bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic patient-reported outcomes and machine learning in predicting immune-related adverse events of immune checkpoint inhibitor therapies
Authors: Iivanainen Sanna , Ekstrom Jussi , Virtanen Henri , Kataja Vesa V. , Koivunen Jussi P.
Published: June 2021

Background

Immune-checkpoint inhibitors (ICIs) have introduced novel immune-related adverse events (irAEs), arising from various organ systems without strong timely dependency on therapy dosing. Early detection of irAEs could result in improved toxicity profile and quality of life. Symptom data collected by electronic (e) patient-reported outcomes (PRO) could be used as an input for machine learning (ML) based prediction models for the early detection of irAEs.

Methods

The utilized dataset consisted of two data sources. The first dataset consisted of 820 completed symptom questionnaires from 34 ICI treated advanced cancer patients, including 18 monitored symptoms collected using the Kaiku Health digital platform. The second dataset included prospectively collected irAE data, Common Terminology Criteria for Adverse Events (CTCAE) class, and the severity of 26 irAEs. The ML models were built using extreme gradient boosting algorithms. The first model was trained to detect the presence and the second the onset of irAEs.

Results

The model trained to predict the presence of irAEs had an excellent performance based on four metrics: accuracy score 0.97, Area Under the Curve (AUC) value 0.99, F1-score 0.94 and Matthew’s correlation coefficient (MCC) 0.92. The prediction of the irAE onset was more difficult with accuracy score 0.96, AUC value 0.93, F1-score 0.66 and MCC 0.64 but the model performance was still at a good level.

Conclusion

The current study suggests that ML based prediction models, using ePRO data as an input, can predict the presence and onset of irAEs with a high accuracy, indicating that ePRO follow-up with ML algorithms could facilitate the detection of irAEs in ICI-treated cancer patients. The results should be validated with a larger dataset.

Trial registration Clinical Trials Register (NCT3928938), registration date the 26th of April, 2019
Attitudes of nursing faculty members toward technology and e-learning in Lebanon
Authors: Nsouli Rona , Vlachopoulos Dimitrios
Published: June 2021

Background

Our transition to an “information society” means that Information and Communication Technology (ICT) has become integral to our lives. ICT has also become an essential aspect of medical institutions and healthcare settings. Healthcare professionals, especially nurses are required to use ICT in their daily work. In Lebanon, however, due to political factors, many universities have not introduced technology or any form of ICT in their curricula. Institutions of higher education do use technology in various ways, however, successful incorporation of ICT in education requires acceptance by instructors who are expected to use ICT in teaching practices. Although international findings reveal that ICT should be used in nursing education, some faculty members experience difficulty integrating it.

Method

A mixed methodological research approach was used to investigate the attitudes of nursing teaching staff toward the use of ICT in nursing education.

Results

Our findings revealed three categories of faculty with differing attitudes to the use of ICT in teaching and learning: pioneers, faculty members who have developed positive attitudes toward ICT usage; followers, faculty members with neutral attitudes; and resisters, faculty members with negative attitudes.

Conclusions

Identification of the nursing faculty members’ attitude toward ICT and the challenges faced by them contributes to the integration of ICT into nursing curricula and further development of educational practices.
A qualitative study on patients’ and their support persons’ preferences for receiving one longer consultation or two shorter consultations when being informed about allogeneic hematopoietic stem cell transplantation
Authors: Herrmann Anne , Holler Ernst , Edinger Matthias , Eickmann Sascha , Wolff Daniel
Published: June 2021

Background

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment option for many patients with hematological disorders but it includes a significant risk of mortality and long-term morbidity. Many patients and their support persons feel overwhelmed when being informed about alloHSCT and may benefit from improvements in consultation style and timing.

Aims

To explore, qualitatively, in a sample of hematological cancer patients and their support persons, their preferences for receiving one longer consultation or two shorter consultations when being informed about alloHSCT. Participants’ perceptions of when and how different consultation styles should be offered were also examined.

Methods

Semi-structured face-to-face and phone interviews were conducted. A purposeful sampling frame was used. Data were analysed using framework analysis.

Results

Twenty patients and 13 support persons were recruited (consent rate: 96%, response rate: 91%). Most patients (60%) and support persons (62%) preferred two shorter consultations over one longer consultation. This helped them digest and recall the information provided, remember questions they had, involve significant others and search for additional information. Patients would have liked to be offered paper and pen to take notes, take a break after 30 min and have their understanding checked at the end of the first consultation, e.g. using question prompt lists. Some patients and support persons preferred both consultations to happen on the same day to reduce waiting times as well as travel times and costs. Others preferred having a few days in-between both consultations to better help them prepare the second consultation. Participants reported varying preferences for different consultation styles depending on personal and disease-related characteristics, such as age, health literacy level and previous treatment.

Conclusion

To our knowledge, this is the first qualitative study to explore patients’ and their support persons’ preferences for having one longer consultation or two shorter consultations when being informed about alloHSCT. Receiving two shorter consultations may help patients process and recall the information provided and more actively involve their support persons. Clinicians should consider offering patients and their support persons to take a break after 30 min, provide paper and pen as well as question prompt lists.
Challenges in delivery of tuberculosis Services in Ethiopian Pastoralist Settings: clues for reforming service models and organizational structures
Authors: Getnet Fentabil , Demissie Meaza , Worku Alemayehu , Gobena Tesfaye , Tschopp Rea , Farah Alinoor Mohamed , Seyoum Berhanu
Published: June 2021

Background

The End-TB strategy aims to see a world free of tuberculosis (TB) by the coming decade through detecting and treating all cases irrespective of socioeconomic inequalities. However, case detections and treatment outcomes have not been as they should be in Somali pastoral settings of Ethiopia. Hence, this study aimed to explore the challenges that hinder the delivery and utilization of TB services in pastoral areas.

Methods

A qualitative study was conducted between December 2017 and October 2018 among pastoralist patients with delay of ≥2 months in seeking healthcare, healthcare providers and programme managers. Data were collected from different sources using 41 in-depth interviews, observations of facilities and a review meeting of providers from 50 health facilities. The data were transcribed, coded and analyzed to identify pre-defined and emerging sub-themes. ATLAS.ti version 7.0 was used for coding data, categorizing codes, and visualizing networks.

Results

Poor knowledge of TB and its services, limited accessibility (unreachability, unavailability and unacceptability), pastoralism, and initial healthcare-seeking at informal drug vendors that provide improper medications were the key barriers hindering the uptake of TB medical services. Inadequate infrastructure, shortage of trained and enthused providers, interruptions of drugs and laboratory supplies, scarce equipment, programme management gaps, lack of tailored approach, low private engagement, and cross-border movement were the major challenges affecting the provision of TB services for pastoral communities. The root factors were limited potential healthcare coverage, lack of zonal and district TB units, mobility and drought, strategy and funding gaps, and poor development infrastructure.

Conclusion

In pastoral settings of Ethiopia, the major challenges of TB services are limited access, illicit medication practices, inadequate resources, structural deficits, and lack of tailored approaches. Hence, for the pastoral TB control to be successful, mobile screening and treatment modalities and engaging rural drug vendors will be instrumental in enhancing case findings and treatment compliance; whereas, service expansion and management decentralization will be essential to create responsive structures for overcoming challenges.
Professionals’ views on working in the field of domestic violence and abuse during the first wave of COVID-19: a qualitative study in the Netherlands
Authors: van Gelder Nicole E. , van Haalen Ditte L. , Ekker Kyra , Ligthart Suzanne A. , Oertelt-Prigione Sabine
Published: June 2021

Background

The COVID-19 pandemic and lockdown evoked great worries among professionals in the field of domestic violence and abuse (DVA) as they expected a rise of the phenomenon. While many countries reported increased DVA, the Netherlands did not. To understand this discrepancy and the overall impact of the lockdown on DVA support services, we interviewed DVA professionals about their experiences with DVA during the rise of COVID-19, the impact of the lockdown on clients and working conditions, and views on eHealth and online tools.

Methods

Semi-structured interviews were conducted among 16 DVA professionals with various specializations. This data was analyzed using open thematic coding and content analysis.

Results

Most professionals did not see an increase in DVA reports but they did notice more severe violence. They experienced less opportunities to detect DVA and worried about their clients’ wellbeing and the quality of (online) care. Furthermore, their working conditions rapidly changed, with working from home and online, and they expressed frustration, insecurity and loneliness. Professionals feel eHealth and online tools are not always suitable but they do see them as an opportunity to increase reach and maintain services when physical contact is not possible.

Conclusion

This study suggests DVA was probably under-detected during the lockdown rather than not having increased. The Dutch system heavily relies on professionals to detect and report DVA, suggesting a need for critical evaluation of the accessibility of professional help. Professionals experienced significant challenges and should themselves be supported psychologically and in their changed work practices to maintain their ability to aid survivors.
Novel homozygous mutations in Pakistani families with Charcot–Marie–Tooth disease
Authors: Kanwal Sumaira , Choi Yu JIn , Lim Si On , Choi Hee Ji , Park Jin Hee , Nuzhat Rana , khan Aneela , Perveen Shazia , Choi Byung-Ok , Chung Ki Wha
Published: June 2021

Background

Charcot–Marie–Tooth disease (CMT) is a group of genetically and clinically heterogeneous peripheral nervous system disorders. Few studies have identified genetic causes of CMT in the Pakistani patients.

Methods

This study was performed to identify pathogenic mutations in five consanguineous Pakistani CMT families negative for PMP22 duplication. Genomic screening was performed by application of whole exome sequencing.

Results

We identified five pathogenic or likely pathogenic homozygous mutations in four genes: c.2599C > T (p.Gln867*) and c.3650G > A (p.Gly1217Asp) in SH3TC2, c.19C > T (p.Arg7*) in HK1, c.247delG (p.Gly83Alafs*44) in REEP1, and c.334G > A (p.Val112Met) in MFN2. These mutations have not been reported in CMT patients. Mutations in SH3TC2, HK1, REEP1, and MFN2 have been reported to be associated with CMT4C, CMT4G, dHMN5B (DSMA5B), and CMT2A, respectively. The genotype–phenotype correlations were confirmed in all the examined families. We also confirmed that both alleles from the homozygous variants originated from a single ancestor using homozygosity mapping.

Conclusions

This study found five novel mutations as the underlying causes of CMT. Pathogenic mutations in SH3TC2, HK1, and REEP1 have been reported rarely in other populations, suggesting ethnic-specific distribution. This study would be useful for the exact molecular diagnosis and treatment of CMT in Pakistani patients.
Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions
Authors: Zheng Qiuxian , Yang Qin , Zhou Jiaming , Gu Xinyu , Zhou Haibo , Dong Xuejun , Zhu Haihong , Chen Zhi
Published: June 2021

Background

Hepatocellular carcinoma (HCC) has a poor prognosis and has become the sixth most common malignancy worldwide due to its high incidence. Advanced approaches to therapy, including immunotherapeutic strategies, have played crucial roles in decreasing recurrence rates and improving clinical outcomes. The HCC microenvironment is important for both tumour carcinogenesis and immunogenicity, but a classification system based on immune signatures has not yet been comprehensively described.

Methods

HCC datasets from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the International Cancer Genome Consortium (ICGC) were used in this study. Gene set enrichment analysis (GSEA) and the ConsensusClusterPlus algorithm were used for clustering assessments. We scored immune cell infiltration and used linear discriminant analysis (LDA) to improve HCC classification accuracy. Pearson's correlation analyses were performed to assess relationships between immune signature indices and immunotherapies. In addition, weighted gene co-expression network analysis (WGCNA) was applied to identify candidate modules closely associated with immune signature indices.

Results

Based on 152 immune signatures from HCC samples, we identified four distinct immune subtypes (IS1, IS2, IS3, and IS4). Subtypes IS1 and IS4 had more favourable prognoses than subtypes IS2 and IS3. These four subtypes also had different immune system characteristics. The IS1 subtype had the highest scores for IFNγ, cytolysis, angiogenesis, and immune cell infiltration among all subtypes. We also identified 11 potential genes, namely, TSPAN15, TSPO, METTL9, CD276, TP53I11, SPINT1, TSPO, TRABD2B, WARS2, C9ORF116, and LBH, that may represent potential immunological biomarkers for HCC. Furthermore, real-time PCR revealed that SPINT1, CD276, TSPO, TSPAN15, METTL9, and WARS2 expression was increased in HCC cells.

Conclusions

The present gene-based immune signature classification and indexing may provide novel perspectives for both HCC immunotherapy management and prognosis prediction.
An immune-related pseudogene signature to improve prognosis prediction of endometrial carcinoma patients
Authors: Tang Shanshan , Zhuge Yiyi
Published: June 2021

Background

Pseudogenes show multiple functions in various cancer types, and immunotherapy is a promising cancer treatment. Therefore, this study aims to identify immune-related pseudogene signature in endometrial cancer (EC).

Methods

Gene transcriptome data of EC tissues and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) through UCSC Xena browser. Spearman correlation analysis was performed to identify immune-related pseudogenes (IRPs) between the immune genes and pseudogenes. Univariate Cox regression, LASSO, and multivariate were performed to develop a risk score signature to investigate the different overall survival (OS) between high- and low-risk groups. The prognostic significance of the signature was assessed by the Kaplan–Meier curve, time-dependent receiver operating characteristic (ROC) curve. The abundance of 22 immune cell subtypes of EC patients was evaluated using CIBERSORT.

Results

Nine IRPs were used to build a prognostic signature. Survival analysis revealed that patients in the low-risk group presented longer OS than those in the high-risk group as well as in multiple subgroups. The signature risk score was independent of other clinical covariates and was associated with several clinicopathological variables. The prognostic signature reflected infiltration by multiple types of immune cells and revealed the immunotherapy response of patients with anti-programmed death-1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) therapy. Function enrichment analysis revealed that the nine IRPs were mainly involved in multiple cancer-related pathways.

Conclusion

We identified an immune-related pseudogene signature that was strongly correlated with the prognosis and immune response to EC. The signature might have important implications for improving the clinical survival of EC patients and provide new strategies for cancer treatment.
Celastrol inhibits the proliferation and angiogenesis of high glucose-induced human retinal endothelial cells
Authors: Fang Jian , Chang Xiaoke
Published: June 2021

Background

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. Celastrol plays a certain role in the improvement of various diabetes complications. Therefore, this study aimed to explore whether celastrol inhibited the proliferation and angiogenesis of high glucose (HG)-induced human retinal endothelial cells (hRECs) by down-regulating the HIF1/VEGF signaling pathway.

Methods

The viability and proliferation of hRECs treated with glucose, celastrol or dimethyloxallyl glycine (DMOG) were analyzed by MTT assay. The invasion and tube formation ability of hRECs treated with glucose, celastrol or DMOG were in turn detected by transwell assay and tube formation assay. The expression of HIF1α and VEGF in hRECs after indicated treatment was analyzed by Western blot analysis and RT-qPCR analysis and ICAM-1 expression in hRECs after indicated treatment was detected by immunofluorescence assay

Results

HG induction promoted the proliferation, invasion and tube formation ability and increased the expression of HIF-1α and VEGF of hRECs, which were gradually suppressed by celastrol changing from 0.5 to 2.0 μM. DMOG was regarded as a HIF1α agonist, which attenuated the effect of celastrol on HG-induced hRECs.

Conclusion

Celastrol inhibited the proliferation and angiogenesis of HG-induced hRECs by down-regulating the HIF1α/VEGF signaling pathway.
Mixture effects of prenatal exposure to per- and polyfluoroalkyl substances and polybrominated diphenyl ethers on maternal and newborn telomere length
Authors: Eick Stephanie M. , Goin Dana E. , Cushing Lara , DeMicco Erin , Park June-Soo , Wang Yunzhu , Smith Sabrina , Padula Amy M. , Woodruff Tracey J. , Morello-Frosch Rachel
Published: June 2021

Background

Per- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are endocrine disrupting chemicals with widespread exposures across the U.S. given their abundance in consumer products. PFAS and PBDEs are associated with reproductive toxicity and adverse health outcomes, including certain cancers. PFAS and PBDEs may affect health through alternations in telomere length. In this study, we examined joint associations between prenatal exposure to PFAS, PBDEs, and maternal and newborn telomere length using mixture analyses, to characterize effects of cumulative environmental chemical exposures.

Methods

Study participants were enrolled in the Chemicals in Our Bodies (CIOB) study, a demographically diverse cohort of pregnant people and children in San Francisco, CA. Seven PFAS (ng/mL) and four PBDEs (ng/g lipid) were measured in second trimester maternal serum samples. Telomere length (T/S ratio) was measured in delivery cord blood of 292 newborns and 110 second trimester maternal whole blood samples. Quantile g-computation was used to assess the joint associations between groups of PFAS and PBDEs and newborn and maternal telomere length. Groups considered were: (1) all PFAS and PBDEs combined, (2) PFAS, and (3) PBDEs. Maternal and newborn telomere length were modeled as separate outcomes.

Results

T/S ratios in newborn cord and maternal whole blood were moderately correlated (Spearman ρ = 0.31). In mixtures analyses, a simultaneous one quartile increase in all PFAS and PBDEs was associated with a small increase in newborn (mean change per quartile increase = 0.03, 95% confidence interval [CI] = -0.03, 0.08) and maternal telomere length (mean change per quartile increase = 0.03 (95% CI = -0.03, 0.09). When restricted to maternal–fetal paired samples (N = 76), increasing all PFAS and PBDEs combined was associated with a strong, positive increase in newborn telomere length (mean change per quartile increase = 0.16, 95% CI = 0.03, 0.28). These associations were primarily driven by PFAS (mean change per quartile increase = 0.11 [95% CI = 0.01, 0.22]). No associations were observed with maternal telomere length among paired samples.

Conclusions

Our findings suggest that PFAS and PBDEs may be positively associated with newborn telomere length.
Transcultural adaptation and psychometric properties of Family Quality of Life Survey for caregivers of people with neurodegenerative disease: a study of Spanish families who live in the rural Spain–Portugal cross-border
Authors: Badia Marta , Orgaz M. Begoña , Vicario-Molina Isabel , González-Ortega Eva , Gómez-Vela María , Aza Alba , Martín-Delgado M. Antonia
Published: June 2021

Background

Neurodegenerative diseases (NDs) are one of the main causes of disability and dependence that have a great impact both on the quality of life of people with disabilities and their families. A majority of people with NDs receive care and support from the family, but there is no tool in Spain with which to measure whole-family QOL. The aim of this study was the translation, cultural adaptation, and validation of theFQOLS–Dementiainto Spanish to assess FQOL among family members of individuals with NDs who live in the Spain–Portugal cross-border area.

Method

The Spanish version was translated and adapted following the international guidelines for cross-cultural adaptation tests. A sample of 300 family caregivers was interviewed, applying an adapted version of theFamily Quality Survey(FQOLS–Dementia). Confirmatory factor analysis was performed to validate the factor structure, and convergent validity was examined with Pearson’s correlation coefficients of the global FQOL with the domains. Internal consistency reliability was determined using Cronbach’s alpha.

Results

The domain structure of theFQOLS–NDshowed a good fit. In the convergent validity, it was found that the total score and the subscale domain scores were associated with the global FQOL score, except for theValuesdomain. Internal consistency of nine domain subscales was strong (α = 0.80 to 0.91), and excellent for the total FQOL (α = 0.85) and the global FQOL (α = 0.87).

Conclusion

TheFQOLS–NDpresented good validity and reliability in caregiver families with individuals with ND, so its application shows its usefulness in detecting areas of improvement and intervention strategies for FQOL in the Spain–Portugal cross-border area.
Clinicopathological features of desmoplastic small round cell tumors: clinical series and literature review
Authors: Wang Ling-Ling , Ji Zhong-He , Gao Ying , Chang Hong , Sun Ping-Ping , Li Yan
Published: June 2021

Background and purpose

Desmoplastic small round cell tumor (DSRCT) is a highly malignant sarcoma that occurs in the abdominopelvic cavities of adolescents. The accurate diagnosis of DSRCT is challenging owing to limited literatures. Our study aimed to investigate the relationship between clinicopathological features and prognosis in patients with DSRCTs.

Methods

Data of 8 patients with DSRCT originating from the abdominal cavity were retrospectively reviewed. The clinical manifestations, pathological characteristics, treatment approaches, and prognosis were analyzed. The histopathological (identified using hematoxylin-eosin staining), immunohistochemical, and molecular diagnostic (using fluorescence in situ hybridization) features were also reviewed.

Results

All patients were male aged between 24 and 45 years (median age, 30 years). The main clinical symptoms included abdominal distension, abdominal pain, and constipation. Seven of the 8 patients developed metastases to either distant organs or lymph nodes. Multiple gray nodules with diameters of 1–10 cm and poorly defined boundaries were scattered throughout the omentum and mesentery. Histopathological examination demonstrated well-defined nests composed of small round blue cells separated by markedly desmoplastic stroma. Immunohistochemical analysis revealed positive expressions of desmin, vimentin and C-terminal of Wilm’s tumor suppressor (WT-1). The Ewing sarcoma breakpoint region 1 gene fused with WT1 (EWSR1-WT1) gene fusion was detected in all patients. Cytoreductive surgery (CRS) was performed in 6 patients. Follow-up period ranged from 7.5 to 28.5 months with a median of 17.2 months. Three patients died during follow-up.

Conclusion

DSRCT is highly aggressive and presents distinctive morphological features. CRS is the essential therapy for DSRCT. A test for the combined expression of desmin, cytokeratins, and C-terminal of WT-1, as well as the analysis of morphologic features, might be helpful during DSRCT diagnosis, and the EWSR1-WT1 gene fusion is the gold standard for definitive diagnosis. Our work will provide new insights into the diagnosis and treatment of DSRCTs.
Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition
Authors: Ortiz Maria A. , Mikhailova Tatiana , Li Xiang , Porter Baylee A. , Bah Alaji , Kotula Leszek
Published: June 2021

Over a century of scientific inquiry since the discovery of v-SRC but still no final judgement on SRC function. However, a significant body of work has defined Src family kinases as key players in tumor progression, invasion and metastasis in human cancer. With the ever-growing evidence supporting the role of epithelial-mesenchymal transition (EMT) in invasion and metastasis,
so does our understanding of the role SFKs play in mediating these processes. Here we describe some key mechanisms through which Src family kinases play critical role in epithelial homeostasis and how their function is essential for the propagation of invasive signals.
Physical activity from adolescence to young adulthood: patterns of change, and their associations with activity domains and sedentary time
Authors: Aira Tuula , Vasankari Tommi , Heinonen Olli Juhani , Korpelainen Raija , Kotkajuuri Jimi , Parkkari Jari , Savonen Kai , Uusitalo Arja , Valtonen Maarit , Villberg Jari , Vähä-Ypyä Henri , Kokko Sami Petteri
Published: June 2021

Background

Longitudinal studies demonstrate an average decline in physical activity (PA) from adolescence to young adulthood. However, while some subgroups of adolescents decrease activity, others increase or maintain high or low activity. Activity domains may differ between subgroups (exhibiting different PA patterns), and they offer valuable information for targeted health promotion. Hence, the aim of this study was to identify PA patterns from adolescence to young adulthood; also to explore the associations of (i) changes in PA domains and in sedentary time, (ii) sociodemographic factors, and (iii) self-rated health with diverging PA patterns.

Methods

The observational cohort study data encompassed 254 adolescents at age 15 and age 19. K-means cluster analysis for longitudinal data was performed to identify participant clusters (patterns) based on their accelerometry-measured moderate-to-vigorous PA (MVPA). Logistic regressions were applied in further analysis.

Results

Five PA patterns were identified: inactivity maintainers (n = 71), activity maintainers (n = 70), decreasers from moderate (to low) PA (n = 61), decreasers from high (to moderate) PA (n = 32), and increasers (n = 20).

At age 15, participation in sports clubs (SC, 41–97%) and active commuting (AC, 47–75%) was common in all the patterns. By age 19, clear dropout from these activities was prevalent (SC participation mean 32%, AC 31–63%). Inactivity maintainers reported the lowest amount of weekly school physical education.

Dropout from SC – in contrast to non-participation in SC – was associated with higher odds of being a decreaser from high PA, and with lower odds of being an inactivity maintainer. Maintained SC participation was associated with higher odds of belonging to the decreasers from high PA, and to the combined group of activity maintainers and increasers; also with lower odds of being an inactivity maintainer. Maintenance/adoption of AC was associated with decreased odds of being an inactivity maintainer. Self-reported health at age 19 was associated with the patterns of maintained activity and inactivity.

Conclusions

PA patterns diverge over the transition to adulthood. Changes in SC participation and AC show different associations with diverging PA patterns. Hence, tailored PA promotion is recommended.
A scoping review of physical activity interventions for older adults
Authors: Taylor Jennifer , Walsh Sarah , Kwok Wing , Pinheiro Marina B. , de Oliveira Juliana Souza , Hassett Leanne , Bauman Adrian , Bull Fiona , Tiedemann Anne , Sherrington Catherine
Published: June 2021

Background

To inform implementation and future research, this scoping review investigates the volume of evidence for physical activity interventions among adults aged 60+. Our research questions are: (1) what is the evidence regarding interventions designed to increase total physical activity in adults aged 60+ years, in accordance with three of the four strategic objectives of GAPPA (active societies, active environments, active people); (2) what is the current evidence regarding the effectiveness of physical activity programmes and services designed for older adults?; and (3) What are the evidence gaps requiring further research?

Methods

We searched PEDro, MEDLINE, CINAHL and Cochrane from 1 January 2010 to 1 November 2020 for systematic reviews and meta-analyses of physical activity interventions in adults aged 60+. We identified interventions designed to: (1) increase physical activity; and (2) deliver physical activity programmes and services in home, community or outpatient settings. We extracted and coded data from eligible reviews according to our proposed framework informed by TIDieR, Prevention of Falls Network Europe (PROFANE), and WHO’s International Classification of Functioning, Disability and Health (ICF). We classified the overall findings as positive, negative or inconclusive.

Results

We identified 39 reviews of interventions to increase physical activity and 342 reviews of programmes/services for older adults. Interventions were predominantly structured exercise programmes, including balance strength/resistance training, and physical recreation, such as yoga and tai chi. There were few reviews of health promotion/coaching and health professional education/referral, and none of sport, workplace, sociocultural or environmental interventions. Fewer reported outcomes of total physical activity, social participation and quality of life/well-being. We noted insufficient coverage in diverse and disadvantaged samples and low-middle income countries.

Conclusions

There is a modest but growing volume of evidence regarding interventions designed to increase total physical activity in older adults, although more interventional studies with long term follow-up are needed, particularly for GAPPA 1. Active Societies and GAPPA 2. Active Environments. By comparison, there is abundant evidence for GAPPA 3. specific programmes and services, but coverage of sport and workplace interventions, and diverse samples and settings is lacking. Comprehensive reviews of individual studies are now needed as well as research targeting neglected outcomes, populations and settings.
International evaluation of the Microscale Audit of Pedestrian Streetscapes (MAPS) Global instrument: comparative assessment between local and remote online observers
Authors: Fox Eric H. , Chapman James E. , Moland Abraham M. , Alfonsin Nicole E. , Frank Lawrence D. , Sallis James F. , Conway Terry L. , Cain Kelli L. , Geremia Carrie , Cerin Ester , Vanwolleghem Griet , Van Dyck Delfien , Queralt Ana , Molina-García Javier , Hino Adriano Akira Ferreira , Lopes Adalberto Aparecido dos Santos , Salmon Jo , Timperio Anna , Kershaw Suzanne E.
Published: June 2021

Objectives

The use of online imagery by non-local observers to conduct remote, centralized collection of streetscape audit data in international studies has the potential to enhance efficiency of collection and comparability of such data for research on built environments and health. The objectives of the study were to measure (1) the consistency in responses between local in-field observers and non-local remote online observers and (2) the reliability between in-country online observers and non-local remote online observers using the Microscale Audit of Pedestrian Streetscapes Global tool to characterize pedestrian-related features along streets in five countries.

Methods

Consistency and inter-rater reliability were analyzed between local and non-local observers on a pooled database of 200 routes in five study regions (Melbourne, Australia; Ghent, Belgium; Curitiba, Brazil; Hong Kong, China; and Valencia, Spain) for microscale environmental feature subscales and item-level variables using the intraclass correlation coefficient (ICC).

Results

A local in-field versus remote online comparison had an ICC of 0.75 (95 % CI: 0.68–0.80) for the grand total score. An ICC of 0.91 (95 % CI: 0.88–0.93) was found for the local online versus remote online comparison. Positive subscales yielded stronger results in comparison to negative subscales, except for the similarly poor-performing positive aesthetics/social characteristics.

Conclusions

This study demonstrated remote audits of microscale built environments using online imagery had good reliability with local in-field audits and excellent reliability with local online audits. Results generally supported remote online environmental audits as comparable to local online audits. This identification of low-cost and efficient data acquisition methods is important for expanding research on microscale built environments and physical activity globally.
Multi-institutional development and external validation of machine learning-based models to predict relapse risk of pancreatic ductal adenocarcinoma after radical resection
Authors: Li Xiawei , Yang Litao , Yuan Zheping , Lou Jianyao , Fan Yiqun , Shi Aiguang , Huang Junjie , Zhao Mingchen , Wu Yulian
Published: June 2021

Background

Surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC) and the survival of patients after radical resection is closely related to relapse. We aimed to develop models to predict the risk of relapse using machine learning methods based on multiple clinical parameters.

Methods

Data were collected and analysed of 262 PDAC patients who underwent radical resection at 3 institutions between 2013 and 2017, with 183 from one institution as a training set, 79 from the other 2 institution as a validation set. We developed and compared several predictive models to predict 1- and 2-year relapse risk using machine learning approaches.

Results

Machine learning techniques were superior to conventional regression-based analyses in predicting risk of relapse of PDAC after radical resection. Among them, the random forest (RF) outperformed other methods in the training set. The highest accuracy and area under the receiver operating characteristic curve (AUROC) for predicting 1-year relapse risk with RF were 78.4% and 0.834, respectively, and for 2-year relapse risk were 95.1% and 0.998. However, the support vector machine (SVM) model showed better performance than the others for predicting 1-year relapse risk in the validation set. And the k neighbor algorithm (KNN) model achieved the highest accuracy and AUROC for predicting 2-year relapse risk.

Conclusions

By machine learning, this study has developed and validated comprehensive models integrating clinicopathological characteristics to predict the relapse risk of PDAC after radical resection which will guide the development of personalized surveillance programs after surgery.
Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia
Authors: Ventura-Espejo Laura , Gracia-Darder Inés , Escribá-Bori Silvia , Amador-González Eva Regina , Martín-Santiago Ana , Ramakers Jan
Published: June 2021

Background

H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia.

Case presentation

8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria.

Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative.

A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome.

Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules.

Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab.

Conclusions

We report the most severe disease course produced by HS described so far in the literature. Our patient’s manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia.

Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment.

Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.
Adolescent-onset anti-MDA5 antibody-positive juvenile dermatomyositis with rapidly progressive interstitial lung disease and spontaneous pneumomediastinum: a case report and literature review
Authors: Yeung Tsz-Wing , Cheong Kai-Ning , Lau Yu-Lung , Tse Kei-Chiu Niko
Published: June 2021

Background

Dermatomyositis with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody has a distinct phenotype associated with small hand joint arthritis, mucocutaneous ulceration, palmar papules and less muscle involvement. It is also associated with increased risk of rapidly progressive interstitial lung disease (RP-ILD) and has a high mortality rate in adults. There is evidence that cases complicated with spontaneous pneumomediastinum (PNM) have an increase in mortality. While most of the evidence for this rare disease is derived from the adult literature, we report a case diagnosed in an adolescent complicated with both RP-ILD and PNM with a good outcome after aggressive immunosuppressive therapy. Our case also illustrates the potential challenges in diagnosis of this condition in the setting of non-specific clinical manifestations, the need for a high index of suspicion, and the importance of testing for myositis-specific antibodies (MSA) early to aid in diagnosis given the risk of rapid progression in these patients.

Case presentation

A 16-year-old Chinese female presented with fever and cough for 1 day, and finger swelling for 3 weeks. Physical examination revealed arthritis of fingers and wrists, ulcers and palmar papules over fingers, hyperpigmentation of interphalangeal joints, and rash over the neck. The diagnosis of dermatomyositis was made 1 month later with the onset of malar rash, Gottron’s papules, calcinosis and myalgia. The diagnosis was supported by the presence of anti-MDA5 antibody and evidence of inflammatory myopathy on magnetic resonance imaging. In retrospect, she already had interstitial lung disease at first presentation manifested as cough and opacity on chest radiograph, which was later confirmed with chest computed tomography. She was treated according to adult guidelines with steroid and calcineurin inhibitor. Her disease was resistant to initial therapy and was complicated by RP-ILD and spontaneous PNM. Intensive immunosuppressive therapy including cyclophosphamide and rituximab were required to induce remission.

Conclusions

Recognition of distinct clinical features of anti-MDA5 antibody-positive dermatomyositis and testing for MSA is crucial in patients with skin ulceration and abnormal pulmonary findings of unknown etiology, as prompt diagnosis with early aggressive treatment and anticipation of complications could make a difference in the outcome of this disease with high mortality.
Factors associated with the intention to undergo Pap smear testing in the rural areas of Indonesia: a health belief model
Authors: Sumarmi Sumarmi , Hsu Yu-Yun , Cheng Ya-Min , Lee Shu-Hsin
Published: June 2021

Purposes

This study aimed to understand the influence of health beliefs, demographic factors, and health characteristics on the intention to undergo Pap smear testing among women in rural areas of Indonesia.

Methods

A descriptive cross-sectional study was conducted and 687 married women participated in the study. A convenience sampling was applied to recruit the participants from community health centres in a rural region in Indonesia. Self-reported data using the Health Beliefs Model Scale for Cervical Cancer and Pap Smear Test was collected to assess the health beliefs. Independent t-tests, simple logistic regressions, and a hierarchical logistic regression with 3 steps were run. Statistical significance for analysis was set at p < 0.05.

Results

The mean age of the participants was 42 years (SD = 8.4). Among the participants, 81% of the women had never undergone a Pap smear test, and 61% (n = 422) of the women reported a high intention of receiving a Pap smear test. Income and education Health beliefs regarding Pap smear testing were different between women who had low and high intentions to undergo Pap smear testing. Health beliefs, such as perceived benefits, severity, barriers to Pap smear testing, and health motivation for a Pap smear test were associated with the intention to undergo Pap smear testing among rural Indonesian women. Overall, the hierarchical multiple regression with 3 steps containing demographic, health characteristics, and health belief variables accounted for 31% variance of the intention to undergo Pap smear test among the Indonesian rural women.

Conclusions

Low screening rates of cervical cancer and high intentions to do the screening exist among rural Indonesian women. Health beliefs significantly affect the rural women’s intention of Pap smear testing in Indonesia.
Assessing the differential impact of chronic CMV and treated HIV infection on CD8+ T-cell differentiation in a matched cohort study: is CMV the key?
Authors: Mueller Matthias C. , Kern Winfried V. , Usadel Susanne , Pauly Marie-Christin , Cathomen Toni , Salzer Ulrich
Published: June 2021

Background

Cytomegalovirus (CMV) infection is one of the main driving forces of T-cell senescence in the general population, whereas its differential impact in people living with HIV (PLWH) is less well characterized. The study explores the effect of latent CMV infection on T-cell subsets, monocyte/macrophages activation markers, and CRP in PLWH on long-term ART.

Methods

Cross-sectional cohort study including PLWH on long-term suppressive ART. Individuals of 4 groups (HIV+CMV−, HIV+CMV+, HIV−CMV+, and HIV−CMV−) were matched 1:1:1:1 for age and sex. Immunophenotyping of lymphocyte and T-cell subsets by multicolor flow cytometry was performed in fresh blood samples collected from patients and healthy donors.

Results

Both, latent CMV and treated HIV infection were associated with an expansion of CD8 T cells, a reduced CD4/CD8 ratio, and with CD8 T-cell activation with a cumulative effect in CMV/HIV-coinfected individuals. CMV was associated with elevated numbers of late effector and terminally differentiated CD8 T-cells. Compared to CMV monoinfection, CMV/HIV coinfection showed to be associated with lower proportion of CD28−CD8+ T cells expressing CD57 suggesting that HIV preferentially expands CD28−CD57−CD8+ T cells and impedes terminal differentiation of CD28−CD8+ T cells. We could not show any association between HIV or CMV infection status and concentration of CRP and CD163.

Conclusions

CMV infection is associated with phenotypic signs of T-cell senescence, promoting exacerbation and persistence of alterations of the T-cell compartment in PLWH on effective ART, which are associated with adverse clinical outcomes and may be an attractive target for therapeutic interventions.
Comments on “Detection and identification of enteroviruses circulating in children with acute gastroenteritis in Pará State, Northern Brazil (2010–2011)”
Authors: Luchs Adriana
Published: June 2021

Investigation of human enterovirus (EV) in diarrheic fecal specimens is valuable to address EV diversity circulating worldwide. However, the detection of EV strains exclusively in fecal specimens must be interpreted cautiously. EV are well known causative agents associated with a spectrum of human diseases, but not acute gastroenteritis. EV isolation in stool samples could not necessarily be associated with diarrheic symptoms, as most EV infections appear to be asymptomatic, and healthy children could excrete EV in their stool. The diagnostic of EV is only confirmed when the neutralization test presents a significant increase in antibody titers (three times or more) in the paired serum samples (acute-phase and convalescent-phase) against the same EV serotype isolated in feces. In addition, patients suffering from acute gastroenteritis, even during an EV investigation, must be screened in parallel for gastroenteric viruses (i.e. norovirus and rotavirus) in order to clarify if the symptoms could be linked to other viral agent detected in their fecal samples. Surveillance of EV diversity among distinct patient groups, including diarrheic individuals, must be taken into consideration and can considerably increase the power of non-polio EV surveillance system in Brazil. More well-designed studies are necessary to further elucidate the role of EV in acute gastroenteritis.