bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of multimodal brain imaging association via a parameter decomposition based sparse multi-view canonical correlation analysis method
Authors: Zhang Jin , Wang Huiai , Zhao Ying , Guo Lei , Du Lei ,   Alzheimer’s Disease Neuroimaging Initiative
Published: April 2022

Background

With the development of noninvasive imaging technology, collecting different imaging measurements of the same brain has become more and more easy. These multimodal imaging data carry complementary information of the same brain, with both specific and shared information being intertwined. Within these multimodal data, it is essential to discriminate the specific information from the shared information since it is of benefit to comprehensively characterize brain diseases. While most existing methods are unqualified, in this paper, we propose a parameter decomposition based sparse multi-view canonical correlation analysis (PDSMCCA) method. PDSMCCA could identify both modality-shared and -specific information of multimodal data, leading to an in-depth understanding of complex pathology of brain disease.

Results

Compared with the SMCCA method, our method obtains higher correlation coefficients and better canonical weights on both synthetic data and real neuroimaging data. This indicates that, coupled with modality-shared and -specific feature selection, PDSMCCA improves the multi-view association identification and shows meaningful feature selection capability with desirable interpretation.

Conclusions

The novel PDSMCCA confirms that the parameter decomposition is a suitable strategy to identify both modality-shared and -specific imaging features. The multimodal association and the diverse information of multimodal imaging data enable us to better understand the brain disease such as Alzheimer’s disease.
Elevated N-terminal pro C-type natriuretic peptide is associated with mortality in patients undergoing transcatheter aortic valve replacement
Authors: Hu Po , Chen Han , Wang Li-Han , Jiang Ju-Bo , Li Jia-Min , Tang Meng-Yao , Guo Yu-Chao , Zhu Qi-Feng , Pu Zhao-Xia , Lin Xin-Ping , Ng Stella , Liu Xian-Bao , Wang Jian-An
Published: April 2022

Background

Unlike N-terminal pro-B-type natriuretic peptide (NT-proBNP), which have been extensively studied, little is known about the role of N-terminal pro-C-type natriuretic peptide (NT-proCNP) for predicting survival post transcatheter aortic valve replacement (TAVR).

Methods

A total of 309 patients were included in the analysis. Patients were grouped into quartiles (Q1–4) according to the baseline NT-proCNP value. Blood for NT-proCNP analysis was obtained prior to TAVR procedure. The primary endpoint was mortality after a median follow-up of 32 months. Multivariable Cox proportional hazards regression models analyzed prognostic factors. The predictive capability was compared between NT-proBNP and NT-proCNP using receiver operator curve (ROC) analysis.

Results

A total of 309 subjects with the mean age of 76.8 ± 6.3 years, among whom 58.6% were male, were included in the analysis. A total of 58 (18.8%) patients died during follow-up. Cox multivariable analyses indicated society of thoracic surgeons (STS)-score was a strong independent predictor for mortality (hazard ratio (HR) 1.08, 95% confidential interval (CI) 1.05–1.12, P < 0.001). Elevated NT-proCNP was associated with a higher risk of cardiovascular mortality (HR 1.02, 95% CI 1.00–1.03, P = 0.025) and All-cause mortality (HR 1.01, 95% CI 1.00–1.03, P = 0.027), whereas NT-proBNP showed a small effect size on mortality. ROC analysis indicated that NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with left ventricular ejection fraction (LVEF) < 50% [(Area under the curve (AUC)-values of 0.79 (0.69; 0.87) vs. 0.59 (0.48; 0.69), P = 0.0453].

Conclusions

NT-proCNP and STS-Score were the independent prognostic factors of mortality among TAVR patients. Furthermore, NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with LVEF < 50%.

Trial registration NCT02803294, 16/06/2016.
Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patterns
Authors: Iatsiuk Veronika , Malinka Frantisek , Pickova Marketa , Tureckova Jolana , Klema Jiri , Spoutil Frantisek , Novosadova Vendula , Prochazka Jan , Sedlacek Radislav
Published: April 2022

Background

Ubiquitin ligases (Ub-ligases) are essential intracellular enzymes responsible for the regulation of proteome homeostasis, signaling pathway crosstalk, cell differentiation and stress responses. Individual Ub-ligases exhibit their unique functions based on the nature of their substrates. They create a complex regulatory network with alternative and feedback pathways to maintain cell homeostasis, being thus important players in many physiological and pathological conditions. However, the functional classification of Ub-ligases needs to be revised and extended.

Methods

In the current study, we used a novel semantic biclustering technique for expression profiling of Ub-ligases and ubiquitination-related genes in the murine gastrointestinal tract (GIT). We accommodated a general framework of the algorithm for finding tissue-specific gene expression clusters in GIT. In order to test identified clusters in a biological system, we used a model of epithelial regeneration. For this purpose, a dextran sulfate sodium (DSS) mouse model, following with in situ hybridization, was used to expose genes with possible compensatory features. To determine cell-type specific distribution of Ub-ligases and ubiquitination-related genes, principal component analysis (PCA) and Uniform Manifold Approximation and Projection technique (UMAP) were used to analyze the Tabula Muris scRNA-seq data of murine colon followed by comparison with our clustering results.

Results

Our established clustering protocol, that incorporates the semantic biclustering algorithm, demonstrated the potential to reveal interesting expression patterns. In this manner, we statistically defined gene clusters consisting of the same genes involved in distinct regulatory pathways vs distinct genes playing roles in functionally similar signaling pathways. This allowed us to uncover the potentially redundant features of GIT-specific Ub-ligases and ubiquitination-related genes. Testing the statistically obtained results on the mouse model showed that genes clustered to the same ontology group simultaneously alter their expression pattern after induced epithelial damage, illustrating their complementary role during tissue regeneration.

Conclusions

An optimized semantic clustering protocol demonstrates the potential to reveal a readable and unique pattern in the expression profiling of GIT-specific Ub-ligases, exposing ontologically relevant gene clusters with potentially redundant features. This extends our knowledge of ontological relationships among Ub-ligases and ubiquitination-related genes, providing an alternative and more functional gene classification. In a similar way, semantic cluster analysis could be used for studding of other enzyme families, tissues and systems.
Ipsilesional arm training in severe stroke to improve functional independence (IPSI): phase II protocol
Authors: Maenza Candice , Sainburg Robert L. , Varghese Rini , Dexheimer Brooke , Demers Marika , Bishop Lauri , Jayasinghe Shanie A. L. , Wagstaff David A. , Winstein Carolee ,   For the IPSI Investigative Team
Published: April 2022

Background

We previously characterized hemisphere-specific motor control deficits in the ipsilesional, less-impaired arm of unilaterally lesioned stroke survivors. Our preliminary data indicate these deficits are substantial and functionally limiting in patients with severe paresis.

Methods

We have designed an intervention (“IPSI”) to remediate the hemisphere-specific deficits in the ipsilesional arm, using a virtual-reality platform, followed by manipulation training with a variety of real objects, designed to facilitate generalization and transfer to functional behaviors encountered in the natural environment. This is a 2-site (primary site – Penn State College of Medicine, secondary site – University of Southern California), two-group randomized intervention with an experimental group, which receives unilateral training of the ipsilesional arm throughout 3 one-hour sessions per week for 5 weeks, through our Virtual Reality and Manipulation Training (VRMT) protocol. Our control group receives a conventional intervention on the contralesional arm, 3 one-hour sessions per week for 5 weeks, guided by recently released practice guidelines for upper limb rehabilitation in adult stroke. The study aims to include a total of 120 stroke survivors (60 per group) whose stroke was in the territory of the middle cerebral artery (MCA) resulting in severe upper-extremity motor impairments. Outcome measures (Primary: Jebsen-Taylor Hand Function Test, Fugl-Meyer Assessment, Abilhand, Barthel Index) are assessed at five evaluation points: Baseline 1, Baseline 2, immediate post-intervention (primary endpoint), and 3-weeks (short-term retention) and 6-months post-intervention (long-term retention). We hypothesize that both groups will improve performance of the targeted arm, but that the ipsilesional arm remediation group will show greater improvements in functional independence.

Discussion

The results of this study are expected to inform upper limb evaluation and treatment to consider ipsilesional arm function, as part of a comprehensive physical rehabilitation strategy that includes evaluation and remediation of both arms.

Trial Registration

This study is registered with ClinicalTrials.gov (Registration ID:NCT03634397; date of registration: 08/16/2018).
Identification of a key glioblastoma candidate gene, FUBP3, based on weighted gene co-expression network analysis
Authors: Li Jianmin , Zhang Zhao , Guo Ke , Wu Shuhua , Guo Chong , Zhang Xinfan , Wang Zi
Published: April 2022

Background

Glioblastoma multiforme (GBM) is the most common aggressive malignant brain tumor. However, the molecular mechanism of glioblastoma formation is still poorly understood. To identify candidate genes that may be connected to glioma growth and development, weighted gene co-expression network analysis (WGCNA) was performed to construct a gene co-expression network between gene sets and clinical characteristics. We also explored the function of the key candidate gene.

Methods

Two GBM datasets were selected from GEO Datasets. The R language was used to identify differentially expressed genes. WGCNA was performed to construct a gene co-expression network in the GEO glioblastoma samples. A custom Venn diagram website was used to find the intersecting genes. The GEPIA website was applied for survival analysis to determine the significant gene, FUBP3. OS, DSS, and PFI analyses, based on the UCSC Cancer Genomics Browser, were performed to verify the significance of FUBP3. Immunohistochemistry was performed to evaluate the expression of FUBP3 in glioblastoma and adjacent normal tissue. KEGG and GO enrichment analyses were used to reveal possible functions of FUBP3. Microenvironment analysis was used to explore the relationship between FUBP3 and immune infiltration. Immunohistochemistry was performed to verify the results of the microenvironment analysis.

Results

GSE70231 and GSE108474 were selected from GEO Datasets, then 715 and 694 differentially expressed genes (DEGs) from GSE70231 and GSE108474, respectively, were identified. We then performed weighted gene co-expression network analysis (WGCNA) and identified the most downregulated gene modules of GSE70231 and GSE108474, and 659 and 3915 module genes from GSE70231 and GSE108474, respectively, were selected. Five intersection genes (FUBP3, DAD1, CLIC1, ABR, and DNM1) were calculated by Venn diagram. FUBP3 was then identified as the only significant gene by survival analysis using the GEPIA website. OS, DSS, and PFI analyses verified the significance of FUBP3. Immunohistochemical analysis revealed FUBP3 expression in GBM and adjacent normal tissue. KEGG and GO analyses uncovered the possible function of FUBP3 in GBM. Tumor microenvironment analysis showed that FUBP3 may be connected to immune infiltration, and immunohistochemistry identified a positive correlation between immune cells (CD4 + T cells, CD8 + T cells, and macrophages) and FUBP3.

Conclusion

FUBP3 is associated with immune surveillance in GBM, indicating that it has a great impact on GBM development and progression. Therefore, interventions involving FUBP3 and its regulatory pathway may be a new approach for GBM treatment.
B4GALT5 high expression associated with poor prognosis of hepatocellular carcinoma
Authors: Han Yang , Li Zhe , Wu Qi , Liu Hui , Sun Zhiqiang , Wu Yong , Luo Judong
Published: April 2022

Background

B4GALT5 is postulated to be an important protein in sugar metabolism that catalyzes the synthesis of lactosylceramide (LacCer). However, its role in hepatocellular carcinoma (HCC) remains unknown.

Method

We characterized the expression of B4GALT5 in HCC tissue compared to normal tissue, and explored its function of B4GALT5 in HCC by enrichment analysis based on its co-expressed gene set. Next, we checked whether B4GALT5 expression is correlated to immune infiltration level and clinical prognosis in hepatocellular carcinoma. Finally, we verified the expression of B4GALT5 using clinical samples evaluated by RT-PCR, and conducted in vitro experiments with B4GALT5-knockdown HCC cells to investigate the function of B4GALT5 in the HCC cell proliferation, migration and invasion.

Results

We found B4GALT5 mRNA and protein expression levels were significantly high in HCC tissue compared to normal tissue. The enrichment analysis of the gene sets that co-expressed with B4GALT5 showed specificity in HCC-related pathways and functions. Also, the expression pattern of B4GALT5 was significantly related to the immune infiltration level, especially CD4+ T cell and macrophage cells. B4GALT5 higher mRNA expression was associated with poor overall survival (OS) in HCC patients. Furthermore,In vitroexperiments showed that depletion of B4GALT5 significantly inhibited HCC cell proliferation, migration and invasion. This study revealed the function and its mediated pathways of B4GALT5 in HCC, indicating that B4GALT5 may serve as a prognostic biomarker of HCC.
Effect of neoadjuvant iodine-125 brachytherapy upon resection of glioma
Authors: Wang Congxiao , Liu Chao , Chen Jun , Jiang Han , Zhang Wei , Yang Lili , Li Xueda , Li Zixiang , Peng Lijing , Hu Xiaokun , Sun Peng
Published: April 2022

Background

A more extensive surgical resection of glioma contributes to improved overall survival (OS) and progression-free survival (PFS). However, some patients miss the chance of surgical resection when the tumor involves critical structures.

Purpose

The present study aimed to assess the feasibility of neoadjuvant 125I brachytherapy followed by total gross resection for initially inoperable glioma.

Methods

Six patients diagnosed with inoperable glioma due to invasion of eloquent areas, bihemispheric diffusion, or large tumor volume received 125I brachytherapy. Surgical resection was performed when the tumor shrank, allowing a safe resection, assessed by the neurosurgeons. Patients were followed up after surgery.

Results

Shrinkage of the tumor after adjuvant 125I brachytherapy enabled a total gross resection of all six patients. Four patients were still alive at the last follow-up, with the longest survival time of more than 50 months, two of which returned to everyday life with a KPS of 100. Another two patients had neurological injuries with KPSs of 80 and 50, respectively. One patient with grade II glioma died 34 months, and another with grade IV glioma died 40 months after the combined therapy.

Conclusions

In the present study, the results demonstrated that 125I brachytherapy enabled a complete resection of patients with initially unresectable gliomas. 125I brachytherapy may offer a proper neoadjuvant therapy method for glioma.
Increased circulating innate lymphoid cell (ILC)1 and decreased circulating ILC3 are involved in the pathogenesis of Henoch-Schonlein purpura
Authors: Zhang Lili , Lin Qiang , Jiang Lijun , Wu Mingfu , Huang Linlin , Quan Wei , Li Xiaozhong
Published: April 2022

Background

Innate lymphoid cell (ILC) dysfunction is involved in numerous immune diseases, but this has not been demonstrated in Henoch-Schonlein purpura (HSP). This study aimed to investigate whether ILC dysfunction or imbalance participate in the pathogenesis of HSP.

Methods

This was a prospective study in patients with HSP who were hospitalized at the Children’s Hospital of Soochow University from June to December 2019. Age- and sex-matched controls were also enrolled. ILC subsets and lymphocyte subpopulations were determined by flow cytometry. The transmission immune turbidimetric method also facilitated the exploration of correlations between ILC subset frequency and lymphocyte subpopulation, as well as serum IgA in HSP patients.

Results

Fifty-one patients with HSP and 22 control patients were included. There were no differences in age and sex between the two groups. Compared with controls, patients with HSP had higher ILCs in relation to lymphocytes (P = 0.036), higher ILCs in relation to PBMCs (P = 0.026), higher ILC1s (P < 0.001), lower ILC3s (P < 0.05), and higher ILC1/ILC3 ratio (P < 0.001). Sixteen patients underwent routine therapy combined with methylprednisolone for 7–10 days; ILC1s were significantly decreased (P < 0.001) and ILC3s were increased (P = 0.033), and ILC1/ILC3 was significantly decreased (P < 0.001). Compared with the controls, the ratios of ILCs/lymphocytes and ILCs/PBMC were higher in patients in the arthritis and mixed groups (all P < 0.05). ILC1 were elevated in the purpura, arthritis, abdominal, and mixed groups (P = 0.027, P = 0.007, P < 0.001, and P < 0.001, respectively). ILC1/ILCs were positively correlated with CD3 + CD8 + T lymphocytes (r = 0.3701, P = 0.0075). The level of IgA did not correlate with ILCs.

Conclusions

Higher circulating ILC1s and lower circulating ILC3s appear to be involved in the pathogenesis of HSP.
The Strengths and Difficulties Questionnaire Parent Form: Dutch norms and validity
Authors: Theunissen Meinou H. C. , de Wolff Marianne S. , Eekhout Iris , Mieloo Cathelijne L. , Stone Lisanne L. , Reijneveld Sijmen A.
Published: April 2022

Objective

This study provides Dutch national norms for the parent-reported Strengths and Difficulties Questionnaire (SDQ) for children aged 3-14 years, and assesses the test performance of the SDQ Total Difficulties Scale (TDS) and impairment Scale. We further compared Dutch SDQ norms with those of the United Kingdom (UK), to determine potential variation in country-specific norms.

Study design

We analyzed data of 3384 children aged 3 to 14 years. The data were obtained in schools, and in the context of Preventive Child Healthcare. Parents completed the SDQ parent form and the Child Behavior Checklist (CBCL). We determined clinical (10% elevated scores) and borderline (20% elevated scores) SDQ TDS norms. We assessed the test performance (validity) of the SDQ TDS and Impairment Score using the CBCL as criterion.

Results

The clinical SDQ TDS norms varied between > 10 and > 14 depending on the age group. The SDQ TDS discriminated between children with and without problems, as measured by the CBCL, for all age groups (AUCs varied from 0.92 to 0.96). The SDQ Impairment Score had added value (beyond the SDQ TDS) only for the age group 12-14 years. For the Netherlands we found lower clinical SDQ TDS norms than those previously reported for the UK (i.e. > 16).

Conclusion

The clinical SDQ TDS norms varied between > 10 and > 14 depending on the age groups. We found good test performance at these proposed norms. Dutch norms differed somewhat from UK norms. In the Netherlands, the SDQ performed better with Dutch-specific norms than with UK-specific norms.
Gamblers’ perceptions of responsibility for gambling harm: a critical qualitative inquiry
Authors: Marko Sarah , Thomas Samantha L. , Robinson Kim , Daube Mike
Published: April 2022

Background

Gambling has traditionally been conceptualised as an issue of addiction and personal responsibility. While there are now clear public health models that recognise that gambling harm is caused by a range of socio-cultural, environmental, commercial and political determinants, government and industry messages about gambling are still largely personal responsibility focused. Given the well-recognised issues associated with personal responsibility paradigms, this study sought to understand how gamblers themselves conceptualised responsibility for gambling harm.

Methods

A qualitatively led online panel survey was conducted with 363 adult gamblers in New South Wales and Victoria, Australia. Participants were asked to respond to what they thought were the causes of gambling harm, and what could be done to prevent harm. A reflexive thematic analysis was conducted.

Results

Six common tropes were constructed from gamblers’ responses: (1) Gambling in moderation; (2) Personal responsibility for rational behaviour; (3) Character flaws; (4) Personal responsibility to seek help; (5) More education is needed; and (6) Governments are responsible for action – but motivation and efficacy are questioned. Gamblers primarily understood gambling harm as being a matter of personal responsibility, and government responsibility was generally seen as limited to providing information to facilitate informed gambling choices.

Conclusions

This study demonstrates that gamblers’ perceptions of gambling harm are similar to the personal responsibility framings and tropes present in industry and government messaging strategies. Refocusing public communication strategies away from ‘responsible gambling’ messaging, and towards evidence-based approaches, will be an important part of addressing the harms associated with gambling.
Can chatbots help to motivate smoking cessation? A study on the effectiveness of motivational interviewing on engagement and therapeutic alliance
Authors: He Linwei , Basar Erkan , Wiers Reinout W. , Antheunis Marjolijn L. , Krahmer Emiel
Published: April 2022

Background

Cigarette smoking poses a major threat to public health. While cessation support provided by healthcare professionals is effective, its use remains low. Chatbots have the potential to serve as a useful addition. The objective of this study is to explore the possibility of using a motivational interviewing style chatbot to enhance engagement, therapeutic alliance, and perceived empathy in the context of smoking cessation.

Methods

A preregistered web-based experiment was conducted in which smokers (n = 153) were randomly assigned to either the motivational interviewing (MI)-style chatbot condition (n = 78) or the neutral chatbot condition (n = 75) and interacted with the chatbot in two sessions. In the assessment session, typical intake questions in smoking cessation interventions were administered by the chatbot, such as smoking history, nicotine dependence level, and intention to quit. In the feedback session, the chatbot provided personalized normative feedback and discussed with participants potential reasons to quit. Engagement with the chatbot, therapeutic alliance, and perceived empathy were the primary outcomes and were assessed after both sessions. Secondary outcomes were motivation to quit and perceived communication competence and were assessed after the two sessions.

Results

No significant effects of the experimental manipulation (MI-style or neutral chatbot) were found on engagement, therapeutic alliance, or perceived empathy. A significant increase in therapeutic alliance over two sessions emerged in both conditions, with participants reporting significantly increased motivation to quit. The chatbot was perceived as highly competent, and communication competence was positively associated with engagement, therapeutic alliance, and perceived empathy.

Conclusion

The results of this preregistered study suggest that talking with a chatbot about smoking cessation can help to motivate smokers to quit and that the effect of conversation has the potential to build up over time. We did not find support for an extra motivating effect of the MI-style chatbot, for which we discuss possible reasons. These findings highlight the promise of using chatbots to motivate smoking cessation. Implications for future research are discussed.
Discordance between perceived risk and actual risky sexual behaviors among undergraduate university students in mainland China: a cross-sectional study
Authors: Liu Yusi , Fu Guochen , Chen Yifan , Wu Lei , Pan Mingliang , Yang Yuli , Chen Zhuo , Cao Yu , Li Yong , Wang Hao , Wang Bixiang , Lv Chengcheng , Du Ruyi , Xiong Yanting , Liu Wei , Xu Nuo , Xia Xiaobao , Li Qianqian , Ruan Fang , Wang Junfang
Published: April 2022

Background

HIV prevention, diagnosis, treatment and care services might be hampered by inaccurate risk assessment. This study aimed to investigate the extent of and factors associated with the discordance between perceived risk and actual risky sexual behaviors among undergraduates in mainland China, guided by the Anderson's behavioral model.

Methods

This study involved a secondary analysis of cross-sectional data collected during the fall semester of 2018–2019 academic year. The present analysis was restricted to 8808 undergraduates with low risk perception. Those who had low perceived risk but actually engaged in risky sexual behaviors were categorized as risk discordance (RD). Univariate and multivariate Logistic regression analyses were conducted to identify factors associated with RD.

Results

Overall, the discordance rate between perceived and actual risk was 8.5% (95% CI: 7.9%-9.1%). Multivariate Logistic regression analysis indicated that non-heterosexual women (AOR = 0.41, 95% CI:0.27–0.60), heterosexual men (AOR = 0.45, 95% CI:0.33–0.61) and women (AOR = 0.26, 95% CI:0.19–0.35) were less likely to exhibit RD, when compared with non- heterosexual men. Furthermore, non-freshmen (AOR = 1.57, 95% CI:1.30–1.90), early initiators of sexual intercourse (AOR = 5.82, 95% CI:4.10–8.26), and those who had lower levels of HIV knowledge (AOR = 1.28, 95% CI:1.08–1.51), displayed higher levels of stigma against PLHIV (AOR = 1.50, 95% CI:1.26–1.77) and had ever been tested for HIV (AOR = 1.36, 95% CI:1.04–1.77) were more prone to reporting RD. Those with more enabling resources [i.e., displaying high levels of condom use self-efficacy (AOR = 0.70, 95% CI:0.59–0.84) and being knowledge of local testing center (AOR = 0.71, 95% CI:0.60–0.83)] were less likely to report RD. However, spending more than 2000 Yuan a month on basic needs (AOR = 2.55, 95% CI:2.07–3.14), residing in urban areas (AOR = 1.35, 95% CI:1.15–1.59) and being knowledgeable of the national AIDS policy (AOR = 1.40,95% CI:1.18–1.66) increased the chance of exhibiting RD.

Conclusions

Comprehensive interventions, including targeting students with high-risk characteristics, improving the acceptability of PrEP and PEP, conducting health education, enhancing self-efficacy for using condoms and making opt-out HIV testing routine in college campus, should be taken to reduce the discordance between perceived and actual HIV risk and finally to reach the goal of Zero AIDS.
Inequalities in childhood stunting: evidence from Sudan multiple indicator cluster surveys (2010–2014)
Authors: Wogderes Bashaw , Shibre Gebretsadik , Zegeye Betregiorgis
Published: April 2022

Background

Leaving no one behind has been an important marker of the Sustainable Development Goals. Closing the gap in malnutrition between children of different backgrounds aligns well with the tenet of this international agenda. To this end, high-quality evidence of the magnitude and trends of socioeconomic and geographic related existing inequalities in the childhood stunting among Sudanese children emanate from this study help for policy maker and planners to design and implement effective interventions to narrow down inequality.

Methods

We used the World Health Organization’s (WHO) Health Equity Assessment Toolkit (HEAT) for our analysis of stunting inequality. Following standard equity analysis methods recommended by the WHO, we performed the disaggregated analysis of stunting across five equity stratifiers: Wealth, education, residence, sex, and sub-national regions. Then, we summarized stunting inequality through four measures of inequality: Difference, Ratio, Slope Index of Inequality (SII), and Relative Index of Inequality (RII). The point estimates of stunting were accompanied by 95% confidence intervals to measure the statistical significance of the findings.

Results

In this study, the national average childhood stunting prevalence was increased by 4% from 2010 to 2014. The findings revealed stark inequalities in stunting in all the studied dimensions of inequality. Huge inequality has existed along the wealth quintiles. Simple difference measure for education was increased by four points and simple relative measure decreased by one point for economic status.

Conclusions

Sex, residence and, geographically related inequalities remain unchanged over time, while economic status and educational inequality had seen a change by some inequality measures over the same time period.
Cross-cultural translation and psychometric properties of the Persian version Manchester respiratory activities of daily living questionnaire (MRADLQ-P)
Authors: Eisapareh Kumars , Nazari Mahin , Mokarami Hamidreza
Published: April 2022

Purpose

The present study was an attempt to investigate cross-cultural adaptability and evaluate the psychometric properties of the Persian version of the Manchester respiratory activities of daily living questionnaire ((MRADLQ-P).

Patients and methods

In a cross-sectional study, we selected 260 patients with severe respiratory diseases who needed to be admitted to the respiratory wards of this city hospital. The process of cultural localization of the questionnaire was performed based on a standard and valid process. Psychometric properties of the instrument were confirmed based on face and content validity assessments, convergent validity, discriminative validity and internal consistency. Data collected by demographic questionnaire, MRADL questionnaire and work ability index. Data were analyzed by SPSS 22 using descriptive statistics (mean and standard deviation), Spearman correlation coefficient, Cronbach's alpha coefficient, and Mann–Whitney test.

Results

The mean age of participants was 48.8 ± 20.1 years. 176 (71.5%) were male. face content validity including content validity index (CVI) was 0.82 and content validity ratio and it was good. The questionnaire was measured at the same time as the work ability index, which Mann–Whitney test showed that the questionnaire has good differential power. Cronbach's alpha coefficient of 0.9 indicates a very good reliability of the questionnaire.

Conclusion

The results show that intercultural psychometrics of MRADL questionnaire has good validity, reliability, and differential power that can be a good tool for use in future studies. Also, the translation of this checklist included translation into the target language, backward translation of the Persian versions into the original language, and comparisons and ambiguities to obtain a final and acceptable version.
Dapagliflozin, sildenafil and their combination in monocrotaline-induced pulmonary arterial hypertension
Authors: Tang Yi , Tan Siyuan , Li Minqi , Tang Yijin , Xu Xiaoping , Zhang Qinghai , Fu Qinghua , Tang Mingxiang , He Jin , Zhang Yi , Zheng Zhaofen , Peng Jianqiang , Zhu Tengteng , Xie Wenlin
Published: April 2022

Background

Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), can reduce cardiovascular events and mortality in patients with heart failure. A number of mechanisms have been proposed to explain the beneficial effects of SGLT2 inhibitors. The purpose of this study was to determine whether dapagliflozin can improve pulmonary vascular remodelling and the efficacy of dapagliflozin as an add-on therapy to sildenafil in rats with pulmonary arterial hypertension (PAH).

Methods

A monocrotaline (MCT)-induced PAH rat model was used in our study. MCT-injected rats were randomly divided into four groups and treated for 3 weeks with daily per os treatment with vehicle, dapagliflozin (1 mg/kg/day), sildenafil (25 mg/kg/day), or a combination of dapagliflozin (1 mg/kg/day) and sildenafil (25 mg/kg/day). Haemodynamic measurements, histological analysis, enzyme-linked immunosorbent assay and western blotting analysis were employed to detect the changes in PAH rats after treatments.

Results

Dapagliflozin significantly attenuated MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) in PAH rats. Dapagliflozin effectively decreased the thickening of pulmonary artery media and decreased the muscularization of pulmonary arterioles in PAH rats. Moreover, dapagliflozin attenuated nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in lung tissues and the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in plasma. However, dapagliflozin as an add-on therapy to sildenafil in rats with PAH did not show a more pronounced beneficial effect on right ventricular systolic pressure and pulmonary vascular remodelling in MCT rats than sildenafil alone.

Conclusions

Dapagliflozin reduces right ventricular systolic pressure and pulmonary vascular remodelling in a rat model of PAH. However, combination therapy with dapagliflozin and sildenafil was not more effective than monotherapy with sildenafil in PAH rats.
Biological distinction between grades 2 and 3 with respect to intravesical recurrence in T1 high-grade bladder tumors: a retrospective study
Authors: Yamamoto Akinaru , Kawashima Atsunari , Uemura Toshihiro , Yamamichi Gaku , Tomiyama Eisuke , Koh Yoko , Matsushita Makoto , Kato Taigo , Hatano Koji , Uemura Motohide , Nonomura Norio
Published: April 2022

Background

The pathological grading system for non-muscle-invasive bladder cancer is based on the WHO 2004/2016 classification system (low-grade: LG/high-grade: HG) and the WHO 1973 classification system (Grade 1: G1/Grade 2: G2/Grade 3: G3). Recently, the usefulness of combining both systems and classifying the tumors as LG/G1, LG/G2, HG/G2, and HG/G3 has been demonstrated. In this study, we compared the prognosis of intravesical recurrence in relation to different treatment intensities between HG/G2 and HG/G3 bladder cancers.

Methods

We retrospectively evaluated the clinical and therapeutic outcomes of 145 patients diagnosed with T1 HG bladder cancer between 2000 and 2020. We classified 145 patients into three groups: (1) patients with T1 HG/G2 and HG/G3 who received intravesical instillation therapy (n = 76), (2) patients with T1 HG/G2 who did not receive intravesical instillation therapy (n = 32), and (3) patients with T1 HG/G3 who did not receive intravesical instillation therapy (n = 37).

Results

The median intravesical recurrence-free survival for all patients was 34.2 months. The number of tumors, the presence of intravesical instillation therapy, and tumor grade were significant prognostic factors for intravesical recurrence in all cases. Groups 2 and 3 showed significantly worse prognosis than group 1 in the multivariate analysis.

Conclusions

Regarding intravesical recurrence, intravesical instillation therapy is necessary for both T1 HG/G3 and T1 HG/G2 bladder cancers.
Regenerative endodontic procedures for two traumatized mature anterior teeth with transverse root fractures
Authors: Lu Jing , Kahler Bill
Published: April 2022

Background

Regenerative endodontic procedures (REPs) are an alternative treatment in immature traumatized teeth with necrotic pulp/apical periodontitis. However, this procedure has been infrequently reported in multiple transverse root fractures of mature teeth. This case report describes management of a patient with multiple horizontal root fractures in 2 maxillary central incisors that were successfully treated with REPs.

Case presentation

A 17-year-old girl had a history of traumatic injury to mature teeth 11 and tooth 21 resulting in multiple transverse root fractures. Clinical examination showed that both teeth responded to electric and thermal pulp sensibility tests with prolonged severe pain and were tender to percussion and palpation. Periapical radiographic examination showed both teeth were fully developed and had multiple transverse fractures in the mid-root. The pulp diagnosis was consistent with symptomatic irreversible pulpitis. REPs were initiated with only the coronal fragments treated to preserve pulp vitality in the apical fragment for potential pulp tissue regeneration. After REPs, clinical signs/symptoms subsided, and the two teeth were followed for 48 months when cone beam computed tomography (CBCT) imaging was also undertaken. At the last review, the case demonstrated root fractures healing with calcified tissue and pulp calcification in the apical fragments. Both teeth were stable and in function.

Conclusions

REPs have the potential to be used to treat traumatized and symptomatic mature permanent teeth that have sustained transverse root fractures.
Distinct gut and vaginal microbiota profile in women with recurrent implantation failure and unexplained infertility
Authors: Patel Nayna , Patel Nidhi , Pal Sejal , Nathani Neelam , Pandit Ramesh , Patel Molina , Patel Niket , Joshi Chaitanya , Parekh Bhavin
Published: April 2022

Background

Female reproductive tract dysbiosis impacts implantation. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains scantly explored. Herein, we examined the gut-vaginal microbiota axis in infertile women.

Methods

We recruited 11 fertile women as the controls, and a cohort of 20 infertile women, 10 of whom had recurrent implantation failure (RIF), and another 10 had unexplained infertility (UE). Using amplicon sequencing, which employs PCR to create sequences of DNA called amplicon, we compared the diversity, structure, and composition of faecal and vaginal bacteria of the controls with that of the infertile cohort. Of note, we could only sequence 8 vaginal samples in each group (n = 24/31).

Result

Compared with the controls, α-diversity and β-diversity of the gut bacteria among the infertile groups differed significantly (p < 0.05). Taxa analysis revealed enrichment of Gram-positive bacteria in the RIF group, whereas Gram-negative bacteria were relatively abundant in the UE group. Strikingly, mucus-producing genera declined in the infertile cohort (p < 0.05).Hungatella,associated with trimethylamine N-oxide (TMAO) production, were enriched in the infertile cohort (p < 0.05). Vaginal microbiota was dominated by the genusLactobacillus,withLactobacillus iners AB-1 being the most abundant species across the groups. Compared with the infertile cohort, overgrowth of anaerobic bacteria, associated with vaginal dysbiosis, such asLeptotrichia and Snethia, occurred in the controls.

Conclusion

The gut microbiota had little influence on the vaginal microbiota. Gut dysbiosis and vaginal eubiosis occurred in the infertile women, whereas the opposite trend occurred in the controls.
The predictive validity of admission criteria for the results of clinical competency assessment with an emphasis on family medicine in the fifth year of medical education: an observational study
Authors: Kötter Thomas , Rose Silvia Isabelle , Goetz Katja , Steinhäuser Jost
Published: April 2022

Background

In many countries, the number of applicants to medical schools exceeds the number of available places. This offers the need, as well as the opportunity to medical schools to select those applicants most suitable for later work as a doctor. However, there is no generally accepted definition of a ‘good doctor’. Clinical competencies may serve as surrogates. The aim of this study was to compare medical students in Germany selected based either on their pre-university grade point average alone or based on the result of a university-specific selection procedure regarding their clinical competencies with an emphasis on family medicine in the later years of training.

Methods

We used the ‘Allgemeinarztbarometer Ausbildung’ (Undergraduate Family Medicine Barometer), an instrument developed to assess clinical competencies with an emphasis on family medicine, to compare students in the pre-university grade point average admission-quota and the university-specific selection procedure admission-quota in the fifth year of training. Students were judged by their supervising general practitioners after a two-week practical course. Competencies were rated on a five-point Likert-scale (1 = ‘totally agree’ i.e. the student is very competent to 5 = ‘totally disagree’ i.e. the student is not competent at all).

Results

We included 94 students (66% female). Students in the university-specific selection procedure quota (n = 80) showed better mean scores in every item of the Undergraduate Family Medicine Barometer. We found a statistically significant difference between the two groups for the item assessing communication skills (M [university-specific selection procedure quota] = 1.81, SD = 0.84 vs. M [pu-GPA quota] = 2.38, SD = 0.96; t[91] = -2.23, p = .03; medium effect size). Logistic regression revealed no statistically significant age or gender contribution.

Conclusions

Despite the small sample-size, our results indicate, that students selected via an university-specific selection procedure show better communicative competencies in the later years of training.
Cysteine-rich protein 2 deficiency attenuates angiotensin II-induced abdominal aortic aneurysm formation in mice
Authors: Chen Chung-Huang , Ho Hua-Hui , Jiang Wei-Cheng , Ao-Ieong Wai-Sam , Wang Jane , Orekhov Alexander N. , Sobenin Igor A. , Layne Matthew D. , Yet Shaw-Fang
Published: April 2022

Background

Abdominal aortic aneurysm (AAA) is a relatively common and often fatal condition. A major histopathological hallmark of AAA is the severe degeneration of aortic media with loss of vascular smooth muscle cells (VSMCs), which are the main source of extracellular matrix (ECM) proteins. VSMCs and ECM homeostasis are essential in maintaining structural integrity of the aorta. Cysteine-rich protein 2 (CRP2) is a VSMC-expressed protein; however, the role of CRP2 in AAA formation is unclear.

Methods

To investigate the function of CRP2 in AAA formation, mice deficient in Apoe (Apoe−/−) or both CRP2 (gene name Csrp2) and Apoe (Csrp2−/−Apoe−/−) were subjected to an angiotensin II (Ang II) infusion model of AAA formation. Aortas were harvested at different time points and histological analysis was performed. Primary VSMCs were generated from Apoe−/− and Csrp2−/−Apoe−/− mouse aortas for in vitro mechanistic studies.

Results

Loss of CRP2 attenuated Ang II-induced AAA incidence and severity, accompanied by preserved smooth muscle α-actin expression and reduced elastin degradation, matrix metalloproteinase 2 (MMP2) activity, deposition of collagen, particularly collagen III (Col III), aortic tensile strength, and blood pressure. CRP2 deficiency decreased the baseline MMP2 and Col III expression in VSMCs and mitigated Ang II-induced increases of MMP2 and Col III via blunting Erk1/2 signaling. Rescue experiments were performed by reintroducing CRP2 into Csrp2−/−Apoe−/− VSMCs restored Ang II-induced Erk1/2 activation, MMP2 expression and activity, and Col III levels.

Conclusions

Our results indicate that in response to Ang II stimulation, CRP2 deficiency maintains aortic VSMC density, ECM homeostasis, and structural integrity through Erk1/2–Col III and MMP2 axis and reduces AAA formation. Thus, targeting CRP2 provides a potential therapeutic strategy for AAA.
Prediction of programmed cell death protein 1 in hepatocellular carcinoma patients using radiomics analysis with radiofrequency-based ultrasound multifeature maps
Authors: Wang Qingmin , Dong Yi , Xiao Tianlei , Zhang Shiquan , Yu Jinhua , Li Leyin , Zhang Qi , Wang Yuanyuan , Xiao Yang , Wang Wenping
Published: April 2022

Background

This study explored the feasibility of radiofrequency (RF)-based radiomics analysis techniques for the preoperative prediction of programmed cell death protein 1 (PD-1) in patients with hepatocellular carcinoma (HCC).

Methods

The RF-based radiomics analysis method used ultrasound multifeature maps calculated from the RF signals of HCC patients, including direct energy attenuation (DEA) feature map, skewness of spectrum difference (SSD) feature map, and noncentrality parameter S of the Rician distribution (NRD) feature map. From each of the above ultrasound maps, 345 high-throughput radiomics features were extracted. Then, the useful radiomics features were selected by the sparse representation method and input into support vector machine (SVM) classifier for PD-1 prediction.

Results and conclusion

Among all the RF-based prediction models and the ultrasound grayscale comparative model, the RF-based model using all of the three ultrasound feature maps had the highest prediction accuracy (ACC) and area under the curve (AUC), which were 92.5% and 94.23%, respectively. The method proposed in this paper is effective for the meaningful feature extraction of RF signals and can effectively predict PD-1 in patients with HCC.
Carbonic anhydrase IX-targeted H-APBC nanosystem combined with phototherapy facilitates the efficacy of PI3K/mTOR inhibitor and resists HIF-1α-dependent tumor hypoxia adaptation
Authors: Liu Jie , Hu Xiaochun , Feng Lei , Lin Yun , Liang Shujing , Zhu Zhounan , Shi Shuo , Dong Chunyan
Published: April 2022

Background

Non-redundant properties such as hypoxia and acidosis promote tumor metabolic adaptation and limit anti-cancer therapies. The key to the adaptation of tumor cells to hypoxia is the transcriptional and stable expression of hypoxia-inducible factor-1 alpha (HIF-1α). The phosphorylation-activated tumorigenic signal PI3K/AKT/mTOR advances the production of downstream HIF-1α to adapt to tumor hypoxia. Studies have elucidated that acid favors inhibition of mTOR signal. Nonetheless, carbonic anhydrase IX (CAIX), overexpressed on membranes of hypoxia tumor cells with pH-regulatory effects, attenuates intracellular acidity, which is unfavorable for mTOR inhibition. Herein, a drug delivery nanoplatform equipped with dual PI3K/mTOR inhibitor Dactolisib (NVP-BEZ235, BEZ235) and CAIX inhibitor 4‐(2‐aminoethyl) benzene sulfonamide (ABS) was designed to mitigate hypoxic adaptation and improve breast cancer treatment.

Results

ABS and PEG-NH2 were successfully modified on the surface of hollow polydopamine (HPDA), while BEZ235 and Chlorin e6 (Ce6) were effectively loaded with the interior of HPDA to form HPDA-ABS/PEG-BEZ235/Ce6 (H-APBC) nanoparticles. The release of BEZ235 from H-APBC in acid microenvironment could mitigate PI3K/mTOR signal and resist HIF-1α-dependent tumor hypoxia adaptation. More importantly, ABS modified on the surface of H-APBC could augment intracellular acids and enhances the mTOR inhibition. The nanoplatform combined with phototherapy inhibited orthotopic breast cancer growth while reducing spontaneous lung metastasis, angiogenesis, based on altering the microenvironment adapted to hypoxia and extracellular acidosis.

Conclusion

Taken together, compared with free BEZ235 and ABS, the nanoplatform exhibited remarkable anti-tumor efficiency, reduced hypoxia adaptation, mitigated off-tumor toxicity of BEZ235 and solved the limited bioavailability of BEZ235 caused by weak solubility.

Graphical Abstract