bluuebunny/crossref_metadata_2025 huggingface dataset:
Nomogram to Assess the Risk of Deep Venous Thrombosis After Posterior Lumbar Fusion: A Retrospective Study
Authors: Li Xiang , Ma Jinlong , Xue Lu , Wang Limin , Jiao Guangjun , Chen Yunzhen
Published: October 2024

Study Design

Retrospective cohort study.

Objectives

Deep venous thrombosis (DVT) is a common complication following lumbar spine surgery, which can lead to adverse consequences such as venous thromboembolism and pulmonary embolism. This study aimed to investigate whether predictors of DVT can improve clinical interventions.

Methods

The study included patients who underwent posterior lumbar fusion between 2012 and 2022. In the training cohort, stepwise logistic regression, based on the Akaike information criterion minimum, was used to identify variables for constructing the nomogram. The nomogram was evaluated and validated using calibration curves, Brier scores, receiver operating characteristic (ROC) curves, C-index, decision curve analyses (DCAs), clinical impact curves (CICs), and risk stratification analyses.

Results

A total of 9216 patients were enrolled after screening. The nomogram included seven variables: cerebrovascular disease, diabetes, body mass index, age, pedicular screw quantity, D-dimer, and hypertension. Calibration plots demonstrated favorable agreement between predicted and observed probabilities. The C-index indicated satisfactory discriminatory ability of the nomogram (0.772 for the training cohort and 0.792 for the validation cohort). Additionally, the DCA and CIC revealed that the nomogram could provide clinical benefits for patients.

Conclusions

This study successfully developed and validated a nomogram that can assess the risk of DVT following posterior lumbar fusion. The nomogram will assist surgeons in making informed clinical decisions.
Association of Self-Reported Improvement After 4 Weeks and Outcomes After 52 Weeks Among Adolescents With Patellofemoral Pain and Osgood-Schlatter Disease
Authors: Rathleff Michael Skovdal , Thorborg Kristian , Andreucci Alessandro , Riel Henrik
Published: October 2024

Background:

Short-term, self-reported changes in symptom severity for musculoskeletal pain disorders may be more strongly associated with long-term prognoses than baseline patient characteristics, because such changes describe a trajectory and not a state.

Purpose:

To investigate whether short-term improvement in self-reported symptom severity is associated with long-term recovery among adolescents with nontraumatic knee pain (patellofemoral pain [PFP] or Osgood-Schlatter disease [OSD]).

Study Design:

Cohort study; Level of evidence, 3.

Methods:

The authors evaluated data from 2 prospective clinical trials that included adolescents aged 10 to 14 years with either PFP (n = 151) or OSD (n = 51). Both groups underwent a self-management rehabilitation program including activity modification, education, and exercise. The primary outcome was a 7-point global rating of change (GROC) scale (from “much improved” to “much worse”); participants were considered to have improved symptoms if they reported being “much improved” or “improved.” Outcomes were collected after 4 and 52 weeks. To investigate whether participants who improved according to GROC scores after 4 weeks were more likely to improve after 52 weeks compared with those who had not improved after 4 weeks, the authors calculated the relative risk (RR) of being improved.

Results:

Among participants with PFP, reporting an improvement after 4 weeks increased the likelihood of an improvement after 52 weeks (RR = 1.26; 95% CI, 1.06-1.50; P = .008); among those with OSD, reporting an improvement after 4 weeks did not increase the likelihood of an improvement after 52 weeks (RR = 1.06; 95% CI, 0.88-1.28; P = .545). Among participants with PFP who did not improve after 4 weeks, 73% reported improvement after 52 weeks, whereas among participants with OSD who did not improve after 4 weeks, 89% reported improvement after 52 weeks.

Conclusion:

Self-reported improvement after 4 weeks of treatment was associated with better outcomes after 52 weeks among adolescents with PFP. This association was present only among adolescents with PFP, as almost all adolescents with OSD improved after 52 weeks, regardless of short-term results. Importantly, even among adolescents reporting no improvement after 4 weeks, a large proportion reported improvement after 52 weeks. This highlights the importance of following the rehabilitation program regardless of the short-term response.
Ethnic Identity and Violence in Urban Spaces: Looking Through the Lens of ‘Cultural Conditioning’
Authors: Pal Gobinda C.
Published: October 2024

In the recent past, the episodes of violence against the Northeast migrants in major metropolitan cities have raised debates on the racial nature of such violence and have drawn scholarly attention. This article maps the experiences of differential treatment and violence among the Northeast migrants in the national capital city and looks into the consequences of such experiences and strategies to cope with various challenges in daily life. It critically examines the experiences through the sociocultural dynamics of the local societies within the city where the ethnic migrants live. It considers the experiential accounts of a sample of 130 Northeast migrants from different urban local cultures in the national capital of India. Data on lived experiences and various perspectives of the Northeast migrants are collected using a mixed-method approach. The article reveals that ethnic identity plays a role in everyday experiences with some sorts of disadvantages. The ‘construction of otherness’ is found to have a disproportionate impact on their day-to-day life. However, there have been perceived positive changes in the ‘perceptual distance’ and inter-group behaviours. Given that most of the experiences of differential treatment and violence among Northeast migrants are located within the context of the local societies in the city and they have everyday encounters for social acceptance, the article argues that the inter-group relationships are exceedingly shaped by the sociocultural orientations of the people in local societies. The article asserts that understanding the violence against a migrant ethnic minority in cosmopolitan cities cannot undermine the role of social and cultural boundaries of urban local societies.
Impact of protein kinase CK2 downregulation and inhibition on oncomir clusters 17 ~ 92 and 106b ~ 25 in prostate, breast, and head and neck cancers
Authors: Kren Betsy T. , Henzler Christine M. , Ahmed Khalil , Trembley Janeen H.
Published: October 2024

Background

Protein kinase CK2 is a ubiquitous and highly conserved protein Ser/Thr kinase with diverse cell functions. CK2 is upregulated in various cancers and affects numerous aspects of their underlying pathobiology. The important role of microRNAs (miRNAs) referred to as oncomirs is also recognized in various cancers. Elevation of both CK2 and altered miRNA expression in cancers raised the question whether there was a connection between CK2 function and oncomirs in cancer.

Methods

PCR array analysis was used to examine the effects of CK2 siRNA-mediated downregulation on miRNA levels in C4-2 prostate cancer cells. We employed prostate cancer, breast cancer, and head and neck squamous cell carcinoma (HNSCC) cells as well as a prostate cancer xenograft orthotopic tumor model to examine the effects of CK2 siRNA-mediated downregulation or chemical inhibition on oncomir cluster miR-17 ~ 92 and miR-106b ~ 25 constituent miRNAs by quantitative reverse-transcriptase stem-loop PCR. Pri-miRNAs were measured in cancer cell lines by quantitative reverse-transcriptase PCR. Protein levels were assessed by western blot. PC3-LN4 prostate cancer orthotopic xenograft tumors and blood were collected from nude mice following repeated treatments with tenfibgen ligand nanocapsules containing RNAi-CK2 or RNAi-Control cargoes.

Results

PCR array analysis demonstrated effect on a subset of miRNAs following CK2 downregulation; we focused our investigation on CK2 regulation of miR-17 ~ 92 and 106b ~ 25 oncomir clusters. Chemical inhibition or molecular downregulation of CK2 greatly reduced expression of miR-17 ~ 92 and 106b ~ 25 in prostate, breast and head and neck cancer cells in vitro. CK2α and CK2α´ protein levels were significantly correlated with many of the miR-17 ~ 92 and some of the miR-106b ~ 25 constituent members in prostate cancer cells. Decreased pri-miRNA levels for the miR-17 ~ 92 gene cluster transcript were observed for 5 of 6 cancer cell lines tested following CK2 downregulation. Nanocapsule-mediated delivery of RNAi-CK2 reduced CK2 protein expression in orthotopic prostate xenograft tumors and decreased intra-tumoral and serum levels of the oncomirs.

Conclusions

Targeting CK2 for the development of new cancer therapies is under active investigation in many laboratories and pharmaceutical companies. Our data suggest a new role for CK2 in cell signaling and survival in multiple cancer types through maintenance of miR-17 ~ 92 and 106b ~ 25 biogenesis.
Impact of community-based precision functional training on older adults’ walking and cognitive abilities in rural Taiwan: a pre–posttest study
Authors: Kuo Fang-Lin , Liao Zih-Yong , Liao Pei-Chun , Wang Hsiu-Hua
Published: October 2024

Background

Functional training is essential for maintaining the independence of older adults, especially in rural areas with limited resources. In this study, we assess the short-term and long-term impacts of the Precision Functional Training (PFT) program on mobility outcomes, specifically walking performance, and cognitive ability in community-dwelling older adults. The unique feature of this training program was its countywide, community-based, and tailored approach, designed to strengthen the functional abilities of older adults living in rural areas.

Methods

158 older adults aged 65 years and above were assessed in this one-group pre–posttest study conducted in 11 community care stations in Chiayi County, Taiwan. Participants had two follow-ups, with data collection on mobility and cognition. The 12-week PFT program, led by certified trainers, integrated aerobic, strength, and cognitive elements. Primary outcomes, including changes in gait, falls, and cognition, were analyzed using linear mixed effects and logit models.

Results

Strengthening mobility is critical to slowing functional decline in older adults. The PFT program led to significant improvements in cognitive function and several gait parameters compared with the baseline. Participants with limited mobility showed enhanced activities of daily living 1-month post-training, but these gains did not persist at the 1-year mark. No significant differences were observed in fall occurrence and knee extension strength.

Conclusions

The training did not have a long-term effect; thus, more frequent practice may be necessary. Risk assessment and community-based interventions, particularly for older adults with a higher risk of falls, are recommended. Future prospective randomized controlled trials are needed to evaluate the PFT program’s effectiveness in preserving mobility.
Measuring fidelity to manualised peer support for people with severe mental health conditions: development and psychometric evaluation of the UPSIDES fidelity scale
Authors: Hiltensperger Ramona , Kotera Yasuhiro , Wolf Philip , Nixdorf Rebecca , Charles Ashleigh , Farkas Marianne , Grayzman Alina , Kalha Jasmine , Korde Palak , Mahlke Candelaria , Moran Galia , Mpango Richard , Mtei Rachel , Ryan Grace , Shamba Donat , Wenzel Lisa , Slade Mike , Puschner Bernd
Published: October 2024

Background

Peer support workers provide support for people experiencing mental health conditions based on their own lived experience of mental health problems. Assessing fidelity to core ingredients of peer support is vital for successful implementation and intervention delivery. Modifications to its implementation are needed when scaling up to different socio-economic settings, raising further uncertainty about fidelity. As part of a large multi-centre study on peer support called Using Peer Support In Developing Empowering Mental Health Services (UPSIDES), we developed and evaluated the psychometric properties of the UPSIDES Fidelity Scale.

Methods

We constructed the fidelity scale based on an initial item pool developed through international expert consultation and iterative feedback. Scale refinement involved site-level expert consultation and translation, resulting in a service user-rated 28-item version and a peer support worker-rated 21-item version assessing receipt, engagement, enactment, competence, communication and peer support-specific components. Both versions are available in six languages: English, German, Luganda, Kiswahili, Hebrew and Gujarati. The scale was then evaluated at six study sites across five countries, with peer support workers and their clients completing their respective ratings four and eight months after initial peer support worker contact. Psychometric evaluation included analysis of internal consistency, construct validity and criterion validity.

Results

For the 315 participants, item statistics showed a skewed distribution of fidelity values but no restriction of range. Internal consistency was adequate (range α = 0.675 to 0.969) for total scores and all subscales in both versions. Confirmatory factor analysis indicated acceptable fit of the proposed factor structure for the service user version (χ2/df = 2.746; RMSEA = 0.084) and moderate fit for the peer support worker version (χ2/df = 3.087; RMSEA = 0.093). Both versions showed significant correlations with external criteria: number of peer support sessions; perceived recovery orientation of the intervention; and severity of illness.

Conclusions

The scale demonstrates good reliability, construct and criterion validity, making it a pragmatic and psychometrically acceptable measure for assessing fidelity to a manualised peer support worker intervention. Recommendations for use, along with research and practical implications, are addressed. As validated, multi-lingual tool that adapts to diverse settings this scale is uniquely positioned for global application.

Trial registration

ISRCTN, ISRCTN26008944. Registered on 30 October 2019.
Daily challenge-hindrance stress and work engagement in preschool teacher: the role of affect and mindfulness
Authors: Zhang Jinghui , Zhang Qing , Wang Yingjie , Xiao Bowen , Wang Shuming , Xu Yige , Li Yan
Published: October 2024

Background

The engagement of preschool teachers in their work is pivotal for maintaining teaching quality, ensuring teacher well-being, and fostering children’s development. Despite its significance, there is limited knowledge regarding the daily fluctuations in work engagement and the underlying factors influencing it. This study, guided by the Job Demands-Resources model and Affect Event Theory, utilized an experience sampling methodology to investigate the impact of challenge and hindrance stressors on daily work engagement, as well as the mediating role of affect and the moderating effect of mindfulness.

Methods

Utilizing an experience sampling method, this study collected data from 220 preschool teachers in Shanghai over five consecutive workdays, conducting surveys once daily. Data analysis was performed using multilevel linear models.

Results

The results from multilevel regression indicated that: (1) daily challenge stressors were positively related to work engagement, (2) daily hindrance stressors were negatively related to work engagement, (3) daily positive affect mediated the relationship between challenge stressors and work engagement, (4) daily negative affect mediated the relationship between hindrance stressors and work engagement, and (5) daily mindfulness played a crucial moderating role by alleviating the adverse effects of hindrance stressors on daily negative affect.

Conclusions

This study provides valuable insights into the daily experiences of preschool teachers and the factors that influence their work engagement. Understanding the impact of stressors, affect, and mindfulness on work engagement can inform the development of interventions and strategies to improve teacher well-being and work engagement.
Insights into psychosocial problems and associated factors among higher education students in Ethiopia: a cross-sectional study
Authors: Gebremariam Hailay Tesfay , Tassew Million Desalegn , Woldemaryam Frehiwot Sahle
Published: October 2024

While there has been extensive research on well-known psychosocial problems like depression, anxiety, and stress among higher education students, emerging issues such as emotional problems, antisocial behavior, trauma experiences, and academic difficulties are not as thoroughly studied, particularly in the context of Ethiopian higher education students. These updated psychosocial problems are crucial to explore due to their potentially significant impact on students’ academic performance, personal development, and future prospects. Therefore, this study aims to explore the current psychosocial issues faced by adolescent students at Arba Minch University and identify the factors associated with them. To accomplish this objective, a survey questionnaire was distributed to a sample of 300 university students through a cross-sectional study. The survey questionnaire was designed to provide a thorough understanding of the various types of psychosocial problems experienced by the students. The findings revealed that the most prevalent psychosocial problems among higher education adolescent students were emotional problems (6.7% high/severe, 46.3% moderate), antisocial behavior (5% high/severe, 54.7% moderate), trauma experiences (7% high/severe, 23% moderate), and academic problems (8.3% high/severe, 23% moderate). The prevalence of no/low psychosocial problems was 47%, 40.3%, 69.3%, and 68.7%, respectively. Additionally, statistically significant (p < 0.05) associated factors to these psychosocial problems were identified: gender for academic problems, religion affiliation for antisocial behavior, trauma experiences, marital status for trauma experiences, living situation during holidays for emotional problems, age for emotional problems and antisocial behavior, and educational sponsorship for antisocial behavior. The study found that students who lacked a support system, such as family or friends, were more likely to experience psychosocial problems. In conclusion, psychosocial problems among adolescent students in higher education are a pressing issue that requires immediate attention. By understanding the challenges faced by these students, universities can implement effective interventions to support their mental well-being.
Blood eosinophil count is associated with early atherosclerotic artery changes in asthma
Authors: Biener Leonie , Frisch Ben Christoph , Skowasch Dirk , Pizarro Carmen , Budimovska Andrea , Nickenig Georg , Stumpf Max Jonathan , Schahab Nadjib , Schaefer Christian
Published: October 2024

Objective

Asthma is linked to atherosclerosis, yet the underlying mediators remain elusive. Eosinophils may contribute to both asthmatic and atherosclerotic inflammation. Hence, this study aimed to explore the potential associations of eosinophils with artery changes among patients with asthma.

Methods

We assessed strain values of the common carotid arteries (CCAs) via vascular speckle tracking and compared asthma patients with low (< 300/µl) and high (≥ 300/µl) blood eosinophil counts (BEC).

Results

We enrolled 100 patients, 42 with a BEC of < 300 and 58 with a BEC of ≥ 300 n/µl. Patients with high BEC exhibited more severe disease, characterized, e.g., by a higher frequency of acute exacerbations (1.3 ± 2.1 vs. 2.6 ± 2.4 n/year, p = 0.005). Both groups presented similar profiles in terms of conventional cardiovascular risk. The high BEC group demonstrated elevated arterial stiffness, reflected by reduced radial strain (mean radial strain of the right CCA: 2.7 ± 1.4% for BEC ≥ 300 n/µl vs. 3.5 ± 1.7% for BEC < 300 n/µl, p = 0.008; left CCA: 2.6 ± 1.4% vs. 4.1 ± 2.2%, p < 0.001). A weak yet statistically significant negative correlation was observed between BEC and radial strain for the right CCA (R2 = 0.131, b=-0.001, p = 0.001) and left CCA (R2 = 0.086, b=-0.001, p = 0.015). However, the prevalence of cerebrovascular disease was similar in both groups (31,0% vs. 50,0%, p = 0.057).

Conclusion

We identified a correlation between BEC and vascular stiffness, which supports the hypothesis that eosinophils may promote atherosclerosis.

Clinical trial number

Due to the exploratory and predominantly retrospective nature of the study, trial registration was not conducted. The only prospective procedure conducted was the angiological sonography to evaluate the current state. No ensuing health-related interventions were performed specifically for this study.
Pilot implementation study of a web-based men’s health screening app in primary care during COVID-19: a mixed-methods approach
Authors: Ooi Chor Yau , Ng Chirk Jenn , Sales Anne , Teo Chin Hai
Published: October 2024

Background

The traditional delivery of healthcare services, including crucial preventive measures such as health screenings, faced significant disruption due to the COVID-19 pandemic. In response, eHealth technology emerged as a practical alternative for conducting screening services. This pilot study introduces ScreenMen, a web-based app for men’s health screening, implemented in a primary care setting. The study aims to assess patient uptake and healthcare provider’s acceptability and feasibility of implementing ScreenMen, emphasizing the importance of implementation science research in healthcare innovation.

Methods

This study employed a mixed-method explanatory sequential design, using a tailored implementation intervention to implement ScreenMen in an urban health clinic. Quantitative phase focused on patient uptake of ScreenMen and healthcare provider involvement, utilizing Google Analytics and provider questionnaires. Qualitative phase, using in-depth interviews with providers, explored factors influencing uptake and implementation. Data analysis employed means and percentages for quantitative data and framework analysis for qualitative data.

Results

We invited 47 healthcare providers to attend the ScreenMen implementation workshop, with 26 participating, resulting in a 55.3% participation rate. Throughout the five-month study, there were 75 recorded accesses, with a completion rate of 20%. The primary way users accessed the app was through QR codes on buntings (38.7%), followed by postcards (12%). In qualitative interviews with three healthcare providers, it was found that the Identify and prepare champions strategy was helpful, as these champions led the implementation and encouraged other providers to promote ScreenMen. The use of QR codes on buntings, part of the Provide education and training strategy, was effective due to their visibility in patient waiting areas. However, the Mandate change strategy was considered ineffective, as providers felt obligated rather than motivated to implement ScreenMen.

Conclusion

This study highlighted the uptake of ScreenMen and found barriers and facilitators during the pilot implementation. Two useful strategies were Identify and prepare champions and QR codes while Mandate change was not helpful. Further studies are needed to study the effectiveness of these implementation strategies to implement web-based apps.

Trial registration

Clinical Trial Number: NCT06388473 (Retrospectively registered 05/04/2024).
TARS2 c.470 C > G is a chinese-specific founder mutation in three unrelated families with mitochondrial encephalomyopathy
Authors: Zhang Shujie , Qin Haisong , Wang Qingming , Wang Yingfei , Liu Yanhui , Yang Qi , Luo Jingsi , Qin Zailong , Ji Xiang , Kan Lijuan , Geng Guoxing , Huang Jing , Wei Shengkai , Chen Qiuli , Shen Yiping , Yuan Haiming , Lai Baoling
Published: October 2024

Biallelic pathogenic variants in TARS2 lead to combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early-onset severe axial hypotonia, limb hypertonia, psychomotor developmental delay, epilepsy and brain anomalies. To date, approximately 28 individuals with COXPD21 and 28 TARS2 variants have been identified. In this study, we reported additional four individuals from three unrelated Chinese families with mitochondrial encephalomyopathy caused by pathogenic variants in TARS2, and described the novel clinical phenotypes and genotypic information. In addition to two novel variants (c.512G > A, p.Arg171Lys; c.988dup, p.Arg330Lysfs*4), one previously reported variant (c.470 C > G, p.Thr157Arg) recurred in six Chinese individuals with COXPD21 but was not present in populations of other races. Our findings expanded the mutation spectrum of TARS2 and confirmed that c.470 C > G is a Chinese-specific founder mutation. The novel phenotypes, including reduced fetal movement, eye anomalies and sleep irregularities, observed in our patients enriched the clinical characteristics of COXPD21.
Rare Disease Focused Antenatal Education and Diagnosis Support: Two Case Studies of Epidermolysis Bullosa Simplex
Authors: Saad Rebecca , Pysar Ryan , Blackwell Alaxandra
Published: October 2024

Many people living with a rare disease (RD) face challenges accessing timely diagnosis and disease-specific specialist care. Early health-care challenges for people living with Epidermolysis Bullosa (EB), a rare genetic disease affecting 1:20,000 individuals, can begin in the antenatal period.

People living with EB in Australia have access to a government funded disease specific antenatal education and support program through the National Epidermolysis Bullosa Dressing scheme (NEBDS). This article discusses two births involving families living with EB Simplex (EBS) in regional Australia. The education and support structures implemented by the NEBDS and clinical teams are discussed in line with the Australian National Strategic Action Plan for rare diseases, and includes access to genetic diagnosis, EB education, and complex care coordination.
Withaferin A ameliorates ovarian cancer-induced renal damage through the regulation of expression of inflammatory cytokines
Authors: Kumar Kusum , Bosch Katherine , Vemuri Vasa , Kratholm Nicholas , Rane Madhavi , Kakar Sham S.
Published: October 2024

Background

Cachexia a multifactorial syndrome is a common sequala in patients with cancer. It varies from 42 to 80% depending upon the oncological stage and is directly responsible for 30% of deaths in these patients. Previous research from our laboratory demonstrated that peritoneal ovarian cancer generated in NSG mice resulted in skeletal and cardiac muscle atrophy - leading to loss of skeletal muscle mass and strength, and cardiac dysfunction (cachexia). Treatment of mice bearing i.p. tumors with withaferin A (WFA) showed reversal of skeletal muscle and cardiac cachexia. The present study is focused on determining effects of peritoneal ovarian tumors on kidney damage and effects of WFA treatment on ameliorating kidney damage.

Methods

We generated intraperitoneal ovarian cancer by injecting female NSG mice with ovarian cancer cell line (A2780). After one week of injecting cancer cells, mice were treated with WFA (4 mg/kg) every third day, for three weeks. After 4 weeks of injection of cancer cells, the mice were sacrificed and various tissues including kidney and blood were collected, snap-frozen in liquid nitrogen, and stored at -800C. The presence of kidney biomarker creatinine, was measured in the plasma by an ELISA. The mRNA was isolated from mouse kidneys and was used to examine the expression levels of signaling proteins, inflammatory cytokines, and genes responsible for inducing cachexia (IL-1β, IL-6, TNF-α, TGF-β, GDF-15, and MYD88).

Results

Our results showed a significant increase in levels of expression of inflammatory cytokine IL-1 β (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.001), and other related genes including TRAF6 (p < 0.01), MYD88 (p < 0.01), and GDF-15 (p = 0.005) in tumor-bearing mice compared to controls. Treatment of mice bearing tumors with WFA attenuated the increase in expression of each gene. In addition, our results showed a significant increase in creatinine levels in circulation in tumor-bearing mice compared to control mice. Treatment of tumor-bearing mice with WFA resulted in a significant decrease in plasma creatinine levels compared to tumor-bearing mice.

Conclusions

Our results conclude that ovarian tumors in NSG mice caused kidney damage and renal dysfunction, which was effectively ameliorated by WFA treatment, suggesting a protective effect of WFA on kidney injury induced by ovarian cancer.
Methotrexate promotes the release of granulocyte–macrophage colony-stimulating factor from rheumatoid arthritis fibroblast-like synoviocytes via autocrine interleukin-1 signaling
Authors: Bergström Beatrice , Selldén Tilia , Bollmann Miriam , Svensson Mattias N. D. , Ekwall Anna-Karin Hultgård
Published: October 2024

Background

Activated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators.

Methods

Primary RA-FLS were activated by stimulation with interleukin-1β (IL-1β) or platelet-derived growth factor + IL-1β in the presence or absence of MTX or TOFA, with or without additional inhibitors. Co-cultures of synovial cells were performed in direct and indirect systems. Cells were collected for RNA sequencing or qPCR, and supernatants were analyzed for protein concentrations.

Results

Six thousand three hundred fifty genes were differentially expressed, the majority being upregulated, in MTX-treated activated RA-FLS and 970 genes, the majority being downregulated, in TOFA-treated samples. Pathway analysis showed that MTX had largest effects on ‘Molecular mechanisms of cancer’ and TOFA on ‘Interferon signaling’. Targeted analysis of disease-associated genes revealed that MTX increased the expression of cell cycle-regulating genes but also of pro-inflammatory mediators like IL-1α (IL1A) and granulocyte–macrophage colony-stimulating factor, GM-CSF (CSF2). The MTX-promoted expression of CSF2 in activated RA-FLS peaked at 48 h, could be mediated via either NF-κB or AP-1 transcription factors, and was abrogated by IL-1 inhibitors (IRAK4 inhibitor and anakinra). In a co-culture setting, MTX-treatment of activated RA-FLS induced IL1B expression in macrophages.

Conclusions

MTX treatment induces secretion of IL-1 from activated RA-FLS which by autocrine signaling augments their release of GM-CSF. This unexpected effect of MTX might contribute to the persistence of synovitis.
Effects of dietary Lactobacillus postbiotics and bacitracin on the modulation of mucosa-associated microbiota and pattern recognition receptors affecting immunocompetence of jejunal mucosa in pigs challenged with enterotoxigenic F18+ Escherichia coli
Authors: Duarte Marcos Elias , Deng Zixiao , Kim Sung Woo
Published: October 2024

Background

Enterotoxigenic Escherichia coli (E. coli) is a threat to humans and animals that causes intestinal disorders. Antimicrobial resistance has urged alternatives, including Lactobacillus postbiotics, to mitigate the effects of enterotoxigenic E. coli.

Methods

Forty-eight newly weaned pigs were allotted to NC: no challenge/no supplement; PC: F18+ E. coli challenge/no supplement; ATB: F18+ E. coli challenge/bacitracin; and LPB: F18+ E. coli challenge/postbiotics and fed diets for 28 d. On d 7, pigs were orally inoculated with F18+ E. coli. At d 28, the mucosa-associated microbiota, immune and oxidative stress status, intestinal morphology, the gene expression of pattern recognition receptors (PRR), and intestinal barrier function were measured. Data were analyzed using the MIXED procedure in SAS 9.4.

Results

PC increased (P < 0.05) Helicobacter mastomyrinus whereas reduced (P < 0.05) Prevotella copri and P. stercorea compared to NC. The LPB increased (P < 0.05) P. stercorea and Dialister succinatiphilus compared with PC. The ATB increased (P < 0.05) Propionibacterium acnes, Corynebacterium glutamicum, and Sphingomonas pseudosanguinis compared to PC. The PC tended to reduce (P = 0.054) PGLYRP4 and increased (P < 0.05) TLR4, CD14, MDA, and crypt cell proliferation compared with NC. The ATB reduced (P < 0.05) NOD1 compared with PC. The LPB increased (P < 0.05) PGLYRP4, and interferon-γ and reduced (P < 0.05) NOD1 compared with PC. The ATB and LPB reduced (P < 0.05) TNF-α and MDA compared with PC.

Conclusions

The F18+ E. coli challenge compromised intestinal health. Bacitracin increased beneficial bacteria showing a trend towards increasing the intestinal barrier function, possibly by reducing the expression of PRR genes. Lactobacillus postbiotics enhanced the immunocompetence of nursery pigs by increasing the expression of interferon-γ and PGLYRP4, and by reducing TLR4, NOD1, and CD14.
Building capacity for testing sterile insect technique against Aedes-borne diseases in the Pacific: a training workshop and launch of sterile insect technique trials against Aedes aegypti and arboviral diseases
Authors: Foley Nicole , Fouque Florence , Zhong Qingxia , Bossin Herve , Bouyer Jeremy , Velayudhan Raman , Nett Randall , Drexler Anna
Published: October 2024

Background

Vector-borne diseases cause morbidity and mortality globally. However, some areas are more impacted than others, especially with climate change. Controlling vectors remains the primary means to prevent these diseases, but new, more effective tools are needed. The World Health Organization (WHO) prioritized evaluating novel control methods, such as sterile insect technique (SIT) for control of Aedes-borne diseases. In response, a multiagency partnership between the U.S. Centers for Disease Control and Prevention (CDC), the Special Programme for Research and Training in Tropical Diseases (TDR), WHO, and the International Atomic Energy Agency (IAEA) supported the operational implementation and evaluation of SIT against Aedes aegypti and arboviral diseases in the Pacific through a consortium of regional partners (PAC-SIT Consortium).

Main text

A workshop was held from 2 to 6 May 2023, during which PAC-SIT country participants, researchers, and stakeholders in SIT, scientific advisory committee members, and organizational partners came together to review the principles and components of SIT, share experiences, visit field sites and the SIT facility, and officially launch the PAC-SIT project. Working in groups focused on entomology, epidemiology, and community engagement, participants addressed challenges, priorities, and needs for SIT implementation.

Conclusions

The PAC-SIT workshop brought together researchers and stakeholders engaged in evaluating SIT for arboviral diseases in the Pacific region and globally. This training workshop highlighted that many countries are actively engaged in building operational capacities and phased testing of SIT. The workshop identified a key need for robust larger-scale studies tied with epidemiological endpoints to provide evidence for the scalability and impact on mosquito-borne diseases.
Volume changes in the contralateral submandibular gland following unilateral gland excision in oral cancer patients
Authors: Kang Yei-Jin , Park Young-Wook , Choi Hang-Moon , Kim Seong-Gon
Published: October 2024

Background

The effects of unilateral submandibular gland excision on the size of the contralateral gland are not well understood, with no human studies reported to date. This study aims to investigate the impact of unilateral submandibular gland excision on the contralateral gland’s size, providing insights into compensatory mechanisms and their clinical implications.

Method

This retrospective study involved patients with oral cancer who underwent unilateral submandibular gland excision and ipsilateral neck dissection at Gangneung-Wonju National University Dental Hospital between 2008 and 2023. Patients were included if they had preoperative and follow-up 3D radiological images. The contralateral submandibular gland volume was measured using 3D Slicer software on preoperative, post-operative, and follow-up radiographic data.

Results

The mean volume change of the contralateral submandibular gland was 1.35 ± 2.06 cm3, with a mean change ratio of 1.18 ± 0.24. These changes were statistically significant (p = 0.006). Other factors such as age, gender, and radiotherapy did not significantly affect the volume change ratio (p > 0.05).

Conclusion

The contralateral submandibular gland exhibits a statistically significant increase in volume following unilateral gland excision, indicating compensatory hypertrophy. This morphological adaptation should be considered in post-operative care and surgical planning for oral cancer patients to optimize outcomes.
Rheumatic fever and long-term use of benzathine penicillin as possible risk factors for extensive macular atrophy with pseudodrusen in a Brazilian cohort
Authors: Moreira-Neto Carlos Augusto , Schmidt Andujar Rafaella Atherino , Chao John Chii Tyng , Vasconcelos Huber , Alves Fábio Eduardo Eberhardt , Rodrigues Gabriela Doná , Hirt Bruno , Arana Jayme , Souza Eduardo Cunha , Maia André , Sallum Juliana Maria Ferraz , Moreira Carlos Augusto
Published: October 2024

Background

Although there has been a large increase in the number of extensive macular atrophy with pseudodrusen (EMAP) cases, the basic aspects of this disease remain unknown. Brazilian patients have a common past history of rheumatic fever (RF) and/or benzathine penicillin (BP) treatment possibly related to the disease. We analyzed how RF and BP might be correlated with EMAP in Brazilian patients.

Design

Observational, retrospective, case-control study.

Methods

The databases of three private eye clinics in Brazil were searched for patients with an EMAP-like appearance. Each patient was asked about a previous history of RF and/or long-term use of BP. Patients underwent best-corrected visual acuity (BCVA) measurement, color fundus imaging, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT) imaging, and electroretinography (ERG). The following characteristics were analyzed: subretinal drusenoid deposits (SDD), pigment mottling, retinal pigment epithelial/basement membrane (RPE/BM) separation, outer retinal or RPE atrophy, and identification of a paving stone-like appearance. The choroidal thickness was measured using enhanced depth imaging OCT. The central atrophic area was measured manually on ultra-wide-field FAF.

Results

A total of 154 eyes of 77 patients (women, 66.2%; mean age, 58.6 years) with EMAP were included; 90.9% of patients were diagnosed with RF; 94.8% had been treated with BP and treatment was started at an average age of 7.3 years (mean duration, 11.8 years). The treatment duration was significant for the area of atrophy (P = 0.027) in which each 1-year increase in treatment duration led to an average reduction of 6.91 mm2 in area. The age at diagnosis of RF was significant (P = 0.026) for SDD. The increase of 1 year in the diagnosis of RF (late disease) led to a reduction of 24% in the chance of central SDD being present. On OCT, 65.5% eyes had SDD and more than 70% had a split RPE/BM and outer retinal or RPE atrophy. The choroidal thickness in patients with EMAP was significantly (P < 0.001) thinner than the control group. The ERG was abnormal in all eyes.

Conclusion

These findings may suggest a relation between RF and EMAP in Brazilian patients. Patients with EMAP should be questioned about a history of RF.
Comparison of heart failure risk assessment tools among cancer survivors
Authors: Soh Cheng Hwee , Marwick Thomas H.
Published: October 2024

Background

Cancer survivors have an increased risk of incident heart failure (HF) attributable to shared risk factors and cancer treatment-induced cardiac dysfunction. Selection for HF screening depends on risk assessment, but the optimal means of assessing risk is undefined. We undertook a comparison of HF risk calculators among survivors.

Methods

In this study from the UK Biobank, cancer and HF diagnoses were determined based on the International Classification of Diseases (ICD)-10 code and non-cancer participants were included as controls. Participants’ risk of incident HF was determined using the Heart Failure Association-International Cardio-oncology Society (HFA-ICOS), the Atherosclerosis Risk in Communities (ARIC-HF) and the Pooled Cohort Equations to Prevent Heart Failure (PCP-HF). The predictive performances of each were compared using the area under the curve (AUC).

Results

After propensity matching with age and sex, 9,232 survivors from breast cancer or lymphoma (mean age 59.9 years, 87.8% female), and 23,800 survivors from other cancer types (mean age 59.1 years, 85.8% female) were included in the analysis. The discriminative value for HFA-ICOS (AUC 0.753 [95%CI: 0.739–0.766]) and ARIC-HF (0.757 [95%CI: 0.744–0.770]) were similar, and superior to PCP-HF (0.717 [95%CI: 0.702–0.732]). The overall performance for each risk score was better among participants in other cancer types than those with breast cancer and lymphoma.

Conclusions

HFA-ICOS and ARIC-HF outperformed the PCP-HF among cancer- and non-cancer cohort, although all showed modest discrimination for incident HF to be applied to clinical practice. A cancer-specific HF prediction tool could facilitate HF prevention among survivors.
Genital findings in adult females: a forensic analysis of photographic records
Authors: Al-Saif Dalia , Al-Farayedhi Maram , Al-Shamsi Ghada , Al-Zahrani Azzah , Al-Bayat Marwah
Published: October 2024

Background

In the investigation of sexual assault cases, a standard practice involves examining female genitalia to identify injuries. The majority of research was done to examine findings in the child age group, but very little research was done on the adult age group. There is a need for guidelines to follow for the interpretation of adult female findings as they hold the same significance as in children. The Dammam Forensic Medicine Center conducted a retrospective chart review study in the period from 2014 to 2021 to examine adult female genital findings utilizing photographic documentation.

Results

One hundred sixty-three cases involving adults between the ages of 18 and 52 were examined. Cases were divided into two groups to focus on hymenal findings that fell in the class of no expert consensus. The first group included self-defined virgins, who denied having ever experienced vaginal penetration in their entire lives, including the reported incidence, which represented 38 cases. The rest of the cases had at least a single incident of vaginal penetration. The normal genitourinary findings were found comparable to those in the child age group. All of the participants who showed notches or clefts, below the 3 o’clock or 9 o’clock location, which extends nearly to the base of the hymen, but is not a complete transection belonged to the group with a history of vaginal penetration. The three participants who showed a notch or a cleft in the hymen rim at 3 o’clock or 9 o’clock which extends nearly to the base of the hymen, but is not a complete transection belonged to the same group.

Conclusions

Findings that lack expert consensus in the child age group are likely the result of injury in the study participants. This result gives valuable information on genital findings in self-identified virgin adult females, which can be utilized in conjunction with other studies to establish standards for the assessment of cases of alleged sexual assault in adult females.
Radioprotective potential of pomegranate peel extract against gamma irradiation-induced hazards
Authors: Hamieda Shimaa Farag , Saied Mona , Abd-El-Nour K. N. , Hassan Amal I.
Published: October 2024

Background

While gamma irradiation’s damaging biological effects are well-established, the natural radioprotective agents from agricultural waste remain an underexplored area of significant potential.

Aim of study

This study was to investigate the novel use of pomegranate peel ethanol extract (PE) as a radioprotective agent against gamma radiation damage.

Methods

We pretreated Wistar rats with PE (100 mg/kg) for 14 days prior to 6 Gy gamma irradiation. We analyzed blood biochemicals, oxidative stress, and inflammatory markers. These included tests of red cell membrane integrity, lipid and protein oxidation, antioxidant enzyme levels, and cytokine profiles.

Results

The study showed that PE demonstrated remarkable radioprotective effects across multiple parameters. Antioxidants were significantly enhanced, as evidenced by increased glutathione peroxidase activity (87.00 ± 6.11 mg/ml in PE-treated irradiated rats compared to 26.40 ± 1.21 mg/ml in irradiated controls). Oxidative damage was markedly reduced, with MDA levels dropping from 9.59 ± 0.24 nmol/ml in irradiated controls to near-control levels in PE-treated rats. Notably, PE treatment resulted in unprecedented maintenance of red blood cell membrane integrity post-irradiation. Furthermore, PE exhibited novel modulation of inflammatory cytokines, effectively reducing pro-inflammatory markers IL-6 and TNF-α while simultaneously boosting anti-inflammatory IL-4 and IL-10 levels. These multifaceted protective effects highlight PE’s potential as a comprehensive radioprotective agent.

Conclusion

This study presents PE as an effective new natural radioprotective agent. Its protective effect is due to its high polyphenol content, which enhances antioxidant defenses, reduces oxidative damage, and prevents inflammation. The findings open new avenues for sustainable, cost-effective radioprotection strategies and demonstrate the potential for repurposing agricultural byproducts for critical health applications.
MVD-HG: multigranularity smart contract vulnerability detection method based on heterogeneous graphs
Authors: Xu Jingjie , Wang Ting , Lv Mingqi , Chen Tieming , Zhu Tiantian , Ji Baiyang
Published: October 2024

Smart contracts have significant losses due to various types of vulnerabilities. However, traditional vulnerability detection methods rely extensively on expert rules, resulting in low detection accuracy and poor adaptability to novel attacks. To address these problems, in this paper, deep learning methods are combined with smart contract vulnerability code detection approaches. Abstract syntax trees (ASTs), which are special isomorphic graph structures, are an important bridge between source code and graph neural networks. By learning the AST, the model can understand the semantics of the source code. Moreover, graph neural networks have an increasing ability to address complex heterogeneous graphs. Therefore, control flow graphs are fused with data flow graphs on the basis of the ASTs to build heterogeneous graphs with richer code semantics. Furthermore, multigranularity analysis of the vulnerability detection results is performed, including coarse-grained contract-level vulnerability detection and fine-grained line-level vulnerability detection. Through this multigranularity detection approach, vulnerabilities in contracts can be identified and analysed more comprehensively, providing a richer perspective and more solutions for vulnerability detection. The experimental results show that the proposed multigranularity vulnerability detection method based on heterogeneous graphs (MVD-HG) improves both the accuracy and range of the detected vulnerability types in contract-level vulnerability detection tasks; moreover, in the line-level vulnerability detection task, the MVD-HG model achieves significant results and addresses the shortcomings of existing methods. In addition, based on code generation methods used in related fields, a data enhancement method based on the source code is developed, which effectively expands the experimental dataset to address the reduced credibility of the results due to insufficient amounts of data.