bluuebunny/crossref_metadata_2025 huggingface dataset:
Sarcopenia and sarcopenic obesity among older adults in the nordic countries: a scoping review
Authors: Baygi Fereshteh , Buhl Sussi Friis , Thilsing Trine , Søndergaard Jens , Nielsen Jesper Bo
Published: May 2024

Background

Sarcopenia and sarcopenic obesity (SO) are age-related syndromes that may compromise physical and mental health among older adults. The Nordic countries differ from other regions on prevalence of disease, life-style behavior, and life expectancy, which may impact prevalence of sarcopenia and SO. Therefore, the aim of this study is to review the available evidence and gaps within this field in the Nordic countries.

Methods

PubMed, Embase, and Web of science (WOS) were searched up to February 2023. In addition, grey literature and reference lists of included studies were searched. Two independent researcher assessed papers and extracted data.

Results

Thirty-three studies out of 6,363 searched studies were included in this scoping review. Overall prevalence of sarcopenia varied from 0.9 to 58.5%. A wide prevalence range was still present for community-dwelling older adults when definition criteria and setting were considered. The prevalence of SO ranged from 4 to 11%, according to the only study on this field. Based on the included studies, potential risk factors for sarcopenia include malnutrition, low physical activity, specific diseases (e.g., diabetes), inflammation, polypharmacy, and aging, whereas increased levels of physical activity and improved dietary intake may reduce the risk of sarcopenia. The few available interventions for sarcopenia were mainly focused on resistance training with/without nutritional supplements (e.g., protein, vitamin D).

Conclusion

The findings of our study revealed inadequate research on SO but an increasing trend in the number of studies on sarcopenia. However, most of the included studies had descriptive cross-sectional design, small sample size, and applied different diagnostic criteria. Therefore, larger well-designed cohort studies that adhere to uniform recent guidelines are required to capture a full picture of these two age-related medical conditions in Nordic countries, and plan for prevention/treatment accordingly.
Investigating the trend of demographic changes, mortality, clinical and paraclinical findings of patients hospitalized in the Corona ward, before and after the start of general vaccination of COVID-19
Authors: Morovatshoar Reza , Hushmandi Kiavash , Orouei Sara , Saadat Seyed Hassan , Raesi Rasoul
Published: May 2024

Background

Prioritizing prevention over treatment has been a longstanding principle in the world health system. This study aims to compare the demographic changes, mortality, clinical, and paraclinical findings of patients hospitalized in the Corona ward before and after the start of general vaccination.

Methods

This cross-sectional study utilized the simple random sampling method in 2022, analyzing 300 medical records of patients admitted to the Corona ward at 22 Bahman Khaf Hospital. Data were collected using a checklist with the help of the Medical Care Monitoring System and analyzed using SPSS-22 statistical software and Chi-square statistical test at a significance level of p < 0.05.

Results

Before the start of general vaccination for COVID-19, the majority of patients were hospitalized in the Corona Intensive Care Unit (59.3%), aged between 51 and 65 years (47.3%), hospitalized for more than 3 days (54%), required intubation (49.3%), had SPO2 < 93% (60.7%), and exhibited common symptoms such as cough, shortness of breath, and loss of consciousness. Paraclinical findings included positive CRP, decreased lymphocytes, and ground glass opacity (GGO). After the start of general vaccination for COVID-19, most patients were hospitalized in the general care department of Corona (68%), aged between 36 and 50 years (47.3%), hospitalized for less than three days (66%), required intubation (20%), had SPO2 ≥ 93% (77.3%), and exhibited common symptoms such as weakness, headache, and body pain. Paraclinical findings were within the normal range.

Conclusions

General vaccination for COVID-19 has significantly reduced patient mortality and morbidity. Health policymakers should prioritize general vaccination to achieve herd immunity and improve public health.
Effects of a ‘Rebuilding Myself’ intervention on enhancing the adaptability of cancer patients to return to work: a randomized controlled trial
Authors: Guo Yujie , Xie Huiwen , Ding Lingyan , Shi Yue , Han Pingping
Published: May 2024

Objectives

To explore the effects of a ‘Rebuilding Myself’ intervention on enhancing the adaptability of cancer patients to return to work.

Methods

A single-center, single-blind, randomized controlled trial design was used. Eligible patients who were receiving routine hospital treatment were recruited from the university-affiliated hospital in our city. Patients in the control group only received usual care, while patients in the intervention group received additional ‘Rebuilding Myself’ intervention. Adaptability to return to work, self-efficacy of returning to work, mental resilience, quality of life and work ability were measured at baseline, the 6th and 12th of the intervention. The general estimation equations were used to compare the overall changes of each outcome index between the two groups at different time points. Considering that there may be patient shedding and rejection, Per-Protocol and Intention-to-Treat analysis were used to analyze the data in this study.

Results

There were statistically significant differences between the two groups of patients in the cancer patients’ adaptability to return to work, self-efficacy to return to work, mental resilience, work abilities, the physical, emotional, cognitive function, fatigue, insomnia and overall health status dimensions of quality of life (P < 0.05). And no significant difference was found in other dimensions (P > 0.05). The group effect, time effect, and interaction effect of patients’ return to work adaptability and return to work self-efficacy were statistically significant in both groups (P < 0.05). Mental resilience, working ability, and quality of life had obvious time effect and interaction effect (P < 0.05).

Conclusion

This intervention could improve cancer patients’ adaptability to return to work, self-efficacy to return to work, mental resilience, work abilities and quality of life. And it can be further expanded to improve the adaptability of patients to return to work, then to help patients achieve comprehensive rehabilitation.

Implications for cancer survivors

The application of ‘Rebuilding Myself’ interventions can effectively improve the adaptability of cancer patients returning to work.

Trial registration

This study was registered at the Chinese Clinical Trial Registry (Registration number: ChiCTR2200057943) on 23 March, 2022.
Association between social capital and utilization of essential public health services among elderly migrants: a multilevel logistic study based on the 2017 China migrant dynamic survey (CMDS)
Authors: Luo Qi , Chen Xiaolei , Zhao Linlin , Hu Qinghua , Du Juan , Shao Shuang
Published: May 2024

Background

As the number of elderly migrants in China continues to grow, it is necessary to pay closer attention to their health and health services. Some studies have confirmed that social capital plays a significant role in the utilization of health services. Therefore, an in-depth exploration of the relationship between social capital and the utilization of essential public health services (EPHS) by elderly migrants will not only contribute to improving their overall health but also facilitate a more balanced development of public health service system in China.

Methods

Based on the cross-sectional data from the 2017 China Migrants Dynamic Survey (CMDS), this study examined the impact of social capital on the utilization of EPHS among elderly migrants. We evaluated social capital at two distinct levels: the individual and the community, and considered two dimensions of social capital: structural social capital (SSC) and cognitive social capital (CSC). The study aimed to delve into the impact of these forms of social capital on the utilization of EPHS among elderly migrants, and whether the migration range moderates this impact by multilevel logistic regression analysis.

Results

A total of 5,728 migrant elderly individuals were selected. The health records establishment rate and health education acceptance rate were approximately 33.0% and 58.6%, respectively. Social capital influenceed the utilization of EPHS among elderly migrants. Specifically, individual-level SSC and CSC have impacts on both the establishment of health records (OR = 1.598, 95%CI 1.366–1.869; OR = 1.705, 95%CI 1.433–2.028) and the acceptance of health education (OR = 1.345, 95%CI 1.154–1.567; OR = 2.297, 95%CI 1.906–2.768) among elderly migrants, while community-level SSC only affected the acceptance of health education (OR = 3.838, 95%CI 1.328–11.097). There were significant differences in individual-level SSC, health records, and health education among different migration range subgroups among elderly migrants. Migration range moderated the effect of social capital on the utilization of EPHS, crossing provinces could weaken the relationship between SSC and health education.

Conclusions

Social capital is associated with a higher utilization rate of EPHS among elderly migrants. It is necessary to encourage them to actively participate in social activities, strengthen public services and infrastructure construction in the area, and improve their sense of belonging and identity.
Nonpharmacological intervention therapies for dementia: potential break-even intervention price and savings for selected risk factors in the European healthcare system
Authors: Maresova Petra , Rezny Lukas , Bauer Petr , Valko Marian , Kuca Kamil
Published: May 2024

Background

New effective treatments for dementia are lacking, and early prevention focusing on risk factors of dementia is important. Non-pharmacological intervention therapies aimed at these factors may provide a valuable tool for reducing the incidence of dementia. This study focused on the development of a mathematical model to predict the number of individuals with neurodegenerative diseases, specifically Alzheimer’s disease, Parkinson’s disease, vascular dementia, and amyotrophic lateral sclerosis. Scenarios for non-pharmacological intervention therapies based on risk factor reduction were also assessed. The estimated total costs and potential cost savings from societal were included.

Methods

Based on demographic and financial data from the EU, a mathematical model was developed to predict the prevalence and resulting care costs of neurodegenerative diseases in the population. Each disease (Alzheimer’s disease, Parkinson’s disease, vascular dementia, and amyotrophic lateral sclerosis) used parameters that included prevalence, incidence, and death risk ratio, and the simulation is related to the age of the cohort and the disease stage.

Results

A replicable simulation for predicting the prevalence and resulting cost of care for neurodegenerative diseases in the population exhibited an increase in treatment costs from 267 billion EUR in 2021 to 528 billion EUR by 2050 in the EU alone. Scenarios related to the reduction of the prevalence of dementia by up to 20% per decade led to total discounted treatment cost savings of up to 558 billion EUR.

Conclusion

The model indicates the magnitude of the financial burden placed on EU healthcare systems due to the growth in the population prevalence of neurodegenerative diseases in the coming decades. Lifestyle interventions based on reducing the most common risk factors could serve as a prevention strategy to reduce the incidence of dementia with substantial cost-savings potential. These findings could support the implementation of public health approaches throughout life to ultimately prevent premature mortality and promote a healthier and more active lifestyle in older individuals.
Navigating health challenges: the interplay between occupation-imposed movement restrictions, healthcare access, and community resilience
Authors: Jabali Oqab , Ayyoub Abed Alkarim , Jabali Shaden
Published: May 2024

Background

Transportation plays a significant role in health, community resilience, and access to basic needs such as healthcare, social services, education, and job opportunities. Health and community resilience are, however, impacted by a multitude of complex and unequal factors, such as transportation restrictions exacerbated by the Israeli occupation. The goal of the research was to examine the intricate relationships that exist in Palestine between movement restrictions imposed by occupation, health outcomes, and community resilience.

Method

A self-structured questionnaire, devised based on expert conversations and previous literature, was used in this descriptive, quantitative study to explore health and resilience outcomes. Age, gender, marital status, place of residence, and means of transportation were among the various factors that were utilized to describe the socio-demographics of the study sample (n = 202). The researchers employed stepwise multiple regression and descriptive statistics for the data analysis.

Results

Study findings indicated that transportation restrictions have significant direct and indirect health consequences. A significant direct effect is observed, signifying a negative correlation between restrictions and health; increased transportation restrictions are consistently correlated with a decline in health. The study emphasized how place of residence affects health outcomes, with higher scores for campers and people living in green line areas. It also underscores that public means of transportation are found to be better for health outcomes than private cars.

Conclusion

This study emphasized that roadblocks, checkpoints, and military incursions make it difficult for Palestinians to receive medical care, which has a detrimental impact on their health and well-being. It also underscores the need for significant reforms in Palestinian health and transportation systems to enhance infrastructure and healthcare access. The Palestinian Authority should invest in public transportation and community resilience programs to address transportation-related health issues, especially in villages, due to frequent settler attacks.
Extrapolation errors in Liu et al.’s CAM integrative review of health care professionals in New Zealand
Authors: McDowell Jillian Marie , Kohut Susan Heather , Betts Debra
Published: May 2024

This letter is to highlight errors made by Liu et al. in their 2020 paper in BMC Complementary Medicine and Therapies, “Complementary and alternative medicine—practice, attitudes, and knowledge among healthcare professionals in New Zealand: an integrative review”. Substantial errors in their citation of the recent research and methodology by McDowell, Kohut & Betts (2019) pertaining to the practice of acupuncture in New Zealand by physiotherapists are presented. The actual results of McDowell et al.’s work and the true state of acupuncture use by their sample group is reported.
Exploring perceptions of pre-clerkship students about workplace learning in the clinical learning environment at Gulf Medical University, UAE
Authors: Adnan Nooreen , Azhar Farah , Azim Syeda Rubaba
Published: May 2024

Background

Medical students view clinical workplace placements as an inspiring and motivating learning environment where active student participation is pivotal to development of students’ identity. The progress from pre-clerkship to clerkship education harbors many challenges which consist of experiential learning, adjusting to the clinical environment, and understanding roles & responsibilities. Workplace learning is underpinned by various adult learning theories including social theories,constructivism, supported participation and legitimate peripheral participation. Workplace learning course was recently initiated for pre-clerkship students at a medical university in UAE, which will enable their smooth entry into the clerkship phase of the curriculum.

Objectives

The research aims to explore students’ perceptions of various domains of their clinical learning environment (CLE), highlight the challenges they face, and extract valuable feedback to improve their environment.

Methods

This study was conducted qualitatively by using focus groups method in order to explore students’ perceptions of the clinical learning environment. Two focus group discussions were conducted (n = 8 +/-10) to determine the common challenges of workplace learning and its potential solutions. Data were analyzed using thematic analysis. The approach used to carry out this study was phenomenology, as it helps to understand the learning and behavior of these students who are undergoing this pre-clerkship training in order to transition smoothly to the clerkship phase.

Result

The focus groups helped to deeply explore the perceptions of students about their clinical learning environment. It helped to reveal the challenges encountered by the students including the significance of proper orientation of staff and students, language barrier, availability of learning opportunities, and supervision quality. The focus groups provided worthwhile suggestions to improve the learning opportunities in the clinical learning environment which include orientation of the staff and students what to expect, improved supervision, mentoring and providing learning opportunities to encourage participation.

Conclusion

This study attempted to identify the pre-clerkship students’ perception of their clinical learning environment and the challenges they face over there. Possible suggestions by the students included a formal orientation for the staff and students to be carried out at the beginning. Efforts should be made by clerkship directors to provide students with learning opportunities by increasing patient exposure, encouraging participation, and providing high-quality supervision.
Is the European Crohn’s and Colitis organisation (ECCO) e-guide an acceptable and feasible tool for increasing gastroenterologists’ guideline adherence? A mixed methods evaluation
Authors: Kanazaki Ria , Smith Ben , Bu Stella , Girgis Afaf , Connor Susan J
Published: May 2024

Background and aims

Management of inflammatory bowel disease is constantly evolving, increasing the importance for gastroenterologists to keep up to date with guidelines. Traditional implementation strategies have had only small positive impacts on clinical practice. eHealth strategies such as the European Crohn’s and Colitis Organisation e-guide may be beneficial for clinician decision making in keeping with guidelines. The aim of this study was to evaluate the feasibility and acceptability of the e-guide.

Methods

A mixed methods approach was used to evaluate feasibility and acceptability. Cognitive (think-aloud) interviews were conducted with Australian gastroenterologists while using the e-guide. Two clinical scenarios were developed to allow evaluation of various aspects of the e-guide. Content analysis was applied to the qualitative interview data and descriptive analysis to the quantitative and observational data.

Results

Seventeen participants completed the study. Data saturation were reached. The ECCO e-guide was largely feasible and acceptable, as demonstrated by most clinical questions answered correctly, 87% reaching the answer within 3 min, and most feeling it was useful, would be beneficial to their practice and would use it again. Issues raised included difficulties with website navigation, layout of the e-guide and difficulties with access (network firewalls, paid subscription required).

Conclusions

The ECCO e-guide is largely acceptable and feasible for gastroenterologists to use. Aspects of the e-guide could be modified to improve user experience. This study highlights the importance of engaging end-users in the development and evaluation of clinician educational tools.
From incivility to outcomes: tracing the effects of nursing incivility on nurse well-being, patient engagement, and health outcomes
Authors: Alsadaan Nourah , Ramadan Osama Mohamed Elsayed , Alqahtani Mohammed
Published: May 2024

Background

Nursing incivility, defined as disrespectful behaviour toward nurses, is increasingly recognized as a pressing issue that affects nurses’ well-being and quality of care. However, research on the pathways linking incivility to outcomes is limited, especially in Saudi hospitals. Methods: This cross-sectional study examined relationships between perceived nursing incivility, nurse stress, patient engagement, and health outcomes in four Saudi hospitals. Using validated scales, 289 nurses and 512 patients completed surveys on exposure to incivility, stress levels, activation, and medication adherence. The outcomes included readmissions at 30 days and satisfaction. Results: More than two-thirds of nurses reported experiencing moderate to severe workplace incivility. Correlation and regression analyzes revealed that nursing incivility was positively associated with nursing stress. An inverse relationship was found between stress and patient participation. Serial mediation analysis illuminated a detrimental cascade, incivility contributing to increased nurse stress, subsequently diminishing patient engagement, ultimately worsening care quality. Conclusions The findings present robust evidence that nursing incivility has adverse ripple effects, directly impacting nurse well-being while indirectly affecting patient outcomes through reduced care involvement. Practical implications advocate for systemic interventions focused on constructive nursing cultures and patient empowerment to improve both healthcare provider conditions and quality of care. This study provides compelling information to inform policies and strategies to mitigate workplace mistreatment and encourage participation among nurses and patients to improve health outcomes.
Modifiable lifestyle factors and lifetime risk of atrial fibrillation: longitudinal data from the Korea NHIS-HealS and UK Biobank cohorts
Authors: Park Hanjin , Kim Daehoon , Jang Eunsun , Yu Hee Tae , Kim Tae-Hoon , Kim Dong-min , Sung Jung-Hoon , Pak Hui-Nam , Lee Moon-Hyoung , Lip Gregory Y. H. , Yang Pil-Sung , Joung Boyoung
Published: May 2024

Background

The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities.

Methods

1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death.

Results

The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16–1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51–1.75), respectively.

Conclusions

The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.
Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank
Authors: Wang Xiaofei , Shi Ziyan , Qiu Yuhan , Sun Dongren , Zhou Hongyu
Published: May 2024

Background

Peripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation and neuronal damage. Previous studies with highly selected participants have shown that peripheral GFAP and NfL levels are elevated in the pre-clinical phase of Alzheimer’s disease (AD) and dementia. However, the predictive value of GFAP and NfL for dementia requires more evidence from population-based cohorts.

Methods

This was a prospective cohort study to evaluate UK Biobank participants enrolled from 2006 to 2010 using plasma GFAP and NfL measurements measured by Olink Target Platform and prospectively followed up for dementia diagnosis. Primary outcome was the risk of clinical diagnosed dementia. Secondary outcomes were cognition. Linear regression was used to assess the associations between peripheral GFAP and NfL with cognition. Cox proportional hazard models with cross-validations were used to estimate associations between elevated GFAP and NfL with risk of dementia. All models were adjusted for covariates.

Results

A subsample of 48,542 participants in the UK Biobank with peripheral GFAP and NfL measurements were evaluated. With an average follow-up of 13.18 ± 2.42 years, 1312 new all-cause dementia cases were identified. Peripheral GFAP and NfL increased up to 15 years before dementia diagnosis was made. After strictly adjusting for confounders, increment in NfL was found to be associated with decreased numeric memory and prolonged reaction time. A greater annualized rate of change in GFAP was significantly associated with faster global cognitive decline. Elevation of GFAP (hazard ratio (HR) ranges from 2.25 to 3.15) and NfL (HR ranges from 1.98 to 4.23) increased the risk for several types of dementia. GFAP and NfL significantly improved the predictive values for dementia using previous models (area under the curve (AUC) ranges from 0.80 to 0.89, C-index ranges from 0.86 to 0.91). The AD genetic risk score and number of APOE*E4 alleles strongly correlated with GFAP and NfL levels.

Conclusions

These results suggest that peripheral GFAP and NfL are potential biomarkers for the early diagnosis of dementia. In addition, anti-inflammatory therapies in the initial stages of dementia may have potential benefits.
Excess glucose alone depress young mesenchymal stromal/stem cell osteogenesis and mitochondria activity within hours/days via NAD+/SIRT1 axis
Authors: Yen B. Linju , Wang Li-Tzu , Wang Hsiu-Huang , Hung Chin-Pao , Hsu Pei-Ju , Chang Chia-Chi , Liao Chien-Yu , Sytwu Huey-Kang , Yen Men-Luh
Published: May 2024

Background

The impact of global overconsumption of simple sugars on bone health, which peaks in adolescence/early adulthood and correlates with osteoporosis (OP) and fracture risk decades, is unclear. Mesenchymal stromal/stem cells (MSCs) are the progenitors of osteoblasts/bone-forming cells, and known to decrease their osteogenic differentiation capacity with age. Alarmingly, while there is correlative evidence that adolescents consuming greatest amounts of simple sugars have the lowest bone mass, there is no mechanistic understanding on the causality of this correlation.

Methods

Bioinformatics analyses for energetics pathways involved during MSC differentiation using human cell information was performed. In vitro dissection of normal versus high glucose (HG) conditions on osteo-/adipo-lineage commitment and mitochondrial function was assessed using multi-sources of non-senescent human and murine MSCs; for in vivo validation, young mice was fed normal or HG-added water with subsequent analyses of bone marrow CD45−MSCs.

Results

Bioinformatics analyses revealed mitochondrial and glucose-related metabolic pathways as integral to MSC osteo-/adipo-lineage commitment. Functionally, in vitro HG alone without differentiation induction decreased both MSC mitochondrial activity and osteogenesis while enhancing adipogenesis by 8 h’ time due to depletion of nicotinamide adenine dinucleotide (NAD+), a vital mitochondrial co-enzyme and co-factor to Sirtuin (SIRT) 1, a longevity gene also involved in osteogenesis. In vivo, HG intake in young mice depleted MSC NAD+, with oral NAD+precursor supplementation rapidly reversing both mitochondrial decline and osteo-/adipo-commitment in a SIRT1-dependent fashion within 1 ~ 5 days.

Conclusions

We found a surprisingly rapid impact of excessive glucose, a single dietary factor, on MSC SIRT1 function and osteogenesis in youthful settings, and the crucial role of NAD+—a single molecule—on both MSC mitochondrial function and lineage commitment. These findings have strong implications on future global OP and disability risks in light of current worldwide overconsumption of simple sugars.
Development of a machine learning-based model to predict prognosis of alpha-fetoprotein-positive hepatocellular carcinoma
Authors: Dong Bingtian , Zhang Hua , Duan Yayang , Yao Senbang , Chen Yongjian , Zhang Chaoxue
Published: May 2024

Background

Patients with alpha-fetoprotein (AFP)-positive hepatocellular carcinoma (HCC) have aggressive biological behavior and poor prognosis. Therefore, survival time is one of the greatest concerns for patients with AFP-positive HCC. This study aimed to demonstrate the utilization of six machine learning (ML)-based prognostic models to predict overall survival of patients with AFP-positive HCC.

Methods

Data on patients with AFP-positive HCC were extracted from the Surveillance, Epidemiology, and End Results database. Six ML algorithms (extreme gradient boosting [XGBoost], logistic regression [LR], support vector machine [SVM], random forest [RF], K-nearest neighbor [KNN], and decision tree [ID3]) were used to develop the prognostic models of patients with AFP-positive HCC at one year, three years, and five years. Area under the receiver operating characteristic curve (AUC), confusion matrix, calibration curves, and decision curve analysis (DCA) were used to evaluate the model.

Results

A total of 2,038 patients with AFP-positive HCC were included for analysis. The 1-, 3-, and 5-year overall survival rates were 60.7%, 28.9%, and 14.3%, respectively. Seventeen features regarding demographics and clinicopathology were included in six ML algorithms to generate a prognostic model. The XGBoost model showed the best performance in predicting survival at 1-year (train set: AUC = 0.771; test set: AUC = 0.782), 3-year (train set: AUC = 0.763; test set: AUC = 0.749) and 5-year (train set: AUC = 0.807; test set: AUC = 0.740). Furthermore, for 1-, 3-, and 5-year survival prediction, the accuracy in the training and test sets was 0.709 and 0.726, 0.721 and 0.726, and 0.778 and 0.784 for the XGBoost model, respectively. Calibration curves and DCA exhibited good predictive performance as well.

Conclusions

The XGBoost model exhibited good predictive performance, which may provide physicians with an effective tool for early medical intervention and improve the survival of patients.
Synergistic effect of mesenchymal stem cell-derived extracellular vesicle and miR-137 alleviates autism-like behaviors by modulating the NF-κB pathway
Authors: Qin Qian , Shan Zhiyan , Xing Lei , Jiang Yutong , Li Mengyue , Fan Linlin , Zeng Xin , Ma Xinrui , Zheng Danyang , Wang Han , Wang Hui , Liu Hao , Liang Shengjun , Wu Lijie , Liang Shuang
Published: May 2024

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.
Comprehensive genetic analysis of facioscapulohumeral muscular dystrophy by Nanopore long-read whole-genome sequencing
Authors: Huang Mingtao , Zhang Qinxin , Jiao Jiao , Shi Jianquan , Xu Yiyun , Zhang Cuiping , Zhou Ran , Liu Wenwen , Liang Yixuan , Chen Hao , Wang Yan , Xu Zhengfeng , Hu Ping
Published: May 2024

Background

Facioscapulohumeral muscular dystrophy (FSHD) is a high-prevalence autosomal dominant neuromuscular disease characterized by significant clinical and genetic heterogeneity. Genetic diagnosis of FSHD remains a challenge because it cannot be detected by standard sequencing methods and requires a complex diagnosis workflow.

Methods

We developed a comprehensive genetic FSHD detection method based on Oxford Nanopore Technologies (ONT) whole-genome sequencing. Using a case–control design, we applied this procedure to 29 samples and compared the results with those from optical genome mapping (OGM), bisulfite sequencing (BSS), and whole-exome sequencing (WES).

Results

Using our ONT-based method, we identified 59 haplotypes (35 4qA and 24 4qB) among the 29 samples (including a mosaic sample), as well as the number of D4Z4 repeat units (RUs). The pathogenetic D4Z4 RU contraction identified by our ONT-based method showed 100% concordance with OGM results. The methylation levels of the most distal D4Z4 RU and the double homeobox 4 gene (DUX4) detected by ONT sequencing are highly consistent with the BSS results and showed excellent diagnostic efficiency. Additionally, our ONT-based method provided an independent methylation profile analysis of two permissive 4qA alleles, reflecting a more accurate scenario than traditional BSS. The ONT-based method detected 17 variations in three FSHD2-related genes from nine samples, showing 100% concordance with WES.

Conclusions

Our ONT-based FSHD detection method is a comprehensive method for identifying pathogenetic D4Z4 RU contractions, methylation level alterations, allele-specific methylation of two 4qA haplotypes, and variations in FSHD2-related genes, which will all greatly improve genetic testing for FSHD.
The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk
Authors: Rahmati Soheil , Moeinafshar Aysan , Rezaei Nima
Published: May 2024

Extracellular vesicles (EVs) are lipid bilayer structures released by all cells and widely distributed in all biological fluids. EVs are implicated in diverse physiopathological processes by orchestrating cell–cell communication. Colorectal cancer (CRC) is one of the most common cancers worldwide, with metastasis being the leading cause of mortality in CRC patients. EVs contribute significantly to the advancement and spread of CRC by transferring their cargo, which includes lipids, proteins, RNAs, and DNAs, to neighboring or distant cells. Besides, they can serve as non-invasive diagnostic and prognostic biomarkers for early detection of CRC or be harnessed as effective carriers for delivering therapeutic agents. Autophagy is an essential cellular process that serves to remove damaged proteins and organelles by lysosomal degradation to maintain cellular homeostasis. Autophagy and EV release are coordinately activated in tumor cells and share common factors and regulatory mechanisms. Although the significance of autophagy and EVs in cancer is well established, the exact mechanism of their interplay in tumor development is obscure. This review focuses on examining the specific functions of EVs in various aspects of CRC, including progression, metastasis, immune regulation, and therapy resistance. Further, we overview emerging discoveries relevant to autophagy and EVs crosstalk in CRC.
Lysosomal dysfunction and overload of nucleosides in thymidine phosphorylase deficiency of MNGIE
Authors: Du Jixiang , Liu Fuchen , Liu Xihan , Zhao Dandan , Wang Dongdong , Sun Hongsheng , Yan Chuanzhu , Zhao Yuying
Published: May 2024

Inherited deficiency of thymidine phosphorylase (TP), encoded by TYMP, leads to a rare disease with multiple mitochondrial DNA (mtDNA) abnormalities, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). However, the impact of TP deficiency on lysosomes remains unclear, which are important for mitochondrial quality control and nucleic acid metabolism. Muscle biopsy tissue and skin fibroblasts from MNGIE patients, patients with m.3243 A > G mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and healthy controls (HC) were collected to perform mitochondrial and lysosomal functional analyses. In addition to mtDNA abnormalities, compared to controls distinctively reduced expression of LAMP1 and increased mitochondrial content were detected in the muscle tissue of MNGIE patients. Skin fibroblasts from MNGIE patients showed decreased expression of LAMP2, lowered lysosomal acidity, reduced enzyme activity and impaired protein degradation ability. TYMP knockout or TP inhibition in cells can also induce the similar lysosomal dysfunction. Using lysosome immunoprecipitation (Lyso- IP), increased mitochondrial proteins, decreased vesicular proteins and V-ATPase enzymes, and accumulation of various nucleosides were detected in lysosomes with TP deficiency. Treatment of cells with high concentrations of dThd and dUrd also triggers lysosomal dysfunction and disruption of mitochondrial homeostasis. Therefore, the results provided evidence that TP deficiency leads to nucleoside accumulation in lysosomes and lysosomal dysfunction, revealing the widespread disruption of organelles underlying MNGIE.

Graphical Abstract
Extracellular vesicles produced by HIV-1 Nef-expressing cells induce myelin impairment and oligodendrocyte damage in the mouse central nervous system
Authors: Schenck Jessica K. , Karl Molly T. , Clarkson-Paredes Cheryl , Bastin Ashley , Pushkarsky Tatiana , Brichacek Beda , Miller Robert H. , Bukrinsky Michael I.
Published: May 2024

HIV-associated neurocognitive disorders (HAND) are a spectrum of cognitive impairments that continue to affect approximately half of all HIV-positive individuals despite effective viral suppression through antiretroviral therapy (ART). White matter pathologies have persisted in the ART era, and the degree of white matter damage correlates with the degree of neurocognitive impairment in patients with HAND. The HIV protein Nef has been implicated in HAND pathogenesis, but its effect on white matter damage has not been well characterized. Here, utilizing in vivo, ex vivo, and in vitro methods, we demonstrate that Nef-containing extracellular vesicles (Nef EVs) disrupt myelin sheaths and inflict damage upon oligodendrocytes within the murine central nervous system. Intracranial injection of Nef EVs leads to reduced myelin basic protein (MBP) staining and a decreased number of CC1 + oligodendrocytes in the corpus callosum. Moreover, cerebellar slice cultures treated with Nef EVs exhibit diminished MBP expression and increased presence of unmyelinated axons. Primary mixed brain cultures and enriched oligodendrocyte precursor cell cultures exposed to Nef EVs display a decreased number of O4 + cells, indicative of oligodendrocyte impairment. These findings underscore the potential contribution of Nef EV-mediated damage to oligodendrocytes and myelin maintenance in the pathogenesis of HAND.
Patient experiences of interprofessional collaboration and intersectoral communication in rare disease healthcare in Germany – a mixed-methods study
Authors: Inhestern Laura , Otto Ramona , Brandt Maja , Zybarth David , Oheim Ralf , Schüler Helke , Mir Thomas S. , Tsiakas Konstantinos , Dibaj Payam , Zschüntzsch Jana , Okun Pamela M. , Hegenbart Ute , Sommerburg Olaf , Schramm Christoph , Weiler-Normann Christina , Härter Martin , Bergelt Corinna
Published: May 2024

Background

Rare diseases are often complex, chronic and many of them life-shortening. In Germany, healthcare for rare diseases is organized in expert centers for rare diseases. Most patients additionally have regional general practicioners and specialists for basic medical care. Thus, collaboration and information exchange between sectors is highly relevant. Our study focuses on the patient and caregiver perspective on intersectoral and interdisciplinary care between local healthcare professionals (HCPs) and centers for rare diseases in Germany. The aims were (1) to investigate patients’ and caregivers’ general experience of healthcare, (2) to analyse patients’ and caregivers’ perception of collaboration and cooperation between local healthcare professionals and expert centers for rare diseases and (3) to investigate patients’ and caregivers’ satisfaction with healthcare in the expert centers for rare diseases.

Results

In total 299 individuals of whom 176 were patients and 123 were caregivers to pediatric patients participated in a survey using a questionnaire comprising several instruments and constructs. Fifty participants were additionally interviewed using a semistructured guideline. Most patients reported to receive written information about their care, have a contact person for medical issues and experienced interdisciplinary exchange within the centers for rare diseases. Patients and caregivers in our sample were mainly satisfied with the healthcare in the centers for rare diseases. The qualitative interviews showed a rather mixed picture including experiences of uncoordinated care, low engagement and communication difficulties between professionals of different sectors. Patients reported several factors that influenced the organization and quality of healthcare e.g. engagement and health literacy in patients or engagement of HCPs.

Conclusions

Our findings indicate the high relevance of transferring affected patients to specialized care as fast as possible to provide best medical treatment and increase patient satisfaction. Intersectoral collaboration should exceed written information exchange and should unburden patients of being and feeling responsible for communication between sectors and specialists. Results indicate a lack of inclusion of psychosocial aspects in routine care, which suggests opportunities for necessary improvements.
A novel approach to exploring the dark genome and its application to mapping of the vertebrate virus fossil record
Authors: Blanco-Melo Daniel , Campbell Matthew A. , Zhu Henan , Dennis Tristan P. W. , Modha Sejal , Lytras Spyros , Hughes Joseph , Gatseva Anna , Gifford Robert J.
Published: May 2024

Background

Genomic regions that remain poorly understood, often referred to as the dark genome, contain a variety of functionally relevant and biologically informative features. These include endogenous viral elements (EVEs)—virus-derived sequences that can dramatically impact host biology and serve as a virus fossil record. In this study, we introduce a database-integrated genome screening (DIGS) approach to investigate the dark genome in silico, focusing on EVEs found within vertebrate genomes.

Results

Using DIGS on 874 vertebrate genomes, we uncover approximately 1.1 million EVE sequences, with over 99% originating from endogenous retroviruses or transposable elements that contain EVE DNA. We show that the remaining 6038 sequences represent over a thousand distinct horizontal gene transfer events across 10 virus families, including some that have not previously been reported as EVEs. We explore the genomic and phylogenetic characteristics of non-retroviral EVEs and determine their rates of acquisition during vertebrate evolution. Our study uncovers novel virus diversity, broadens knowledge of virus distribution among vertebrate hosts, and provides new insights into the ecology and evolution of vertebrate viruses.

Conclusions

We comprehensively catalog and analyze EVEs within 874 vertebrate genomes, shedding light on the distribution, diversity, and long-term evolution of viruses and reveal their extensive impact on vertebrate genome evolution. Our results demonstrate the power of linking a relational database management system to a similarity search-based screening pipeline for in silico exploration of the dark genome.
Engineering non-conventional yeast Rhodotorula toruloides for ergothioneine production
Authors: Liu Ke , Xiang Gedan , Li Lekai , Liu Tao , Ke Jie , Xiong Liangbin , Wei Dongzhi , Wang Fengqing
Published: May 2024

Background

Ergothioneine (EGT) is a distinctive sulfur-containing histidine derivative, which has been recognized as a high-value antioxidant and cytoprotectant, and has a wide range of applications in food, medical, and cosmetic fields. Currently, microbial fermentation is a promising method to produce EGT as its advantages of green environmental protection, mild fermentation condition, and low production cost. However, due to the low-efficiency biosynthetic process in numerous cell factories, it is still a challenge to realize the industrial biopreparation of EGT. The non-conventional yeast Rhodotorula toruloides is considered as a potential candidate for EGT production, thanks to its safety for animals and natural ability to synthesize EGT. Nevertheless, its synthesis efficiency of EGT deserves further improvement.

Results

In this study, out of five target wild-type R. toruloides strains, R. toruloides 2.1389 (RT1389) was found to accumulate the highest EGT production, which could reach 79.0 mg/L at the shake flask level on the 7th day. To achieve iterative genome editing in strain RT1389, CRISPR-assisted Cre recombination (CACR) method was established. Based on it, an EGT-overproducing strain RT1389-2 was constructed by integrating an additional copy of EGT biosynthetic core genes RtEGT1 and RtEGT2 into the genome, the EGT titer of which was 1.5-fold increase over RT1389. As the supply of S-adenosylmethionine was identified as a key factor determining EGT production in strain RT1389, subsequently, a series of gene modifications including S-adenosylmethionine rebalancing were integrated into the strain RT1389-2, and the resulting mutants were rapidly screened according to their EGT production titers with a high-throughput screening method based on ergothionase. As a result, an engineered strain named as RT1389-3 was selected with a production titer of 267.4 mg/L EGT after 168 h in a 50 mL modified fermentation medium.

Conclusions

This study characterized the EGT production capacity of these engineered strains, and demonstrated that CACR and high-throughput screening method allowed rapid engineering of R. toruloides mutants with improved EGT production. Furthermore, this study provided an engineered RT1389-3 strain with remarkable EGT production performance, which had potential industrial application prospects.
Retraction Note: The design of network security protection trust management system based on an improved hidden Markov model
Authors: Chen Shaojun
Published: May 2024

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13635-023-00146-z.