bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructing the boundary between potent and ineffective siRNAs by MG-algorithm with C-features
Authors: Jia Xingang , Han Qiuhong , Lu Zuhong
Published: August 2022

Background

In siRNA based antiviral therapeutics, selection of potent siRNAs is an indispensable step, but these commonly used features are unable to construct the boundary between potent and ineffective siRNAs.

Results

Here, we select potent siRNAs by removing ineffective ones, where these conditions for removals are constructed by C-features of siRNAs, C-features are generated by MG-algorithm, Icc-cluster and the different combinations of some commonly used features, MG-algorithm and Icc-cluster are two different algorithms to search the nearest siRNA neighbors. For the ineffective siRNAs in test data, they are removed from test data by I-iteration, where I-iteration continually updates training data by adding these successively removed siRNAs. Furthermore, the efficacy of siRNAs of test data is predicted by their nearest neighbors of training data.

Conclusions

By siRNAs of Hencken dataset, results show that our algorithm removes almost ineffective siRNAs from test data, gives the clear boundary between potent and ineffective siRNAs, and accurately predicts the efficacy of siRNAs also. We suggest that our algorithm can provide new insights for selecting the potent siRNAs.
Bioinformatic analysis of PD-1 checkpoint blockade response in influenza infection
Authors: Ou Huilin , Chen Keda , Chen Linfang , Wu Hongcheng
Published: August 2022

Background

The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling pathway is significantly upregulated in influenza virus infection, which impairs the antiviral response. Blocking this signaling pathway may reduce the damage, lower the virus titer in lung tissue, and alleviate the symptoms of infection to promote recovery. In addition to the enhanced viral immune response, using of immune checkpoint inhibitors in influenza virus infection is controversial, the aim of this study was to identify the key factors and regulatory mechanisms in the PD-1 checkpoint blockade response microenvironment in influenza infection.

Methods

A BALB/c mouse model of influenza A/PR8(H1N1) infection was established then constructed, and whole-transcriptome sequencing including mRNAs, miRNAs (microRNAs), lncRNAs (long noncoding RNAs), and circRNAs (circular RNAs) of mice treated with PD-1 checkpoint blockade by antibody treatment and IgG2a isotype control before infection with A/PR8(H1N1) were performed. Subsequently, the differential expression of transcripts between these two groups was analyzed, followed by functional interaction prediction analysis to investigate gene-regulatory circuits.

Results

In total, 84 differentially expressed dif-mRNAs, 36 dif-miRNAs, 90 dif-lncRNAs and 22 dif-circRNAs were found in PD-1 antagonist treated A/PR8(H1N1) influenza-infected lungs compared with the controls (IgG2a isotype control treated before infection). In spleens between the above two groups, 45 dif-mRNAs, 36 dif-miRNAs, 57 dif-lncRNAs, and 24 dif-circRNAs were identified. Direct function enrichment analysis of dif-mRNAs and dif-miRNAs showed that these genes were mainly involved in myocardial damage related to viral infection, mitogen activated protein kinase (MAPK) signaling pathways, RAP1 (Ras-related protein 1) signaling pathway, and Axon guidance. Finally, 595 interaction pairs were obtained for the lungs and 462 interaction pairs for the spleens were obtained in the competing endogenous RNA (ceRNA) complex network, in which the downregulated mmu-miR-7043-3p and Vps39–204 were enriched significantly in PD-1 checkpoint blockade treated A/PR8(H1N1) infection group.

Conclusions

The present study provided a basis for the identification of potential pathways and hub genes that might be involved in the PD-1 checkpoint blockade response microenvironment in influenza infection.
Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy
Authors: Zhang Rui , Xu Xuan , Chen Xi , Hao Chunshu , Ji Zhenjun , Zuo Pengfei , Yang Mingming , Ma Genshan , Li Yongjun
Published: August 2022

Background

Hypertension-induced cardiac hypertrophy is one of the most common pre-conditions that accompanies heart failure. This study aimed to identify the key pathogenic genes in the disease process.

Methods

GSE18224 was re-analyzed and differentially expressed genes (DEGs) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Networks of transcription factor (TF)-mRNA, microRNA (miRNA)-mRNA and Protein-Protein interaction (PPI) were constructed, and a key module was further screened out from PPI network. GSE36074 dataset and our transverse aortic constriction (TAC) mouse model were used to validate gene expression in the module. Finally, the correlation between the genes and biomarkers of cardiac hypertrophy were evaluated.

Results

Totally, there were 348 DEGs in GSE18224, which were mainly enriched in biological processes including collagen fibril organization, cellular response to transforming growth factor-beta stimulus and were involved in ECM-receptor interaction and Oxytocin signaling pathway. There were 387 miRNAs targeted by 257 DEGs, while 177 TFs targeted 71 DEGs. The PPI network contained 222 nodes and 770 edges, with 18 genes screened out into the module. After validation, 8 genes, which were also significantly upregulated in the GSE36074 dataset, were selected from the 18 DEGs. 2 of the 8 DEGs, including Eln and Tgfb3 were significantly upregulated in our mouse model of myocardial hypertrophy. Finally, the expression of Eln and Tgfb3 were found to be positively correlated with the level of the disease biomarkers.

Conclusions

Upregulated key genes Eln and Tgfb3 were positively correlated with the severity of cardiac hypertrophy, which may provide potential therapeutic targets for the disease.
High-throughput transcriptome sequencing reveals the key stages of cardiovascular development in zebrafish embryos
Authors: Zhou Chune , Zhao Wei , Zhang Shuqiang , Ma Junguo , Sultan Yousef , Li Xiaoyu
Published: August 2022

Background

The cardiovascular developmental process is a tightly regulated network involving multiple genes. The current understanding of the molecular mechanism behind cardiovascular development is insufficient and requires further research.

Results

Transcriptome sequencing of three developmental stages in zebrafish embryos was performed and revealed three key cardiovascular developmental stages. Then, the differentially expressed genes (DEGs) involved in cardiovascular development were screened out. The three developmental stages were 18 (T1), 24 (T2), and 42 h post fertilization (hpf) (T3), and the three stages were confirmed by detecting differences in expression between cardiomyocyte and endothelial marker genes (cmlc2, fli1) using in situ hybridization, which represents the characteristics of cardiovascular development. Thousands of DEGs were identified using transcriptome analysis. Of them, 2605 DEGs were in T1-vs-T2, including 2003 up-regulated and 602 down-regulated genes, 6446 DEGs were in T1-vs-T3, consisting of 4608 up-regulated and 1838 down-regulated genes, and 3275 DEGs were in T2-vs-T3, including 2420 up-regulated and 855 down-regulated genes. There were 644 common DEGs and 167 common five-fold higher differentially expressed genes (HDEGs) identified, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Significant differences was observed in the levels of gene expression among different developmental stages in multiple GO terms and KEGG pathways, such as cell migration to the midline involved in heart development, cardiovascular system development, circulatory system process for biological processes of GO terms; and cardiac muscle contraction, adrenergic signaling in cardiomyocytes for KEGG pathways. These results demonstrated that these three stages were important period for the development of the cardiovascular system. Lastly, we used quantitative real-time PCR (qPCR) to validate the reliability of RNA-sequencing by selecting 21 DEGs.

Conclusions

These results demonstrated that these three stages represented the important periods for cardiovascular system development of zebrafish and some candidate genes was obtained and provided a solid foundation for additional functional studies of the DEGs.
A qualitative research study of primary care physicians’ views of telehealth in delivering postnatal care to women
Authors: Poon Zhimin , Tan Ngiap Chuan
Published: August 2022

Background

The postpartum period is a critical time for women to optimise their physical and mental health. Primary care physicians (PCP) often manage postpartum women in the community setting after uneventful births. However, women encounter difficulties accessing care before and after their conventional 6-week physical review. Telehealth-based interventional studies have demonstrated their successful applications in several areas of postpartum care but is not widely adopted. The study aimed to explore the PCPs’ views on their acceptability and perceived barriers of telehealth in delivering postpartum care to women in primary care.

Methods

Twenty-nine PCPs participated in eleven in-depth interviews and four focus group discussions for this qualitative study conducted in Singapore. The purposively sampled PCPs had varied demographic background and medical training. Two investigators independently coded the audited transcripts. Thematic content analysis was performed using the codes to identify issues in the pertaining to the perceived usefulness, ease of use and attitudes towards telehealth in postpartum care as described in the “Telehealth Acceptance Model” framework.

Results

Most PCPs perceived usefulness and ease of use of video consultation in delivering postpartum care. They recognised telehealth service to complement and support the current face-to-face postpartum care amidst the pandemic. However, training, leadership support, organizational infrastructure, healthcare financial policy and personal demographic profile influence their acceptance of a new care model for postnatal mothers.

Conclusion

Addressing the barriers and strengthening the facilitators will enhance PCPs’ acceptance and utilisation of the proposed hybrid (telehealth and in-person) postnatal care model for mothers.
Protocol for a randomized controlled trial of mindfulness-based stress reduction to improve attentional control in older adults (HealthyAgers trial)
Authors: Prakash Ruchika Shaurya , Fountain-Zaragoza Stephanie , Fisher Megan , Gbadeyan Oyetunde , Andridge Rebecca , Kiecolt-Glaser Janice , Manglani Heena R. , Duraney Elizabeth J. , Shankar Anita , McKenna Michael R. , Teng James , Phansikar Madhura , Canter Rosie
Published: August 2022

Background

Mindfulness meditation is a form of mind–body intervention that has increasing scientific support for its ability to reduce age-related declines in cognitive functioning, improve affective health, and strengthen the neural circuitry supporting improved cognitive and affective health. However, the majority of existent studies have been pilot investigations with small sample sizes, limited follow-up data, and a lack of attention to expectancy effects. Here, we present the study design of a Phase I/II, efficacy trial—HealthyAgers trial—that examines the benefits of a manualized mindfulness-based stress reduction program in improving attentional control and reducing mind-wandering in older adults.

Methods

One hundred fifty older adults (ages 65–85 years) will be randomized into one of two groups: an eight-week mindfulness program or an eight-week, placebo-controlled, lifestyle education program. Behavioral and neuroimaging assessments are conducted before and after the training. Participants are then invited to booster sessions once every three months for a period of 12 months with post-intervention follow-up assessments conducted at 6-months and 12-months. The primary outcomes for the study are behavioral measures of attentional control and mind-wandering. Additional, secondary outcomes include network strength in an a priori defined neuromarker of attentional control, fluid and everyday cognition, emotion regulation strategy use, and markers of inflammation.

Discussion

This study will establish the efficacy of a group-based, low-cost mind–body intervention for the inter-related facets of attentional control and mind-wandering in older adults. Strengths of this study include a well-designed, placebo-controlled comparison group, use of web/mobile application to track study adherence, and longitudinal follow-up.

Trial registration

Clinicaltrials.gov (#NCT03626532). Registered August 4, 2018.
Malnutrition-related conditions and interventions in US state/territorial Older Americans Act aging plans
Authors: Arensberg Mary Beth , Gahche Jaime J. , Dwyer Johanna T. , Mosey Adam , Terzaghi Damon
Published: August 2022

Background

Factors that decrease independence and increase morbidity must be reduced to improve the nutrition, health, and other challenges confronting older adults. In the United States (US), the Older Americans Act (OAA) requires each state/territory develop multi-year aging plans for spending federal funds that foster healthy aging (including support of congregate/home delivered meals programs) and separately requires grant applications for nutrition service programs supporting older Native Americans. Malnutrition (particularly protein-energy undernutrition), sarcopenia, frailty, and obesity can all result in disability but are potentially changeable. The study goal was to collect baseline information on mentions of these malnutrition-related conditions and interventions that address them in US state/territorial OAA program multi-year aging plans.

Methods

OAA program multi-year aging plans available on the ADvancing States website in February 2021 (n = 52) were searched for number of mentions of defined nutrition terms including malnutrition, sarcopenia, frailty, obesity, and whether terms were included in plans’ goals/objectives, strategies/actions, or solely in the narrative.

Results

Malnutrition, sarcopenia, frailty, and obesity were mentioned infrequently in US state/territorial OAA program multi-year aging plans. 33% of plans mentioned malnutrition but only 8% as goals/objectives and 15% as strategies/actions. 62% mentioned frailty; 6% (goals/objectives), 15% (strategies/actions). None mentioned sarcopenia whereas in contrast, 21% mentioned obesity; 2% (goals/objectives), 2% (strategies/actions). Nutrition intervention mentions were nearly nil. There were no significant differences in frequency of term mentions by US region or by states with higher percentages of older adults or obese adults.

Conclusions

Clearly specifying definitions of malnutrition-related conditions and incorporating them into measurable goals/objectives, defined strategies/actions, and outcomes may help improve future state/territorial OAA program multi-year aging plans to better support healthy aging.
Hospital nursing factors associated with decreased odds of mortality in older adult medicare surgical patients with depression
Authors: Kumar Aparna , Sloane Douglas , Aiken Linda , McHugh Matthew
Published: August 2022

Background

Depression is common, costly, and has deleterious effects in older adult surgical patients. Little research exists examining older adult surgical patient outcomes and depression and the potential for nursing factors to affect these outcomes. The purpose of this study was to determine the relationship between hospital nursing resources, 30-day mortality; and the impact of depression on this relationship.

Methods

This was a retrospective cohort study employing a national nurse survey, hospital data, and Medicare claims data from 2006–2007. The sample included: 296,561 older adult patients, aged 65–90, who had general, orthopedic, or vascular surgery in acute care general hospitals from 2006–2007, 533 hospitals and 24,837 nurses. Random effects models were used to analyze the association between depression, hospital nursing resources, and mortality.

Results

Every added patient per nurse was associated with a 4% increase in the risk-adjusted odds of mortality in patients with depression (p < 0.05). Among all patients, every 10% increase in the proportion of bachelor’s prepared nurses was associated with a 4% decrease in the odds of mortality (p < 0.001) and a one standard deviation increase in the work environment was associated with a 5% decrease in the odds of mortality (p < 0.05).

Conclusions

For older adult patients hospitalized for surgery, the risk of mortality is associated with higher patient to nurse ratio, lower proportion of BSN prepared nurses in the hospital, and worse hospital work environment. Addressing the mental health care needs of older adults in the general care hospital setting is critical to ensuring positive outcomes after surgery. Hospital protocols to lower the risk of surgical mortality in older adults with and without depression could include improving nurse resources.
What contributes most to the SPPB and its subscores in hospitalized geriatric patients: an ICF model-based approach
Authors: Kudelka Jennifer , Geritz Johanna , Welzel Julius , Hildesheim Hanna , Maetzler Corina , Emmert Kirsten , Niemann Katharina , Hobert Markus A. , Pilotto Andrea , Bergmann Philipp , Maetzler Walter
Published: August 2022

Background

Mobility deficits are highly prevalent among geriatric patients and have serious impact on quality of life, hospitalizations, and mortality. This study aims to capture predictors of mobility deficits in hospitalized geriatric patients using the International Classification of Functioning, Disability and Health (ICF) model as a framework.

Methods

Data were obtained from n = 397 patients (78 ± 7 years, 15 ± 7 ICD-11 diagnoses) on a geriatric ward at time of admission. Mobility was assessed using the Short Physical Performance Battery (SPPB) total score and gait, static balance and transfer subscores. Parameters from an extensive assessment including medical history, neuropsychological and motor examination, and questionnaires were assigned to the five components of the ICF model. Spearman’s Correlation and multiple linear regression analyses were calculated to identify predictors for the SPPB total score and subscores.

Results

Use of walking aid, fear of falling (FOF, but not occurrence of previous falls), participation in society, ADL and grip strength were strongly associated with the SPPB total score and all subscores (p < .001). FOF and grip strength were significant predictors for the SPPB total score as well as for gait and transfer subscores. FOF also showed a strong association with the static balance subscore. The clinical parameters of the ICF model could only partially explain the variance in the SPPB total score (24%) and subscores (12–23%), with no parameter from the activities and participation component being significantly predictive.

Conclusions

FOF and reduced grip strength are associated with mobility deficits in a hospitalized geriatric cohort. Further research should focus on interventions to reduce FOF and increase muscle strength in geriatric patients. Moreover, there is a need for ICF-based assessments instruments (especially in the activities and participation components) that allow a holistic view on mobility and further daily life-relevant health aspects in geriatric patients.
Prevalence of inappropriate use behaviors of antibiotics and related factors among chinese antibiotic users: an online cross-sectional survey
Authors: Yin Xiaoxv , Gong Yanhong , Sun Na , Li Dandan , Wu Jianxiong , Wang Jing , Qiu Lei , Li Hui
Published: August 2022

Background

Inappropriate use of antibiotics could have a profound negative impact on individual and community. This study aimed to assess the prevalence of inappropriate use behaviors of antibiotics in Chinese antibiotic users and explored their related factors.

Methods

A cross-sectional survey was conducted from July 1, 2018 to September 30, 2018. A structured questionnaire was widely distributed on the online survey platform (Questionnaire Star, https://www.wjx.cn) and was used to collect data from respondents in China on demographic and sociological characteristics, antibiotic use and related knowledge. Main outcomes included self-medication with antibiotics (SMA), self-storage with antibiotics (SSA), and non-adherence to antibiotic treatment (NAAT). Logistic regression was used to identify the related factors of above inappropriate use behaviors of antibiotics.

Results

Of the 15,526 participants, 37.1% reported SMA in the past 6 months, 67.9% reported SSA in the past 6 months, and 48.3%, 15.2%, 25.5% and 78.0% of respondents said that they had missed antibiotics, increased antibiotic dosage, decreased antibiotic dosage, and discontinued antibiotics once symptoms disappear, respectively. Overall, 53.3% reported NAAT during this period. After adjusting for other variables, multivariate logistic regression analyses showed that those aged 30–44 years old, with higher levels of education, poorer status of self-perceived health, or lower levels of antibiotic knowledge were more likely to have these inappropriate use behaviors of SMA, SSA, and NAAT (P < 0.05).

Conclusions

The prevalence of SMA, SSA, and NAAT is high in China. Developing a nationwide action plan for the rational use of antibiotics among publics, including national media publicity, online and offline health education, and medication guidance from general practitioners, is urgently needed.
Metrics of sexual behavior stigma among cisgender men who have sex with men in Mexico: exploratory and confirmatory factor analyses
Authors: Wiginton John Mark , Murray Sarah M. , Algarin Angel B. , Baral Stefan D. , Sanchez Travis H. , Smith Laramie R.
Published: August 2022

Cisgender gay, bisexual, and other men who have sex with men (MSM) in Mexico experience disparities in sexual health outcomes, perhaps most notably in HIV prevalence, HIV testing and status awareness, and condom use. Sexual behavior stigma, underpinned by socio-structural factors specific to Mexico (e.g., machismo), uniquely shapes these sexual health disparities. However, few reliable, valid measures are available to document, track, and ultimately mitigate sexual behavior stigma in this context. Exploratory and confirmatory factor analyses were performed on responses to a 13-item sexual behavior stigma scale from 15,681 MSM recruited online across Mexico. Associations with extracted factors were tested to assess construct validity. Three subscales were identified in exploratory factor analysis and validated in confirmatory factor analysis: “stigma from family and friends” (α = 0.65), “anticipated healthcare stigma” (α = 0.84), and “general social stigma” (α = 0.70). External construct validity was indicated through each subscale’s strong association (all p < 0.001) with perceived community intolerance of MSM and perceived community discrimination toward people living with HIV. These subscales show promise as reliable, valid measures for assessing sexual behavior stigma among MSM in Mexico, and as tools for documenting and tracking sexual behavior stigma trends, comparing regional burdens of sexual behavior stigma, and tracking the progress of stigma-mitigation interventions among MSM in Mexico. Future research is needed to understand the extent to which each subscale is differentially associated with sexual (and other) health outcomes, which can inform the development and implementation of uniquely tailored stigma-mitigation, HIV-prevention, HIV-care, and other needed interventions for MSM in Mexico.
Prevalence of frailty and cognitive impairment in older transplant candidates - a preview to the Kidney Transplantation in Older People (KTOP): impact of frailty on outcomes study
Authors: Thind Amarpreet K. , Rule Annabel , Goodall Dawn , Levy Shuli , Brice Sarah , Dor Frank J. M. F. , Evans Nicola , Ospalla David , Thomas Nicola , Wellsted David , Johansson Lina , Willicombe Michelle , Brown Edwina A.
Published: August 2022

Background

Kidney transplantation in older people has increased, however older transplant recipients experience mixed outcomes that invariably impacts on their quality of life. The increased vulnerability of older end stage kidney disease patients to frailty and cognitive impairment, may partially explain the differences in outcomes observed.

The Kidney Transplantation in Older People (KTOP): impact of frailty on clinical outcomes study is an active clinical study aiming to explore the experience of older people waiting for and undergoing transplantation. In this manuscript we present the study protocol, the study cohort, and the prevalence of frailty and cognitive impairment identified at recruitment.

Methods

The KTOP study is a single centre, prospective, mixed methods, observational study. Recruitment began in October 2019. All patients aged 60 or above either active on the deceased donor waitlist or undergoing live donor transplantation were eligible for recruitment. Recruited participants completed a series of questionnaires assessing frailty, cognition, and quality of life, which are repeated at defined time points whilst on the waitlist and post-transplant. Clinical data was concurrently collected. Any participants identified as frail or vulnerable were also eligible for enrolment into the qualitative sub-study.

Results

Two hundred eight participants have been recruited (age 60–78). Baseline Montreal Cognitive Assessments were available for 173 participants, with 63 (36.4%) participants identified as having scores below normal (score < 26). Edmonton Frail Scale assessments were available for 184 participants, with 29 participants (15.8%) identified as frail (score ≥ 8), and a further 37 participants (20.1%) identified as being vulnerable (score 6–7).

Conclusion

In the KTOP study cohort we have identified a prevalence of 36.4% of participants with MoCA scores suggestive of cognitive impairment, and a prevalence of frailty of 15.8% at recruitment. A further 20.1% were vulnerable. As formal testing for cognition and frailty is not routinely incorporated into the work up of older people across many units, the presence and significance of these conditions is likely not known. Ultimately the KTOP study will report on how these parameters evolve over time and following a transplant, and describe their impact on quality of life and clinical outcomes.
Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer
Authors: Gondhowiardjo Soehartati A. , Adham Marlinda , Rachmadi Lisnawati , Atmakusuma Tubagus Djumhana , Tobing Demak Lumban , Auzan Mahesa , Hariyanto Agustinus Darmadi , Sulaeman Dede , Permata Tiara Bunga Mayang , Handoko
Published: August 2022

Introduction

EBV infection in nasopharyngeal cancer ensued in latent infection mode. In this latent infection various EBV oncoproteins such as EBNA1 and LMP1 was expressed. EBV oncoproteins could theoretically recruit immune cells, which might help to control cancer. Therefore, this study was aimed to elucidate the association with EBV oncoproteins (EBNA1 and LMP1), immune markers (CD4, CD8, and FOXP3) from nasopharyngeal cancer microenvironment with tumor progression.

Method

Nasopharyngeal biopsy was obtained from patients suspected to have nasopharyngeal cancer. Those samples with microscopically confirmed nasopharyngeal cancer were tested for EBNA1, LMP1, CD4, CD8, and FOXP3 concentration with ELISA, then verified with IHC. Each patient tumor volume was assessed for primary nasopharyngeal tumor volume (GTVp) and neck nodal metastases tumor volume (GTVn). Correlation test with Spearman correlation and scatterplot were carried out.

Result

Total 23 samples with nasopharyngeal cancer were analyzed. There was moderate correlation (ρ = 0.45; p value = 0.032) between LMP1 and GTVp. There was strong correlation (ρ = 0.81; p value < 0.001) between CD8 and GTVp. There was also moderate correlation (ρ = 0.6; p value = 0.002) between FOXP3 and GTVp. The CD8 concentration has moderate correlation with both EBNA1 (ρ = 0.46; p value = 0.026) and LMP1 (ρ = 0.47; p value = 0.023). While FOXP3 has moderate correlation with only LMP1 (ρ = 0.58; p value = 0.004). No correlation was found between all the markers tested here with GTVn.

Discussion

We found larger primary nasopharyngeal tumor was associated with higher CD8 marker. This was thought due to the presence of abundance CD8 T cells in the nasopharynx, but those abundance CD8 T cells were suspected to be dysfunctional. The nasopharyngeal cancer was also known to upregulate chemokines that could recruit T regulatory FOXP3 cells. Furthermore, T regulatory FOXP3 cells differentiation was induced through several pathways which was triggered by EBNA1. The correlation found in this study could guide further study to understand nasopharyngeal carcinogenesis and the relationship with our immune system.
Patient stratification based on urea cycle metabolism for exploration of combination immunotherapy in colon cancer
Authors: Zhao Zirui , Liu Haohan , Fang Deliang , Zhou Xingyu , Zhao Shaoji , Zhang Chaoyue , Ye Jinning , Xu Jianbo
Published: August 2022

Background

Owing to the low ratio of patients benefitting from immunotherapy, patient stratification becomes necessary. An accurate patient stratification contributes to therapy for different tumor types. Therefore, this study aimed to subdivide colon cancer patients for improved combination immunotherapy.

Methods

We characterized the patients based on urea cycle metabolism, performed a consensus clustering analysis and constructed a risk model in the cancer genome atlas cohort. Colon cancer patients were further categorized into two tags: clusters, and risk groups, for the exploration of combination immunotherapy. In addition to external validation in the Gene Expression Omnibus datasets, several images of immunohistochemistry were used for further validation.

Results

Patient characterization based on urea cycle metabolism was related to immune infiltration. An analysis of consensus clustering and immune infiltration generated a cluster distribution and identified patients in cluster 1 with high immune infiltration levels as hot tumors for immunotherapy. A risk model of seven genes was constructed to subdivide the patients into low- and high-risk groups. Validation was performed using a cohort of 731 colon cancer patients. Patients in cluster 1 had a higher immunophenoscore (IPS) in immune checkpoint inhibitor therapy, and those other risk groups displayed varying sensitivities to potential combination immunotherapeutic agents. Finally, we subdivided the colon cancer patients into four groups to explore combination immunotherapy. Immunohistochemistry analysis showed that protein expression of two genes were upregulated while that of other two genes were downregulated or undetected in cancerous colon tissues.

Conclusion

Using subdivision to combine chemotherapy with immunotherapy would not only change the dilemma of immunotherapy in not hot tumors, but also promote the proposition of more rational personalized therapy strategies in future.
Short stature and melanocytic nevi in a girl with ARID1B-related Coffin-Siris syndrome: a case report
Authors: Tao Dong-Ying , Niu Huan-Hong , Zhang Jing-Jing , Zhang Hui-Qin , Zeng Ming-Hua , Cheng Sheng-Quan
Published: August 2022

Background

Coffin-Siris syndrome (CSS) is a rare autosomal dominant disorder characterized by intellectual disability, developmental delay, and characteristic facial features. Few patients with cutaneous phenotype in this rare syndrome have been reported.

Case presentation

Herein, we describe a 12-year-old Chinese girl diagnosed with CSS, who was referred to our hospital because of intellectual disability and short stature. Prominent characteristics of the cutaneous system were observed: (1) A congenital giant nevus from the left frontal and temporal regions to the entire left scalp; and (2) multiple melanocytic nevi on the face and trunk. Whole exome sequencing revealed a novel heterozygous variant in the ARID1B gene. Recombinant human growth hormone (rhGH) was given for short stature, and resulted in significantly improved height. No enlargement or malignant transformation of nevi occurred within 4 years of follow-up.

Conclusion

The symptoms in cutaneous system is noteworthy,which may be a neglected phenotype in CSS.The therapeutic response of growth hormone is effective in this patient and no tumor related signs were found.
Relationship between daily swallowing frequency and pneumonia in patients with severe cerebral palsy
Authors: Tanaka Nobukazu , Nohara Kanji , Uota Chisato , Fujii Nami , Obana Aya , Tanaka Katsuji , Sakai Takayoshi
Published: August 2022

Background

Aspiration pneumonia is a major complication that occurs in patients with severe cerebral palsy and is associated with their survival prognosis, necessitating appropriate assessment and response. We focused on swallowing frequency as an index of daily swallowing function due to the difficulty in evaluating the risk of pneumonia. The swallowing motion protects the airway by safely directing the food, saliva, and secretions accumulated in the pharynx into the esophagus to prevent aspiration and entry into the trachea. Thus, swallowing frequency may be correlated with the incidence of pneumonia. In this study, we aimed to investigate the relationship between swallowing frequency and history of pneumonia in patients with severe cerebral palsy.

Methods

Fifty-seven patients with cerebral palsy were included in this study. Swallowing frequency was measured three times for each patient on separate days, and the reproducibility was examined by calculating the intraclass correlation coefficient. Further, the relationship between swallowing frequency and history of pneumonia was investigated using multivariate logistic regression analysis.

Results

While swallowing frequency differed between participants, it was constant within individuals (intraclass correlation coefficient: 0.941). Furthermore, the swallowing frequencies per hour were 12.2 ± 12.2 and 27.0 ± 20.4 in the patient groups with and without a history of pneumonia, respectively (P < 0.001). Swallowing frequency (odds ratio: 10.489, 95% confidence interval: 2.706–40.663,P = 0.001) was significantly associated with the incidence of pneumonia in the previous year.

Conclusions

Swallowing frequency could be used as an index for assessing the risk of dysphagia and pneumonia in patients with severe cerebral palsy.
Effectiveness and implementation success of a co-produced physical activity referral scheme in Germany: study protocol of a pragmatic cluster randomised trial
Authors: Weissenfels Anja , Klamroth Sarah , Carl Johannes , Naber Inga , Mino Eriselda , Geidl Wolfgang , Gelius Peter , Abu-Omar Karim , Pfeifer Klaus
Published: August 2022

Background

While effective physical activity referral schemes (PARSs) and related structures for promoting physical activity (PA) already exist in several countries, in Germany, PARSs have not yet been implemented systematically and nationwide. Through a co-production approach with relevant actors in the German healthcare system, a PARS was developed, and an implementation plan was created (e.g. financing). This study protocol aims to evaluate the developed PARS for people with non-communicable diseases (NCDs) in Germany regarding its potential effectiveness and implementation success.

Methods

To evaluate the effectiveness and implementation success of the PARS, we will apply a pragmatic cluster-randomised controlled trial (cRCT) in Hybrid II design by comparing two intervention groups (PARS vs PA advice [PAA]). The trial will take place in the Nürnberg metropolitan region, with 24 physician practices recruiting 567 people with NCDs. Both groups will receive brief PA advice from a physician to initially increase the participants’ motivation to change their activity level. Subsequently, the PARS group will be given individualised support from an exercise professional to increase their PA levels and be transferred to local exercise opportunities. In contrast, participants in the PAA group will receive only the brief PA advice as well as information and an overview of regional PA offerings to become more active at their own initiative. After 12 and 24 weeks, changes in moderate to vigorous PA and in physical activity-related health competence (movement competence, control competence, self-regulation competence) will be measured as primary outcomes. Secondary outcomes will include changes in quality of life. To measure implementation success, we refer to the RE-AIM framework and draw on patient documentation, interviews, focus groups and surveys of the participating actors (physicians, exercise professionals).

Discussion

Through a between-group comparison, we will investigate whether additional individual support by an exercise professional compared to brief PA advice alone leads to higher PA levels in people with NCDs. The acceptance and feasibility of both interventions in routine care in the German healthcare system will also be evaluated.

Trial registration

ClinicalTrials.gov, NCT04947787. Registered 01 June 2021.
Improving access to public physical activity events for disadvantaged communities in Australia
Authors: Smith Janette L. , Reece Lindsey J. , Rose Catriona L. , Owen Katherine B.
Published: August 2022

Background

Physical activity has numerous health benefits, but participation is lower in disadvantaged communities. ‘parkrun’ overcomes one of the main barriers for disadvantaged communities, the cost of activities, by providing a free, regular community-based physical activity event for walkers, runners and volunteers. This study assesses equity of access (in terms of distance to the nearest parkrun) stratified by socioeconomic deprivation, and identifies the optimal location for 100 new events to increase equity of access.

Methods

We combined information about population location and socioeconomic deprivation, with information about the location of 403 existing parkrun events, to assess the current level of access by deprivation quintile. We then used a two-step location-allocation analysis (minimising the sum of deprivation-weighted distances) to identify optimal regions, then optimal towns within those regions, as the ideal locations for 100 new parkrun events.

Results

Currently, 63.1% of the Australian population lives within 5 km of an event, and the average distance to an event is 14.5 km. A socioeconomic gradient exists, with the most deprived communities having the largest average distance to an event (27.0 km), and the least deprived communities having the best access (living an average 6.6 km from an event). Access improves considerably after the introduction of new event locations with around 68% of the population residing within 5 km of an event, and the average distance to the nearest event approximately 8 km. Most importantly, the improvement in access will be greatest for the most deprived communities (now an average 11 km from an event).

Conclusions

There is a socioeconomic gradient in access to parkrun events. Strategic selection of new parkrun locations will improve equity of access to community physical activity events, and could contribute to enabling greater participation in physical activity by disadvantaged communities.
Improving CT-guided transthoracic biopsy diagnostic yield of lung masses using intraprocedural CT and prior PET/CT fusion imaging
Authors: Lin Yue , Xu Yanyan , Lin Jie , Fu Liping , Sun Hongliang , Huang Zhenguo , Ooi Bee Yen , Xie Sheng
Published: August 2022

Objective

The purpose of this study was to evaluate the usefulness of intraprocedural CT and prior PET/CT fusion imaging in improving the diagnostic yield of CT-guided transthoracic core-needle biopsy (CNB) in lung masses.

Methods

In total, 145 subjects with lung masses suspicious for malignancy underwent image-guided transthoracic CNB. According to imaging modality the subjects were divided into two groups. PET/CT images obtained no more than 14 days before the biopsy were integrated with intraprocedural CT images. The integrated or fused images were then used to plan the puncture sites. The clinical characteristics, diagnostic yield of CNB, diagnostic accuracy rate, procedure-related complications and procedure duration were recorded and compared between the two groups. Final clinical diagnosis was determined by surgical pathology or at least 6-months follow-up. The diagnostic accuracy of CNB was obtained by comparing with final clinical diagnosis.

Results

145 subjects underwent CNB with adequate samples, including 76 in fusion imaging group and 69 in routine group. The overall diagnostic yield and diagnostic accuracy rate were 80.3% (53/66), 82.9% (63/76) for fusion imaging group, 70.7% (41/58), 75.4% (52/69) for routine group, respectively. In addition, the diagnostic yield for malignancy in fusion imaging group (98.1%, 52/53) was higher than that in routine group (81.3%, 39/48). No serious procedure-related complications occurred in both two groups.

Conclusion

CNB with prior PET/CT fusion imaging is particularly helpful in improving diagnostic yield and accurate rate of biopsy in lung masses, especially in heterogeneous ones, thus providing greater potential benefit for patients.
Cervical spine and muscle adaptation after spaceflight and relationship to herniation risk: protocol from ‘Cervical in Space’ trial
Authors: Belavy Daniel L. , Armbrecht Gabriele , Albracht Kirsten , Brisby Helena , Falla Deborah , Scheuring Richard , Sovelius Roope , Wilke Hans-Joachim , Rennerfelt Kajsa , Martinez-Valdes Eduardo , Arvanitidis Michail , Goell Fabian , Braunstein Bjoern , Kaczorowski Svenja , Karner Vera , Arora Nitin Kumar
Published: August 2022

Background

Astronauts have a higher risk of cervical intervertebral disc herniation. Several mechanisms have been attributed as causative factors for this increased risk. However, most of the previous studies have examined potential causal factors for lumbar intervertebral disc herniation only. Hence, we aim to conduct a study to identify the various changes in the cervical spine that lead to an increased risk of cervical disc herniation after spaceflight.

Methods

A cohort study with astronauts will be conducted. The data collection will involve four main components: a) Magnetic resonance imaging (MRI); b) cervical 3D kinematics; c) an Integrated Protocol consisting of maximal and submaximal voluntary contractions of the neck muscles, endurance testing of the neck muscles, neck muscle fatigue testing and questionnaires; and d) dual energy X-ray absorptiometry (DXA) examination. Measurements will be conducted at several time points before and after astronauts visit the International Space Station. The main outcomes of interest are adaptations in the cervical discs, muscles and bones.

Discussion

Astronauts are at higher risk of cervical disc herniation, but contributing factors remain unclear. The results of this study will inform future preventive measures for astronauts and will also contribute to the understanding of intervertebral disc herniation risk in the cervical spine for people on Earth. In addition, we anticipate deeper insight into the aetiology of neck pain with this research project.

Trial registration

German Clinical Trials Register, DRKS00026777. Registered on 08 October 2021.
Genetic variants of interleukin 1B and 6 are associated with clinical outcome of surgically treated lumbar degenerative disc disease
Authors: Biczo Adam , Bereczki Ferenc , Koch Kristóf , Varga Peter Pal ,   the Genodisc Consortium, Urban Jill , Fairbank Jeremy , Heywood Chris , Sivan Sarit , Roberts Sally , Neidlinger-Wilke Corneia , Kaprio Jaakko , Battie Michele Crites , Kletsas Dimitris , Ito Keita , Huyghe Jaques , Brayda-Bruno Marco , Velikonja Nevenka Kregar , Lazary Aron
Published: August 2022

Background

Successfully surgically treating degenerative disc diseases can be challenging to the spine surgeons, the long-term outcome relies on both the physical and mental status of the patient before and after treatment. Numerous studies underlined the role of inflammatory cytokines – like interleukin 1B and 6 – in the development of chronic diseases such as failed back surgery syndrome (FBSS) and major depressive disorder (MDD) which alter the outcome after spinal surgery. Our aim was to evaluate the associations of IL6 and IL1B gene polymorphisms with the long-term outcome of degenerative lumbar spine surgeries.

Methods

An international genetical database (GENODISC) was combined with our institute’s clinical database to create a large pool with long term follow up data. Altogether 431 patient’s data were analysed. Patient reported outcome measures and surgical outcome was investigated in association with IL1B and IL6 SNPs with the help of ‘SNPassoc’ R genome wide association package.

Results

Interleukin 1B variants analysis confirmed association with improvement of pain after surgery on individual SNP level and on haplotype level, moreover relationship with patient reported outcome and preoperative level of depression was found on individual SNP level. IL6 variants were associated with preoperative depression, somatization and with subsequent surgery.

Conclusion

Understanding the complexity of spinal surgery patients’ long-term well-being is crucial in effectively treating chronic debilitating somatic diseases and the associated mental illnesses. Further studies should investigate more comprehensively the linkage of chronic physical and mental illnesses focusing on their simultaneous treatment.
Validation of the Musculoskeletal Health Questionnaire in a general population sample: a cross-sectional online survey in Hungary
Authors: Hölgyesi Áron , Poór Gyula , Baji Petra , Zrubka Zsombor , Farkas Miklós , Dobos Ágota , Gulácsi László , Kovács Levente , Péntek Márta
Published: August 2022

Background

The Versus Arthritis Musculoskeletal Health Questionnaire (MSK-HQ) measures symptom severity and health-related quality of life (HRQoL) of people with musculoskeletal (MSK) conditions. We aimed to test the psychometric properties of the MSK-HQ among the general adult population and identify the determinants of MSK-HQ states. In addition, we aimed to explore the relationship between MSK-HQ and standard well-being measurement tools.

Methods

The translation proccess of the MSK-HQ into Hungarian followed the standard methods provided by the developer. A cross-sectional online survey was performed in Hungary involving a population normative sample (N = 2004, women: 53.1%; mean age: 48.3, SD = 16.6 years). Socio-demographic characteristics and self-reported MSK disorders were recorded. Alongside the MSK-HQ, standard measures of HRQoL (EQ-5D-5L), physical functioning (HAQ-DI) and well-being (ICECAP-A/O, WHO-5, Happiness VAS) were applied. Clinical and convergent validity were assessed by subgroup comparisons (Mann–Whitney-U and Kruskal–Wallis tests) and Spearman’s rank correlations. Internal consistency was assessed by Cronbach’s alpha. Test–retest reliability (N = 50) was evaluated by intraclass correlation coefficient (ICC). Predictors of MSK-HQ were analysed by ordinary least square multiple regressions.

Results

The mean MSK-HQ index score was 44.1 (SD = 9.9). MSK-HQ scores were significantly lower in subgroups with self-reported MSK disorders. Correlations were strong between MSK-HQ and EQ-5D-5L (0.788), EQ VAS (0.644) and HAQ-DI (-0.698) and moderate with the well-being measures (p < 0.05). Cronbach’s alpha was 0.924 and ICC was 0.936 (p < 0.05). Being a man, living in the capital, having higher income and education were positively associated with MSK-HQ scores.

Conclusions

This is the first study to prove the validity and reliability of the MSK-HQ among the general public. The impact of socio-demographic characteristics on MSK-HQ scores deserves consideration in clinical studies.