bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripapillary Vascular Density Differentiates Glaucomatous Cupping From Physiological Cupping Using Optical Coherence Tomography Angiography
Authors: Ashour Doaa Maamoun , Madkour Nesrin Said , Ebeid Weam Mohamed , Mahmoud Rabab Aboelmaaty
Published: December 2024

Précis:

In glaucoma, peripapillary vascular density was reduced compared to normal eyes, with or without physiological cupping.

Purpose:

To assess the ability of radial peripapillary capillaries vessel density (RPC VD) to distinguish between physiological and glaucomatous cupping using optical coherence tomography angiography (OCTA)

Patients and Methods:

An observational study was conducted at Ain Shams University, involving 98 eyes from 98 patients, divided into three groups. Group 1 included thirty eyes with primary open angle glaucoma, group 2 included twenty-eight normal eyes with physiological cupping (vertical cup/ disc ratio 0.6 or more based on structural OCT and no evidence of glaucoma), and group 3 included forty age-matched normal eyes (vertical cup/disc ratio ≤ 0.5). Participants were subjected to ophthalmological examination, structural optical coherence tomography (OCT), and OCTA of the optic disc.

Results:

Group 1 exhibited significantly lower RPC VD than the other groups (P<0.001), while no significant differences were noted between group 2 and 3 (P=0.559). Moderate negative correlations were observed between C/D vertical (r=−0.556, P=0.002), and horizontal ratios (r=−0.430, P=020), and RPC VD in glaucomatous eyes across the whole image and its four quadrants. No significant correlations were found between these parameters in the other groups.

Conclusion:

Using OCTA, glaucomatous eyes showed reduced RPC VD compared to normal eyes, even in the presence of physiological cupping. This finding may help to differentiate between physiological and glaucomatous cupping.
Physiotherapeutic Guidelines for Initiating and Terminating Early Mobility for Patients on Extracorporeal Membrane Support
Authors: Kargela Mallory , Sigler Julie
Published: December 2024

Background:

Extracorporeal membrane oxygenation (ECMO) therapy is a crucial intervention for critically ill patients, but prolonged immobilization can lead to physical deconditioning and complications. Early progressive mobility (EPM) protocols aim to mitigate these challenges, yet uncertainties exist regarding the optimal timing and criteria for initiating and terminating physical therapy during ECMO support.

Objective:

This scoping review aims to synthesize existing literature to address key questions concerning physical therapy management during ECMO therapy, focusing on the physiological parameters guiding the initiation and termination of therapy sessions.

Methods:

A systematic search was conducted using PRISMA guidelines to identify relevant studies from January 2013 to October 2023. Eligibility criteria were established, and data extraction was performed to identify physiological parameters utilized in physical therapy decision-making for ECMO patients.

Results:

Thirteen studies, comprising various study designs and expert consensus documents, were included in the review. Physiological parameters such as hemodynamic stability, oxygenation, sedation scales, and specific thresholds emerged as crucial considerations for initiating and terminating physical therapy interventions. While some consensus exists, variability in criteria highlights the need for standardized guidelines.

Conclusion:

Despite the growing recognition of the importance of early mobility and physical therapy in ECMO patients, gaps in evidence remain regarding optimal management strategies. Formal protocols integrating detailed physiological parameters could enhance patient safety and optimize rehabilitation practices. Further research and consensus-building efforts are essential to establish definitive guidelines for physical therapy management during ECMO support, ultimately improving patient outcomes and enhancing the quality of care.
Causal relationship between inflammatory bowel disease and gingivitis or periodontal disease: A two-sample Mendelian randomized analysis
Authors: Ma Yi-Chao , Li Wen-Qi , Wei Chen , Wang Fei , Liao Yi-Qun , Zhao Bin , Chen Yu-Ji , Zhao Qi , Qiu Jie , Tang Dong
Published: December 2024

Background

Observational studies have shown that inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn disease (CD), is associated with gingivitis and periodontal disease (GP). This study aims to investigate whether there is a causal relationship between IBD and GP.

Methods

This study assessed the causal relationship between IBD and GP through a two-sample Mendelian randomization (MR) study. The required data were obtained through the IEU OpenGWAS project. Instrumental variable screening and the MR and sensitivity analyses were performed using the “TwoSampleMR” R package.

Results

IBD, UC, and CD may have a causal effect on GP (IBD, inverse variance weighting [IVW] OR = 1.05, 95% CI = 1.00–1.10, P = 0.03; UC, IVW OR = 1.05, 95% CI = 1.00–1.11, P = 0.03; CD, weighted median OR = 1.06, 95% CI = 1.00–1.13, P = 0.04; simple mode OR = 1.15, 95% CI = 1.02–1.31, P = 0.03). Scatterplots, forest plots, and funnel plots showed a significant relationship between IBD and GP and confirmed the robustness of the model. In sensitivity testing, no horizontal pleiotropy or heterogeneity was found in this study.

Conclusions

This study found a possible causal relationship between IBD (UC and CD) and GP, which deserves to be considered in clinical practice.
Treatment of cancer cachexia with exercise
Authors: Wang Yan , Zhuo Wen-Lei
Published: December 2024

Cancer cachexia is a multifactorial syndrome characterized by the irreversible loss of body weight, fat, and muscle. Its main characteristics include nutrient intake and absorption disorders, systemic inflammation, mitochondrial dysfunction, immune imbalance, and protein and fat consumption, which ultimately lead to patient death. So far, there has been no effective method identified to combat the malignant progression of cancer cachexia. The effects of a single nutritional supplement or drug intervention strategy are insufficient. Exercise training is considered a potential treatment for cancer cachexia. Both clinical studies and animal experiments suggest that exercise training can help improve the intake and absorption of nutrients, inhibit inflammatory signaling pathways, regulate immunity and metabolism, alleviate insulin resistance, promote protein synthesis, maintain muscle mass, and so on. The use of multimodal methods that combine nutritional support and/or other treatments with exercise provides a potential prospect for the treatment of cancer cachexia. However, the optimal prescription of exercise for the treatment of cancer cachexia is still unclear. The main purpose of this review is to summarize the growing body of research on the impact of exercise on cancer cachexia and to provide evidence supporting the use of exercise as an intervention for cancer cachexia in the clinical setting.
Multiple pulmonary ground-glass nodules: Challenges and advances
Authors: Guo Fei-Fei , Huang Jue , Chen Fei , Cui Jiu-Wei
Published: December 2024

Multiple pulmonary ground-glass nodules (GGNs), a typical clinical manifestation of multiple primary lung cancers (MPLCs), are of great significance for the early screening, diagnosis, and accurate treatment of lung cancer. Thus, the recent increase in the detection rate of multiple pulmonary GGNs has attracted much attention. However, compared with the more widely studied single GGNs, evaluating GGNs is more challenging because of the uncertainty of the etiology, difficult differential diagnosis, and lack of optimal management standards and guidelines. Most current solutions for multiple GGNs are based on the management experiences and principles of a single GGN. Therefore, it is necessary to obtain better understanding of multiple GGNs and to optimize the diagnostic methods and treatments. Both the existing challenges and potential of new methods for diagnosing and treating multiple pulmonary GGNs are reviewed and discussed in this article, with the aim of providing a reference for the clinical management of this highly prevalent condition.
Correlation of dietary mineral intake and malnutrition in cancer patients: A multicenter cross-sectional study
Authors: Wang Ying , Xue Hong-Mei , Miao Jun-Jie , Du Hong-Zhen , Luo Bin , Li Zeng-Ning
Published: December 2024

Background

To examine the correlation between the dietary mineral intake and the nutritional status of patients suffering from malignancies.

Methods

This multicenter cross-sectional study included a total of 866 patients with malignant tumors recruited from seven hospitals throughout China. The information of sociodemographic characteristics and biochemical indicators was obtained from electronic medical records of inpatients. Dietary data were collected using a 3-day 24-hour dietary recall questionnaire. The intakes of energy, dietary calcium (Ca), phosphorus (P), potassium (K), sodium (Na), magnesium (Mg), iron (Fe), zinc (Zn), selenium (Se), copper (Cu), and manganese (Mn) were estimated according to the Chinese Food Composition Tables (standard edition). The weight and height of patients were measured, and the body mass index (BMI) was calculated. Nutritional risk and malnutrition were assessed by the Nutritional Risk Screening 2002 (NRS 2002) and Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria. We used a multivariable logistic regression model to estimate the associations between dietary minerals and malnutrition.

Results

The patients had an average age of (61.98 ± 15.49) years, and 40.6% (n = 352) were female. Slightly less than half (44.5%) of the patients were at nutritional risk (NRS 2002 ≥ 3), and 32.7% were diagnosed with malnutrition (using the GLIM criteria). Univariate analyses revealed that there was a statistically significant relationship between dietary mineral intake and the occurrence of nutritional risk (P < 0.001). After adjusting the collinearity, we found that higher levels of P, Mn, and Se intake were negatively associated with nutritional risk assessed by the NRS 2002 score. Moderate intake of Ca and high intake of Zn might also decrease the nutritional risk [Ca: odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.32–0.88; Zn: OR = 0.36, 95% CI = 0.19–0.68]. However, no significant relationships were observed between any dietary mineral intake and malnutrition identified by the GLIM criteria.

Conclusions

Dietary minerals, especially P, Se, and Mn, may have a protective effect on the occurrence of nutritional risk in patients with malignant tumors. In addition, patients should maintain appropriate levels of Ca and Zn.
Bioinformatics analysis of key genes associated with the prognosis of breast cancer
Authors: Zhou Kun , Huang Dao-Lai , Ruan Hui-Chao , Wu Xiang-Hua
Published: December 2024

Background

We sought to identify potential therapeutic targets for breast cancer patients by employing a bioinformatics analysis to screen for genes linked with an unfavorable prognosis.

Methods

The Gene Expression Omnibus (GEO) database was utilized to obtain 3 gene expression profile datasets, namely, GSE42568, GSE86374, and GSE71053. To identify differentially expressed genes (DEGs), the GEO2R online tool was employed. Subsequently, a functional enrichment analysis was conducted. Moreover, a protein-protein interaction network was established using STRING, and DEGs were subjected to module analysis via Cytoscape software to identify pivotal genes. Additionally, the selected pivotal genes underwent further examination and validation utilizing 3 databases: GEPIA, UALCAN, and Kaplan-Meier Plotter.

Results

A total of 121 DEGs were detected, comprising 74 genes with increased expression and 47 genes with decreased expression. Ten key genes were identified: HMMR, RRM2, CDK1, TOP2A, AURKA, CCNB1, MAD2L1, KIF2C, BUB1B, and UBE2C. Validation in the GEPIA database revealed high expression levels for all key genes except CDK1. A survival analysis conducted using the Kaplan-Meier Plotter database revealed noteworthy associations between 9 crucial genes and the overall survival of individuals diagnosed with breast cancer. Moreover, these 9 key genes exhibited significantly increased expression across different molecular subtypes of breast cancer according to the UALCAN data platform.

Conclusions

We identified 9 crucial genes significantly linked to the onset, progression, and unfavorable prognosis of breast cancer providing potential targets for novel treatment options and biomarkers to predict patient outcomes.
Impact of weight loss on the progression of cancer cachexia and the patient prognosis: insights from a retrospective study
Authors: Ji Wei , He Yu-Wei , Liu Xiang-Liang , Li Wei
Published: December 2024

Background

Cachexia is a metabolic state with weight and muscle mass loss as its basic characteristics. This study aims to reveal the influence of weight loss on the progression of cancer cachexia and to determine its impact on the patient prognosis.

Methods

A total of 2,990 cancer patients were enrolled in this retrospective study. Demographic information, clinical materials, and follow-up data were collected for all patients. A receiver operating characteristic curve was used to determine threshold values for weight loss within the past 6 months (WL). Kaplan-Meier curves and Cox proportional hazard regression models were adopted for survival analyses.

Results

After excluding ineligible patients, 2,480 patients were included in the analysis, 705 (28.4%) of whom were considered to be cachexic. WL of 10% was determined to be the optimal threshold for diagnosing malnutrition according to the Patient-Generated Subjective Global Assessment. Notably, WL > 10% was a predictor of survival outcomes only in the general population [hazard ratio (HR) = 1.218, 95% confidence interval (CI) = 1.002–1.481, P = 0.048], but not in the cachexic population, based on the multivariable Cox regression model. A larger proportion of cachexic patients with WL > 10% had a Nutritional Risk Screening 2002 score ≥ 3 (25.7% vs. 13.7%, P < 0.001) and a modified Glasgow Prognosis Score = 2 (12.8% vs. 7.8%, P = 0.032). No significant difference was observed in the degree of decreased muscle strength or quality of life (P > 0.05).

Conclusions

Weight loss is a predictor of impaired survival in the general population, but not in the cachexic population. The present study shows that cachexic patients with severe weight loss had a higher risk of malnutrition, a worse systemic inflammation status, and more severe malnutrition, but that the weight loss itself was not associated with the prognosis of these patients or the progression of their cachexia.
Association of frailty and malnutrition with overall survival in adults with gastrointestinal cancer: A prospective cohort study
Authors: Zheng Xi-Te , Zhang Xiao-Rui , Zhang Yi-Jun , Huang Feng-Yi , Wang Yi-Jie , Gao Ran , Li Quan-Mei , Liu Wan-Qi , Luo Chu-Ning , Liu Fen ,   Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) Group
Published: December 2024

Background

The mortality burden of patients with gastrointestinal malignancies is increasing worldwide, suggesting the need for more effective prognostic indicators. This study utilized a prospective cohort to (1) analyze the relationship between frailty and malnutrition and their association with the overall survival (OS) in adults with gastrointestinal cancer and (2) explore which specific frailty-related factors most significantly affect the OS.

Methods

Participants diagnosed with gastrointestinal cancer from 2013 to 2018 who were enrolled in the Investigation on Nutrition Status and Clinical Outcome of Common Cancers study were identified. Malnutrition was determined using the Patient-Generated Subjective Global Assessment, whereas frailty was assessed using the FRAIL scale. The main outcome measured was the all-cause mortality. Multivariable-adjusted logistic regression was used to analyze the cross-sectional link between the nutritional status and frailty. Univariate and multivariate Cox regression analyses were conducted to explore the longitudinal association of these with the OS.

Results

Among the 4,361 patients enrolled in the study, 1,136 deaths were observed over a median follow-up of 43.4 months. Malnourished patients had a significantly higher risk of frailty than well-nourished patients (OR = 6.25, 95% CI = 5.23–7.51). Frailty and malnutrition independently predicted the OS, with frailty showing an HR of 1.50 (95% CI = 1.33–1.69) and malnutrition showing an HR of 1.51 (95% CI = 1.31–1.74). Patients with both frailty and malnutrition had the highest all-cause mortality risk (HR = 1.82, 95% CI = 1.55–2.14) compared with patients with neither risk factor. Mortality rates rose with the accumulation of additional frailty-related factors.

Conclusions

Malnutrition and frailty are interrelated prognostic factors in patients with gastrointestinal malignancies, and their simultaneous presence worsens the patient outcomes. Higher scores for resistance and ambulation are major factors associated with a poorer outcome. Future large-scale prospective studies with repeated measurements are necessary to further explore the complex associations among frailty, malnutrition, and the prognosis in patients with gastrointestinal cancer.
Investigation on quality of life of hospitalized patients in China with digestive system malignancy
Authors: Zhang Kai-Lun , Xu Hong-Xia , Li Wei , Cui Jiu-Wei , Weng Min , Yao Qing-Hua , Guo Zeng-Qing , Ba Yi , Zhou Fu-Xiang , Chen Zhi-Kang , Li Su-Yi , Zhao Qing-Chuan , Zhou Chun-Ling , Liu Ming , Zhou Lan , Shi Han-Ping , Song Chun-Hua
Published: December 2024

Background

The purpose of this study is to evaluate the quality of life (QoL) of hospitalized patients in China suffering from digestive system malignancies and to identify potential risk factors for a decrease in QoL.

Methods

The European Organization for Research and Treatment Core Quality of Life questionnaire (EORTC QLQ-C30) was applied to evaluate the QoL of 23,519 patients with six digestive malignancies (esophageal cancer, gastric cancer, colorectal cancer, liver cancer, biliary tract cancer, and pancreatic cancer). A t test or analysis of variance was employed to analyze the total EORTC QLQ-C30 scale scores and domain scores of the EORTC QLQ-C30 scale among patients in different subgroups.

Results

The average QoL score was 50.4 ± 10.8. The tumor type, age, sex, and TNM stage all had an impact on QoL ratings. Colorectal cancer patients had a better total QoL score (49.3 ± 10.3) and scores in the domains of functioning, with milder symptoms, except for diarrhea. Patients with biliary tract cancer (54.2 ± 12.3) and pancreatic cancer (54.2 ± 12.3) reported a poorer QoL, significant functional impairment, and more pronounced symptoms. Patients with esophageal cancer experienced the most severe financial difficulties (35.2 ± 27.5). Patients aged ≥65 years, women, and those with TNM stage III/IV reported lower QoL. In addition, the disparities in total QoL scores and scores in specific domains were significant among patients with some types of tumors, and based on ethnicity, educational level, occupation, treatment(s) received, and place of residence.

Conclusions

There is a need to focus on elderly individuals, those with low educational levels, and patients with progressive malignant tumors and to improve routine disease monitoring and symptom management to enhance the quality of life for patients with malignancies of the digestive system.
Prognostic value of cachexia defined by the Asian Working Group for Cachexia criteria in patients with gastric cancer
Authors: Xie Hai-Lun , Wei Li-Shuang , Wang Shu-Yao , Xu Chang-Hong , Ruan Guo-Tian , Zhang He-Yang , Shi Han-Ping , Chen Jun-Qiang
Published: December 2024

Background

The Asian Working Group for Cachexia (AWGC) criteria are newly proposed diagnostic standards specifically designed for Asian populations. This research focused on validating the predictive value of the AWGC criteria for assessing the prognosis and medical burden of patients with gastric cancer.

Methods

Cox proportional hazards analysis was conducted to evaluate the association between cachexia and overall survival. Logistic regression analysis was used to assess whether there was an independent association between cachexia and the 90-day mortality, the length of stay and the quality of life. Harrell’s concordance index was utilized to demonstrate the discriminative ability of different diagnostic criteria for cachexia.

Results

AWGC-defined cachexia was an independent risk factor for a reduced overall survival in patients (HR = 1.397, 95%
CI = 1.209–1.615, P < 0.001). The predictive accuracy of the AWGC criteria was markedly superior to that of the Fearon criteria (χ
2 = 39.025 vs 13.877). Compared with Fearon standards, the AWGC criteria offered a 2.9% enhancement in clinical benefit (0.029, 95% CI = 0.048–0.008, P = 0.005). Logistic regression analysis showed that only AWGC-defined cachexia was an independent risk factor for 90-day mortality (OR = 2.142, 95% CI = 1.397–3.282, P < 0.001) and prolonged hospitalization (OR = 1.958, 95% CI = 1.587–2.416, P < 0.001) in patients with gastric cancer, whereas cachexia defined by the Fearon criteria was not. Patients with AWGC-defined cachexia exhibited significant reductions in physical function, role function, emotional function, cognitive function, social functioning, and overall quality-of-life scores. Conversely, cachectic patients showed higher levels of fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, and financial difficulties. A multivariate logistic regression showed that patients with AWGC-defined cachexia had a 126.1% increased risk of impaired quality of life (OR = 2.261, 95% CI = 1.859–2.749, P < 0.001).

Conclusions

The AWGC criteria are an effective tool for predicting adverse survival outcomes, 90-day mortality, a prolonged hospital stay, and poorer quality of life in patients with gastric cancer.
Recognizing Grace in Grief Through Reflection in Nursing Education
Authors: Thornton Erin , Moseley Lindsey , Noll Kelley , Lambert Ann W.
Published: December 2024

Diverse teaching and learning strategies are needed to develop emotionally intelligent new-graduate nurses who can empathetically care for dying patients. Reflective pedagogy, a teaching strategy that infuses reflection into education, is an effective strategy to enhance nursing student learning, educational enrichment, and emotional intelligence. This project aimed to explore nursing students’ thoughts and feelings about end-of-life care through participation in the Grace in Grief intervention. This study examined the implementation of the student-centered intervention with mindful reflection and artistic expression to discuss emotions surrounding death and grief. The intervention was completed in a safe learning environment where course faculty facilitated the navigation of emotions, attitudes, and fears about death and how to care for dying patients and families through classroom discussion, artistic expression, and private reflection. After the intervention, students were asked to complete an online survey to reflect on the experience. Thematic analysis was used to analyze the students’ responses to the survey. Four themes emerged from the qualitative analysis of open-ended responses. Summative themes indicated that educators could utilize reflection-based, student-centered learning activities to assist nursing students’ development of emotional intelligence.
Associations between salivary microbiota and KSHV infection in people with HIV: a cross-sectional study in ili prefecture, Xinjiang, China
Authors: Wang Tianye , Xu Yiyun , Zhou Sujuan , Zhang Xin , Fang Qiwen , Yuan Huangbo , Wu Xuefu , Li Yi , Chen Tao , Zhang Tiejun
Published: December 2024

Objective:

Kaposi's sarcoma-associated herpesvirus (KSHV) infection, essential for Kaposi sarcoma development especially in people with HIV (PWH), has been proposed to be transmitted through saliva. The potential role of salivary microbiota played in the infection of KSHV is largely obscure. This study aimed to explore the association between salivary microbiota and KSHV infection among PWH.

Design:

Cross-Sectional Study.

Methods:

During May to Dec 2022, we conducted a cross-sectional study among PWH in Ili prefecture Xinjiang, China. Participants completed face-to-face questionnaires, plasma and saliva samples were collected to assay KSHV infection status and 16S rRNA sequencing. We distinguished demographic characteristics between groups with/without KSHV, and compared the α and β diversity of the salivary microbiota. LEfSe identified key bacterial genera for Random Forest and XGBoost models to recognize the important discriminatory features.

Results:

Among 876 PWH in Xinjiang, 38.7% were KSHV seropositive. Regression models indicated that moderate drinking, absence of dental treatment history, higher CD4 counts, and higher CD4/CD8 ratios were negatively associated with KSHV seropositivity. LEfSe analysis demonstrated that 14 bacterial genera were significantly enriched at the genus level in the group with/without KSHV. Machine learning analyses gave an AUC of 0.66 for Random Forest and 0.85 for XGBoost in predicting KSHV infection status. The bacterial genera, including Alloprevotella, Fusobacterium, Prevotella_7, Porphyromonas, Rothia, and Leptotrichia, were identified as important discriminatory features.

Conclusions:

This study suggests the potential role of salivary microbiota in KSHV transmission among PWH. Identified microbial genera offer promising biomarkers for monitoring and managing KSHV in PWH.
Differential systemic immune-inflammation index levels in people with and without HIV infection
Authors: Wang Crystal , Letendre Scott L. , Hong Suzi , Andalibi Mohammad , Iudicello Jennifer , Ellis Ronald J.
Published: December 2024

Background:

HIV infection is linked to persistent inflammation despite effective antiretroviral therapy (ART). The Systemic Immune-Inflammation Index (SII) is a marker of inflammation in various conditions.

Methods:

We compared SII values between PWH and PWoH. Clinical blood laboratory data were used to calculate the SII for each participant using the formula [(Platelet count × Neutrophil count) / Lymphocyte count]. Differences in SII values between the groups were analyzed using the Wilcoxon test, and the impact potential confounders was assessed with multivariable regression models.

Results:

The study included 343 PWH and 199 PWoH. Age and race did not significantly differ, but sex distribution did (83.1% male in PWH vs. 55.8% in PWoH, P < 0.0001). Among PWH, median [IQR] nadir and current CD4 counts were 199 cells/μL [50, 350] and 650 [461,858], respectively. Nearly all PWH were on ART, with 97.2% achieving viral suppression. PWH had lower SII values than PWoH (327 [224, 444] vs. 484 [335,657], P = 1.35e-14). PWH also had lower neutrophils and platelets (ps < 0.001) and higher lymphocyte counts (P = 0.001). These differences remained significant after adjusting for age, sex, and other potential confounders.

Discussion:

Contrary to expectations, PWH had lower SII levels, likely due to altered hematologic parameters influenced by HIV and ART. These findings suggest that SII interpretation in PWH requires consideration of unique hematologic profiles and underscore the need for further research to understand the mechanisms and clinical implications of SII in HIV management.
Onsager-symmetric constitutive laws for three-dimensional granular flow in the inertial regime
Authors: Hu Y. , Schaeffer D.G. , Barker T.
Published: December 2024

This paper introduces a new mathematical technique for deriving continuum rheological models of granular matter. Specifically, it is shown that, under the hypothesis of Onsager symmetry, three-dimensional dynamic constitutive laws for general strain rates can be derived from a three-dimensional yield condition plus steady-state empirical data of quasi-two-dimensional flow. To illustrate the technique, a new rate-dependent three-dimensional yield condition, suitable for dry granular materials in the inertial regime, is proposed and combined with discrete-element method (DEM) particle simulation data of simple shear flow. In combination with Onsager symmetry, this generates a complete three-dimensional viscoplastic model for such materials. Despite the simplicity of the inputs, the resulting constitutive laws agree very well with the pioneering non-planar DEM simulations of Clemmer
et al
.
Phys. Rev. Lett
.
127
(2021). Unlike several previous theories, the novel Onsager-symmetric constitutive relations incorporate a non-zero second normal stress difference in simple shear and are able to distinguish between general triaxial deformations via dependence on the Lode angle.
Complete Genome Analysis of Human Influenza C Virus Co-Infection with WU Polyomavirus in a Sri Lankan Child: A Brief Report
Authors: Pattiyakumbura T T , De Silva I. , Bowatte A. , Perera S. , Rathnayake D. , Kudagammana H.D.W.S , Muthugala M.A.R.V , Sumathipala T.K.G.S
Published: December 2024

Background

Influenza C virus (ICV) is a lesser-known member of the Orthomyxoviridae family, primarily causing respiratory tract infections in children. Co-infection with WU polyomavirus (WUPyV), a recently identified human polyomavirus, is rarely reported. This study presents the first laboratory-confirmed case of ICV infection in Sri Lanka and its co-infection with WUPyV.

Methods

Nasopharyngeal and oropharyngeal swabs were collected from children aged 3 months to 14 years with respiratory tract symptoms between November 2022 and February 2023. Samples were screened using multiplex real-time PCR and SARS-CoV-2 RT-PCR. A nasopharyngeal swab from a 14-month-old baby showing an insignificant curve in respiratory PCR was subjected to whole-genome sequencing using the Illumina platform. Data were analyzed for genomic characterization, and phylogenetic analysis was performed using the haemagglutinin-esterase (HE) gene of ICV.

Results

Full genome sequencing identified ICV and WUPyV in the sample. Phylogenetic analysis revealed that the ICV isolate belonged to the C/Sao Paulo lineage. The patient presented with mild symptoms, including fever, cough, and cold, with normal inflammatory markers, and recovered with supportive care.

Discussion

This case highlights the importance of considering ICV in pediatric respiratory illnesses, despite its under-diagnosis due to limited diagnostic tools. Unlike Influenza A and B, ICV lacks neuraminidase, rendering neuraminidase inhibitors ineffective. The absence of ICV in current influenza vaccines further complicates preventive strategies. Co-detection of WUPyV raises questions about its role as a co-pathogen, with its clinical significance requiring further investigation.

Conclusion

This report underscores the need for enhanced molecular diagnostic techniques and surveillance to better understand the epidemiology and clinical impact of ICV and its co-infections.
Towards personalized nicotinamide mononucleotide (NMN) supplementation: nicotinamide adenine dinucleotide (NAD) concentration
Authors: Kuerec Ajla Hodzic , Wang Weilan , Yi Lin , Tao Rongsheng , Lin Zhigang , Vaidya Aditi , Pendse Sohal , Thasma Sornaraja , Andhalkar Niranjan , Avhad Ganesh , Kumbhar Vidyadhar , Maier Andrea B.
Published: December 2024

Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40 to 65 years. The participants received a placebo or daily 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement. A significant dose-dependent increase in NAD concentration change (NADΔ) was observed following NMN supplementation, with a large coefficient of variation (29.2-113.3%) within group. The increase in NADΔwas associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score. The median effect dose of NADΔfor the 6-minute walk test and SF-36 score was 15.7 nmol/L (95% CI: 10.9-20.5 nmol/L) and 13.5 nmol/L (95% CI; 10.5-16.5 nmol/L), respectively. Because of the high interindividual variability of the NADΔafter NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization.

Highlights

Large interindividual variability in blood NAD response to NMN supplement was observed.

The median effective dose of blood NAD concentration improvement to achieve clinically significant improvement in functional outcome and quality of life was around 15 nmol/L.

A close monitoring of NAD concentration change and personalized regimen of NMN supplements is needed.
Higher FSH Level Is Associated With Increased Risk Of Incident Hip Fracture In Older Adults, Independent Of Sex Hormone Levels
Authors: Koh Eileen H. , Ewing Susan K. , Sigurdsson Sigurdur , Gudnason Vilmundur , Hue Trisha F. , Vittinghoff Eric , Ohlsson Claes , Tivesten Åsa , Grahnemo Louise , Yuen Tony , Zaidi Mone , Rosen Clifford J. , Schwartz Ann V. , Schafer Anne L.
Published: December 2024

Context

Higher levels of follicle stimulating hormone (FSH) are associated with bone loss among women during the perimenopausal transition and among older men, independent of estradiol and testosterone levels, but it is unknown whether higher FSH is an independent risk factor for fracture.

Objective

Determine whether baseline FSH level predicts subsequent hip fracture in older adults.

Setting, Design, Participants

Using a case-cohort design, we randomly sampled 295 participants stratified by sex from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort, including 25 participants with incident hip fracture within 10 years after baseline. We sampled an additional 230 sex-stratified participants with incident hip fracture. Serum FSH and sex hormone levels were measured at baseline. Robust weighted Cox proportional hazards models were used to determine the relationship between FSH and hip fracture risk.

Main Outcome

Incident hip fracture

Results

As no interaction was identified between FSH and sex for the relationship with fracture, men and women were pooled for analysis. Higher levels of FSH were associated with a significantly increased risk of incident hip fracture in models adjusted for age and sex [hazard ratio (HR) 1.24 (95% CI 1.04-1.48, p=0.02)] and after further adjustment for estradiol, testosterone, and sex hormone binding globulin levels [HR 1.20 (95% CI 1.01-1.44, p=0.04) per sex-specific SD increase in FSH level].

Conclusions

Higher FSH is associated with increased risk of subsequent hip fracture. Our findings support a growing body of evidence for direct pleiotropic effects of FSH on bone, and for a role for FSH in aging and disability independent of sex hormone levels.
How good are large language models for automated data extraction from randomized trials?
Authors: Sun Zhuanlan , Zhang Ruilin , Doi Suhail A. , Furuya-Kanamori Luis , Yu Tianqi , Lin Lifeng , Xu Chang
Published: December 2024

In evidence synthesis, data extraction is a crucial procedure, but it is time intensive and prone to human error. The rise of large language models (LLMs) in the field of artificial intelligence (AI) offers a solution to these problems through automation. In this case study, we evaluated the performance of two prominent LLM-based AI tools for use in automated data extraction. Randomized trials from two systematic reviews were used as part of the case study. Prompts related to each data extraction task (e.g., extract event counts of control group) were formulated separately for binary and continuous outcomes. The percentage of correct responses (Pcorr) was tested in 39 randomized controlled trials reporting 10 binary outcomes and 49 randomized controlled trials reporting one continuous outcome. ThePcorrand agreement across three runs for data extracted by two AI tools were compared with well-verified metadata. For the extraction of binary events in the treatment group across 10 outcomes, thePcorrranged from 40% to 87% and from 46% to 97% for ChatPDF and for Claude, respectively. For continuous outcomes, thePcorrranged from 33% to 39% across six tasks (Claude only). The agreement of the response between the three runs of each task was generally good, with Cohen’s kappa statistic ranging from 0.78 to 0.96 and from 0.65 to 0.82 for ChatPDF and Claude, respectively. Our results highlight the potential of ChatPDF and Claude for automated data extraction. Whilst promising, the percentage of correct responses is still unsatisfactory and therefore substantial improvements are needed for current AI tools to be adopted in research practice.

Highlights

1.

What is already known

In evidence synthesis, data extraction is a crucial procedure, but it is time intensive and prone to human error, with reported data extraction error rates at meta-analyses level reaching up to 67%.

The rise of large language models (LLMs) in the field of artificial intelligence (AI) offers a solution to these problems through automation.

2.

What is new

In this case study, we investigated the performance of two AI tools for data extraction and confirmed that AI tools can reach the same or better performance than humans in terms of data extraction from randomized trials for binary outcomes.

However, AI tools performed poorly at extracting data from continuous outcomes.

3.

Potential impact for Research Synthesis Methods readers outside the authors’ field

Our study suggests LLMs have great potential in assisting data extraction in evidence syntheses through (semi-)automation. Further efforts are needed to improve accuracy, especially for continuous outcomes data.
Accidental Exposure to Body Fluids Among Healthcare Workers in a Referral Hospital in the Security-Challenged Region of South West Cameroon
Authors: Takougang Innocent , Lekeumo Cheuyem Fabrice Zobel , Asongu Changeh Blessing , Nyonga Ngati Denetria , Mengong Moneboulou Hortense
Published: December 2024

Introduction

Accidental exposure to body fluids (AEBs) increases the risk of blood-borne infections among susceptible HCWs. While 90% of the AEB reported occur in developed nations, developing countries bear 90% of the burden of healthcare associated infections, especially those of sub-Saharan Africa. Social insecurity may contribute further to the vulnerability of HCWs. Our study sought to determine the prevalence, reporting and management of AEBs among HCWs in the security-challenged Region of South-West Cameroon.

Methods

A cross-sectional study was carried out from February 2023 to April 2023, at the Buea Regional Hospital. Following informed consent, a 28-item interviewer-administered questionnaire to HCW was used. Data was entered and analyzed using R Statistics version 4.3.1.

Results

Out of the 230 HCWs that were approached, 200 were responded for a participation rate of >85%. The prevalence of AEB was high (93%). Exposures occurred while administering injections (37%), during blood sample collection (16%), delivery (11%), surgery (10.2%) and washing. The main risk factors for AEB included female gender (aOR=2.86) and those exercising in the medical (aOR=5.95), pediatrics (aOR=10.5), obstetrical (aOR=22.6), dental (aOR=26.3) units. Only 46.8% of AEBs were reported. Post-exposure management was carried out for 67.2% of the reported cases. Most HCW were unaware of the existence of an Infection Control Committee within the study setting, corroborating gaps in the observance of Standard Precautions.

Conclusions

Most HCWs experienced AEBs over the last year. There is a need to sensitize and enforce the observance of universal precautions among HCW of the Buea Regional Hospital. Such measures should be extended to other health facilities in related settings.
The Cost Outcome Pathway Framework: Integrating socio-economic impacts to Adverse Outcome Pathways
Authors: Coustillet Thibaut , Coumoul Xavier , Villégier Anne-Sophie , Bisson Michèle , Fritsche Ellen , Brignon Jean-Marc , Zeman Florence , Audouze Karine
Published: December 2024

Several chemical’s families are linked to a loss of intellectual quotient (IQ) points in children. This may lead to reduced working productivity and/or lower wages in adulthood and contribute to increasing the substantial socio-economic burden worldwide. The Adverse Outcome Pathway (AOP) concept, that leverages existing data to formalize knowledge, is a well-accepted concept in risk assessment although it does not handle the socio-economic impact that environment-induced diseases may generate. Here, we propose to extend the AOP framework by bridging an adverse outcome (AO) to a cost outcome (CO) creating so-called Cost Outcome Pathways (COPs) for including the socio-economic costs of exposure to chemicals. As a case study, a COP related to neurodevelopmental toxicity was designed, with a connection between the AO ‘decreased, IQ’ and the CO ‘increased, socio-economic burden’. For support to policymaking in the public health sector, this framework might also hold great potential for environmental exposure-related diseases such as cancer or obesity which are diseases with known detrimental socio-economic impacts.
An economic evaluation of routine hepatocellular carcinoma surveillance for high-risk patients using a novel approach to modelling competing risks
Authors: Worthington Joachim , He Emily , Caruana Michael , Wade Stephen , de Graaff Barbara , Nguyen Anh Le Tuan , George Jacob , Canfell Karen , Feletto Eleonora
Published: December 2024

Introduction

Liver cancer is the only cancer in Australia for which mortality rates have consistently risen, despite tests to identify high-risk individuals. Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Curative treatment for HCC is typically only available if detected early. Australian clinical guidelines recommend routine 6-monthly ultrasound surveillance, with or without serum alpha-fetoprotein, for individuals with liver cirrhosis. This study assesses the health and economic implications of this recommendation, utilizing novel modeling techniques.

Methods

We designed thesojourn time density modelmathematical framework to develop a model of the evolving risk of HCC, liver disease, and death based on time since diagnosis, incorporating data on liver decompensation, HCC incidence, and HCC survival, and the impact of surveillance on cancer stage and survival.

Results

We estimated that adherence to 6-monthly ultrasound, with or without alpha-fetoprotein, can increase early-stage diagnosis rates, reducing HCC mortality by 22%. We estimate a cost-effectiveness ratio of $33,850 per quality-adjusted life-year (QALY) saved for 6-monthly ultrasound HCC surveillance, under the $50,000/QALY cost-effectiveness threshold. HCC surveillance was also estimated to be cost-effective at any interval from 3-24 months.

Conclusions

These findings support the current clinical guideline recommendation for 6-monthly ultrasound surveillance, affirming its health benefits and cost-effectiveness, and show that alternative surveillance intervals would remain beneficial and cost-effective. Our model may be used to refine surveillance recommendations for other at-risk population subgroups and inform evidence-based clinical practice recommendations, and the framework can be adapted for other epidemiological modelling. Supporting the clinical guidelines and their ongoing development as evidence evolves may be key to reversing increasing HCC mortality rates in Australia, which are predicted to increase by more than 20% by 2040.
Evaluation of a district-wide sanitation programme in rural Malawi: does it include people living with disabilities?
Authors: Davies Katherine , Panulo Mindy , MacLeod Clara , Wilbur Jane , Morse Tracy , Chidziwisano Kondwani , Dreibelbis Robert
Published: December 2024

Community-led total sanitation (CLTS) is embraced as a key strategy to achieve universal sanitation coverage (Sustainable Development Goal 6.2). Although inclusion is identified as a predictor of CLTS success, people living with disabilities are often excluded from community sanitation programmes and there is limited research exploring CLTS participation amongst people living with disabilities. This study aims to explore the extent to which people living with disabilities participated in a CLTS intervention delivered in rural Malawi.

This cross-sectional study was conducted in the Chiradzulu district of Malawi. A household questionnaire was administered to collect information about CLTS participation. Multivariable logistic regression was performed to compare participation in different CLTS activities between households with (n=80) and without a member with a disability (n=167), and between household members with (n=55) and without a disability (n=226). No difference in CLTS participation was observed at the household-level, but there were marked differences in CLTS participation between household members with and without a disability. Household members without a disability reported higher attendance at the triggering session (OR=2.09, 95%CI 1.00–4.37), gave more input in triggering activities (OR=3.72, 95%CI 1.46-9.51), and reported higher participation in the transect walk (OR=4.03, 95%CI 1.52-10.68), community action planning (OR=2.89, 95%CI 1.23-6.79), and follow-up visits (OR=3.37, 95%CI 1.67-6.82) compared to household members with disabilities. There was no difference in the likelihood of being invited to triggering (OR=0.98, 95%CI 0.43–2.22) or participating in community mapping (OR=2.38, 95%CI 0.63-8.99) between household members with and without a disability.

This study revealed intra-household inequalities in CLTS participation. To improve participation in CLTS interventions, facilitators should be trained on action steps to make CLTS more inclusive. Further research could include an in-depth analysis of predictors of CLTS participation amongst people living with disabilities, including disability types, severity and age.
The Use of Home-Based Behaviours for Detecting Early Dementia:Protocol for the CUBOId Study
Authors: Selwood James , Twomey Niall , Craddock Ian , Coulthard Liz , Kumpik Daniel , Newson Margaret , Poyiadzi Rafael , Santos-Rodriguez Raul , Yang Weisong , Ben-Shlomo Yoav
Published: December 2024

Introduction

There is a pressing need to automatically understand the state and progression of chronic neurological diseases such as dementia. The emergence of state-of-the-art sensing platforms offers unprecedented opportunities for indirect and automatic evaluation of disease state through the lens of behavioural monitoring. The ContinUous behavioural Biomarkers Of cognitive Impairment (CUBOId) project specifically seeks to characterise behavioural signatures of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in the early stages of the disease. Bespoke behavioural models will be introduced and deployed on a novel dataset of longitudinal sensor data from persons with MCI and AD to analyse key symptoms of the disease.

Methods and analysis

CUBOId is a longitudinal observational study. Participants have diagnoses of MCI or AD, and controls are their live-in partners with no such diagnosis. Multimodal activity data were passively acquired from wearables and in-home fixed sensors over timespans of 2–22 months. Behavioural testing is supported by neuropsychological assessment for deriving ground truths on cognitive status. Machine learning will be used to generate fused multimodal sensor data for optimisation of diagnostic and predictive performance from localisation, activity, and speech together.

Ethics and dissemination

CUBOId was approved by an NHS Research Ethics Committee (Wales REC; ref: 18/WA/0158) and is sponsored by the University of Bristol. It is also supported by the National Institute for Health Research (NIHR) Clinical Research Network West of England. Results will be reported at conferences and in peer-reviewed scientific journals.