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Reliable RNA-seq analysis from FFPE specimens as a means to accelerate cancer-related health disparities research

Whole transcriptome sequencing (WTS/ RNA-Seq) is a ubiquitous tool for investigating cancer biology. RNA isolated from frozen sources limits possible studies for analysis of associations with phenotypes or clinical variables requiring long-term follow-up. Although good correlations are reported in RNA-Seq data from paired frozen and formalin fixed paraffin embedded (FFPE) samples, uncertainties regarding RNA quality, methods of extraction, and data reliability are hurdles to utilization of archival samples. We compared three different platforms for performing RNA-seq using archival FFPE oropharyngeal squamous carcinoma (OPSCC) specimens stored up to 20 years, as part of an investigation of transcriptional profiles related to health disparities. We developed guidelines to purify DNA and RNA from FFPE tissue and perform downstream RNA-seq and DNA SNP arrays. RNA was extracted from 150 specimens, with an average yield of 401.8 ng/cm 2 of tissue. Most samples yielded sufficient RNA reads >13,000 protein coding genes which could be used to differentiate HPV-associated from HPV-independent OPSCCs. Co-isolated DNA was used to identify reliably define patient ancestry which correlated well with patient-reported race. Utilizing the methods described in this study provides a robust, reliable, and standardized means of DNA & RNA extraction from FFPE as well as a means by which to assure the quality of the data generated. Optimized RNA extraction techniques, combined with robust bioinformatic approaches designed to optimize data homogenization, analysis and biological validation can revolutionize our ability to transcriptomically profile large solid tumor sets derived from ancestrally varied patient populations.

Deaths “due to” COVID-19 and deaths “with” COVID-19 during the Omicron variant surge, among hospitalized patients in seven tertiary-care hospitals, Athens, Greece

Abstract In Greek hospitals, all deaths with a positive SARS-CoV-2 test are counted as COVID-19 deaths. Our aim was to investigate whether COVID-19 was the primary cause of death, a contributing cause of death or not-related to death amongst patients who died in hospitals during the Omicron surge and were registered as COVID-19 deaths. Additionally, we aimed to analyze the factors associated with the classification of these deaths. We retrospectively re-viewed all in-hospital deaths, that were reported as COVID-19 deaths, in 7 hospitals, serving Athens, Greece, from January 1, 2022, until August 31, 2022. We retrieved clinical and laboratory data from patient records. Each death reported as COVID-19 death was characterized as: (A) death “due to” COVID-19, or (B) death “with” COVID-19. We reviewed 530 in-hospital deaths, classified as COVID-19 deaths (52.4% males; mean age 81.7 ± 11.1 years). We categorized 290 (54.7%) deaths as attributable or related to COVID-19 and in 240 (45.3%) deaths unrelated to COVID-19 In multivariable analysis The two groups differed significantly in age (83.6 ± 9.8 vs. 79.9 ± 11.8, p = 0.016), immunosuppression history (11% vs. 18.8%, p = 0.027), history of liver disease (1.4% vs. 8.4%, p = 0.047) and the presence of COVID-19 symptoms (p < 0.001). Hospital stay was greater in persons dying from non-COVID-19 related causes. Among 530 in-hospital deaths, registered as COVID-19 deaths, in seven hospitals in Athens during the Omicron wave, 240 (45.28%) were reassessed as not directly attributable to COVID-19. Accuracy in defining the cause of death during the COVID-19 pandemic is of paramount importance for surveillance and intervention purposes.

Separated or joint models of repeated multivariate data to estimate individuals’ disease trajectories with application to scleroderma

Estimating a patient’s disease trajectory as defined by clinical measures is an essential task in medicine. Given multiple biomarkers, there is a practical choice of whether to estimate the joint distribution of all biomarkers in a single model or to model the univariate marginal distribution of each marker separately ignoring the covariance structure among measures. To fully utilize all trajectory-relevant information in multiple longitudinal markers, a joint model is required, but its complexity and computational burden may only be warranted when joint estimates of trajectories are substantially more efficient than separate estimates. This paper derives general expressions for the inefficiency of univariate or “separated" estimates of population-average trajectories and individual’s random effects as compared to the fully efficient multivariate or “combined" estimates. Then, in two settings: (1) a general bivariate case; and (2) our motivating clinical case study with 5 measures, we find that separated estimates of fixed effects are nearly fully efficient. However, joint estimates of random effects can be meaningfully more efficient for measures with substantial missing data when other strongly correlated measures are observed more frequently. This increased efficiency of the joint model derives more from joint shrinkage of random effects in multivariate space than from improved estimates of the subject-specific trajectories obtained when accounting for correlations in measurements. These findings have application to a diverse array of chronic diseases where biomarkers’ trajectories guide clinical decisions.

LINC01123 aggravates cerebral ischemia reperfusion injury by targeting miR-654-5p to upregulate METTL7A

Capecitabine metronomic chemotherapy for metastatic colorectal cancer patients reaching NED: A protocol for a prospective, randomized, controlled trial

Introduction An increasing number of patients with metastatic colorectal cancer (mCRC) have achieved no evidence of diseases (NED) status after surgery or other treatments. However, the latest guidelines for colorectal cancer do not recommend an appropriate treatment for patients with mCRC who achieve NED status. Capecitabine metronomic chemotherapy has the advantages of significant efficacy and minimal adverse reactions, it is a potential effective method for maintenance treatment for mCRC, but no RCTs have been reported. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of capecitabine metronomic chemotherapy for mCRC patients who achieve NED. Methods/design This study is a prospective, randomized controlled study that evaluates the efficacy and safety of capecitabine metronomic chemotherapy for patients with mCRC who achieve NED status. 240 eligible participants will be randomly assigned to either a capecitabine metronomic chemotherapy group or a “watch and wait” group at a 1:1 allocation ratio. Eligible patients diagnosed with stage IV mCRC, both the primary tumor and the metastases, are those who have achieved R0 resection (or complete destruction by ablation) and reached NED. Participants who are enrolled in the capecitabine group will receive capecitabine (500 mg/m2 body surface area twice daily) for 2 years. Meanwhile, those who are assigned to the control group will receive regular imaging examination and follow-up only. All participants will follow up for 1 year after receiving 2 years of intervention. The primary outcomes will be disease-free survival (DFS) from randomization, stratified by preoperative chemotherapy, metastatic organs, number of metastases, lenght of previous systemic treatment, response to previous chemotherapy. Secondary outcomes will include overall survival (OS), 1-year,2-year,3-year survival rate and adverse reactions. Discussion As a potentially effective treatment, low-dose capecitabine metronomic chemotherapy has been explored in clinical practice. The results of this trial will provide evidence on the efficacy and safety of capecitabine metronomic chemotherapy for patients with mCRC who have reached NED status. Trial registration Chinese Clinical Trial Registry (ChiCTR2100047149, protocol version number F2.0)

Safety and efficacy of robotic-assisted laparoscopic pyeloplasty for ureteropelvic junction obstruction in infants under 6 months

Cognitive functional therapy versus therapeutic exercises for the treatment of individuals with chronic shoulder pain: A protocol for a randomized controlled trial

Introduction Shoulder pain is a debilitating musculoskeletal condition with functional, physical, and psychological impacts. Interventions for chronic shoulder pain should address the biopsychosocial model, with Cognitive Functional Therapy (CFT) emerging as a promising physiotherapy approach. CFT approaches the multidimensional nature of pain, integrating physical and cognitive aspects. To date, no study has assessed the effectiveness of CFT in individuals with chronic shoulder pain. Therefore, this randomized controlled trial aims to compare the effects of CFT to therapeutic exercises on pain intensity, disability, self-efficacy, sleep quality, biopsychosocial aspects, and central pain processing in individuals with chronic shoulder pain. Methods This will be a randomized controlled trial, single-blinded with two parallel groups. Seventy-two individuals with chronic shoulder pain will be randomly assigned to one of two groups: CFT or Therapeutic exercise. The interventions will last 8 weeks, with the CFT group receiving therapy once a week and the therapeutic exercise group receiving sessions twice a week. The primary outcomes will be pain intensity and disability, while the secondary outcomes will include function, self-efficacy, sleep quality, biopsychosocial factors, perception of improvement/deterioration, and central pain processing. The outcome measures will be assessed at baseline, 4th week, end of treatment (8th week), and 12th-week follow-up. Conclusion The results of this study will contribute to understanding the effectiveness of CFT in treating individuals with chronic shoulder pain. Trial registration number: NCT06542666

Improving deep learning-based neural distinguisher with multiple ciphertext pairs for speck and Simon

Association of mean corpuscular volume with 28-day mortality in sepsis patients: A retrospective cohort study using eICU data

Introduction The issue of mortality due to sepsis remains a significant concern in the field of medicine. Previous researches have demonstrated an association between mean corpuscular volume (MCV) and mortality from a range of diseases. The objective of this study was to investigate the relationship between MCV and the risk of mortality from sepsis in a large multicentre cohort. Method A retrospective cohort study was conducted using data from the eICU Collaborative Research Database from 2014–2015. MCV was determined within the initial 24 hours of ICU admission, with patients subsequently classified into quartiles based on their MCV levels. Multivariate regression models were employed to investigate the correlation between MCV and 28-day mortality, with adjustments made for potential confounding factors such as age, sex, body mass index, vital signs and comorbidities. To evaluate the dose-response relationship between MCV and 28-day mortality in patients with sepsis, smoothed curve fitting and threshold effects analysis were utilised. Results A total of 9,415 patients with sepsis were included in the study and the 28-day ICU mortality rate of the sepsis patients was 9.38% (883/9415). After adjusting for confounding variables, it was found that the odds ratio (OR) for 28-day mortality was 1.11 (95% CI 1.01, 1.23, P=0.04) increased followed by each 1 fl increase in MCV. The smoothed fitted curves demonstrated a nonlinear positive correlation between MCV and 28-day mortality. The inflection point for the level of MCV was 83 fl. At MCV <83 fl, there was a significant increase in the risk of 28-day mortality with each 1 fl increase in MCV (OR 1.10, 95% CI 1.02, 1.17, P=0.004). Conclusions There is a non-linear positive correlation between MCV and 28-day risk of death in patients with sepsis. Clinicians should be aware of changes in this indicator, especially in patients with high MCV levels.

An improved GRU method for slope stress prediction

Thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, and biotin hard gelatin capsules prepared in advance and stored for the treatment of pediatric metabolic diseases: a safer alternative

The treatment of several pediatric metabolic diseases involves vitamins supplementation. Among these, thiamine, riboflavin, pyridoxine and biotin can be prescribed and compounded as hard gelatin capsules. In compounding practice, a medication can be done extemporaneously, leading to a risk of error. However, a medication can also be done in advance, analytically controlled and stored. Such practice reduce the risk of error and decrease the cost, but also imposes the realization of stability studies to establish beyond-use-dates. Thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, and biotin hard gelatin capsules chromatographic and microbiological methods were both validated and used to perform stability studies. Thiamine hydrochloride 50 mg hard gelatin capsules with microcrystalline cellulose and silica as excipients are stable for 6 months when stored at 25 °C/ 60% RH protected from light. Riboflavin 50 mg with microcrystalline cellulose, pyridoxine hydrochloride 50 mg with microcrystalline cellulose and biotin 40 mg with microcrystalline cellulose/silica are stable for one year when stored at 25 °C/ 60% RH protected from light. These results allow the compounding in advance of batches of 300 capsules controlled, stored, and quickly dispensed in case of an emergency, such decreasing the risk of error and/or iatrogenic event.

Benchmarking of variant calling software for whole-exome sequencing using gold standard datasets

Confidence interval forecasting model of small watershed flood based on compound recurrent neural networks and Bayesian

Flood forecasting exhibits rapid fluctuations, water level forecasting shows great uncertainty and inaccuracy in small watersheds, and the reliability and accuracy performance of traditional probability forecasting is often unbalanced. This study combined Recurrent Neural Networks (RNN) and Bayesian to establish a comprehensive forecasting model framework of RNNs-Bayesian for the forecasting of water level confidence interval, to achieve both reasonable reliability and accuracy. In the Bayesian structure, weight training was used. In the RNNs, base RNN, Long Short-term Memory (LSTM), and Gated Recurrent Unit (GRU) are used for comparative analysis, and experiments are carried out at the point of the Qixi Reservoir in a small watershed in Zhejiang Province of China. We used the multidimensional disaster data input unit for water level forecasting, including hydrology, meteorology, and geography, and 5 days of time windows for forecasting, The comprehensive reliability of LSTM-Bayesian for 0~102 hours flood reached 92.31%, and the comprehensive accuracy reached 89.15%, and confidence interval forecasting using LSTM is the best method, and achieved reasonable balance of reliability and accuracy. Overall, compound RNN could be a good alternative for forecasting hourly streamflow and extreme water level in small watersheds.

Modeling radiologists’ cognitive processes using a digital gaze twin to enhance radiology training

Abstract Predicting human gaze behavior is critical for advancing interactive systems and improving diagnostic accuracy in medical imaging. We present MedGaze, a novel system inspired by the “Digital Gaze Twin” concept, which models radiologists’ cognitive processes and predicts scanpaths in chest X-ray (CXR) images. Using a two-stage training approach—Vision to Radiology Report Learning (VR2) and Vision-Language Cognition Learning (VLC)—MedGaze combines visual features with radiology reports, leveraging large datasets like MIMIC to replicate radiologists’ visual search patterns. MedGaze outperformed state-of-the-art methods on the EGD-CXR and REFLACX datasets, achieving IoU scores of 0.41 [95% CI 0.40, 0.42] vs. 0.27 [95% CI 0.26, 0.28], Correlation Coefficient (CC) of 0.50 [95% CI 0.48, 0.51] vs. 0.37 [95% CI 0.36, 0.41], and Multimatch scores of 0.80 [95% CI 0.79, 0.81] vs. 0.71 [95% CI 0.70, 0.71], with similar improvements on REFLACX. It also demonstrated its ability to assess clinical workload through fixation duration, showing a significant Spearman rank correlation of 0.65 (p < 0.001) with true clinical workload ranks on EGD-CXR. The human evaluation revealed that 13 out of 20 predicted scanpaths closely resembled expert patterns, with 18 out of 20 covering 60–80% of key regions. MedGaze’s ability to minimize redundancy and emulate expert gaze behavior enhances training and diagnostics, offering valuable insights into radiologist decision-making and improving clinical outcomes.

Prevalence of sickle cell anemia in Africa: A protocol for a meta-analysis of existing studies

Background Sickle cell anemia (SCA) rank 11th among all causes of mortality in Sub-Saharan Africa, with the region accounting for 75% of global cases. Inconsistent diagnostic methods and country-specific data gaps hinder current prevalence estimates. This systematic review and meta-analysis aim to provide pooled prevalence estimates and examine geographic and temporal trends in SCA. Objectives This systematic review and meta-analysis aim to determine the pooled prevalence of SCA across Africa and analyze its geographic and temporal distribution patterns by synthesizing data from existing studies. Methods We will search four major databases: PubMed, Google Scholar, BASE, and Scopus, for studies on SCA prevalence in Africa published between 1994 and 2024. We will use Zotero to remove duplicates and screen titles and abstracts. We will assess the methodological quality with the JBI critical appraisal checklist for studies reporting prevalence data and extract data using a tested MS Excel form from studies with low to moderate bias. We will use random-effects meta-analysis to calculate pooled prevalence estimates and conduct subgroup analyses for heterogeneity. We will evaluate publication bias with funnel plots and Egger’s test, using trim-and-fill analysis if asymmetry is detected. The strength of evidence will be assessed using the AMSTAR (A Measurement Tool to Assess systematic Reviews). Expected Results We expect to find significant variations in SCA prevalence across different regions and age groups, reflecting underlying environmental, diagnostic and methodological factors. We aim to identify any shifts in SCA prevalence and distribution patterns, which could inform future public health strategies and interventions Discussion Our analysis will reveal the pooled prevalence of SCA in Africa, influencing diagnostic, environmental, and methodological factors, guiding targeted public health interventions. Registration Our meta-analysis protocol was registered with the Open Science Framework (OSF) on 8th January, 2025. https://doi.org/10.17605/OSF.IO/M8JXV

Identification of atopic dermatitis-associated diseases based on the National health and nutrition examination survey (NHANES) 2013–2018

The impact of long-term care insurance on household expenditures of the elderly: Evidence from China

This study aims to investigate the impact of China’s long-term care insurance (LTCI) pilot on household expenditures of the elderly. Utilizing the China Health and Retirement Longitudinal Study (CHARLS) 2015–2020 three-period longitudinal panel data, we examine the policy effects of LTCI using the Differences-in-Differences (DID) approach. The results indicate that the implementation of LTCI significantly reduces medical (p<0.05) and healthcare expenditures (p<0.05) for elderly households, while substantially increasing non-medical healthcare expenditures (p<0.01) and total expenditures (p<0.01). This effect is more pronounced for older households in rural areas or with lower levels of education. Furthermore, the improvement in household expenditures is strongly associated with the health status of the elderly and intergenerational economic support. These findings provide empirical evidence that LTCI enhances household expenditures and the quality of life for the elderly, which is crucial for the development of LTCI in China and other middle-income developing countries.

Optimization of residual coalbed methane extraction wells and analysis of development and emission reduction benefits in the Songzao mining area

Effect of match load on perceived wellness in highly trained female football players

Background Exposure to match loads significantly affects physiological and psychological indicators and, consequently, players’ wellness. However, this information is still scarce in women’s football. Therefore, the aims of this study were twofold: a) to compare the wellness variation from matchday (MD) to two days post-match (MD+2); b) and to analyse the correlations between the players’ external load on MD and the self-reported wellness on the day after the match (MD+1) and MD+2. Methods This retrospective cohort study included data from 22 weeks and 33 official matches from 18 professional and semi-professional female football players competing in the Norwegian top-tier. Signals for total distance, high-speed running distance (>16 km/h-1), sprint distance (>20 km/h-1), acceleration distance, and number of sprints were collected using a Global Positioning System. Sleep duration and four wellness subsets were included in this study: sleep quality, delayed onset muscular soreness, fatigue and stress levels. Individual models were run using the respective wellness variable as the dependent variable, with matchday as a predictor. Data was modelled using cumulative link regression models. The model allowed random slopes for subjects to account for repeated measurements. Correlation analysis was computed using Spearman’s rank correlations. Results Our results from the cumulative link regression model suggest that fatigue increased on MD+1 (Estimate: 1.30; SE=0.16; p<0.001) and remained elevated on MD+2 (Estimate: 0.75; SE=0.15; p<0.001), when compared to MD. Sleep quality decreased on MD+1 (Estimate: -0.72; SE=0.14; p<0.001). Sleep duration decreased on MD+1 (Estimate: -0.70; SE=0.13; p<0.001) and on MD+2 (Estimate: -0.61; SE=0.13; p<0.001). Moderate correlations were observed on MD+2 between sleep duration and acceleration distance (0.32, p<0.001) and high-speed running distance (0.30, p<0.001). Conclusions Competitive matches are associated with a disruption in the stability of the players’ sleep patterns and wellness. The results also suggest that univariate external load measures may not be strong enough to predict the players’ wellness status variation in the days following matches.

NF-E2-related factor 1 suppresses the expression of a spermine oxidase and the production of highly reactive acrolein

Abstract Polyamines (putrescine, spermidine, and spermine) are among the most abundant intracellular small molecular metabolites, with concentrations at the mM level. The ratios of these three molecules remain constant under physiological conditions. Stress (i.e. polyamine overload, oxidative stress, aging, infection, etc.) triggers the catabolic conversion of spermine to spermidine, ultimately yielding acrolein and hydrogen peroxide. The potential of acrolein to induce DNA damage and protein denaturation is 1,000 times greater than that of reactive oxygen species. We have shown that these polyamine metabolic pathways also involve the nuclear factor erythroid-2-related factor 1 (NRF1) transcription factor. In our chemically-inducible, liver-specific Nrf1 -knockout mice, the polyamine catabolic pathway dominated the anabolic pathway, producing free acrolein and accumulating acrolein-conjugated proteins in vivo. This metabolic feature implicates SMOX as an important causative enzyme. Chromatin immunoprecipitation and reporter assays confirmed that NRF1 directly suppressed Smox expression. This effect was also observed in vitro. Ectopic overexpression of SMOX increased the accumulation of free acrolein and acrolein-conjugated proteins. SMOX knockdown reversed the accumulation of free acrolein and acrolein-conjugated proteins. Our results show that NRF1 typically suppresses Smox expression when NRF1 is downregulated, SMOX is upregulated, and polyamine metabolic pathways are altered, producing low molecular weight polyamines and acrolein.