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Tracking has been criticized for relegating disadvantaged students to lower track courses in which students encounter a greater lack of instructional support. While an end to tracks through detracking is a possible solution, there are concerns that detracking will create more heterogeneous classrooms, making it harder for teachers to provide adequate support to their students. Using the 2015 PISA dataset, this study conducts a causal inferential analysis to understand the differences in student perceptions of teaching in tracked and untracked environments. The results provide evidence that students needs, with respect to adaptation of instruction and provision of individualized feedback and support, are being met to the same extent on average in tracked and untracked science classes, suggesting that teachers may not necessarily have a harder time meeting the needs of students in untracked classes.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

PurposeIn young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population.MethodsA retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS.ResultsAmong the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%).ConclusionTrough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

Baseball is an international sport with participation from tens of thousands of people worldwide. In the United States, the Prospect Development Pipeline (PDP) is a collaborative effort between Major League Baseball and USA Baseball to establish a developmental pipeline leading to the professional draft. Players participating in the PDP undergo comprehensive evaluations that measure athletic performance, speed-of-processing, visual function, and on-field talent. The present study evaluated data from 1352 elite junior male PDP participants (aged 14 to 21) who signed informed consent, collected between 2017 and 2020, to identify latent abilities and their association with player specialization. Data were first subjected to Exploratory Factor Analysis (EFA) to reduce the 22 measured variables to a smaller set of latent abilities. The resulting factors were evaluated using multiple linear regression to predict each factor using age, height, weight, and position. EFA revealed a combination of physical and psychomotor skills accounting for 52% of the overall variance that grouped into four abilities: grip strength, functional vision, explosiveness, and rapid decision-making. Regression analyses demonstrated that these skills are associated with position assignments, controlling for age, weight, and height, and revealed that outfielders are the most explosive, infielders perform best on psychomotor measures, and catchers perform best on functional vision tests (ps < 0.001). These findings indicate skills that contribute to player specialization, providing new information about the developmental trajectory of junior elite baseball athletes that can be used for scouting and player development.

Background/purposeDistal radius fractures (DRFs) account for approximately 18% of fractures in patients 65 years and older. While plain radiographs are standard, the value of high-resolution computed tomography (CT) for detailed imaging crucial for diagnosis, prognosis, and intervention planning, and increasingly recognized. High-definition 3D reconstructions from CT scans are vital for applications like 3D printing in orthopedics and for the utility of mobile C-arm CT in orthopedic diagnostics. However, concerns over radiation exposure and suboptimal image resolution from some devices necessitate the exploration of advanced computational techniques for refining CT imaging without compromising safety. Therefore, this study aims to utilize conditional Generative Adversarial Networks (cGAN) to improve the resolution of 3 mm CT images (CT enhancement).MethodsFollowing institutional review board approval, 3 mm-1 mm paired CT data from 11 patients with DRFs were collected. cGAN was used to improve the resolution of 3 mm CT images to match that of 1 mm images (CT enhancement). Two distinct methods were employed for training and generating CT images. In Method 1, a 3 mm CT raw image was used as input with the aim of generating a 1 mm CT raw image. Method 2 was designed to emphasize the difference value between the 3 mm and 1 mm images; using a 3 mm CT raw image as input, it produced the difference in image values between the 3 mm and 1 mm CT scans. Both quantitative metrics, such as peak signal-to-noise ratio (PSNR), mean squared error (MSE), and structural similarity index (SSIM), and qualitative assessments by two orthopedic surgeons were used to evaluate image quality by assessing the grade (1~4, which low number means high quality of resolution).ResultsQuantitative evaluations showed that our proposed techniques, particularly emphasizing the difference value in Method 2, consistently outperformed traditional approaches in achieving higher image resolution. In qualitative evaluation by two clinicians, images from method 2 showed better quality of images (grade: method 1, 2.7; method 2, 2.2). And more choice was found in method 2 for similar image with 1 mm slice image (15 vs 7, p = 201).ConclusionIn our study utilizing cGAN for enhancing CT imaging resolution, the authors found that the method, which focuses on the difference value between 3 mm and 1 mm images (Method 2), consistently outperformed.

PurposeTo compare the efficacy of a 0.15% HA with that of 0.1% HA eye drops for DES after cataract surgery.MethodsThis study was double blinded, randomized and prospective study, and conducted in 69 participants (70 eyes) from Pusan National University Yangsan Hospital and executed from February 1, 2022 to November 30, 2022. Participants were adult cataract patients with normal lid position, not suffering from any other ocular disease and not meet the exclusion cirteria of clinical trial. Participants were randomly divided into two groups: 35 participants (17 males and 18 females) in the 0.1% HA group and 34 participants (19 males and 15 females) in the 0.15% HA group, receiving treatment six times daily for 6 weeks following cataract surgery. Subjective and objective assessments were performed at preoperative and postoperative visits, including ocular surface disease index score, tear break up time, corneal staining score, Schirmer's I test score, lipid layer thickness), meiboscore, and biochemical analysis of the eye drops.ResultsThroughout the study, the postoperative ocular surface disease index score was significantly lower in the group receiving 0.15% hyaluronic acid than in the group receiving 0.1% hyaluronic acid. Additionally, the postoperative ocular surface disease index score showed a significant positive correlation with the postoperative use of 0.15% hyaluronic acid and the preoperative Schirmer's I test score. In multivariate analysis, treatment with 0.15% hyaluronic acid and the preoperative ocular surface disease index score were significant independent parameters affecting the postoperative ocular surface disease index score.ConclusionThe use of 0.15% hyaluronic acid is recommended for its potential advantages in alleviating symptoms following cataract surgery, making it a viable alternative to traditional 0.1% hyaluronic acid treatment.Trial registrationISRCTN95830348.

Longitudinal research has provided systematic empirical data on the short- and long-term outcomes of admissions policies, curricular innovations, and complex decisions on students' academic progress. This study aimed to investigate the academic performance of medical students and related factors using cohort database collected from a medical school. The study participants included 134 medical students who graduated from Chonnam National University Medical School in 2022. The medical school's cohort database was used to collect data on demographics, admission, academic performance, extracurricular activities, and performance on the National Korean Medical Licensing Examination (KMLE). Participating in club activities had a significant association with medical students' academic advancement delay or leave of absence during the entire course of medical school (P = 0.007). Logistic regression analysis indicated that the nationwide clinical knowledge mock examination during the fourth year of medical school was significantly associated with passing the KMLE (adjusted odds ratio 1.12, 95% confidence interval 1.02-1.22; P = 0.014). Extracurricular school activities (a non-cognitive student attribute) and a wide range of cognitive student attributes captured from the cohort database were associated with medical students' academic performance. In conclusion, this study can reinforce a strong emphasis on the inclusion of cognitive and non-cognitive information in medical school curricula and assessments in order to improve medical education programs and future postgraduate performance.

A growing evidence base suggests that complex healthcare problems are optimally tackled through cross-disciplinary collaboration that draws upon the expertise of diverse researchers. Yet, the influences and processes underlying effective teamwork among independent researchers are not well-understood, making it difficult to fully optimize the collaborative process. To address this gap in knowledge, we used the annual NIH mHealth Training Institutes as a testbed to develop stochastic actor-oriented models that explore the communicative interactions and psychological changes of its disciplinarily and geographically diverse participants. The models help investigate social influence and social selection effects to understand whether and how social network interactions influence perceptions of team psychological safety during the institute and how they may sway communications between participants. We found a degree of social selection effects: in particular years, scholars were likely to choose to communicate with those who had more dissimilar levels of psychological safety. We found evidence of social influence, in particular, from scholars with lower psychological safety levels and from scholars with reciprocated communications, although the sizes and directions of the social influences somewhat varied across years. The current study demonstrated the utility of stochastic actor-oriented models in understanding the team science process which can inform team science initiatives. The study results can contribute to theory-building about team science which acknowledges the importance of social influence and selection.

The ability of Mycobacterium tuberculosis (Mtb) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies.

IntroductionThe NIH All of Us Research Program will have the scale and scope to enable research for a wide range of diseases, including cancer. The program's focus on diversity and inclusion promises a better understanding of the unequal burden of cancer. Preliminary cancer ascertainment in the All of Us cohort from two data sources (self-reported versus electronic health records (EHR)) is considered.Materials and methodsThis work was performed on data collected from the All of Us Research Program's 315,297 enrolled participants to date using the Researcher Workbench, where approved researchers can access and analyze All of Us data on cancer and other diseases. Cancer case ascertainment was performed using data from EHR and self-reported surveys across key factors. Distribution of cancer types and concordance of data sources by cancer site and demographics is analyzed.Results and discussionData collected from 315,297 participants resulted in 13,298 cancer cases detected in the survey (in 89,261 participants), 23,520 cancer cases detected in the EHR (in 203,813 participants), and 7,123 cancer cases detected across both sources (in 62,497 participants). Key differences in survey completion by race/ethnicity impacted the makeup of cohorts when compared to cancer in the EHR and national NCI SEER data.ConclusionsThis study provides key insight into cancer detection in the All of Us Research Program and points to the existing strengths and limitations of All of Us as a platform for cancer research now and in the future.

BackgroundEvidence shows that using the AWARD (Ask, Warn, Advise, Refer, Do-it-again) model with service-learning model in youngsters may be an appropriate strategy to refer young smokers for early smoking cessation services. Therefore this study aims to promote smoking cessation by training secondary school students as anti-smoke ambassadors (ASAs) with increased knowledge, skills and self-efficacy on smoking cessation and AWARD model using service-learning model.MethodsA cluster randomized controlled trial will be conducted in 14 secondary schools in Hong Kong. Also, a hybrid type 1 effectiveness-implementation design with the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework will be adopted. For the intervention group, participants (n = 184) will attend a 3-hour training workshop, followed by hands-on sessions supervised by trained nursing students, then a 6-month smoker referral competition and an award presentation ceremony. The control group (n = 184) will only attend the 3-hour training workshop. The research assistant will contact participants at the start and the end of training program, and at 3, 6, and 12 months after the end of the training program by telephone to complete a set of questionnaires. Participating secondary schools, participating nursing students, ASAs, and responsible organizational staff will be randomly invited for a one-to-one semi-structured interview. The primary outcome will be the number of smokers who referred by secondary school students. Descriptive statistics, mixed between-within-subjects ANOVA, logistic regressions, and content analysis will be used.DiscussionThis study will bridge the gap in existing literature by determining the effectiveness and exploring facilitators and barriers in implementing our intervention with the use of the AWARD model and service-learning model in training young people to refer smokers to anti-smoke organizations in the real-world. This can enhance our community capacity and enable youngsters to take a proactive role to support smoking cessation.Trial registrationClinicalTrials.gov, NCT05897346. Registered on 11 May 2023.

[This corrects the article DOI: 10.1371/journal.pone.0303758.].

Alzheimer's disease (AD) is characterized by cognitive decline and memory loss, involving mechanisms such as tau hyperphosphorylation and mitochondrial dysfunction. Increasing evidence suggests that age-related alterations in metabolite levels are crucial for the pathogenesis of AD. Here, we analyzed serum metabolites from mice of various ages (2, 4, 14, and 21 months old) using mass spectrometry. We identified palmitoyl-L-carnitine as a key metabolite with significantly increased levels in aged mice. In vitro experiments with SH-SY5Y neuronal cells demonstrated that palmitoyl-L-carnitine treatment enhanced tau phosphorylation, increased mitochondrial fission, and elevated intracellular calcium levels. Furthermore, the increased levels of tau phosphorylation were significantly reduced by the inhibition of GSK-3β, CDK5, and calpain, indicating that tau kinases activated by calcium overload are directly involved in the increase of tau phosphorylation. Considering that mitochondrial fission is related to mitochondrial dysfunction, we propose that the elevated level of serum palmitoyl-L-carnitine during aging contributes to AD pathology through these pathways. These findings highlight the significant role of lipid metabolism in neurodegeneration and offer potential therapeutic targets for age-related diseases, including AD.

Climate change has caused extreme weather events, including frequent summer heat waves. We examined how the effects of high air temperatures on mortality have changed between the two study periods (1991-1995 and 2015-2019), including 1994 and 2018, the worst heat wave years in the meteorological history of South Korea. Temperature data from the Korea Meteorological Administration and mortality data from Statistics Korea were used in this study. We used distributed lag nonlinear models to estimate the cumulative relative risks (CRRs) to determine the association between daily maximum temperature in summer (June to September) and mortality. CRRs were estimated for each province and pooled using a random-effects meta-analysis for all provinces. Maximum temperature and annual average days in heat wave were 37.7°C and 11.8 in 1991-1995 and 38.3°C and 18.8 in 2015-2019. The slope of the CRR for mortality increases with increasing temperature and has been steeper in the past than in recent years and steeper in those over 65 than in those under 65. Excess mortality has recently declined compared with that in the past. The impact of high summer temperatures on mortality changed between the two periods, suggesting improved population resilience.

ObjectiveThis proposed scoping review aims to examine studies assessing the impact of drug shortages on population-level drug utilization trends. The objectives of this review are to a) assess which drugs have been studied and describe associated drug characteristics, b) determine jurisdictions and healthcare settings that have conducted these studies, and c) describe how changes in drug use and the extent of shortage impacts are reported in literature.IntroductionDrug shortages continue to impair drug access and delivery of quality care across the world. However, the impact of drug supply disruptions on availability and drug use are understudied in current literature. This proposed scoping review will identify this gap and inform future research initiatives aimed at determining the real-world impacts of drug shortages.Inclusion criteriaPublished and unpublished observational studies reporting on the effects of drug supply chain disruptions (shortages, discontinuations, and safety-based withdrawals) on consequent utilization trends faced by pharmaceutical products (i.e. prescription drugs, over-the-counter drugs, vaccines, therapy products, pharmaceutical solutions). Literature reviews, meta-analyses, randomized control trials, case series, case reports, and opinion pieces will be excluded.MethodsThe search strategy will combine two key search concepts: drug shortages and drug utilization. The search will be conducted in MEDLINE and EMBASE. This will be followed by an extensive grey literature search in grey literature databases, targeted websites and Google. Furthermore, reference lists of included articles will be searched. Articles will be independently screened, selected and extracted by two reviewers. Data will be descriptively analyzed and presented in tables.Trial registrationReview registration number: Open Science Framework, https://osf.io/2p6e5.

Background and purposeThe coronavirus disease 2019 (COVID-19) pandemic has significantly impacted people's lifestyles, changing sleep patterns. This study investigated changes in sleep patterns and disturbances in South Koreans over the past decade, including during the pandemic.MethodsWe compared data from the Korean Sleep Headache Society Phase I survey (n = 2484; conducted in 2010) and the National Sleep Survey of South Korea 2022 (n = 3729; conducted in 2022), involving participants aged 20-69 years. Changes in sleep schedule, sleep duration, social jet lag, insomnia, and daytime sleepiness were explored.ResultsWorkday bedtimes were advanced and free-day bedtimes and workday and free-day waking times were delayed during the pandemic. Increased circadian preference for eveningness and social jet lag were noted. A significant decrease in sleep duration and sleep efficiency, along with an increased prevalence of insomnia and daytime sleepiness, was noted with age- and sex-specific variations.ConclusionsOver the past decade, including during the COVID-19 pandemic, sleep habits have changed significantly and sleep problems worsened. This study emphasize the need for more comprehensive public health strategies and research to facilitate sleep recovery in the post-pandemic period within a society known for its high prevalence of sleep deprivation.

ObjectivesSymptomatic vestibulopathy impairs patients' lives. However, few studies have explored the lives of patients with compensated or asymptomatic vestibulopathy. This study investigated the quality of life (QOL), psychological health, and physical function of patients with vestibulopathy.Materials and methodsUsing the eighth Korea National Health and Nutrition Examination Survey database, we included individuals with data on demographic factors, diabetes, hypertension, dizziness experiences, pure-tone audiometry, video head impulse test (vHIT), Health-related Quality of Life Instrument with 8 Items, General Anxiety Disorder 7-item scale, stress, and walking and sitting times. Participants were classified into the following groups: an uncompensated group with abnormal vHIT result and chronic dizziness, a compensated group with abnormal vHIT result and a history of dizziness, an asymptomatic group with abnormal vHIT result and no history of dizziness, and a normal group without abnormal vHIT result or a history of dizziness.ResultsUncompensated vestibulopathy was more common in older individuals and women. The uncompensated group showed impairments in climbing stairs (P < 0.001), pain (P < 0.001), vitality (P = 0.001), working (P < 0.001), depression (P < 0.001), sleep (P = 0.001), happiness (P = 0.002), anxiety (P = 0.006), and stress (P = 0.003). The compensated group showed deficits in pain (P < 0.001), work (P = 0.006), sleep (P = 0.001), and happiness (P = 0.001). The asymptomatic group had no deficits in QOL, psychological health, or physical function. These tendencies were similar after controlling for age and gender.ConclusionVestibulopathy with a history of dizziness has a long-lasting impact on QOL and emotional status, even after compensation. Uncompensated vestibulopathy has a significant effect on QOL and mental health. Notably, though, the compensated group also showed a reduction in QOL. Appropriate interventions for each category of patients should be provided based on their impaired functions.

Periodontitis is associated with elevated C-reactive protein (CRP) levels. Although the coexistence of periodontitis and elevated CRP levels may heighten the risk of mortality, previous studies have not confirmed their synergistic effect. Understanding this interaction is crucial for identifying potential interventions to reduce mortality risk in individuals with periodontitis. This study aimed to assess the synergistic effects of periodontitis and elevated CRP levels on mortality in 7,938 adult individuals who participated in the National Health and Nutrition Examination Study 2001-2004. The association of periodontitis status and CRP levels with mortality was assessed using a survey-weighted Cox model. The interactive effect was estimated; the synergistic effect of CRP levels and periodontitis status on mortality was assessed using the relative excess risk due to interaction (RERI). Periodontitis was diagnosed in 1,065 (13.4%) participants. Compared with the participants without periodontitis and possessing CRP levels of ≤ 0.5 mg/dL, those with periodontitis (hazard ratio [HR], 1.38) or CRP levels of > 0.5 mg/dL (HR 1.23) had higher HRs. The participants with both periodontitis and CRP levels of > 0.5 mg/dL had the highest HR of 2.01. The additive scale interactive effect of the periodontal status and CRP levels, measured using RERI 0.41 (-0.07, 0.95), was positive and nearly significant in the total population. The synergy between the periodontal status and CRP levels was more prominent in the participants aged ≥60 years than that in younger individuals. Periodontitis with high CRP levels may indicate a high mortality rate, indicating the importance of active monitoring and intensive management of periodontitis and inflammatory markers.

ObjectivesThis study aimed to determine whether the olfactory bulb height (OBH) measured using magnetic resonance imaging (MRI) has clinical utility as an imaging biomarker in the evaluation of patients with idiopathic Parkinson's disease (iPD) through its correlation with movement impairment.MethodsThis retrospective study included cognitively intact patients with suspected parkinsonism. All participants underwent T2-weighted imaging to measure OBH. Logistic regression was used to determine whether OBH was an independent risk factor for distinguishing iPD patients from disease controls, and its relation with clinical parameters related to motor impairment, including clinical laterality, modified Hoehn and Yahr (HY) stage, and Unified Parkinson's Disease Rating Scale (UPDRS) III score, was investigated.ResultsBased on the final clinical diagnosis, 79 patients with iPD and 16 disease controls were included. The mean OBH was significantly smaller in iPD than in disease controls (p < 0.0001). OBH was a significant independent predictor of iPD, with a cutoff of 1.52 mm. In the comparison among the ipsilateral, contralateral side of iPD with clinical laterality, and disease control group, the OBH of the disease control group was significantly larger than both the ipsilateral and contralateral sides (P < 0.05). However, there was no significant difference in OBH between the ipsilateral and contralateral sides (p > 0.05). OBH according to HY stage was significantly smaller in HY stage 2-3 groups than in the disease control group (p < 0.001). The correlation analysis between UPDRS III and OBH showed a mild negative correlation (r = -0.32, p = 0.013).ConclusionsMRI-measured OBH is decreased in iPD regardless of age and sex and may be correlated with the progression of motor symptoms in the iPD.

Traumatic brain injury (TBI) results from sudden accidents, leading to brain damage, subsequent organ dysfunction, and potentially death. Despite extensive studies on rodent TBI models, there is still high variability in terms of target points, and this results in significantly different symptoms between models. In this study, we established a more concise and effective TBI mouse model, which included locomotor dysfunctions with increased apoptosis, based on the controlled cortical impact method. Behavioral tests, such as elevated body swing, rotarod, and cylinder tests were performed to assess the validity of our model. To investigate the underlying mechanisms of injury, we analyzed the expression of proteins associated with immune response and the apoptosis signaling pathway via western blotting analysis and immunohistochemistry. Upon TBI induction, the mouse subjects showed motor dysfunctions and asymmetric behavioral assessment. The expression of Bax gradually increased over time and reached its maximum 3 days post-surgery, and then declined. The expression of Mcl-1 showed a similar trend to Bax. Furthermore, the expression of caspase-3, ROCK1, and p53 were highly elevated by 3 days post-surgery and then declined by 7 days post-surgery. Importantly, immunohistochemistry revealed an immediate increase in the level of Bcl-2 at the lesion site upon TBI induction. Also, we found that the expression of neuronal markers, such as NeuN and MAP2, decreased after the surgery. Interestingly, the increase in NFH level was in line with the symptoms of TBI in humans. Collectively, our study demonstrated that the established TBI model induces motor dysfunction, hemorrhaging, infarctions, and apoptosis, closely resembling TBI in humans. Therefore, we predict that our model may be useful for developing effective treatment option for TBI.

BackgroundObesity, characterized by excessive fat accumulation, poses a significant public health challenge globally. Recent advancements in medical technology have heralded the emergence of endoscopic bariatric treatments (EBTs) as innovative alternatives to conventional obesity interventions. Despite previous systematic reviews and network meta-analyses, they also highlighted discrepancies in outcomes and efficacy among different EBTs. Here, we will update a systematic review and network meta-analysis of randomized controlled trials (RCTs) focusing on EBTs and presents a protocol for the reproducibility and transparency.MethodsThe core protocol of this study was registered at PROSPERO database (CRD42024514249) on Jan 2024. Core databases including MEDLINE through PubMed, Embase, and Cochrane library will be searched relevant studies, and a systematic review with network meta-analysis will be performed. Two evaluators (EJ Gong and CS Bang) will independently screen the titles and abstracts following the eligibility criteria; (1) RCTs investigated the compared the efficacy of EBTs and controls; (2) studies published in English; and (3) studies in full-text format. We will exclude studies meeting the following criteria; (1) studies that did not report the treatment outcomes, such as percent excess weight loss or percent total body weight loss; (2) case reports and review articles; (3) ineligible research objects, for example, animals or children; and (4) insufficient data regarding treatment outcome. The primary outcomes will be the common efficacy metric found after systematic review of relevant studies, such as percent excess weight loss or percent total body weight loss with a follow-up of at least 6 months. Narrative (descriptive) synthesis is planned and quantitative synthesis will be used if the included studies are sufficiently homogenous. The quality of the identified studies will be assessed using the Cochrane Risk of Bias assessment tool version 2.0 (ROB 2.0). All the systematic review and network meta-analysis process will be undertaken keeping the principles of the Preferred Reporting Items for a Systematic Review and Meta-analysis for systematic review protocols (PRISMA-P) and PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (PRISMA-NMA).DiscussionThis updated systematic review and network meta-analysis will provide information about comparative efficacy of various EBTs and this will help physicians in the decision-making process for the selection of treatment modalities in the clinical practice.

PurposeWe investigated the vertical implantation of a toric implantable collamer lens (ICL) and compared the rotational stability with that of horizontal implantation.MethodsThis matched comparative study retrospectively reviewed and analyzed data from patients who underwent ICL implantation from 2003-2022 by 1:1 matching vertical and horizontal (V and H toric groups, respectively) implantation patients according to preoperative astigmatism, spherical equivalent, sulcus-to-sulcus, anterior chamber depth, and ICL size. Visual acuity, manifest refraction, vaulting, and rotation were measured 3 months postoperatively.ResultsWe included 646 eyes (323 each in the V and H toric groups). No statistically significant difference was observed between groups in postoperative visual acuity, refractive error, and astigmatism. Vaulting was lower in the V toric group. (P < 0.001). The mean lens rotation in the V toric group was less than that in the H toric group (1.11 ± 2.84° versus 3.02 ± 10.34°, P = 0.001). The proportion of eyes in the V and H toric groups showing ≥10° of rotation was 2.5% (8 eyes) and 6.5% (21 eyes), respectively (P = 0.014). Despite repositioning from rotation, three (0.9%) and eight (2.5%) eyes required removal owing to lens re-rotation in the V and H toric groups, respectively.ConclusionToric ICL vertical implantation showed good rotational stability, and appropriate visual acuity correction results with relatively low vaulting. This procedure therefore presents an effective novel method that could replace horizontal toric ICL implantation.

This cross-sectional study investigated the association between participation in traditional sports and esports performance, analyzing data from 1,549 survey respondents, with a specific focus on 617 individuals assessed for their esports capabilities. The analysis suggests that participation in traditional sports is associated with enhanced performance in first-person shooters. However, no similar association was observed in multiplayer online battle arena games across various platforms. Furthermore, although no substantial link was found between overall gameplay duration and esports performance for the majority of the games examined, time spent playing Honor of Kings was significantly associated with improved in-game rankings, likely due to its unique matchmaking and rating system. The findings also indicate that participants from different categories of traditional sports show no significant differences in esports performance, suggesting similar physical and athletic requirements across these sports. This underscores the necessity for further exploration and methodological refinement to investigate the associations between specific types of physical exercise and enhancements in esports performance. Additionally, esports participants demonstrated higher levels of engagement in traditional sports compared to their non-esports counterparts, suggesting potential reciprocal benefits between esports and physical exercise. Future research should further investigate these mutual advantages. Conducting additional rigorous empirical research to substantiate these associations is essential for the sustainable development of esports.

Human capital is a nation's primary source of inner strength to achieve sustainable economic growth and development. Meanwhile, income inequality is a critical issue preventing sustainable economic growth and social transformation, especially in developing countries. This paper investigates the effect of human capital on income inequality in both the short and long term using the mean group, pooled mean group, and threshold regressions for the ASEAN-7 (including Indonesia, Laos, Malaysia, the Philippines, Singapore, Thailand, and Vietnam) from 1992 to 2018. The paper develops a theoretical linkage between human capital and income inequality by combining the learning theory and the Kuznets hypothesis. This linkage is then tested using data from the ASEAN countries. Findings from the paper indicate that human capital reduces income inequality in the short run in the ASEAN countries. However, the effect is reverted in the long run, suggesting that human capital may increase the income gap in these countries. Particularly, the inverted U-shaped relationship between human capital and income inequality is established for the ASEAN countries whose GDP per capita is lower than USD 8.2 thousand per year. In contrast, the U-shaped relationship is found for the countries with income per capital of more than USD 8.2 thousand. All these findings suggest that social policies targeting reducing income inequality should be prioritized and stay at the centre of any economic policies to achieve sustainable economic growth and development in the ASEAN countries.

Photon-counting detector (PCD)-based computed tomography (CT) offers several advantages over conventional energy-integrating detector-based CT. Among them, the ability to discriminate energy exhibits significant potential for clinical applications because it provides material-specific information. That is, material decomposition (MD) can be achieved through energy discrimination. In this study, deep learning-based material decomposition was performed using live animal data. We propose MD-Unet, which is a deep learning strategy for material decomposition based on an Unet architecture trained with data from three energy bins. To mitigate the data insufficiency, we developed a pretrained model incorporating various simulation data forms and augmentation strategies. Incorporating these approaches into model training results in enhanced precision in material decomposition, thereby enabling the identification of distinct materials at individual pixel locations. The trained network was applied to the acquired animal data to evaluate material decomposition results. Compared with conventional methods, the newly generated MD-Unet demonstrated more accurate material decomposition imaging. Moreover, the network demonstrated an improved material decomposition ability and significantly reduced noise. In addition, they can potentially offer an enhancement level similar to that of a typical contrast agent. This implies that it can acquire images of the same quality with fewer contrast agents administered to patients, thereby demonstrating its significant clinical value.

IntroductionHigh grade astrocytic glioma (HGG) is a lethal solid malignancy with high recurrence rates and limited survival. While several cytotoxic agents have demonstrated efficacy against HGG, drug sensitivity testing platforms to aid in therapy selection are lacking. Patient-derived organoids (PDOs) have been shown to faithfully preserve the biological characteristics of several cancer types including HGG, and coupled with the experimental-analytical hybrid platform Quadratic Phenotypic Optimization Platform (QPOP) which evaluates therapeutic sensitivity at a patient-specific level, may aid as a tool for personalized medical decisions to improve treatment outcomes for HGG patients.MethodsThis is an interventional, non-randomized, open-label study, which aims to enroll 10 patients who will receive QPOP-guided chemotherapy at the time of first HGG recurrence following progression on standard first-line therapy. At the initial presentation of HGG, tumor will be harvested for primary PDO generation during the first biopsy/surgery. At the point of tumor recurrence, patients will be enrolled onto the main study to receive systemic therapy as second-line treatment. Subjects who undergo surgery at the time of recurrence will have a second harvest of tissue for PDO generation. Established PDOs will be subject to QPOP analyses to determine their therapeutic sensitivities to specific panels of drugs. A QPOP-guided treatment selection algorithm will then be used to select the most appropriate drug combination. The primary endpoint of the study is six-month progression-free survival. The secondary endpoints include twelve-month overall survival, RANO criteria and toxicities. In our radiological biomarker sub-study, we plan to evaluate novel radiopharmaceutical-based neuroimaging in determining blood-brain barrier permeability and to assess in vivo drug effects on tumor vasculature over time.Trial registrationThis trial was registered on 8th September 2022 with ClinicalTrials.gov Identifier: NCT05532397.

[This corrects the article DOI: 10.1371/journal.pone.0300306.].

Metabolic-associated fatty liver disease (MAFLD) is predominantly associated with metabolic disturbances representing aberrant liver function and increased uric acid (UA) levels. Growing evidences have suggested a close relationship between metabolic disturbances and the gut microbiota. A placebo-controlled, double-blinded, randomized clinical trial was therefore conducted to explore the impacts of daily supplements with various combinations of the probiotics, Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 with a focus on liver function and serum UA levels. Test subjects with abnormal levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and UA were recruited and randomly allocated into six groups. Eighty-two participants successfully completed the 60-day intervention without any dropouts or occurrence of adverse events. The serum AST, ALT, and UA levels were significantly reduced in all treatment groups (P < 0.05). The fecal microbiota analysis revealed the intervention led to an increase in the population of commensal bacteria and a decrease in pathobiont bacteria, especially Bilophila wadsworthia. The in vitro study indicated the probiotic treatments reduced lipid accumulation and inflammatory factor expressions in HepG2 cells, and also promoted UA excretion in Caco-2 cells. The supplementation of multi-strain probiotics (TSF331, TSR332, and TSP05) together can improve liver function and UA management and may have good potential in treating asymptomatic MAFLD. Trial registration. The trial was registered in the US Library of Medicine (clinicaltrials.gov) with the number NCT06183801 on December 28, 2023.

Hospital CEO salaries have grown quickly over the past two decades. We investigate correlates of rising nonprofit hospital CEO pay between 2012 and 2019 by merging compensation data from Candid's IRS 990 forms with hospital data from the National Academy for State Health Policy Hospital Cost Tool. Almost half of the measured increase in CEO compensation (44.5%) accrued to a "base case" CEO, who was leading a non-teaching hospital system or independent hospital with fewer than 100 beds that earned 0 profits and provided no charity care. Another 28.5% of the measured salary increase resulted from changes in the generosity with which observable metrics were rewarded, particularly the reward for heading a system with 500 or more beds. The remaining 27% resulted mostly from hospital systems or single hospitals that increased their profits or bed size over time. The increase in CEO compensation associated with leading larger healthcare systems and earning greater profits may explain the increase in healthcare system consolidation which has occurred over the last several years.

This study aimed to assess the predictive ability of the shock index (SI) and the shock index, pediatric age-adjusted (SIPA) for mortality among pediatric patients with trauma (aged ≤ 18 years). A systematic search used PubMed, Embase, and Cochrane Library databases to identify pertinent articles published from their inception to 13 February 2023. For each SI and SIPA, the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals were calculated. We planned a priori meta-regression analyses to explore heterogeneity using the following covariates: country, clinical setting, type of center, data source, and cutoff value. Twelve studies were included based on the inclusion criteria. Among them, nine studies with 195,469 patients were included for the SIPA at the hospital, four studies with 4,970 patients were included for the pre-hospital SIPA, and seven studies with 606,445 patients were included to assess the ability of the SI in predicting mortality. The pooled sensitivity and specificity with 95% confidence interval for predicting mortality were as follows: 0.58 (0.44-0.70) and 0.72 (0.60-0.82), respectively, for the SIPA at the hospital; 0.61 (0.47-0.74) and 0.67 (0.61-0.73), respectively, for the pre-hospital SIPA; and 0.71 (0.59-0.81) and 0.45 (0.31-0.59), respectively for the SI. The DOR were 3.80, 3.28, and 2.06 for the SIPA at the hospital, pre-hospital SIPA, and SI, respectively. The AUC were 0.693, 0.689, and 0.618 for the SIPA at the hospital, pre-hospital SIPA, and SI, respectively. The SI and SIPA are simple predictive tools with sufficient accuracy that can be readily applied to pediatric patients with trauma, but SIPA and SI should be utilized cautiously due to their limited sensitivity and specificity, respectively.

ObjectiveThis study examines the association between changes in mental health before and during the COVID-19 pandemic and COVID-19 mortality across geographic areas and by race/ethnicity.MethodsA cross-sectional survey was conducted in Los Angeles County between April and May 2021. The study used the Patient Health Questionnaire-2 to assess major depression risk. Participants' home ZIP codes were classified into low, middle, and high COVID-19 mortality impacted areas (CMIA).ResultsWhile there were existing mental health disparities due to differences in demographics and social determinants of health across CMIA in 2018, the pandemic exacerbated the disparities, especially for residents living in high CMIA. Non-White residents in high CMIA reported the largest deterioration in mental health. Differences in mental health by CMIA persisted after controlling for resident characteristics.ConclusionsLiving in an area with higher COVID-19 mortality rates may have been associated with worse mental health, with Non-White residents reporting worse mental health outcomes in the high mortality area.Policy implicationsIt is crucial to advocate for greater mental health resources in high COVID-19 mortality areas especially for racial/ethnic minorities.

BackgroundMyopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.01% atropine administered twice daily with optical defocus for myopia control in schoolchildren.Methods and designThis is a prospective, parallel-group, single-blinded, randomized, active-control trial (ClinicalTrials.gov identifier: NCT06358755). Myopic schoolchildren with no previous myopic control interventions aged between 7 to 12 years will be recruited. They will be randomly allocated into two groups (n = 56 per group) after baseline measurement. Both groups will receive 0.01% atropine twice per day for 18 months (one drop in the morning and the other drop at night before bedtime). Defocus incorporated multiple segments (DIMS) spectacle lenses will be prescribed in atropine plus optical defocus (ATD) treatment group while single vision spectacle lenses will be given in atropine only (AT) group. Cycloplegic refraction and axial lengths will be monitored every 6 months over 18-month study period. The primary outcomes are changes in cycloplegic refraction and axial lengths relative to the baseline over the study period.DiscussionThe result will examine the combination effect of low dose atropine and myopic defocus on myopia control in a randomized controlled study. The findings will also explore the potential benefits of applying 0.01% atropine twice per day on myopic control and its potential side effects.

BackgroundAbsolute lymphocyte count (ALC) is a crucial indicator of immunity in critical illness, but studies focusing on long-term outcomes in critically ill patients, particularly surgical patients, are still lacking. We sought to explore the association between week-one ALC and long-term mortality in critically ill surgical patients.MethodsWe used the 2015-2020 critical care database of Taichung Veterans General Hospital (TCVGH), a referral hospital in central Taiwan, and the primary outcome was one-year all-cause mortality. We assessed the association between ALC and long-term mortality by measuring hazard ratios (HRs) with 95% confidence intervals (CIs). Furthermore, we used propensity score-matching and -weighting analyses, consisting of propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and covariate balancing propensity score (CBPS), to validate the association.ResultsA total of 8052 patients were enrolled, with their one-year mortality being 24.2%. Cox regression showed that low ALC was independently associated with mortality (adjHR 1.140, 95% CI 1.091-1.192). Moreover, this association tended to be stronger among younger patients, patients with fewer comorbidities and lower severity. The association between low ALC and mortality in original, PSM, IPTW, and CBPS populations were 1.497 (95% CI 1.320-1.697), 1.391 (95% CI 1.169-1.654), 1.512 (95% CI 1.310-1.744), and 1.511 (95% CI 1.310-1.744), respectively. Additionally, the association appears to be consistent, using distinct cutoff levels to define the low ALC.ConclusionsWe identified that early low ALC was associated with increased one-year mortality in critically ill surgical patients, and prospective studies are warranted to confirm the finding.

ObjectiveTo investigate the correlation between oxygen saturation index (OSI) and oxygenation index (OI) for evaluating the blood oxygenation status in neonates with respiratory failure requiring mechanical ventilation support and to assess the predictive capability of OSI in determining clinically relevant OI cutoffs.MethodsA prospective study was conducted on neonates who received invasive mechanical ventilation at the neonatal intensive care unit of tertiary hospital in Vietnam. Bland-Altman analysis was utilized to evaluate the agreement between OSI and OI.ResultsA total of 123 neonates, including both term and preterm infants, were included in the study. A high agreement rate of 94.3% within the 95% limits of agreement (between OI and OSI), with a narrow similarity value of 3.3 (95% CI: -5.1 to 11.8) and high correlation coefficient (r = 0.791, p15 was determined to be 7.45, with a sensitivity of 100% and a specificity of 87.4% (AUC 0.955; 95% CI: 0.922-0.989, p < 0.05). Similarly, an OSI cutoff value of 9.9 corresponded to an OI of 25, displaying a sensitivity of 100% and specificity of 87.4% (AUC 0.92). The receiver operating characteristic (ROC) curves for OSI exhibited statistically significant results (p < 0.05).ConclusionThe findings demonstrate a strong correlation between OSI and OI in neonates with respiratory failure. Furthermore, OSI, as a non-invasive method, can serve as a substitute for OI to evaluate the severity of hypoxic respiratory failure and lung injury in neonates.

Nitric oxide (NO) promotes angiogenesis via various mechanisms; however, the effective transmission of NO in ischemic diseases is unclear. Herein, we tested whether NO-releasing nanofibers modulate therapeutic angiogenesis in an animal hindlimb ischemia model. Male wild-type C57BL/6 mice with surgically-induced hindlimb ischemia were treated with NO-releasing 3-methylaminopropyltrimethoxysilane (MAP3)-derived or control (i.e., non-NO-releasing) nanofibers, by applying them to the wound for 20 min, three times every two days. The amount of NO from the nanofiber into tissues was assessed by NO fluorometric assay. The activity of cGMP-dependent protein kinase (PKG) was determined by western blot analysis. Perfusion ratios were measured 2, 4, and 14 days after inducing ischemia using laser doppler imaging. On day 4, Immunohistochemistry (IHC) with F4/80 and gelatin zymography were performed. IHC with CD31 was performed on day 14. To determine the angiogenic potential of NO-releasing nanofibers, aorta-ring explants were treated with MAP3 or control fiber for 20 min, and the sprout lengths were examined after 6 days. As per either LDPI (Laser doppler perfusion image) ratio or CD31 capillary density measurement, angiogenesis in the ischemic hindlimb was improved in the MAP3 nanofiber group; further, the total nitrate/nitrite concentration in the adduct muscle increased. The number of macrophage infiltrations and matrix metalloproteinase-9 (MMP-9) activity decreased. Vasodilator-stimulated phosphoprotein (VASP), one of the major substrates for PKG, increased phosphorylation in the MAP3 group. MAP3 nanofiber or NO donor SNAP (s-nitroso-n-acetyl penicillamine)-treated aortic explants showed enhanced sprouting in an ex vivo aortic ring assay, which was partially abrogated by KT5823, a potent inhibitor of PKG. These findings suggest that the novel NO-releasing nanofiber, MAP3 activates PKG and promotes therapeutic angiogenesis in response to hindlimb ischemia.

ObjectiveThe objective of this study was to evaluate the relationship between the platelet-to-lymphocyte ratio (PLR) and systemic lupus erythematosus (SLE). Additionally, the study aimed to establish an association between PLR and SLE disease activity, specifically lupus nephritis (LN).MethodsWe conducted a comprehensive search across Medline, Embase, and Cochrane databases to identify relevant articles. Subsequently, we performed meta-analyses to compare PLR between SLE patients and controls, as well as active and inactive SLE cases, along with LN and non-LN groups. Furthermore, a meta-analysis was conducted on correlation coefficients between PLR and various parameters in SLE patients, including the SLE Disease Activity Index (SLEDAI), C3, C4, anti-dsDNA, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).ResultsIn total, fifteen studies comprising 1,522 SLE patients and 1,424 controls were eligible for inclusion. The meta-analysis demonstrated a significant elevation of PLR in the SLE group compared to the control group (Standardized Mean Difference [SMD] = 0.604, 95% Confidence Interval [CI] = 0.299-0.909, p < 0.001). Upon stratification by ethnicity, an elevated PLR was observed in the SLE group among both Asian and Arab populations. Subgroup analysis based on sample size revealed consistently higher PLR in both small (n < 200) and large sample (n ≥ 200) SLE groups. Moreover, when considering disease activity, there was a noteworthy trend of increased PLR in the active disease group compared to the inactive group (SMD = 0.553, 95% CI = 0.000-1.106, p = 0.050). However, the meta-analysis did not demonstrate a significant distinction in PLR between the LN and non-LN groups. Notably, a positive association was established between PLR and SLEDAI (correlation coefficient = 0.325, 95% CI = 0.176-0.459, p < 0.001). Furthermore, PLR exhibited positive correlations with ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.ConclusionsThe outcomes of this meta-analysis underscored the elevated PLR in SLE patients, suggesting its potential as a biomarker for gauging systemic inflammation in SLE. Additionally, PLR exhibited correlations with SLEDAI, as well as with key indicators such as ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood. In this prospective study, we aimed to compare gene expression differences between blood samples of aged beagle dogs with stage B1 MMVD and those of healthy controls using RNA sequencing. Clinical evaluation was also conducted, which revealed minimal differences in radiographic and echocardiographic measurements despite distinct biomarker variations between the two groups. Comparative transcriptomics revealed differentially expressed genes associated with extracellular matrix remodeling, prostaglandin metabolism, immune modulation, and interferon-related pathways, which bear functional relevance for MMVD. In particular, the top 10 over- and under-expressed genes represent promising candidates for influencing pathogenic changes in MMVD stage B1. Our research findings, which include identified variations in clinical markers and gene expression, enhance our understanding of MMVD. Furthermore, they underscore the need for further research into early diagnosis and treatment strategies, as, to the best of our knowledge, no prior studies have explored the precise molecular mechanisms of stage B1 in MMVD through total RNA sequencing.

BackgroundChronic rhinosinusitis (CRS) is an inflammatory disease affecting the sinuses or nose. Persistent inflammatory responses can lead to tissue remodeling, which is a pathological characteristics of CRS. Activation of fibroblasts in the nasal mucosal stroma, differentiation and collagen deposition, and subepithelial fibrosis have been associated with CRS.ObjectivesWe aimed to assess the inhibitory effects of doxycycline and deoxycholic acid-polyethyleneimine conjugate (DA3-Doxy) on myofibroblast differentiation and extracellular matrix (ECM) production in nasal fibroblasts stimulated with TGF-β1.MethodsTo enhance efficacy, we prepared DA3-Doxy using a conjugate of low-molecular-weight polyethyleneimine (PEI) (MW 1800) and deoxycholic acid (DA) and Doxy. The synthesis of the DA3-Doxy polymer was confirmed using nuclear magnetic resonance, and the critical micelle concentration required for cationic micelle formation through self-assembly was determined. Subsequently, the Doxy loading efficiency of DA3 was assessed. The cytotoxicity of Doxy, DA3, PEI, and DA-Doxy in nasal fibroblasts was evaluated using the WST-1 assay. The anti-tissue remodeling and anti-inflammatory effects of DA3-Doxy and DA3 were examined using real-time polymerase chain reaction (Real-time PCR), immunocytochemistry, western blot, and Sircol assay.ResultsBoth DA3 and DA3-Doxy exhibited cytotoxicity at 10 μg/ml in nasal fibroblasts. Doxy partially inhibited α-smooth muscle actin, collagen types I and III, and fibronectin. However, DA3-Doxy significantly inhibited α-SMA, collagen types I and III, and fibronectin at 5 μg/ml. DA3-Doxy also modulated TGF-β1-induced changes in the expression of MMP 1, 2, and 9. Nonetheless, TGF-β1-induced expression of MMP3 was further increased by DA3-Doxy. The expression of TIMP 1 and 2 was partially reduced with 5 μg/ml DA3-Doxy.ConclusionsAlthough initially developed for the delivery of genetic materials or drugs, DA3 exhibits inhibitory effects on myofibroblast differentiation and ECM production. Therefore, it holds therapeutic potential for CRS, and a synergistic effect can be expected when loaded with CRS treatment drugs.

BackgroundWith recent advances in magnetic resonance imaging (MRI) technology, the practical role of lung MRI is expanding despite the inherent challenges of the thorax. The purpose of our study was to evaluate the current status of the concurrent dephasing and excitation (CODE) ultrashort echo-time sequence and the T1-weighted volumetric interpolated breath-hold examination (VIBE) sequence in the evaluation of thoracic disease by comparing it with the gold standard computed tomography (CT).MethodsTwenty-four patients with lung cancer and mediastinal masses underwent both CT and MRI including T1-weighted VIBE and CODE. For CODE images, data were acquired in free breathing and end-expiratory images were reconstructed using retrospective respiratory gating. All images were evaluated through qualitative and quantitative approaches regarding various anatomical structures and lesions (nodule, mediastinal mass, emphysema, reticulation, honeycombing, bronchiectasis, pleural plaque and lymphadenopathy) inside the thorax in terms of diagnostic performance in making specific decisions.ResultsDepiction of the lung parenchyma, mediastinal and pleural lesion was not significant different among the three modalities (p > 0.05). Intra-tumoral and peritumoral features of lung nodules were not significant different in the CT, VIBE or CODE images (p > 0.05). However, VIBE and CODE had significantly lower image quality and poorer depiction of airway, great vessels, and emphysema compared to CT (p < 0.05). Image quality of central airways and depiction of bronchi were significantly better in CODE than in VIBE (p < 0.001 and p = 0.005). In contrast, the depiction of the vasculature was better for VIBE than CODE images (p = 0.003). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were significant greater in VIBE than CODE except for SNRlung and SNRnodule (p < 0.05).ConclusionsOur study showed the potential of CODE and VIBE sequences in the evaluation of localized thoracic abnormalities including solid pulmonary nodules.

Study objectiveThis study assessed the overall satisfaction with oncological care, including barriers to care, and identified its associated predictors among adult cancer patients in Vietnam.MethodsIn this cross-sectional study, we enrolled 300 adult cancer patients receiving inpatient care at a large urban oncological hospital between June and July 2022. Multivariable linear regression analyses examined associations between patient experiences and overall satisfaction ratings with cancer care.ResultsThe mean overall satisfaction with oncological care was 8.82 out of 10, with 98.0% recommending this facility to their friends and family. In an adjusted model, being female (β = 0.29, 95%CI: 0.04, 0.53), endorsing satisfaction with patient-nurse communication (β = 0.33, 95%CI: 0.13, 0.53), patient-doctor communication (β = 0.40, 95%CI: 0.11, 0.70), and psychoeducation about oncological medication management (β = 0.30, 95%CI: 0.14, 0.45) were positively associated with overall ratings. In contrast, individuals with delays in treatment scheduling reported lower overall satisfaction with oncological care (β = -0.38, 95%CI: -0.64, -0.13). Patients perceived health system, social/environmental, and individual barriers to care: worries about income loss due to attending treatment (43.3%); fear, depression, anxiety, and distress (36.8%); concerns about affordability of treatment (36.7%) and transportation problems (36.7%); and excessive waiting times for appointments (28.8%).ConclusionThis study showed high overall patient satisfaction with cancer care quality. Patient-centered communication strategies and psychoeducation about oncological medication management may be targeted to further enhance the cancer inpatient experience. Raising awareness about treatment options and services, and integrating mental health awareness into oncological care may ameliorate patient distress and facilitate greater satisfaction with oncological treatment processes.

Electroless nickel plating is a suitable technology for the hydrogen industry because electroless nickel can be mass-produced at a low cost. Investigating in a complex environment where hydrogen permeation and friction/wear work simultaneously is necessary to apply it to hydrogen valves for hydrogen fuel cell vehicles. In this research, the effects of hydrogen permeation on the mechanical characteristics of electroless nickel-plated free-cutting steel (SUM 24L) were investigated. Due to the inherent characteristics of electroless nickel plating, the damage (cracks and delamination of grain) and micro-particles by hydrogen permeation were clearly observed at the grain boundaries and triple junctions. In particular, the cracks grew from grain boundary toward the intergranualr. This is because the grain boundaries and triple junctions are hydrogen permeation pathways and increasing area of the hydrogen partial pressure. As a result, its surface roughness increased by a maximum of two times, and its hardness and adhesion strength decreased by hydrogen permeation. In particular, hydrogen permeation increased the friction coefficient of the electroless nickel-plated layer, and the damage caused by adhesive wear was significantly greater, increasing the wear depth by up to 5.7 times. This is believed to be due to the decreasing in wear resistance of the electroless nickel plating layer damaged by hydrogen permeation. Nevertheless, the Vickers hardness and the friction coefficient of the electroless nickel plating layer were improved by about 3 and 5.6 times, respectively, compared with those of the free-cutting steel. In particular, the electroless nickel-plated specimens with hydrogen embrittlement exhibited significantly better mechanical characteristics and wear resistance than the free-cutting steel.

[This corrects the article DOI: 10.1371/journal.pone.0266610.].

PurposeTo investigate the treatment efficacy of intra-arterial (IA) trastuzumab treatment using multiparametric magnetic resonance imaging (MRI) in a human breast cancer xenograft model.Materials and methodsHuman breast cancer cells (BT474) were stereotaxically injected into the brains of nude mice to obtain a xenograft model. The mice were divided into four groups and subjected to different treatments (IA treatment [IA-T], intravenous treatment [IV-T], IA saline injection [IA-S], and the sham control group). MRI was performed before and at 7 and 14 d after treatment to assess the efficacy of the treatment. The tumor volume, apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) MRI parameters (Ktrans, Kep, Ve, and Vp) were measured.ResultsTumor volumes in the IA-T group at 14 d after treatment were significantly lower than those in the IV-T group (13.1 mm3 [interquartile range 8.48-16.05] vs. 25.69 mm3 [IQR 20.39-30.29], p = 0.005), control group (IA-S, 33.83 mm3 [IQR 32.00-36.30], pConclusionIA treatment with trastuzumab potentially affects the early response to treatment, including decreased tumor growth and decrease of Ktrans, in a preclinical brain tumor model.