patient. The presence of HEV antigens and anti-HEV antibodies (IgG) were assessed by commercial ELISA kits, based on the manufacturers’ instructions.ResultsOut of 251 cases, 158 (62.9%) were male and 91 (36.3%) were female. Patients’ age varied from 14 to 83 (mean: 40 ± 9.7) years. Out of 251 HIV positive cases, 26 (10.4%) were positive for anti-HEV IgG antibodies and 6 (2.4%) were positive for HEV-antigens. Also, 2 (0.8%) of the patients were positive for both anti-HEV IgG antibodies and antigens. Statistical analysis revealed no significant association between sex and seropositivity to either HEV antigen or antibodies. Moreover, no significant association was seen between age and seropositivity to HEV antigen or antibody (P = 0.622 and 0.945, respectively).ConclusionOur results showed a relatively low prevalence of HEV-antibodies in HIV-infected patients, indicating that HIV positive patients may not be at greater risk of HEV infection than the general population. Moreover, HEV-antigen was detected in a few cases of HIV-infected individuals which indicate an acute or chronic HEV infection in these patients.
Fasciotomy through multiple small skin incisions for the treatment of early acute osteofascial compartment syndrome in children
Authors: Yuan Xiaowei , Wu Jun , Qu Xiangyang , Li Ming , Jiang Linjun , Liu Xing 
Published: July 2020

Abstract
Background
The purpose of the present study is to investigate the therapeutic effect of fasciotomy through multiple small skin incisions for the treatment of early osteofascial compartment syndrome in children.

Methods
From January 2009 to May 2017, 56 pediatric patients with early osteofascial compartment syndrome in their limbs were admitted into our department and treated with multiple small skin incisions for decompression at the early stage. The skin incisions, function, and sensation of the limbs were followed up.

Results
The osteofascial compartment syndrome was diagnosed at 7.4 ± 2.1 h after injury, and then fasciotomy was performed at 1.4 ± 0.4 h later. The average procedure time of fasciotomy was 12.7 ± 4.8 min. No postoperative incision infections or neurovascular injuries were observed in all the patients. The incisions completely healed in 7–10 days with an average healing time of 8 days without secondary suture. The patients were followed up for an average of 5.1 years. No Volkmann’s contractures in the injured limbs were found. The appearance, electromyography, and nerve conduction velocity of the affected limbs were not significantly different from that of the contralateral limbs. All the patients were free of symptoms and were fully recovered of sensation and function, being an “excellent” outcome at the latest follow-up.

Conclusion
Fasciotomy through multiple small skin incisions, which can be useful to decompress the compartment pressure with fewer complications, is a simple and effective strategy for the treatment of early osteofascial compartment syndrome in children.
Maintenance of certification for radiologists: an overview of European countries
Authors: Kwee Robert M. , Kwee Thomas C. 
Published: July 2020

Abstract
Background
It is currently unclear whether the continuing medical education (CME) requirements for radiologists to keep up their certification are equal across Europe, which would be desirable for uniform cross-border quality of radiology and because of the fundamental principle of free movement of workers in the European Union. This study aimed to determine the maintenance of certification requirements for radiologists in different European countries.

Methods
National radiological societies of European countries and/or their delegates as listed on the European Society of Radiology website were contacted to inquire about the maintenance of licensure requirements for radiologists in their country. Data were analysed using descriptive statistics.

Results
Forty-six European countries were contacted. Response rate was 80%. Twenty-two of 36 responding countries (59%) reported mandatory requirements to maintain a radiologist’s license to practise. The median license period was 5 years (range 1–7). The median required number of CME points per year was 40 (range 8–58, interquartile range 30). Eight countries reported additional requirements, including practising clinical radiology, attending quality meeting/clinical audit, and attending additional courses (such as radiation safety training and advanced medical training course). Fifteen of 37 responding countries (41%) did not report mandatory requirements.

Conclusions
There is considerable heterogeneity across European countries regarding the maintenance of certification requirements for radiologists. More homogeneity is desired for uniform quality assurance and professional mobility of radiologists across Europe. The data from our overview may be used to establish a benchmark for national societies who issue maintenance of licensure requirements for radiologists.