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Cost profiles of cancer patients at the end of life: Estimates from the EPICOST-study
Objectives The study aims to analyze care and cost patterns in the Veneto region for cancer patients in the final phase of their disease. Methods The study cohort includes adult patients alive on 1.1.2018, which have been diagnosed with cancer at the age 15+ in a 28-years period, spanning from 1990 to 2017, and died within 12 months from prevalence date. The end-of-life (EOL) prevalent cases included in the study cohort are identified by the Veneto Tumor Registry. Primary tumors considered in the analysis are colon, rectum, skin melanoma, female breast, thyroid. Patient monthly average EOL costs, patient annual average EOL costs and total regional costs have been estimated separately for each cancer site/sex/age group/health care service database. Results The estimated EOL total cost, for the five analyzed cancer types in the Veneto Region, is approximately 53 million euros. Costs associated with cancer treatment tend to increase in the final phase of the disease. In general, Hospital Admission is the main driver cost in all types of cancer considered, with the only exception in melanoma, where Hospital Drugs features the highest contribution. Moreover, costs differ significantly depending on the type of cancer, gender, and age, revealing highest average costs associated with younger patients. Conclusions This study provides a comprehensive analysis of healthcare budget distribution in the last year of life, enabling healthcare planners to predict cancer burden in the future. This model can be applied to other Italian regions and countries with different healthcare systems.
No detectable effect of urbanization on genetic drift or gene flow in specialist herbivorous insects of milkweed
Urbanization is hypothesized to isolate populations and restrict dispersal, leading to reduced genetic diversity and increased genetic differentiation. We tested this hypothesis in specialist herbivorous insects of milkweed, positing that higher dispersal ability would mitigate the negative effects of urbanization on genetic drift and gene flow, and that these effects would vary with city size. In this study, we collected 383 milkweed insects from urban and rural sites in Toronto, Canada, and five surrounding cities. Using ddRADseq, we generated 145,000 SPNs for monarchs, 10,000 SNPs for beetles, 6,000 SNPs for weevils to quantify genetic diversity, demographic history and population genetic structure. Contrary to our hypotheses, our results indicated no effect of urbanization or dispersal ability on diversity or genetic differentiation. Genetic diversity, measured as π, varied between 0.0013 and 0.0044 across species, with no urban vs. rural component, but with monarchs having >2 X higher diversity compared to beetles and weevils. Similarly, genetic differentiation was generally low, FST varying between 0.01 and 0.28, but there are no consistent trends among urban vs. rural samples for any of the three species. However, demographic analyses revealed a consistent decline in effective population size for all three sampled species, beginning around the last glacial maximum and intensifying over the past 1,000 years. Our findings suggest that both urbanization and dispersal ability have not been a major factor in reducing gene flow or increasing genetic drift among milkweed’s herbivorous insect populations. Instead, historical events such as climatic change since the last glacial maximum, and large-scale anthropogenic disturbance in general, have had a more pronounced impact on demography. These results highlight the importance of considering the combined effects of natural and anthropogenic long-term historical processes when studying population genetics in the context of urbanization.
Interval price prediction of livestock product based on fuzzy mathematics and improved LSTM
Livestock product prices serve as a barometer and bellwether for the agricultural market. However, traditional point prediction techniques focus mainly on tracking or fitting, resulting in limited information and challenges in evaluating the uncertainty of future prices. A comprehensive livestock price prediction model with joint point and interval prediction capabilities is proposed, with fuzzy mathematics and long short-term memory. Three main steps are taken: (1) data composition and reconstruction, to extract a set of relatively stationary subsequence components by complementary ensemble empirical mode decomposition (CEEMD) from original signal, and divide these components into three groups according to fuzzy entropy (FE) value. (2) characteristics categorization, determining the lower bound, mean, and upper bound of the rebuilt data via fuzzy information granulation (FIG) to better characterize the price fluctuation range. (3) price prediction, including point and interval predictions with attention mechanism long short-term memory (AM-LSTM). An empirical study was conducted on the weekly price data of pork, beef, and mutton in China from 2009 to 2023, incorporating discussions on different embedding dimensions, prediction step, fuzzy granulation window sizes, decomposition techniques, and prediction algorithms. The results indicate that the proposed interval prediction model can not only achieve high accuracy in point prediction, but also better capture price change intervals.
Bioinformatics analysis of genes associated with disulfidptosis in spinal cord injury
Research findings indicate that programmed cell death (PCD) plays a pivotal role in the pathophysiology of spinal cord injury (SCI), and a recently discovered form of cell death, disulfidptosis, has emerged as a novel phenomenon. However, the characterization of disulfidptosis-related genes in SCI remains insufficiently explored. We retrieved SCI-related data from the Gene Expression Omnibus (GEO) database and identified three key genes associated with disulfidptosis in human SCI (CAPZB, SLC3A2, and TLN1), whose mediated signaling pathways are closely intertwined with SCI. Subsequent functional enrichment analysis suggested that these genes may regulate multiple pathways and exert corresponding roles in SCI pathology. Moreover, we predicted potential targeted drugs for the key genes along with their transcription factors and constructed an intricate regulatory network. CIBERSORT analysis revealed that CAPZB, SLC3A2, and TLN1 might be implicated in modulating changes within the immune microenvironment of individuals with SCI. Our study provides compelling evidence confirming the significant involvement of disulfidptosis following SCI while offering valuable insights into its underlying pathological mechanisms.
Maternity care providers’ experiences of work-related serious events (MATES): An International survey
Internationally, many women experience physiological childbirth with positive experiences and good health outcomes for them and their baby. For some, due to health complications and context of childbirth they may experience or be perceived as having had a traumatic birth. Ultimately, whether an individual experiences an event as traumatic or not, is a personal experience. Caring for women who experience their birth as traumatic can be challenging. The risk of exposure to a traumatic birth event(s) as part of maternity care providers (MCPs) work, ranges from 67% to 90%. Thereby to support MCPs to provide quality maternal and newborn care, it is important to explore the impact of work-related events. An anonymised online survey relating to MATernity serious EventS (MATES) was developed utilising validated instruments and hosted on QualtricsXM. Following ethical approval, the questionnaire was disseminated internationally across 33 countries between 1st July and 31st December 2022 via social media and the COST Action DEVOTION (CA18211 www.ca18211.eu) network. In total, 579 MCPs responded with a wide age range and years of experience. Descriptive and inferential statistical analyses were performed, including univariate and multivariate linear regression. Data analyses and management were undertaken using SPSS v.20 and two-sided significance tests were applied (α 0.05). The findings suggest that MCPs are exposed to a large variation of serious events and continue to be intensely affected, up to the present day. Events ranged from stillbirth, neonatal death, maternal death, severe or life-threatening maternal or infant incidents and violence and aggression from women or family member. Institutional support for staff is limited, and when available, seldom used. Family and friends were relied on for support, but this does not appear to be associated with MCPs experiencing less secondary traumatic stress. Subsequently MCPs were absence from work through sickness (22%), changed their professional allocation (19%) and seriously considered leaving (42%). Moreover, many reported low to moderate compassion satisfaction and burnout (65–80%). With international scarcity of MCPs, the impact of these events seem to contribute to this shortage. Effective support for MCPs is required if staff are to be recruited and retained.
Long-term consumption of hydrogen-rich water provides hepatoprotection by improving mitochondrial biology and quality control in chronically stressed mice
Background Chronic stress has emerged as a prevalent facet of contemporary existence, significantly jeopardizing overall bodily health. The liver, a pivotal organ responsible for metabolic equilibrium, is particularly vulnerable to its adverse effects. This study delves into the hepatoprotective properties of extended consumption of HRW in mice subjected to chronic stress. Methods Mice subjected to chronic stress via CUMS and HRW administration for seven months underwent liver pathological examination. Key liver function indicators (AST, ALT), oxidative stress markers (SOD, CAT, GSH), and markers related to lipid peroxidation and ferroptosis (MDA, Fe) were measured using standard kits. ELISA determined corticosterone and 4-HNE levels. Immunofluorescence evaluated ROS, Nrf2, and apoptosis in liver tissues. Western blotting analyzed markers for ferroptosis (GPX4, SLC7A11, HO-1, Nrf2), apoptosis (Bax, Bcl-2, Cytc, Caspase-3, Caspase-8), mitochondrial biogenesis (Nrf1, PGC-1α, Tfam), and quality control (Drp1, Fis1, Mfn1, Mfn2, OPA1, PINK1, Parkin, LC3 I/II). Results The findings indicate a noteworthy improvement in liver health among mice exposed to HRW, as evidenced by histological analysis. Furthermore, the consumption of HRW exhibited hepatoprotection, as evidenced by the normalization of AST and ALT levels. Mechanistically, our results indicate that HRW elevates the levels of SOD, CAT, and GSH, while effectively clearing ROS within mitochondria. It was observed led to a regulation in the expression of mitochondrial quality control proteins, consequently improving mitochondrial biogenesis (Nrf1, PGC-1α, Tfam), and increasing ATP production. Furthermore, HRW decreased Cytc, Bax, Caspase-3, and Caspase-8 levels, and increasing the expression of Bcl-2. Additionally, HRW reduced MDA and 4-HNE levels, alleviating ferroptosis through the Nrf2/HO-1 pathway, and upregulating the expression of GPX4 and SLC7A11. By mitigating hepatocyte death through the aforementioned mechanisms, HRW fulfills its crucial role in safeguarding liver health. Conclusions This study reveals that long-term hydrogen-rich water (HRW) consumption provides significant hepatoprotection in mice under chronic stress. HRW normalizes liver enzyme levels, enhances antioxidant capacity, and reduces lipid peroxidation and ferroptosis. It improves mitochondrial biogenesis, function, and ATP production, and attenuates apoptosis by modulating related proteins. Behavioral tests show HRW alleviates stress-induced anxiety and enhances exploratory behavior. These findings suggest HRW is a promising non-invasive intervention for preventing and treating stress-related liver disorders by targeting oxidative stress and mitochondrial dysfunction.
Risk factors associated with the recurrence of diabetic foot ulcers: A meta-analysis
Aims Diabetic foot ulcers have caused significant medical, economic and social consequences for patients, families and society. With appropriate treatment, many diabetic foot ulcers can heal, temporarily avoiding possible amputation. Unfortunately, even if foot ulcers subside, recurrence is still common. The recurrence of ulcer has brought another physical and psychological trauma to diabetic foot patients who yearn for a better life. Therefore, it may be more useful to evaluate the factors associated with ulcer recurrence in diabetic foot ulcer patients. Methods The PubMed, Web of Science, Embase and China National Knowledge Infrastructure databases were comprehensively searched for prospective or retrospective studies published up to February 1, 2024. All English or Chinese language studies on diabetic foot ulcer patients who experience recurrence were included, and RevMan 5.3 software was used to analyze the data. Results A total of 22 studies meeting the eligibility criteria were ultimately included in this meta-analysis. 1861 of 5252 diabetic foot ulcer patients experienced recurrence during follow-up. The following variables were associated with an increased risk of ulcer recurrence: male (OR = 1.26, 95% CI = 1.10 ~ 1.44, P = 0.0009), smoking history (OR = 1.18, 95% CI = 1.04 ~ 1.35, P = 0.01), living alone (OR = 1.86, 95% CI = 1.21 ~ 2.86, P = 0.004), plantar ulcers (OR = 2.44, 95% CI = 1.41 ~ 4.23, P = 0.001), diabetic retinopathy (OR = 1.59, 95% CI = 1.35 ~ 1.88, P < 0.00001), diabetic nephropathy (OR = 1.37, 95% CI = 1.12 ~ 1.68, P = 0.002), diabetic peripheral neuropathy (OR = 1.78, 95% CI = 1.45 ~ 2.19, P < 0.00001), foot deformity (OR = 2.51, 95% CI = 1.85 ~ 3.40 P < 0.00001) and peripheral arterial disease (OR = 3.10, 95% CI = 2.43 ~ 3.95 P < 0.00001). However, hypertension (OR = 1.16, 95% CI = 0.96 ~ 1.40, P = 0.13) and body mass index (MD = 0.20, 95% CI = −0.12 ~ 0.53, P = 0.22) were not associated with diabetic foot ulcer recurrence. Conclusions Our meta-analysis identified the following important risk factors for diabetic foot ulcer recurrence: male sex, smoking history, living alone, plantar ulcer, diabetic retinopathy, diabetic nephropathy, diabetic peripheral neuropathy, foot deformity, and peripheral arterial disease. Understanding these factors and their impact on ulcer recurrence is crucial for multidisciplinary teams to develop management and treatment plans for diabetic foot ulcer patients.
The perspectives of women on sustainable fashion consumption: Comparative study of university teachers and students
In the recent decade, fashion industry has been receiving extensive criticisms for having a significant negative impact on the environment and people. As the counterpoint of rapid pace and cheap prices which trigger overconsumption, sustainable fashion started turning into a new trend and demand for business. As the interest of consumers in sustainability continues to grow, the literature started analysing what drives or hinders them from sustainable consumption. However, acknowledging the gender differences, there is a gap in literature regarding sustainable fashion consumption from the perspective of female consumers. The purpose of this paper is to reveal the sustainable fashion consumption of females, comparing the clusters of university teachers and students. In doing this, a qualitative research was conducted, with 24 semi-structured interviews in total. The findings revealed a huge contradiction. Although females are aware of sustainable fashion elements, at the same time, they, especially students, do not consider sustainability as a primary motivation for their behaviour. As such, the gap between attitude and behaviour was revealed. Although teachers try to find the good ratio between quality and price, for students, the price usually wins when it comes to purchasing clothes. The representatives from both clusters do shopping from fast fashion retailers; however, students do it much more often and intensively in comparison to teachers. The teachers mainly use swapping and redesigning as sustainable fashion consumption practices. In case of students, second-hand shops and Vinted were prevailing. Among the drivers leading to sustainable consumption, awareness, uniqueness and personal style, and item life-cycle extension were mentioned. Regarding the barriers, high price and low income, personal restrictions, and lack of information and knowledge were mainly emphasised. The findings could be considered to initiate changes, which could enable closing the attitude-behaviour gap.
Bayesian spatio-temporal disease mapping of COVID-19 cases in Bangladesh
Background COVID-19 is a highly transmittable respiratory illness induced by SARS-CoV-2, a novel coronavirus. The spatio-temporal analysis considers interactions between space and time is essential for understanding the virus’s transmission pattern and developing efficient mitigation strategies. Objective This study explicitly examines how meteorological, demographic, and vaccination with all doses of risk factors are interrelated with COVID-19’s complex evolution and dynamics in 64 Bangladeshi districts over space and time. Methods The study employed Bayesian spatio-temporal Poisson modeling to determine the most suitable model, including linear trend, analysis of variance (ANOVA), separable models, and Poisson temporal model for spatiotemporal effects. The study employed the Deviance Information Criterion (DIC) and Watanabe-Akaike information criterion (WAIC) for model selection. The Markov Chain Monte Carlo approach also provided information regarding both prior and posterior realizations. Results The results of our study indicate that the spatio-temporal Poisson ANOVA model outperformed all other models when considering various criteria for model selection and validation. This finding underscores the significant relationship between spatial and temporal variations and the number of cases. Additionally, our analysis reveals that maximum temperature does not appear to have a significant association with infected cases. On the other hand, factors such as humidity (%), population density, urban population, aging index, literacy rate (%), households with internet users (%), and complete vaccination coverage all play vital roles in correlating with the number of affected cases in Bangladesh. Conclusions The research has demonstrated that demographic, meteorological, and vaccination variables possess significant potential to be associated with COVID-19-affected cases in Bangladesh. These data show that there are interconnections between space and time, which shows how important it is to use integrated modeling in pandemic management. An assessment of the risks particular to an area allows government agencies and communities to concentrate their efforts to mitigate those risks.
Impact of overwork on self-assessed health of rural-to-urban migrants: Limitations of work incentives moderation effect and industry heterogeneity
Overwork is widely recognized as harmful to workers’ physical and mental health, yet studies focusing on income-driven rural-to-urban migrants are lacking. This research aims to explore the effects of working hours on the health of rural-to-urban migrants in China, examining the moderating role of work incentives and industry heterogeneity. Using 2018 China Labor-force Dynamics Survey (CLDS) data, we analyzed 3,475 valid samples with a binary logit model, categorizing working hours into comfortable work, tolerable work, moderate overwork, and severe overwork. Interaction and subgroup regression models were employed to examine the moderating effects of work incentives across industries. The results indicate that comfortable work does not improve health, while moderate overwork is harmful, with severe overwork having a greater negative impact. This effect is stronger for rural-to-urban migrants in capital-intensive industries compared to labor-intensive industries. Work incentives only mitigate health damage from overwork in labor-intensive sectors, but this effect disappears under severe overwork across all industries. This study contributes by highlighting the unique health impacts of overwork on income-driven rural-to-urban migrants and revealing the limitations of work incentives and industry differences, offering new insights into the relationship between employment and health.
NPR1-like genes in Theobroma cacao: Evolutionary insights and potential in enhancing resistance to Phytophthora megakarya
Nonexpressor of pathogenesis-related 1 (NPR1) is crucial for activating the plant immune system through the signaling molecule salicylic acid (SA), which triggers systemic acquired resistance (SAR) in Arabidopsis. In this study, three putative genes associated with NPR1 from Arabidopsis have been identified in the genome of Theobroma cacao, namely, TcNPR1, TcNPR2, and TcNPR3, suggesting a functional diversification among the three gene entities. Phylogenetic analysis revealed that TcNPR1 and TcNPR2 branched alongside their Arabidopsis orthologs, NPR1 and NPR2, indicating that these genes maintain a conserved role in SA signaling pathways across different species. In contrast, TcNPR3 exists in a separate clade, suggesting unique functional roles and evolutionary divergence. A comparative analysis of the physiochemical properties of these TcNPRs showed a different subcellular localization, as TcNPR1 persists in the cytoplasm, while TcNPR3 is found in the nucleus, aligning with its proposed role in SA signaling and transcriptional regulation. Furthermore, we identified microRNAs that target TcNPR3, suggesting that P. megakarya may exploit the transcriptional regulatory network to bypass plant defense activation. Transient overexpression or suppression of TcNPR gene expression through RNA interference-mediated gene silencing could be sufficient to study the impact on the production of other molecules, such as SA, some PR protein expressions, and resistance against P. megakarya. The interactions between proteins encoded by TcNPRs and cellular proteins of P. megakarya will provide insight into whether the pathogen manipulates host defenses. Finally, the expression of TcNPR genes in response to infection by P. megakarya offers valuable information regarding the temporal and spatial activation during the defense response.
Photogrammetric approach to detect road pavement friction
This paper deals with evaluation of photogrammetric measurements of pavement macrotexture for the purposes of new non-contact method for determination of pavement skid resistance. The aim was to create a method that yields results comparable to existing pavement friction measurement techniques, particularly the sand method, and to assess whether the measurements obtained using the non-contact approach are equally effective. Additionally, the goal was to introduce and define limits for camera calibration applicable to similar cases of object measurements at close distances. Based on existing standards, specific pavement samples exhibiting various macrotexture qualities were selected. The authors conducted 23 different combinations of photogrammetric measurements based on their findings during the evaluations. A comparison of the applied procedures with a reference measurement using the sand method was made, and the measurement error rate was calculated. By evaluating the different variations of the road surface models created, it was concluded that the most reliable results for defining friction are obtained by interleaving the test specimen through a plane based on the principle of best fit using the four highest points of the macrotexture. The ideal size of the sub-areas for applying the mask is 7.5–10 mm. Photogrammetry has proven to be a suitable and accurate tool for assessing pavement surface texture and can be considered as a suitable alternative to other skid resistance measurement approaches.
Effects of initial foot position on neuromuscular and biomechanical control during the stand-to-sit movement: Implications for rehabilitation strategies
Background Initial foot position (IFP) is one of the important movement strategies that influence neuromuscular and biomechanical control during sit-to-stand (STS) movements. Similarly, stand-to-sit (StandTS) is vital in rehabilitation settings for evaluating strength and balance control during descending movements. Understanding how IFP impacts changes in biomechanical and neuromuscular movement control factors during StandTS can provide valuable insights for designing effective rehabilitation programs. Methods Twelve healthy young adults participated in this study, examining three symmetric IFPs: (1) REF (reference); (2) wide: each foot was shifted outwards by 30% from REF; (3) TO (toes-out): symmetric toes-out angle of 30° from REF. Kinematic and kinetic differences among the three IFPs during StandTS were analyzed, along with the characteristics of muscle activation patterns using muscle synergy analysis. Results In the wide IFP, trunk flexion angle was reduced, and valgus angle was greater than in the other IFPs. The TO IFP resulted in greater dorsiflexion and knee flexion angles compared to the REF and wide IFPs. Compared to the REF IFP, both wide and TO IFPs showed greater eccentric work at the hip joint in the anterior-posterior (power absorption) and the vertical direction (gravitational force control) and demonstrated reduced postural sway in medio-lateral and vertical directions. Muscle synergy analysis of EMG activity revealed increased activation of back and plantar flexor muscle in the wide IFP, and increased contribution of hip joint muscles in the TO IFP. Conclusion The wide IFP increased the valgus angle, leading to reduced trunk flexion with increased back muscle activation. The TO IFP enabled greater angular displacement at the ankle and knee joints, enhancing hip joint muscle involvement in StandTS movement control. Both the wide and TO IFPs facilitated hip joint work, improving postural sway control during the descent phase of StandTS. These findings provide valuable insights for designing rehabilitation strategies tailored to specific patient needs.
Disease trajectory and competing risks of patients with cirrhosis in the US
Background Cirrhosis is a dynamic disease process leading to liver-related death, which has increased by over 65% over the last decade. Unpredictable hepatic decompensation complications are a major source of morbidity and mortality. Thus, accurately characterizing disease progression through discrete stages of cirrhosis is critical towards implementing timely intervention and liver transplant (LT) waitlisting. Methods A retrospective, longitudinal, population-cohort study of adult patients with cirrhosis from a US metropolitan area (2006–2012) was conducted. Clinical diagnoses were defined by ICD-9 and CPT codes. Cirrhosis stages were defined as: compensated without portal hypertension (Stage 1), compensated with portal hypertension (Stage 2), variceal bleeding (Stage 3), hepatic encephalopathy (Stage 4a), ascites (Stage 4b), and ≥2 different decompensating complications (Stage 5). Multivariate Fine-Gray competing risk survival analysis adjusted for clinicodemographic covariates. Results Among 12,196 patients with cirrhosis, the mean (±SD) age was 56.8 (±11.7) years with a follow-up time of 2.35 (±1.81) years. A novel 5-stage disease progression framework was used. The 1-year mortality rates for each stage were 7.3% for Stage 1, 5.4% for Stage 2, 11.4% for Stage 3, 10.0% for Stage 4a, 20.2% for Stage 4b, and 43.8% for Stage 5. Compared to those in Stage 1, Stage 3 (sHR:1.83, 95% CI:1.36–2.48, P<0.001), Stage 4b (sHR:1.45, 95% CI:1.23–1.70, P<0.001), and Stage 5 (sHR:1.95, 95% CI:1.71–2.23, P<0.001) patients had higher risks of mortality. Additional disease progression rates were identified. Conclusion Even among patients with compensated cirrhosis, the 1-year mortality rate was as high as 7.3% and subsequently increases with each decompensation complication. This one-year mortality rate is higher than 5-years mortality rate reported in previously known non-US studies. The highest associated risk of death was observed among patients with ≥2 different decompensating complications (95.2%), variceal bleeding (83.2%) and ascites (44.9%). Overall, patients in advanced stages of cirrhosis were more likely to die than they were to receive a LT, suggesting that patients should be referred and waitlisted for LT earlier in the disease process.
Mixed attention ensemble for esophageal motility disorders classification
Esophageal motility disorders result from dysfunction of the lower esophageal sphincter and abnormalities in esophageal peristalsis, often presenting symptoms such as dysphagia, chest pain, or heartburn. High-resolution esophageal manometry currently serves as the primary diagnostic method for these disorders, but it has some shortcomings including technical complexity, high demands on diagnosticians, and time-consuming diagnostic process. Therefore, based on ensemble learning with a mixed voting mechanism and multi-dimensional attention enhancement mechanism, a classification model for esophageal motility disorders is proposed and named mixed attention ensemble(MAE) in this paper, which integrates four distinct base models, utilizing a multi-dimensional attention mechanism to extract important features and being weighted with a mixed voting mechanism. We conducted extensive experiments through exploring three different voting strategies and validating our approach on our proprietary dataset. The MAE model outperforms traditional voting ensembles on multiple metrics, achieving an accuracy of 98.48% while preserving a low parameter. The experimental results demonstrate the effectiveness of our method, providing valuable reference to pre-diagnosis for physicians.
Efficacy of Ginkgo biloba on parameters in glaucoma: A systematic review
Purpose This study aims to analyse the efficacy of GBE administration in patients with glaucoma and healthy volunteers. Methods This systematic review was performed according to the PRISMA 2020 guidelines. All clinical studies investigating the efficacy of GBE administration on the intraocular pressure (IOP), the corrected pattern standard deviation (CPSD) and the mean deviation of visual field testing, and heart rate were considered. The weighted mean difference (MD) effect measure, 95% confidence interval (CI), and t-test were used for continuous variables. Results Data from 8 studies, including 428 patients, were retrieved. The mean age of all patients was 51.1 ± 15.5 years. The median follow-up was 3.7 (IQR 9.4) months. The administration of GBE was not associated with an improvement in IOP (MD -1.5; 95%CI -7.1 to 9.6; P = 0.5), mean deviation (MD 0.7; 95%CI -9.4 to 8.2; P = 0.8), CPSD (MD -1.6; 95%CI -3.8 to 6.9; P = 0.5), or heart rate (MD -2.5; 95%CI -11.5 to 16.5; P = 0.4) from baseline to the last follow-up. There was no difference between GBE versus the control group in IOP (MD 1.1; 95%CI -5.7 to 3.5; P = 0.4), mean deviation (MD -0.4; 95%CI -9.1 to 9.9; P = 0.9), CPSD (MD 0.3; 95%CI -6.8 to 6.2; P = 0.9), and heart rate (MD -1.3; 95%CI -15.1 to 17.7; P = 0.8) at the last follow-up. Conclusion Currently, the evidence is not sufficient to conclude that GBE affects IOP, mean deviation, CPSD, or heart rate in glaucoma patients and healthy volunteers. These conclusions must be interpreted with caution given the limitations of the reviewed studies, particularly the follow-up time of the included studies.
Semi-rational evolution of a recombinant DNA polymerase for modified nucleotide incorporation efficiency
Engineering improved B-family DNA polymerases to catalyze 3′-O-modified nucleotide reversible terminators is limited by an insufficient understanding of the structural determinants that define polymerization efficiency. To explore the key mechanism for unnatural nucleotide incorporation, we engineered a B-family DNA polymerase from Thermococcus Kodakaraenis (KOD pol) by using semi-rational design strategies. We first scanned the active pocket of KOD pol through site-directed saturation mutagenesis and combinatorial mutations and identified a variant Mut_C2 containing five mutation sites (D141A, E143A, L408I, Y409A, A485E) using a high-throughput microwell-based screening method. Mut_C2 demonstrated high catalytic efficiency in incorporating 3’-O-azidomethyl-dATP labeled with a Cy3 dye, whereas the wild-type KOD pol failed to catalyze it. Computational simulations were then conducted of the DNA binding region of KOD pol to predict additional mutations with enhanced catalytic activity, which were subsequently experimentally verified. By a stepwise combinatorial mutagenesis approach, we obtained an eleven-mutation variant, named Mut_E10 by introducing additional mutations to the Mut_C2 variant. Mut_E10, which carried six specific mutations (S383T, Y384F, V389I, V589H, T676K, and V680M) within the DNA-binding region, demonstrated over 20-fold improvement in enzymatic activity as compared to Mut_C2. In addition, Mut_E10 demonstrated satisfactory performance in two different sequencing platforms (BGISEQ-500 and MGISEQ-2000), indicating its potential for commercialization. Our study demonstrates that a significant enhancement in its catalytic efficiency towards modified nucleotides can be achieved efficiently through combinatorial mutagenesis of residues in the active site and DNA binding region of DNA polymerases. These findings contribute to a comprehensive understanding of the mechanisms that underlie the incorporation of modified nucleotides by DNA polymerase. The sites of beneficial mutations, as well as the nucleotide incorporation mechanism identified in this study, can provide valuable guidance for the engineering of other B-family DNA polymerases.
Adult male-specific inverse association between dry eye disease and intraocular pressure: KNHANES 2010–2012
Purpose To investigate the association between dry eye disease (DED) and intraocular pressure (IOP) in the general adult population of South Korea. Methods We enrolled 13,194 adults (age ≥19 years) who had participated in the fifth Korea National Health and Nutrition Examination Survey conducted from 2010 to 2012. IOP was measured using Goldman applanation tonometry. DED was defined as the presence of self-reported symptoms along with a diagnosis by an ophthalmologist. As the correlation between the left and right eyes was high (r = 0.833), only the measurement values of the right eye were used. We sequentially conducted multiple linear and logistic regression analyses to investigate the association between DED and IOP and prevalence of high IOP (>21 mmHg). Results The prevalence of DED in Korean adults was 7.8%, and the geometric mean of IOP in the right eye was 13.7 ± 1.0 mmHg. In the fully adjusted model, participants with DED had a significantly lower IOP compared to those without DED in the overall population (β = -0.032; 95% confidence interval [CI]: -0.059, -0.004). This trend was evident in males (β = -0.059; 95% CI: -0.106, -0.012) but not in females. Similarly, males with DED had a significantly lower prevalence of high IOP compared to those without DED (odds ratio [OR] = 0.18; 95% CI: 0.04, 0.91), but this association was not evident in females. Conclusions This study suggests that DED is associated with lower IOP in adult Korean males.
Association between anthropometric indices and chronic kidney disease: Insights from NHANES 2009–2018
Introduction The strong association between obesity and chronic kidney disease (CKD) has been empirically validated, yet traditional measures like the Body Mass Index (BMI) fail to accurately assess the extent of obesity due to CKD’s characteristics, such as reduced muscle mass and increased visceral fat. This study investigates the association between CKD and several anthropometric indices, including A Body Shape Index (ABSI), Body Roundness Index (BRI), Waist-to-Height Ratio (WHtR), and the Conicity Index (C-index), to determine their predictive capabilities. Methods Based on the datasets from the National Health and Nutrition Examination Survey (NHANES) 2009–2018, weighted multivariable regression analyses were carried out to examine the independent relationship between two anthropometric indices and CKD. Also, subgroup analyses, restricted cubic spline regression (RCS), and receiver operating characteristic curve analysis were conducted for further data analyses. Results A total of 24,162 participants were enrolled in this study. After adjusting for confounding factors, ABSI, BRI, WHtR, and the C-index were significantly associated with an increased risk of CKD, while BMI was not. Height showed a protective effect against CKD. ABSI and the C-index demonstrated the highest areas under the curve (AUCs), indicating superior predictive capabilities compared to traditional measures like BMI and waist circumference (WC). Subgroup analyses revealed significant interactions between the anthropometric indices and factors such as age, disease status, dietary intake, and physical activity levels. Conclusions This study highlights the significant associations between various anthropometric indices (including ABSI, BRI, WHtR, and C-index) and the risk of CKD. ABSI and the C-index demonstrated the strongest predictive capabilities for CKD, with the highest AUC values.
Hybrid-RViT: Hybridizing ResNet-50 and Vision Transformer for Enhanced Alzheimer’s disease detection
Alzheimer’s disease (AD) is a leading cause of disability worldwide. Early detection is critical for preventing progression and formulating effective treatment plans. This study aims to develop a novel deep learning (DL) model, Hybrid-RViT, to enhance the detection of AD. The proposed Hybrid-RViT model integrates the pre-trained convolutional neural network (ResNet-50) with the Vision Transformer (ViT) to classify brain MRI images across different stages of AD. The ResNet-50 adopted for transfer learning, facilitates inductive bias and feature extraction. Concurrently, ViT processes sequences of image patches to capture long-distance relationships via a self-attention mechanism, thereby functioning as a joint local-global feature extractor. The Hybrid-RViT model achieved a training accuracy of 97% and a testing accuracy of 95%, outperforming previous models. This demonstrates its potential efficacy in accurately identifying and classifying AD stages from brain MRI data. The Hybrid-RViT model, combining ResNet-50 and ViT, shows superior performance in AD detection, highlighting its potential as a valuable tool for medical professionals in interpreting and analyzing brain MRI images. This model could significantly improve early diagnosis and intervention strategies for AD.