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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.

Cultivating key disciplinary competencies among university students against the background of China’s new engineering education initiative

The development of students’ core disciplinary competencies is crucial to the quality of talent cultivation against the background of China’s New Engineering Education initiative. We condensed a literacy–ability–knowledge model of the core competence structure of university students based on the results of a survey and then applied this model with a special focus on competence structures. We coded the core competency indicators of the course area using a software engineering course as an example to construct a map of the core competencies of the course (area). New teaching and instruction methods to promote the development of students’ core competencies were then explored. Finally, to shape core subject competence, we suggest building a course recommendation system that aligns with an employment guidance service based on the certification of core subject competence to realize a new mode of cultivating competence.

Barriers to participation in Iran’s Integrated Geriatric Care Program: A qualitative study

Background A significant number of older adults still have unfulfilled needs related to healthcare and social services. Policymakers and health administrators can turn this challenge into a golden opportunity through proper planning and policymaking. This study aimed to identify barriers to participation in Iran’s “Integrated Geriatric Care Program (IGCP)”. Methods A qualitative study with conventional content analysis approach was conducted in Yazd City, Iran, from January to March 2023. A purposive sampling method with maximum variation was used. Nineteen healthcare providers and community-dwelling older adults participated in the study. Data were collected using semi-structured in-depth interviews until data saturation and were concurrently analyzed. Results Nine older persons (3 women and 6 men) with a Mean±SD age of 71.33±5.75 and ten healthcare providers (6 women and 4 men) with a Mean±SD age of 38.2±9.16 participated in the study. Two main categories, with ten sub-categories, emerged from the data analysis. The main categories were “personal challenges of older adults” and “structural defects of Integrated Geriatric Care Program”. Conclusion The participation of community-dwelling older adults in the Iranian IGCP is constrained by a combination of personal and structural factors. Our findings seem to be informative for health policymakers and health practitioners who aim to enhance the quality and quantity of healthcare services for older adults in developing communities.

Wave packet splitter and rectificator based on the Dirac delta potentials in a fractional medium

Cloning and bioinformatics analysis of key gene ShOMT3 of podophyllotoxin biosynthesis pathway in Sinopodophyllum hexandrum

Sinopodophyllum hexandrum (S. hexandrum) is an endangered traditional Chinese medicine as abundant podophyllotoxin with powerful anticancer activity. In this study, the rootstalks of S. hexandrum from different geographical locations in China [S1 (Gansu) and S2 (Shaanxi)] were used as research materials to clone the key gene pluviatolide O-methyltransferase 3 (ShOMT3) in the podophyllotoxin biosynthetic pathway. Subsequently, bioinformatics analysis of the ShOMT3 gene and its encoded protein was subjected to bioinformatics analysis using various analysis software including ProtParam, DeepTMHMM, SubLoc, Signal-P 5.0, and Swiss-model. The results of the analysis revealed that the CDS region of the ShOMT3 gene is 1119 bp long, encoding 372 amino acids. The theoretical molecular weight of the ShOMT3 protein is 41.32784 kD, and the theoretical isoelectric point (pI) is 5.27. The instability coefficient of the protein is 46.05, the aliphatic index is 93.58, and the grand average of hydropathicity (GRAVY) is 0.037, indicating that it is an unstable hydrophobic protein. The protein does not contain transmembrane domains or signal peptides, indicating that it is a non-secreted protein. Secondary structure prediction results suggests that the protein consists of alpha helices, random coils, extended strands, and beta-turns. Tertiary structure prediction results suggests that the protein functions as a monomer. In the phylogenetic tree, the ShOMT3 protein has the highest homology with Podophyllum peltatum (P. peltatum). The successful cloning and bioinformatics analysis of the ShOMT3 gene provide theoretical basis and excellent genetic resources for the molecular regulatory mechanism analysis of the podophyllotoxin biosynthetic pathway and molecular breeding in S. hexandrum.

Deciphering the code of resistance: a genomic and transcriptomic exploration of the Cystoisospora suis Holland-I strain

Abstract Cystoisospora suis, a member of the apicomplexan order Coccidia and causative agent of neonatal porcine coccidiosis, poses a challenge to pig production due to the emergence of reduced efficacy of toltrazuril, the only EU-approved treatment. To address the critical gaps in understanding toltrazuril resistance and possibilities of early diagnostics, our study investigated the genetic basis of resistance through whole-genome DNA sequencing and transcriptome analysis of two C. suis strains, the toltrazuril-susceptible Wien-I and the resistant Holland-I. Additionally, we studied the mitochondrial genome and analysed mitochondrial gene expression in both strains. Our results show that genes encoding proteins involved in host-cell invasion displayed variable expression patterns and genetic mutations, suggesting adaptive changes in invasion mechanisms. Moreover, substantial fluctuations in the expression of genes linked to retrotransposons, accompanied by genetic alterations, were observed, highlighting their potential involvement in genomic rearrangements. Finally, our mitochondrial genome analyses revealed important insights into its genetic organization and conservation. Notably, the marked downregulation of CoI, CoIII and Cytb mRNA levels in the resistant strain Holland-I upon toltrazuril exposure highlights the dynamic response of mitochondrial genes to toltrazuril. These mitochondrial adaptations appear to be closely linked to the parasite drug resistance mechanism, potentially facilitating its survival under pharmacological stress. These findings enhance our knowledge of drug resistance mechanisms in Coccidia and highlight the need for novel management strategies, leading to the development of targeted treatments and controls.

Study on lean production management of new energy vehicle body painting based on the dual perspectives of digital transformation and VSM

The automobile body painting production system exists in the backward management concept of focusing on production and ignoring environmental protection, focusing on traditional technology and unwilling to innovate, etc., high production cost and environmental protection standards, which have had a negative impact on the industry’s long-term growth. Based on the value stream mapping (VSM) analysis technology, the current situation of the value stream of the body spraying process of TJ Automobile Manufacturing Company is analyzed, the problem of waste in the production process of automobile body painting system affected by Eliminate Combine Rearrange Simplify (ECRS)a four-step problem-solving technique was studied and analyzed, a new method for the application of value stream graph analysis technology in the digital transformation environment is proposed, and a suitable production improvement scheme for the body painting system is formulated by using the new method, which increases the value-added operation time of the painting production process by 9.5% and reduces the non-value-added operation time by 12.5%. The number of operators was reduced by 18.8%, the value-added ratio was increased accordingly, the scrap rate was reduced by 8%, and the exhaust gas purification rate was increased by 66%, which brought good economic and social benefits to the enterprise and provided a successful case for the application of lean production VSM in the digital transformation environment. The paper extends knowledge in the area of digital transformation and lean production by helping us to establish and explain the relationship between lean production management methods and the promotion of new energy vehicle body coating performance from a dual perspective of digital transformation and VSM. None of the previous studies have considered the combined application of the studied digital transformation and VSM lean management approaches.

Individual differences in wellbeing are supported by separable sets of co-active self- and visual-attention-related brain networks

Abstract How does the brain support ‘wellbeing’? Because it is a multidimensional construct, it is likely the product of multiple co-active brain networks that vary across individuals. This is perhaps why prior neuroimaging studies have found inconsistent anatomical associations with wellbeing. Furthermore, these used ‘laboratory-style’ or ‘resting-state’ methods not amenable to finding manifold networks. To address these issues, we had participants watch a full-length romantic comedy-drama film during functional magnetic resonance imaging. We hypothesised that individual differences in wellbeing measured before scanning would be correlated with individual differences in brain networks associated with ‘embodied’ and ‘narrative’ self-related processing. Indeed, searchlight spatial inter-participant representational similarity and subsequent analyses revealed seven sets of co-activated networks associated with individual differences in wellbeing. Two were ‘embodied self’ related, including brain regions associated with autonomic and affective processing. Three sets were ‘narrative self’ related, involving speech, language, and autobiographical memory-related regions. Finally, two sets of visual-attention-related networks emerged. These results suggest that the neurobiology of wellbeing in the real world is supported by diverse but functionally definable and separable sets of networks. This has implications for psychotherapy where individualised interventions might target, e.g., neuroplasticity in language-related narrative over embodied self or visual-attentional related processes.

Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A clinical study protocol

Background Non-cystic fibrosis bronchiectasis (NCFBE) is a disease that exhibits dilatation of airways, airflow obstruction, persistent cough, excessive sputum production, and refractory respiratory infections. NCFBE exhibits clinical and pathological manifestations similar to key features of cystic fibrosis (CF) lung disease. In CF, pathogenesis results from dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR), and diagnosis is made by demonstrating elevated sweat chloride concentrations (typically ≥60 mEq/L), two CFTR mutations known to be causal, multi-organ tissue injury, or combination(s) of these findings. Objective Based on a considerable body of evidence, we believe many patients with NCFBE have disease likely to benefit from drugs such as elexacaftor/tezacaftor/ivacaftor (ETI) that activate CFTR-dependent ion transport. ETI is currently prescribed solely for treatment of CF and has not been adequately tested or proposed for patients with NCFBE, many of whom exhibit decreased CFTR function. Accordingly, we are conducting a clinical trial of ETI in subjects carrying a diagnosis of NCFBE. Methods Participants will exhibit one disease-causing CFTR mutation and/or sweat chloride measurements of 30–59 mEq/L. Cutaneous punch biopsy or blood samples will be obtained for iPS cell differentiation into airway epithelial monolayers–which will then be tested for response to ETI. Each patient will be given CFTR modulator treatment for approximately four weeks, with monitoring of clinical endpoints that include FEV1 (forced expiratory volume in one second), sweat chloride, quality of life questionnaire, and weight. The study will evaluate response of patients with NCFBE to ETI, and test usefulness of iPSC-derived airway epithelial monolayers as a novel in vitro technology for predicting clinical benefit. Trial registration This trial is registered at clinicaltrials.gov (Identifier: NCT05743946. Date: 02/23/2023).

Association of 25-hydroxyvitamin D with Parkinson’s disease based on the results from the NHANES 2007 to 2018 and Mendelian randomization analysis