bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tyrosine capsid mutations on retrograde adeno-associated virus accelerates gene transduction efficiency
Authors: Nakahama Ryota , Saito Aika , Nobe Sensho , Togashi Kazuya , Suzuki Ikuo K. , Uematsu Akira , Emoto Kazuo 
Published: August 2022

AbstractAdeno-associated virus (AAV) vector is a critical tool for gene delivery through its durable transgene expression and safety profile. Among many serotypes, AAV2-retro is typically utilized for dissecting neural circuits with its retrograde functionality. However, this vector requires a relatively long-term incubation period (over 2 weeks) to obtain enough gene expression levels presumably due to low efficiency in gene transduction. Here, we aimed to enhance transgene expression efficiency of AAV2-retro vectors by substituting multiple tyrosine residues with phenylalanines (YF mutations) in the virus capsid, which is previously reported to improve the transduction efficiency of AAV2-infected cells by evading host cell responses. We found that AAV2-retro with YF mutations (AAV2-retroYF)-mediated transgene expression was significantly enhanced in the primary culture of murine cortical neurons at 1 week after application, comparable to that of the conventional AAV2-retro at 2 week after application. Moreover, transgene expressions in the retrogradely labeled neurons mediated by AAV2-retroYF were significantly increased both in the cortico-cortical circuits and in the subcortical circuits in vivo, while the retrograde functionality of AAV2-retroYF was equally effective as that of AAV2-retro. Our data indicate that YF mutations boost AAV2-retro-mediated retrograde gene transduction in vivo and suggest that the AAV2-retroYF should be useful for efficient targeting of the projection-defined neurons, which is suited to applications for dissecting neural circuits during development as well as future clinical applications.
Clinical validation of a multiplex droplet digital PCR for diagnosing suspected bloodstream infections in ICU practice: a promising diagnostic tool
Authors: Wu Jing , Tang Bin , Qiu Yuzhen , Tan Ruoming , Liu Jialin , Xia Jiang , Zhang Jing , Huang Jingjing , Qu Jieming , Sun Jingyong , Wang Xiaoli , Qu Hongping 
Published: August 2022

Abstract
Background
Droplet digital PCR (ddPCR) has emerged as a promising tool of pathogen detection in bloodstream infections (BSIs) in critical care medicine. However, different ddPCR platforms have variable sensitivity and specificity for diverse microorganisms at various infection sites. There is still a lack of prospective clinical studies aimed at validating and interpreting the discrepant ddPCR results for diagnosing BSI in intensive care unit (ICU) practice.

Methods
A prospective diagnostic study of multiplex ddPCR panels was conducted in a general ICU from May 21, 2021, to December 22, 2021. Paired blood cultures (BCs) and ddPCRs (2.5 h) were obtained synchronously to detect the 12 most common BSI pathogens and three antimicrobial resistance (AMR) genes. Firstly, ddPCR performance was compared to definite BSI. Secondly, clinical validation of ddPCR was compared to composite clinical diagnosis. Sensitivity, specificity, and positive and negative predictive values were calculated. Thirdly, the positive rate of AMR genes and related analysis was presented.

Results
A total of 438 episodes of suspected BSIs occurring in 150 critical patients were enrolled. BC and ddPCR were positive for targeted bacteria in 40 (9.1%) and 180 (41.1%) cases, respectively. There were 280 concordant and 158 discordant. In comparison with BCs, the sensitivity of ddPCR ranged from 58.8 to 86.7% with an aggregate of 72.5% in different species, with corresponding specificity ranging from 73.5 to 92.2% with an aggregate of 63.1%. Furthermore, the rate of ddPCR+/BC− results was 33.6% (147/438) with 87.1% (128 of 147) cases was associated with probable (n = 108) or possible (n = 20) BSIs. When clinically diagnosed BSI was used as true positive, the final sensitivity and specificity of ddPCR increased to 84.9% and 92.5%, respectively. In addition, 40 blaKPC, 3blaNDM, and 38 mecA genes were detected, among which 90.5% were definitely positive for blaKPC. Further, 65.8% specimens were predicted to be mecA-positive in Staphylococcus sp. according to all microbiological analysis.

Conclusions
The multiplexed ddPCR is a flexible and universal platform, which can be used as an add-on complementary to conventional BC. When combined with clinical infection evidence, ddPCR shows potential advantages for rapidly diagnosing suspected BSIs and AMR genes in ICU practice.
Combined analysis of whole-exome sequencing and RNA sequencing in type 2 diabetes mellitus patients with thirst and fatigue
Authors: Lv Bohan , Yang Xiuyan , An Tian , Wu Yanxiang , He Zhongchen , Li Bowu , Wang Yijiao , Tan Fang , Wang Tingye , Zhu Jiajian , Hu Yuanyuan , Liu Xiaokun , Jiang Guangjian 
Published: August 2022

Abstract
Background
The principal objective of this study was to gain a better understanding of the mechanisms of type 2 diabetes mellitus (T2DM) patients with fatigue (D-T2DM) through exome and transcriptome sequencing.

Methods
After whole-exome sequencing on peripheral blood of 6 D-T2DM patients, the consensus mutations were screen out and analyzed by a series of bioinformatics analyses. Then, we combined whole-exome sequencing and transcriptome sequencing results to find the important genes that changed at both the DNA and RNA levels.

Results
The results showed that a total of 265,393 mutation sites were found in D-T2DM patients compared with normal individuals, 235 of which were consensus mutations shared with D-T2DM patients. These genes significantly enriched in HIF-1 signaling pathway and sphingolipid signaling pathway. At the RNA level, a total of 375 genes were identified to be differentially expressed. After the DNA-RNA joint analysis, eight genes were screened that changed at both DNA and RNA levels. Among these genes, FUS and LMNA were related to carbohydrate metabolism, energy metabolism, and mitochondrial function. Subsequently, we predicted the herbs, including Qin Pi and Hei Zhi Ma, that might play a therapeutic role in D-T2DM through the SymMap database.

Conclusion
These findings have significant implications for understanding the mechanisms of D-T2DM and provide potential targets for D-T2DM diagnosis and treatment.
Integrated multi-omics analyses reveal that BCAM is associated with epigenetic modification and tumor microenvironment subtypes of clear cell renal cell carcinoma
Authors: Zhao Junjie , Liang Jiayu , Yang Yang , Sun Guangxi , Zhang Xingming , Zhao Jinge , Hu Xu , Chen Junru , Zhu Sha , Ni Yuchao , Zhang Yaowen , Dai Jindong , Wang Zhipeng , Wang Zilin , Zeng Yuhao , Yao Jin , Chen Ni , Shen Pengfei , Liu Zhenhua , Zeng Hao 
Published: August 2022

Abstract
Background
Clear cell renal cell carcinoma (ccRCC) is the most common and highly heterogeneous subtype of renal cell carcinoma. Dysregulated basal cell adhesion molecule (BCAM) gene is associated with poor prognosis in various cancers. However, the dysregulated functions and related multi-omics features of BCAM in ccRCC stay unclear.

Results
BCAM expression was aberrantly downregulated in ccRCC and correlated with adverse pathological parameters and poor prognosis. Low mRNA expression of BCAM was remarkably associated with its CpG methylation levels and BAP1 mutation status. Patients with lower-expressed BCAM concomitant with BAP1 mutation had a worse prognosis. Using RNA-seq data from The cancer genome atlas, we found that compared to the BCAM-high expression subgroup, ccRCC patients in the BCAM-low expression subgroup had significantly higher levels of immune infiltration, higher immune checkpoint expression levels and lower TIDE (tumor immune dysfunction and exclusion) score, indicating potential better response to immunotherapy. Data from the Clinical Proteomic Tumor Analysis Consortium further validated the association between low BCAM expression and CD8 + inflamed phenotype at protein level. Meanwhile, our results suggested that the angiogenesis-related pathways were enriched in the BCAM-high expression subgroup. More importantly, according to the data from the GDSC database, we revealed that the BCAM-high expression subgroup should be more sensitive to anti-angiogenetic therapies, including sorafenib, pazopanib and axitinib.

Conclusions
These results suggest that BCAM could serve as a biomarker distinguishing different tumor microenvironment phenotypes, predicting prognosis and helping therapeutic decision-making for patients with ccRCC.
Imaging features of COVID-19-associated secondary sclerosing cholangitis on magnetic resonance cholangiopancreatography: a retrospective analysis
Authors: Ghafoor Soleen , Germann Manon , Jüngst Christoph , Müllhaupt Beat , Reiner Cäcilia S. , Stocker Daniel 
Published: August 2022

Abstract
Background
Despite emerging reports of secondary sclerosing cholangitis (SSC) in critically ill COVID-19 patients little is known about its imaging findings. It presents as delayed progressive cholestatic liver injury with risk of progression to cirrhosis. Diagnosis cannot be made based on clinical presentation and laboratory markers alone. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) can aid in the diagnosis. The aim of this study was to describe MRI/MRCP imaging features of COVID-19-associated SSC.

Results
Seventeen patients (mean age 60.5 years, 15 male) who underwent MRI/MRCP were included. All had been admitted to intensive care unit (ICU) (median duration of ICU stay 10 weeks, range, 2–28 weeks) and developed acute respiratory distress syndrome requiring mechanical ventilation. On imaging, all patients had intrahepatic bile duct strictures and 10 (58.8%) had associated upstream dilatation. Intrahepatic bile duct beading was seen in 14 cases (82.3%). Only one patient (5.9%) had extrahepatic bile duct stricturing. Patchy arterial phase hyperenhancement and high signal on T2- and diffusion-weighted images were seen in 7 cases (53.8%) and 9 cases (52.9%), respectively. Biliary casts were seen in 2 cases (11.8%). Periportal lymphadenopathy and vascular complications were not seen.

Conclusion
On MRI/MRCP, COVID-19-associated SSC presents with multiple intrahepatic bile duct strictures with or without upstream dilatation and intrahepatic bile duct beading. Surrounding hepatic parenchymal changes including alterations in enhancement and T2 signal are common. The extrahepatic biliary tree was typically spared and periportal lymphadenopathy was missing in all patients.
Investigation of geomechanical properties of tephra relevant to roof loading for application in vulnerability analyses
Authors: Osman Sara , Thomas Mark , Crummy Julia , Carver Stephen 
Published: August 2022

AbstractTephra fall can lead to significant additional loading on roofs. Understanding the relevant geomechanical properties of tephra is critical when assessing the vulnerability of buildings to tephra fall and designing buildings to withstand tephra loads. Through analysis of published data and new experimental results on dry tephra (both natural samples from Ascension Island, South Atlantic and synthetic tephra made from crushed aggregates), we discuss the geomechanical properties of tephra relevant to roof loading, which include bulk density, grain size distribution and internal angle of friction. Compiled published data for deposits from 64 global eruptions reveal no clear trend in deposit densities based on magma composition or eruption size. The global data show a wide range of values within single eruptions and between eruptions of similar compositions. Published grain size distributions near to source (≤ 10 km) vary widely but again there are no clear trends relating to magma composition. We used laboratory tests to investigate the internal angle of friction, which influences deposit sliding behaviour. For dry tephra, at the low normal stresses likely to be experienced in roof loads (≤ 35 kPa), we found similar values across all our tests (35.8° - 36.5°) suggesting that any internal sliding will be consistent across a variety of deposits. By considering different magma compositions, densities and grain size distributions, we have provided an envelope of values for deposit parameters relevant to roof loading, in which future eruptions are likely to sit. Finally, we created synthetic tephra (fine- and coarse-grained pumice and scoria) by crushing volcanic aggregates and compared it to samples from Ascension and published data. Our results reveal that synthetic tephra successfully replicated the properties relevant to loading, potentially reducing the need to collect and transport natural samples.
The efficacy of imagery in the rehabilitation of people with Parkinson’s disease: protocol for a systematic review and meta-analysis
Authors: Singer Tabitha , Fahey Paul , Liu Karen P. Y. 
Published: August 2022

Abstract
Background
Parkinson’s disease (PD) is a neurodegenerative disorder of the nervous system that affects movement. Individuals with PD commonly experience difficulty initiating movements, slowness of movements, decreased balance, and decreased standing ability. It has been shown that these motor symptoms adversely affect the independence of individuals with PD. Imagery is the cognitive process whereby a motor action is internally reproduced and repeated without overt physical movement. Recent studies support the use of imagery in improving rehabilitation outcomes in the PD population. However, these data have inconsistencies and have not yet been synthesised. The study will review the evidence on the use of imagery in individuals with PD and to determine its efficacy in improving rehabilitation outcomes.

Methods
Randomised controlled clinical trials comparing the effects of imagery and control on activities, body structure and function, and participation outcomes for people with PD will be included. A detailed computer-aided search of the literature will be performed from inception to June 2021 in the following databases: MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library, Web of Science, and Scopus. Two independent reviewers will screen articles for relevance and methodological validity. The Physiotherapy Evidence Database (PEDro) scale will be utilised to evaluate the risk of bias of selected studies. Data from included studies will be extracted by two independent reviewers through a customised, pre-set data extraction sheet. Studies using imagery with comparable outcome measures will be pooled for meta-analysis using the random effect model with 95% CI. If individual studies are heterogeneous, a descriptive review will analyse variance in interventions and outcomes. A narrative data analysis will be considered where there is insufficient data to perform a meta-analysis.

Discussion
Several studies investigating imagery in the PD population have drawn dissimilar conclusions regarding its effectiveness in rehabilitation outcomes and clinical applicability. Therefore, this systematic review will gather and critically appraise all relevant data, to generate a conclusion and recommendations to guide both clinical practice and future research on using imagery in the rehabilitation of people with PD.

Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Systematic review registration
PROSPERO registration number CRD42021230556.
The role and mechanism of TXNDC5 in diseases
Authors: Wang Xueling , Li Haoran , Chang Xiaotian 
Published: August 2022

AbstractThioredoxin domain-containing protein 5 (TXNDC5) is a member of the protein disulfide isomerase (PDI) family. It can promote the formation and rearrangement of disulfide bonds, ensuring proper protein folding. TXNDC5 has three Trx-like domains, which can act independently to introduce disulfide bonds rapidly and disorderly. TXNDC5 is abnormally expressed in various diseases, such as cancer, rheumatoid arthritis (RA), etc. It can protect cells from oxidative stress, promote cell proliferation, inhibit apoptosis and promote the progression of disease. Aberrant expression of TXNDC5 in different diseases suggests its role in disease diagnosis. In addition, targeting TXNDC5 in the treatment of diseases has shown promising application prospects. This article reviews the structure and function of TXNDC5 as well as its role and mechanism in cancer, RA and other diseases.
The association of nonalcoholic fatty liver disease with bone mineral density in type 2 diabetes
Authors: Du Juan , Ma Yan , Lang Hongmei , Huang Changquan , Zhang Xingping 
Published: August 2022

Abstract
Objective
We examined the association between nonalcoholic fatty liver disease and lumbar spine bone mineral density in individuals with and without type 2 diabetes.

Methods
The lumbar BMD of 1088 subjects was measured using dual-energy X-ray absorptiometry (DXA). Liver fat content was quantified via B-mode ultrasound. Multivariable linear regression was used to study the association between NAFLD and lumbar BMD in participants with and without T2DM.

Results
The lumbar BMD in the T2DM group and the non-diabetes group was higher in the NAFLD group than in the non-NAFLD group (P < 0.001). Multivariate regression analysis in the T2DM group showed that after adjusting for confounders, the positive association between lumbar spine BMD and NAFLD remained (P = 0.027). In the non-diabetes group, after adjusting for confounders, the association between NAFLD and lumbar spine BMD disappeared.

Conclusions
The relationship between nonalcoholic fatty liver disease and lumbar bone mineral density may differ in individuals with and without diabetes. The effect of nonalcoholic fatty liver disease on bone mineral density needs to be evaluated in different clinical contexts.
Social network addiction symptoms and body dissatisfaction in young women: exploring the mediating role of awareness of appearance pressure and internalization of the thin ideal
Authors: Delgado-Rodríguez Rafael , Linares Rocío , Moreno-Padilla María 
Published: August 2022

AbstractBackgroundPrevious studies testing for a direct relationship between social networking sites (SNS) addiction and body dissatisfaction (BD) have yielded inconsistent results. Here, we aimed to identify underlying processes that could mediate this relationship. Specifically, we studied the relationship between SNS addiction symptoms and BD through the awareness of appearance pressures and the internalization of beauty ideals, both individually and serially: SNS addiction → Awareness → BD; SNS addiction → Internalization → BD; SNS addiction → Awareness → Internalization → BD.MethodA total of 368 female undergraduates with SNS accounts completed scales to assess SNS addiction symptoms (Social Network Addiction Questionnaire), BD (Body Shape Questionnaire), awareness, and internalization (Sociocultural Attitudes Towards Appearance Questionnaire-4; awareness and internalization scales). A theoretical serial mediation model was constructed to examine the proposed relationships. Body mass index was included as a covariate to control the influence of this important variable.ResultsThe results indicated that both awareness and internalization independently mediated the relationship between SNS addiction symptoms and BD. Also, there was a significant serial mediation effect; women with more SNS addiction symptoms tended to be more aware of appearance pressure, which was associated with the internalization of beauty ideals. In turn, this internalization was positively related to BD symptoms.ConclusionsThese findings shed light on the indirect relationship between SNS addiction and BD, demonstrating independent and accumulative mediating effects of awareness and internalization.
Psychometric properties of the Farsi version of the gaming disorder scale for adolescents (GADIS-A)
Authors: Mazaherizadeh Ali , Taherifar Zahra , Farahani Hojjatollah 
Published: August 2022

Abstract
Background
Gaming disorder was added to the 11th version of the international classification of disease by the world health organization in early 2019. Adolescents are the most vulnerable group in this area. Thus, a screening tool for this age range is essential. This study aims to examine the psychometric properties of the gaming disorder scale for adolescents (GADIS-A) in an Iranian male sample.

Methods
260 male students-7th to 12th grade-from Isfahan city in the academic year 2020–2021 were selected using convenience sampling. The participants responded to the Farsi version of the GADIS-A and problematic online game questionnaire (POGQ). Thirty participants answered the scale again to assess the validity of the retest. Pearson’s correlation analysis, Cronbach’s alpha, and confirmatory factor analysis were used. The data were analyzed by SPSS version 24 and R software packages psych and lavaan.

Results
Confirmatory factor analysis revealed that the two-factor model, which included cognitive-behavioral symptoms and negative consequences, had good fitness indices. The GADIS-A convergent validity is confirmed by the scale’s significant correlation with the POGQ. Cronbach’s alpha coefficient was used to determine the scale’s validity, which was 0.85 for the full scale and 0.70 and 0.75 for two factors. The validity of the retest after two weeks also showed a correlation of 0.88.

Conclusion
The Farsi version of the gaming disorder scale for adolescents has a two-factor structure and is valid for use in Iran.
Nutrient-limited subarctic caves harbour more diverse and complex bacterial communities than their surface soil
Authors: Reboleira Ana Sofia , Bodawatta Kasun H. , Ravn Nynne M. R. , Lauritzen Stein-Erik , Skoglund Rannveig Øvrevik , Poulsen Michael , Michelsen Anders , Jønsson Knud Andreas 
Published: August 2022

Abstract
Background
Subarctic regions are particularly vulnerable to climate change, yet little is known about nutrient availability and biodiversity of their cave ecosystems. Such knowledge is crucial for predicting the vulnerability of these ecosystems to consequences of climate change. Thus, to improve our understanding of life in these habitats, we characterized environmental variables, as well as bacterial and invertebrate communities of six subarctic caves in Northern Norway.

Results
Only a minuscule diversity of surface-adapted invertebrates were found in these caves. However, the bacterial communities in caves were compositionally different, more diverse and more complex than the nutrient-richer surface soil. Cave soil microbiomes were less variable between caves than between surface communities in the same area, suggesting that the stable cave environments with tougher conditions drive the uniform microbial communities. We also observed only a small proportion of cave bacterial genera originating from the surface, indicating unique cave-adapted microbial communities. Increased diversity within caves may stem from higher niche specialization and levels of interdependencies for nutrient cycling among bacterial taxa in these oligotrophic environments.

Conclusions
Taken together this suggest that environmental changes, e.g., faster melting of snow as a result of global warming that could alter nutrient influx, can have a detrimental impact on interactions and dependencies of these complex communities. This comparative exploration of cave and surface microbiomes also lays the foundation to further investigate the long-term environmental variables that shape the biodiversity of these vulnerable ecosystems.