bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel diagnostic model for tuberculous meningitis using Bayesian latent class analysis
Authors: Dong Trinh Huu Khanh , Donovan Joseph , Ngoc Nghiem My , Thu Do Dang Anh , Nghia Ho Dang Trung , Oanh Pham Kieu Nguyet , Phu Nguyen Hoan , Hang Vu Thi Ty , Vinh Chau Nguyen Van , Thuong Thuong Nguyen Thuy , Tan Le Van , Thwaites Guy E. , Geskus Ronald B.
Published: February 2024

Background

Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of a gold standard. Current microbiological tests lack sensitivity and clinical diagnostic approaches are subjective. We therefore built a diagnostic model that can be used before microbiological test results are known.

Methods

We included 659 individuals aged $$\ge 16$$

≥
16

years with suspected brain infections from a prospective observational study conducted in Vietnam. We fitted a logistic regression diagnostic model for TBM status, with unknown values estimated via a latent class model on three mycobacterial tests: Ziehl–Neelsen smear, Mycobacterial culture, and GeneXpert. We additionally re-evaluated mycobacterial test performance, estimated individual mycobacillary burden, and quantified the reduction in TBM risk after confirmatory tests were negative. We also fitted a simplified model and developed a scoring table for early screening. All models were compared and validated internally.

Results

Participants with HIV, miliary TB, long symptom duration, and high cerebrospinal fluid (CSF) lymphocyte count were more likely to have TBM. HIV and higher CSF protein were associated with higher mycobacillary burden. In the simplified model, HIV infection, clinical symptoms with long duration, and clinical or radiological evidence of extra-neural TB were associated with TBM At the cutpoints based on Youden’s Index, the sensitivity and specificity in diagnosing TBM for our full and simplified models were 86.0% and 79.0%, and 88.0% and 75.0% respectively.

Conclusion

Our diagnostic model shows reliable performance and can be developed as a decision assistant for clinicians to detect patients at high risk of TBM.

Diagnosis of tuberculous meningitis is hampered by the lack of gold standard. We developed a diagnostic model using latent class analysis, combining confirmatory test results and risk factors. Models were accurate, well-calibrated, and can support both clinical practice and research.
The prevalence and risk factors for phantom limb pain: a cross-sectional survey
Authors: Limakatso Katleho , Ndhlovu F. , Usenbo A. , Rayamajhi S. , Kloppers C. , Parker R.
Published: February 2024

Background

We previously performed a systematic review and meta-analysis which revealed a Phantom Limb Pain (PLP) prevalence estimate of 64% [95% CI: 60.01–68.1]. The prevalence estimates varied significantly between developed and developing countries. Remarkably, there is limited evidence on the prevalence of PLP and associated risk factors in African populations.

Methods

Adults who had undergone limb amputations between January 2018 and October 2022 were recruited from healthcare facilities in the Western and Eastern Cape Provinces. We excluded individuals with auditory or speech impairments that hindered clear communication via telephone. Data on the prevalence and risk factors for PLP were collected telephonically from consenting and eligible participants. The prevalence of PLP was expressed as a percentage with a 95% confidence interval. The associations between PLP and risk factors for PLP were tested using univariate and multivariable logistic regression analyses. The strength of association was calculated using the Odds Ratio where association was confirmed.

Results

The overall PLP prevalence was 71.73% [95% CI: 65.45–77.46]. Persistent pre-operative pain, residual limb pain, and non-painful phantom limb sensations were identified as risk factors for PLP.

Conclusion

This study revealed a high prevalence of PLP. The use of effective treatments targeting pre-amputation pain may yield more effective and targeted pre-amputation care, leading to improved quality of life after amputation.
Antenatal care addressing gestational weight gain (GWG): a cross sectional study of pregnant women’s reported receipt and acceptability of recommended GWG care and associated characteristics
Authors: Hollis Jenna L , Deroover Kristine , Licata Milly , Tully Belinda , Farragher Eva , Lecathelinais Christophe , Bennett Nicole , Foster Michelle , Pennell Craig E , Wiggers John , Daly Justine , Kingsland Melanie
Published: February 2024

Background

The Australian Clinical Practice Guidelines for Pregnancy Care recommend that during the first and subsequent antenatal visits all pregnant women are weighed; advised of recommended gestational weight gain (GWG), dietary intake and physical activity; and offered referrals for additional support if needed. The extent to which these recommendations are implemented and women’s acceptability of recommended care is unknown. This study examines women’s reported receipt and acceptability of guideline care for GWG, and characteristics associated with receipt of such care and its acceptability.

Methods

From September 2018 to February 2019 a telephone survey was undertaken with women who had recently had a baby and received antenatal care from five public maternity services within a health district in Australia. Women self-reported their demographic characteristics, and receipt and acceptability of recommended GWG care. Receipt and acceptability of such care, and their association with the characteristics of women and the maternity service they attended, were examined using descriptive statistics and multivariable logistic regression analyses.

Results

Of 514 women, 13.1% (95%CI:10.3–16.5) reported that they received an assessment of weight at both their first and a subsequent antenatal visit, and less than one third (30.0%; 95%CI:26.0-33.9) received advice on their recommended GWG range, dietary intake and physical activity. Just 6.6% (95%CI:4.8–9.1) of women reported receiving all assessment and advice components of recommended antenatal care, and 9.9% (95%CI:7.6–12.8) of women reported being referred for extra support. Women who were younger (OR = 1.13;95%CI:1.05–1.21), identifying as Aboriginal and Torres Strait Islander (OR = 24.54;95%CI:4.98-120.94), had a higher pre-pregnancy BMI (OR = 1.13;95%CI:1.05–1.21), were experiencing their first pregnancy (OR = 3.36;95%CI:1.27–8.86), and lived in a least disadvantaged area (compared to mid-disadvantaged area (OR = 18.5;95%CI:2.6-130.5) and most disadvantaged area (OR = 13.1;95%CI:2.09–82.4)) were more likely to receive recommended assessment and advice. Most Aboriginal (92%) and non-Aboriginal (93%) women agreed that recommended GWG care is acceptable.

Conclusion

Most women perceive antenatal care for GWG as recommended by the Clinical Practice Guidelines as acceptable, but did not receive it. When provided, such care is not delivered consistently to all women regardless of their characteristics or those of the maternity service they attend. There is a need for service-wide practice change to increase routine GWG care in pregnancy for all women.
Health-related risk behaviors among U.S. childhood cancer survivors: a nationwide estimate
Authors: Nghiem Van T. , Jin Jing , Mennemeyer Stephen T. , Wong F. Lennie
Published: February 2024

Background

Childhood cancer survivors (CCS) are subject to a substantial burden of treatment-related morbidity. Engaging in health protective behaviors and eliminating risk behaviors are critical to preventing chronic diseases and premature deaths. This study is aimed to provide updated information on currently smoking, physical inactivity, binge drinking patterns and associated factors among CCS using a nationwide dataset.

Methods

We constructed a sample of CCS (cancer diagnosis at ages < 21y) and healthy controls (matched on age, sex, residency, race/ethnicity) using 2020 Behavioral Risk Factor Surveillance System. We used Chi-square tests and Wilcoxon rank-sum test to examine differences in sociodemographics and clinical characteristics between two groups. Logistic, ordinal regression and multivariable models (conditional models for matching) were used to determine factors associated with risk behaviors.

Results

The final sample (18-80y) included 372 CCS and 1107 controls. Compared to controls, CCS had a similar proportion of binge drinking (~ 18%) but higher prevalence of currently smoking (26.6% vs. 14.4%, p < 0.001), physical inactivity (23.7% vs. 17.7%, p = 0.012), and of having 2-or-3 risk behaviors (17.2% vs. 8.1%, p < 0.001). Younger age, lower educational attainment, and having multiple chronic health conditions were associated with engaging in more risk behaviors among CCS. Females, compared to male counterparts, had lower odds of binge drinking (adjusted odds ratio (aOR) = 0.30, 95% confidence interval (CI): 0.16–0.57) among CCS but not in all sample. Having multiple chronic health conditions increased odds of both currently smoking (aOR = 3.52 95%CI: 1.76–7.02) and binge drinking (aOR = 2.13 95%CI: 1.11–4.08) among CCS while it only increased odds of currently smoking in all sample.

Discussion

Our study provided risk behavior information for wide age-range CCS, which is currently lacking. Every one in four CCS was currently smoking. Interventions targeting risk behavior reduction should focus on CCS with multiple chronic health conditions.
Molecular docking as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity
Authors: Alkafaas Samar Sami , Abdallah Abanoub Mosaad , Hassan Mai H. , Hussien Aya Misbah , Elkafas Sara Samy , Loutfy Samah A. , Mikhail Abanoub , Murad Omnia G. , Elsalahaty Mohamed I. , Hessien Mohamed , Elshazli Rami M. , Alsaeed Fatimah A. , Ahmed Ahmed Ezzat , Kamal Hani K. , Hafez Wael , El-Saadony Mohamed T. , El-Tarabily Khaled A. , Ghosh Soumya
Published: February 2024

Recently, COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, caused > 6 million deaths. Symptoms included respiratory strain and complications, leading to severe pneumonia. SARS-CoV-2 attaches to the ACE-2 receptor of the host cell membrane to enter. Targeting the SARS-CoV-2 entry may effectively inhibit infection. Acid sphingomyelinase (ASMase) is a lysosomal protein that catalyzes the conversion of sphingolipid (sphingomyelin) to ceramide. Ceramide molecules aggregate/assemble on the plasma membrane to form “platforms” that facilitate the viral intake into the cell. Impairing the ASMase activity will eventually disrupt viral entry into the cell. In this review, we identified the metabolism of sphingolipids, sphingolipids' role in cell signal transduction cascades, and viral infection mechanisms. Also, we outlined ASMase structure and underlying mechanisms inhibiting viral entry 40 with the aid of inhibitors of acid sphingomyelinase (FIASMAs). In silico molecular docking analyses of FIASMAs with inhibitors revealed that dilazep (S = − 12.58 kcal/mol), emetine (S = − 11.65 kcal/mol), pimozide (S = − 11.29 kcal/mol), carvedilol (S = − 11.28 kcal/mol), mebeverine (S = − 11.14 kcal/mol), cepharanthine (S = − 11.06 kcal/mol), hydroxyzin (S = − 10.96 kcal/mol), astemizole (S = − 10.81 kcal/mol), sertindole (S = − 10.55 kcal/mol), and bepridil (S = − 10.47 kcal/mol) have higher inhibition activity than the candidate drug amiodarone (S = − 10.43 kcal/mol), making them better options for inhibition.
Understanding factors influencing people with disabilities’ participation in sports and cultural activities
Authors: Chen Ming , Li Qianxue , Wang Luqi
Published: February 2024

Background

Improving people with disabilities’ participation in sports and cultural activities benefits their physical and mental health. However, only a few studies have examined the factors that influence participation systematically.

Methods

Using the survey data gathered from 4,319 disabled people living in a district in Wuhan, China, this study explored the impacts of sports and cultural activity participation in terms of individual physiological characteristics, socioeconomic factors, and built environmental features. The sports and cultural facility supply and the walkability index of their community environment were calculated to assess built environment features. Binary logistic regression models were also used to investigate the influence of the aforementioned variables.

Results

There is a significant positive correlation between sports and cultural activity participation and education (OR = 3.44, p < 0.01), employment status (OR = 2.04, p < 0.01), as well as the number of cultural facilities (OR = 1.33, p < 0.01) in the neighborhood area. No significant association was found between the inclination to participate frequently and individual psychological factors.

Conclusion

Regarding people with disabilities’ participation in sports and cultural activities, socioeconomic and built environment factors are more influential than individual psychological ones. The findings can give ideas for identifying targeted and comprehensive interventions to promote a healthy lifestyle for people with disabilities.
Modelling cost-effectiveness of replacement strategies for ambulance services in the Ministry of Health Malaysia
Authors: Mohd Hassan Nor Zam Azihan , Bahari Mohd Shahri , Raman Sivaraj , Aminuddin Farhana , Mohd Nor Sham Kunusagaran Mohd Shaiful Jefri , Zaimi Nur Amalina , Wong Min Fui , Mostapha Marhaini , Mohamad Nor Ahmad Tajuddin , Shahari Mohd Ridzwan
Published: February 2024

Background

Emergency Medical Service (EMS) is a very crucial aspect of the healthcare system in providing urgent management and transportation of patients during emergencies. The sustainability of the services is however greatly impacted by the quality and age of ambulances. While this has led to numerous replacement policy recommendations, the implementations are often limited due to a lack of evidence and financial constraints. This study thus aims to develop a cost-effectiveness model and testing the model by evaluating the cost-effectiveness of 10-year and 15-year compulsory ambulance replacement strategies in public healthcare for the Malaysian Ministry of Health (MOH).

Methods

A Markov model was developed to estimate the cost and outcomes ambulance replacement strategies over a period of 20 years. The model was tested using two alternative strategies of 10-year and 15-year. Model inputs were derived from published literature and local study. Model development and economic analysis were accomplished using Microsoft Excel 2016. The outcomes generated were costs per year, the number of missed trips and the number of lives saved, in addition to the Incremental Cost-Effectiveness Ratio (ICER). One-Way Deterministic Sensitivity Analysis (DSA) and Probabilistic Sensitivity Analysis (PSA) were conducted to identify the key drivers and to assess the robustness of the model.

Results

Findings showed that the most expensive strategy, which is the implementation of 10 years replacement strategy was more cost-effective than 15 years ambulance replacement strategy, with an ICER of MYR 11,276.61 per life saved. While an additional MYR 13.0 million would be incurred by switching from a 15- to 10-year replacement strategy, this would result in 1,157 deaths averted or additional live saved per year. Sensitivity analysis showed that the utilization of ambulances and the mortality rate of cases unattended by ambulances were the key drivers for the cost-effectiveness of the replacement strategies.

Conclusions

The cost-effectiveness model developed suggests that an ambulance replacement strategy of every 10 years should be considered by the MOH in planning sustainable EMS. While this model may have its own limitation and may require some modifications to suit the local context, it can be used as a guide for future economic evaluations of ambulance replacement strategies and further exploration of alternative solutions.
Circular RNAs and their roles in idiopathic pulmonary fibrosis
Authors: Surendran Akshaya , Huang Chaoqun , Liu Lin
Published: February 2024

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited treatment options. Circular RNAs (circRNAs) have emerged as a novel class of non-coding RNAs with diverse functions in cellular processes. This review paper aims to explore the potential involvement of circRNAs in the pathogenesis of IPF and their diagnostic and therapeutic implications. We begin by providing an overview of the epidemiology and risk factors associated with IPF, followed by a discussion of the pathophysiology underlying this complex disease. Subsequently, we delve into the history, types, biogenesis, and functions of circRNAs and then emphasize their regulatory roles in the pathogenesis of IPF. Furthermore, we examine the current methodologies for detecting circRNAs and explore their diagnostic applications in IPF. Finally, we discuss the potential utility of circRNAs in the treatment of IPF. In conclusion, circRNAs hold great promise as novel biomarkers and therapeutic targets in the management of IPF.
CD47—a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features
Authors: Luo Xukai , Mo Jiahang , Zhang Min , Huang Wu , Bao Yiting , Zou Ruoyao , Yao Liangqing , Yuan Lei
Published: February 2024

Background

Epithelial ovarian cancer (EOC) is insensitive to immunotherapy due to its poor immunogenicity; thus, suitable biomarkers need to be identified for better prognostic stratification and individualized treatment. CD47 is a novel immunotherapy target; however, its impact on EOC prognosis is controversial and correlation with genetic features is unclear. The aim of this study was to investigate the prognostic significance of CD47 and its correlations with biological behaviors and genetic features of EOC.

Methods

Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to examine expressions of CD47, PD-L1, and genomic mutations in the tissue samples of 75 EOC patients. Various clinicopathologic and genomic features were then evaluated to determine their correlation with CD47 expression. Kaplan–Meier analysis and Cox regression analysis were used to identify independent prognostic factors. Risk score modeling was then established, and the predictive capacity of this model was further confirmed by nomogram analysis.

Results

CD47 was mainly expressed in the tumor cell membrane and cytoplasm, and the rate of high CD47 expression was 63.7%. CD47 expression was associated with various clinicopathological factors, including FIGO stage, CA125 and HE4 value, presence of multidisciplinary surgeries, presence and volume of ascites, lymph-node metastasis, Ki-67 index and platinum-resistant, as well as genetic characteristics like BRCA mutation, HRD status, and TP53 mutation in EOC. Patients with high CD47 expression showed worse prognosis than the low-expression group. Cox regression analysis demonstrated that CA125, CD47, and BRCA mutation were independent factors for EOC prognosis. Patients were then categorized into high-risk and low-risk subgroups based on the risk score of the aforementioned independent factors, and the prognosis of the high-risk group was worse than those of the low-risk group. The nomogram showed adequate discrimination with a concordance index of 0.777 (95% CI, 0.732–0.822). The calibration curve showed good consistency.

Conclusion

CD47 correlated with various malignant biology and genetic characteristics of EOC and may play pivotal and multifaceted roles in the tumor microenvironment of EOC Finally, we constructed a reliable prediction model centered on CD47 and integrated CA125 and BRCA to better guide high-risk population management.
Algorithm-assisted diagnosis of Hirschsprung’s disease – evaluation of robustness and comparative image analysis on data from various labs and slide scanners
Authors: Greenberg Ariel , Samueli Benzion , Farkash Shai , Zohar Yaniv , Ish-Shalom Shahar , Hagege Rami R. , Hershkovitz Dov
Published: February 2024

Background

Differences in the preparation, staining and scanning of digital pathology slides create significant pre-analytic variability. Algorithm-assisted tools must be able to contend with this variability in order to be applicable in clinical practice. In a previous study, a decision support algorithm was developed to assist in the diagnosis of Hirschsprung's disease. In the current study, we tested the robustness of this algorithm while assessing for pre-analytic factors which may affect its performance.

Methods

The decision support algorithm was used on digital pathology slides obtained from four different medical centers (A-D) and scanned by three different scanner models (by Philips, Hamamatsu and 3DHISTECH). A total of 192 cases and 1782 slides were used in this study. RGB histograms were constructed to compare images from the various medical centers and scanner models and highlight the differences in color and contrast.

Results

The algorithm was able to correctly identify ganglion cells in 99.2% of cases, from all medical centers (All scanned by the Philips slide scanner) as well as 95.5% and 100% of the slides scanned by the 3DHISTECH and Hamamatsu brand slide scanners, respectively. The total error rate for center D was lower than the other medical centers (3.9% vs 7.1%, 10.8% and 6% for centers A-C, respectively), the vast majority of errors being false positives (3.45% vs 0.45% false negatives). The other medical centers showed a higher rate of false negatives in relation to false positives (6.81% vs 0.29%, 9.8% vs 1.2% and 5.37% vs 0.63% for centers A-C, respectively). The total error rates for the Philips, Hamamatsu and 3DHISTECH brand scanners were 3.9%, 3.2% and 9.8%, respectively. RGB histograms demonstrated significant differences in pixel value distribution between the four medical centers, as well as between the 3DHISTECH brand scanner when compared to the Philips and Hamamatsu brand scanners.

Conclusions

The results reported in this paper suggest that the algorithm-based decision support system has sufficient robustness to be applicable for clinical practice. In addition, the novel method used in its development – Hierarchial-Contexual Analysis (HCA) may be applicable to the development of algorithm-assisted tools in other diseases, for which available datasets are limited. Validation of any given algorithm-assisted support system should nonetheless include data from as many medical centers and scanner models as possible.
Global exact optimisations for chloroplast structural haplotype scaffolding
Authors: Epain Victor , Andonov Rumen
Published: February 2024

Background

Scaffolding is an intermediate stage of fragment assembly. It consists in orienting and ordering the contigs obtained by the assembly of the sequencing reads. In the general case, the problem has been largely studied with the use of distances data between the contigs. Here we focus on a dedicated scaffolding for the chloroplast genomes. As these genomes are small, circular and with few specific repeats, numerous approaches have been proposed to assemble them. However, their specificities have not been sufficiently exploited.

Results

We give a new formulation for the scaffolding in the case of chloroplast genomes as a discrete optimisation problem, that we prove the decision version to be $$\mathcal{NP}$$
NP
-Complete. We take advantage of the knowledge of chloroplast genomes and succeed in expressing the relationships between a few specific genomic repeats in mathematical constraints. Our approach is independent of the distances and adopts a genomic regions view, with the priority on scaffolding the repeats first. In this way, we encode the structural haplotype issue in order to retrieve several genome forms that coexist in the same chloroplast cell. To solve exactly the optimisation problem, we develop an integer linear program that we implement in Python3 package khloraascaf. We test it on synthetic data to investigate its performance behaviour and its robustness against several chosen difficulties.

Conclusions

We succeed to model biological knowledge on genomic structures to scaffold chloroplast genomes. Our results suggest that modelling genomic regions is sufficient for scaffolding repeats and is suitable for finding several solutions corresponding to several genome forms.
Combined Systemic Immune-inflammatory Index (SII) and Geriatric Nutritional Risk Index (GNRI) predict survival in elderly patients with hip fractures: a retrospective study
Authors: Zhou Ling , Huang Chao , Zhu Xianjie , Ma Zhenhua
Published: February 2024

Purpose

The Systemic Immune-inflammatory Index (SII) and Geriatric Nutritional Risk Index (GNRI) have undergone comprehensive examination and validation in forecasting the outcomes of diverse medical conditions. Nevertheless, the correlation between the combined use of GNRI and SII metrics and hip fractures has yet to be elucidated. This study aimed to determine whether the amalgamation of SII and GNRI scores constitutes an independent prognostic factor for elderly patients with hip fractures.

Methods

We conducted a retrospective analysis of elderly patients admitted to our facility with hip fractures, encompassing both femoral neck and intertrochanteric fractures. Demographic information, experimental parameters, and postoperative complications were systematically recorded. The Geriatric Nutritional Risk Index (GNRI) and Systemic Immunoinflammatory Index (SII) were meticulously computed. Receiver operating characteristic (ROC) curves were generated, and optimal cutoff values for each parameter were determined. Subsequently, a multivariate Cox regression analysis was employed to assess the predictive utility of the SII–GNRI score in relation to 1-year postoperative mortality among elderly patients with hip fractures.

Results

In a study involving 597 patients, 90 of whom experienced mortality within 1 year, it was observed that the SII-GNRI score in the group of patients who passed away was significantly higher compared to the group that survived. Following a multifactorial adjustment, it was established that a high SII–GNRI score served as an independent predictor of 1-year all-cause mortality in older patients with hip fractures. In addition to the SII–GNRI score, factors such as length of hospital stay, CCI > 2, and blood transfusion were also identified as independent risk factors for survival. Notably, the incidence of postoperative complications in patients with high SII–GNRI scores was significantly greater than in patients with low scores.

Conclusion

The SII–GNRI score proves valuable in predicting the 1-year survival rate for elderly patients with hip fractures who have undergone surgery.
Rare subclonal sequencing of breast cancers indicates putative metastatic driver mutations are predominately acquired after dissemination
Authors: Lawrence-Paul Matthew R. , Pan Tien-chi , Pant Dhruv K. , Shih Natalie N. C. , Chen Yan , Belka George K. , Feldman Michael , DeMichele Angela , Chodosh Lewis A.
Published: February 2024

Background

Evolutionary models of breast cancer progression differ on the extent to which metastatic potential is pre-encoded within primary tumors. Although metastatic recurrences often harbor putative driver mutations that are not detected in their antecedent primary tumor using standard sequencing technologies, whether these mutations were acquired before or after dissemination remains unclear.

Methods

To ascertain whether putative metastatic driver mutations initially deemed specific to the metastasis by whole exome sequencing were, in actuality, present within rare ancestral subclones of the primary tumors from which they arose, we employed error-controlled ultra-deep sequencing (UDS-UMI) coupled with FFPE artifact mitigation by uracil-DNA glycosylase (UDG) to assess the presence of 132 “metastasis-specific” mutations within antecedent primary tumors from 21 patients. Maximum mutation detection sensitivity was ~1% of primary tumor cells. A conceptual framework was developed to estimate relative likelihoods of alternative models of mutation acquisition.

Results

The ancestral primary tumor subclone responsible for seeding the metastasis was identified in 29% of patients, implicating several putative drivers in metastatic seeding including LRP5 A65V and PEAK1 K140Q. Despite this, 93% of metastasis-specific mutations in putative metastatic driver genes remained undetected within primary tumors, as did 96% of metastasis-specific mutations in known breast cancer drivers, including ERRB2 V777L, ESR1 D538G, and AKT1 D323H. Strikingly, even in those cases in which the rare ancestral subclone was identified, 87% of metastasis-specific putative driver mutations remained undetected. Modeling indicated that the sequential acquisition of multiple metastasis-specific driver or passenger mutations within the same rare subclonal lineage of the primary tumor was highly improbable.

Conclusions

Our results strongly suggest that metastatic driver mutations are sequentially acquired and selected within the same clonal lineage both before, but more commonly after, dissemination from the primary tumor, and that these mutations are biologically consequential. Despite inherent limitations in sampling archival primary tumors, our findings indicate that tumor cells in most patients continue to undergo clinically relevant genomic evolution after their dissemination from the primary tumor. This provides further evidence that metastatic recurrence is a multi-step, mutation-driven process that extends beyond primary tumor dissemination and underscores the importance of longitudinal tumor assessment to help guide clinical decisions.
AdductHunter: identifying protein-metal complex adducts in mass spectra
Authors: Long Derek , Eade Liam , Sullivan Matthew P. , Dost Katharina , Meier-Menches Samuel M. , Goldstone David C. , Hartinger Christian G. , Wicker Jörg S. , Taškova Katerina
Published: February 2024

Mass spectrometry (MS) is an analytical technique for molecule identification that can be used for investigating protein-metal complex interactions. Once the MS data is collected, the mass spectra are usually interpreted manually to identify the adducts formed as a result of the interactions between proteins and metal-based species. However, with increasing resolution, dataset size, and species complexity, the time required to identify adducts and the error-prone nature of manual assignment have become limiting factors in MS analysis. AdductHunter is a open-source web-based analysis tool that  automates the peak identification process using constraint integer optimization to find feasible combinations of protein and fragments, and dynamic time warping to calculate the dissimilarity between the theoretical isotope pattern of a species and its experimental isotope peak distribution. Empirical evaluation on a collection of 22 unique MS datasetsshows fast and accurate identification of protein-metal complex adducts in deconvoluted mass spectra.
Estimation of lifetime productivity loss from patients with chronic diseases: methods and empirical evidence of end-stage kidney disease from Taiwan
Authors: Wang Fuhmei , Hwang Jing-Shiang , Huang Wen-Yen , Chang Yu-Tzu , Wang Jung-Der
Published: February 2024

Objective

Studies that examine the broad allocation of resources, regardless of who bears the costs, should ideally estimate costs from a societal perspective. We have successfully integrated survival rates, employment ratios, and earnings to address the significant challenge of evaluating societal value through productivity assessments of patients with end-stage kidney disease (ESKD) in Taiwan.

Methods

Using a theoretical framework, we interconnected two nationwide databases: the Taiwan National Health Insurance (NHI) and the Taiwan Mortality Registry from 2000 to 2017. Due to the statutory retirement age of 65, we collected data on all patients (83,358) aged 25–64 years diagnosed with ESKD and undergoing maintenance dialysis. We estimated the lifetime survival function through a rolling extrapolation algorithm, which was then combined with the monthly employment ratio and wages to calculate the lifetime employment duration and productivity up to the legal retirement age of ESKD patients. These were compared with sex-, age-, and calendar year-matched referents to determine the loss of employment duration and productivity of ESKD patients.

Results

ESKD patients experienced a loss of approximately 25–56% in lifetime employment duration and a larger loss of about 32–66% in lifetime productivity after adjustments for different age, sex, and calendar year. The annual productivity loss per male (female) ESKD patient relative to that of the age-and calendar year-matched referent ranges from 75.5% to 82.1% (82.3% to 90.3%). During the periods when they are able to work (over the on-the-job duration) male ESKD patients lose between 34 and 56% of their income, and female ESKD patients lose between 39 and 68% of their income, compared to the age-and calendar year-matched referents. The loss of lifetime productivity is a combination of reduced lifetime employment duration, functional disability, absenteeism, and presenteeism at the workplace. The loss related to presenteeism is implied by the reduced wages.

Conclusions

In addition to the loss of employment duration, we have empirically demonstrated the lifetime loss of productivity in patients with ESKD, also indicating the “presenteeism” resulted from inability to perform their job with full capacity over long-term periods.
Graph convolution networks for social media trolls detection use deep feature extraction
Authors: Asif Muhammad , Al-Razgan Muna , Ali Yasser A. , Yunrong Long
Published: February 2024

This study presents a novel approach to identifying trolls and toxic content on social media using deep learning. We developed a machine-learning model capable of detecting toxic images through their embedded text content. Our approach leverages GloVe word embeddings to enhance the model's predictive accuracy. We also utilized Graph Convolutional Networks (GCNs) to effectively analyze the intricate relationships inherent in social media data. The practical implications of our work are significant, despite some limitations in the model's performance. While the model accurately identifies toxic content more than half of the time, it struggles with precision, correctly identifying positive instances less than 50% of the time. Additionally, its ability to detect all positive cases (recall) is limited, capturing only 40% of them. The F1-score, which is a measure of the model's balance between precision and recall, stands at around 0.4, indicating a need for further refinement to enhance its effectiveness. This research offers a promising step towards more effective monitoring and moderation of toxic content on social platforms.
Life and disease status of patients with Parkinson’s disease during and after zero-COVID in China: an online survey
Authors: Huang Pei , Tan Yu-Yan , Chen Biao , Shang Hui-Fang , Wang Li-Juan , Liu Chun-Feng , Chen Ling , Chang Ying , Wang Han , Wang Xue-Lian , Lei Xiao-Guang , Yao Li-Fen , Yu Yang , Ye Zheng , Chen Hai-Bo , Chen Sheng-Di
Published: February 2024

Background

Little is known about the impact of the COVID-19 pandemic on patients with Parkinson’s disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy.

Methods

This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management.

Results

A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%,P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%,P < 0.0001). (3) During zero-COVID, 62.36% of patients felt worried, and ‘limited outdoor activities’ (55.39%) was the top reason for mental health problems. After zero-COVID, 59.03% of patients felt worried, with ‘poor health’ (58.10%) being the top reason. The PD patients tended to change their daily activities from offline to online, and their economic and caregiver burdens increased both during and after zero-COVID. (4) Most PD patients would like to choose online rehabilitation during (69.56%) and after zero-COVID (69.27%). The demand for online medication purchasing also increased during (47.00%) and after zero-COVID (26.63%).

Conclusions

The COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy period. The PD patients also experienced prominent mental health problems, changes in daily activities, and increases in economic and caregiver burdens. The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation.
“When people who use drugs can’t differentiate between medical care and cops, it’s a problem.” Compounding risks of law Enforcement Harassment & Punitive Healthcare Policies
Authors: Ostrach Bayla , Hixon Vanessa , Bryce Ainsley
Published: February 2024

Background

Community-based harm reduction programming is widely recognized as an effective strategy for reducing the increased risks for and spread of HIV, HCV, and for reducing the growing rate of overdose deaths among people who use drugs (PWUD). PWUD in the United States (US) are a highly justice-involved population, also at increased risk for law enforcement interaction, arrest, and incarceration. These risks compound and interact in the context of criminalization and law enforcement surveillance. Justice involvement increases risks for overdose and for riskier injecting behavior among PWUD, in turn increasing HCV and HIV risks. In Central and Southern Appalachia specifically, PWUD have identified fear of law enforcement harassment and arrest as a barrier to engaging in harm reduction behavior, and a deterrent to seeking help at the scene of an overdose. Moreover, stigmatizing and punitive treatment in healthcare settings can deter PWUD from seeking care, with life or death consequences. This evaluation research study assessing the successes and impacts of a grant-funded project to increase access to safer drug consumption supplies and overdose prevention education for PWUD, including justice-involved participants of a syringe access program (SAP), in public housing and beyond in a South-Central Appalachian setting used key informant and opportunistic sampling. Mixed-methods data were compiled and collected including secondary program data; primary interview and participant-observation data.

Results

The evaluation research identified that grant deliverables were largely achieved, despite challenges presented by the COVID-19 pandemic. In addition, SAP participants and staff reported larger themes surrounding grant-funded activities, in which they perceived that widespread local law enforcement harassment of PWUD increased participants’ risks for overdose death and infectious disease risks and that punitive local healthcare settings and policies acted as deterrents to care-seeking for many PWUD.

Conclusions

Overall, the evaluation research found that participants’ experiences with and perceptions of local law enforcement harassment combined with their understandings and experiences of local punitive healthcare settings and policies; together compounding and increasing overdose risks and negative health consequences for local justice-involved PWUD.
The relationship between family resilience and the psychological well-being and life satisfaction of pregnant women: the mediating role of individual resilience
Authors: Yousefi Afrashteh Majid , Hanifeh Parinaz , Morovati Zekrollah
Published: February 2024

Background

Pregnancy period is an important experience in the life process of married women, which leads them to growth and development and is considered as a part of the puberty process. The aim of this research is to determine the mediating role of individual resilience in relation to family resilience, psychological well-being and life satisfaction of the pregnant women. The current study is correlational according to the practical purpose and based on data collection.

Methodes

The study population of the current research is all pregnant women in 2021, and 361 of them responded to the self-report questionnaires of family resilience, psychological well-being, life satisfaction, and individual resilience. To analysis the model, the path analysis method was used utilization spss-26 and Lisrel 10.2 software.

Results

The results show a good fit of the model with the data. The results also showed a direct and significant effect between life satisfaction with obligation (β = 0.22 and t = 3.42), with challenge (β = 0.28 and t = 3.98), with control (β = 0.11 and t = 2.13), psychological well-being with obligation (β = 0.20 and t = 3.11), with challenge (β = 0.20 and t = 2.73) and with control (β = 0.45 and t = 10.34).

Conclusion

The upshot of this research can be considered in interventions related to pregnant women. Strengthening resilience in this group can be useful for increasing life satisfaction and psychological well-being of pregnant women.
Anatomy-based correction of kidney PVE on $$^{177}\text{Lu}$$ SPECT images
Authors: Salvadori Julien , Allegrini Oreste , Opsommer Thomas , Carullo Josefina , Sarrut David , Porot Clemence , Ritzenthaler Florian , Meyer Philippe , Namer Izzie-Jacques
Published: February 2024

Background

In peptide receptor radionuclide therapy (PRRT), accurate quantification of kidney activity on post-treatment SPECT images paves the way for patient-specific treatment. Due to the limited spatial resolution of SPECT images, the partial volume effect (PVE) is a significant source of quantitative bias. In this study, we aimed to evaluate the performance and robustness of anatomy-based partial volume correction (PVC) algorithms to recover the accurate activity concentration of realistic kidney geometries on $$^{177}$$

177

Lu SPECT images recorded under clinical conditions.

Methods

Based on the CT scan data from patients, three sets of fillable kidneys with surface-to-volume (S:V) ratios ranging from 1.5 to 2.8 cm−1, were 3D printed and attached in a IEC phantom. Quantitative $$^{177}$$

177

Lu SPECT/CT acquisitions were performed on a GE Discovery NM CT 870 DR camera for the three modified IEC phantoms and for 6 different Target-To-Background ratios (TBRs: 2, 4, 6, 8, 10, 12). Two region-based (GTM and Labbé) and five voxel-based (GTM + MTC, Labbé + MTC, GTM + RBV, Labbé + RBV and IY) methods were evaluated with this data set. Additionally, the robustness of PVC methods to Point Spread Function (PSF) discrepancies, registration mismatches and background heterogeneity was evaluated.

Results

Without PVC, the average kidney RCs across all TBRs ranged from 0.66 ± 0.05 (smallest kidney) to 0.80 ± 0.03 (largest kidney). For a TBR of 12, all anatomy-based method were able to recover the kidneys activity concentration with an error < 6%. All methods result in a comparable decline in RC restoration with decreasing TBR. The Labbé method was the most robust against PSF and registration mismatches but was also the most sensitive to background heterogeneity. Among the voxel-based methods, MTC images were less uniform than RBV and IY images at the outer edge of high uptake areas (kidneys and spheres).

Conclusion

Anatomy-based PVE correction allows for accurate SPECT quantification of the $$^{177}$$

177

Lu activity concentration with realistic kidney geometries. Combined with recent progress in deep-learning algorithms for automatic anatomic segmentation of whole-body CT, these methods could be of particular interest for a fully automated OAR dosimetry pipeline with PVE correction.
Randomised controlled feasibility study protocol of the Carers-ID online intervention to support the mental health of family carers of people with intellectual disabilities
Authors: Linden Mark A. , Leonard Rachel , Forbes Trisha , Brown Michael , Marsh Lynne , Todd Stuart , Hughes Nathan , Truesdale Maria
Published: February 2024

Background

Family carers play a crucial role in supporting the health and well-being of people with intellectual disabilities. Given their role and responsibilities, many family carers experience significant and ongoing stress and mental health difficulties. Programmes and interventions which provide training and support to family carers have been shown to have a positive impact on levels of stress and quality of life. However, these are often face to face which can create barriers to full participation. Online interventions have been shown to offer flexibility in delivery compared with traditional face-to-face approaches. The primary objective of this study is to determine the feasibility of delivering the Carers-ID online intervention, while the secondary outcome is improved mental health in family carers of people with intellectual disabilities.

Methods

Family carers (n = 120) will be randomised to receive the intervention (n = 60) or assigned to a wait-list control (n = 60) group. The intervention (www.Carers-ID.com) consists of 14 modules which cover topics including the following: promoting resilience, providing peer support, reducing anxiety, managing stress, accessing local supports and managing family conflict and information for siblings who are carers. The intervention has been co-produced with voluntary sector organisations and family carers and tested for acceptability. Primary outcomes for this study include acceptability and feasibility of the outcome measures, recruitment, participation and retention rates and effect sizes. Secondary outcomes will be completed at three time points (baseline, following intervention completion and 3 months after completion). These include the following: the Depression, Anxiety and Stress Scale, the Warwick–Edinburgh Mental Well-being Scale, the Resilience Scale and the Social Connectedness Scale Revised. Participants (n = 12) who have taken part in the intervention arm of the research will be invited to participate in semi-structured interviews as part of the process evaluation.

Discussion

The Carers-ID intervention provides an online resource for family carers to support their mental health and well-being and promote their resilience. It represents an affordable and accessible means of delivering such support. Testing the feasibility of the intervention and related trial procedures is required to determine whether a full-scale randomised controlled trial to evaluate the intervention’s effectiveness is warranted.

Trial registration

ClinicalTrials.gov: NCT05737823