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Tuberculosis (TB) is a serious global public health problem. Detecting the changes of adenosine deaminase (ADA), interleukin (IL)-1β, IL-2, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) released from macrophages and monocytes is greatly valuable in the diagnosis of TB. Hence, this study was designed to determine the optimal cut-off points of ADA, IL-1β, IL-2, TNF-α, and IFN-γ, allowing to differentiate pleural TB (PLTB), peritoneal TB (PTB), and meningeal TB (MTB). The study included 386 patients with pleural effusion, 47 patients with peritoneal effusion, and 134 patients with encephalitis and meningoencephalitis suspect of TB. ADA was determined by an enzyme kinetics method; cytokine concentration was measured by a test based on the competitive enzyme-linked immunosorbent assay principle. Sensitivity, specificity, and positive and negative predictive value were calculated and described. In the aspiration fluid, ADA activity was greatly different between PLTB, PTB, and MTB groups with values of 37.5 U/L, 30.5 U/L, and 8.1 U/L and sensitivity and specificity of 87.7% and 83.4%; 100% and 88.9%; 97.3% and 98.6%, respectively. Similar, IFN-γ concentrations were distinctively different between PLTB, PTB, and MTB patients (with values of 120 pg/mL, 200 pg/mL, and 30 pg/mL with sensitivity and specificity of 80.3% and 80.9%; 80.0% and 92.6%; 98.6% and 61.7%, respectively). The determination of ADA and IFN-γ levels in the aspiration fluid is potentially considered a highly sensitive and specific test for differentiating PLTB, PTB, and MTB.

Abstract Prematurity is associated with lower exercise capacity, which relies on the integrity of the cardiovascular, pulmonary, and skeletal muscle systems. Our animal model mimicking prematurity-associated conditions showed altered muscle composition and atrophy in adulthood. This study aimed to compare muscle composition and strength in adults born preterm versus full-term controls. This observational cohort study recruited 55 adults born preterm, ≤ 29 weeks’ of gestation and 53 full-term controls who underwent musculoskeletal ultrasound imaging to assess morphology of the rectus femoris at rest and during a maximal voluntary contraction. Maximal voluntary contraction of the hands and legs were measured by manual dynamometry. In adults born preterm, there was lower muscle strength (handgrip: − 4.8 kg, 95% CI − 9.1, − 0.6; knee extensor: − 44.6 N/m, 95% CI − 63.4, − 25.8) and smaller muscle area (− 130 mm2, 95% CI − 207, − 53), which was more pronounced with a history of bronchopulmonary dysplasia. Muscle stiffness was increased in the preterm versus term group (0.4 m/s, 95% CI 0.04, 0.7). Prematurity is associated with alterations in skeletal muscle composition, area, and function in adulthood. These findings highlight the necessity to implement preventive and/or curative approaches to improve muscle development and function following preterm birth to enhance overall health in this population.

Abstract While selenium is a cofactor of several antioxidant enzymes against cancer and is essential for human health, its excess intake may also be harmful. Though a safe intake of selenium has recently been recommended, it is not well understood in the Asian population. We aimed to determine the association between dietary intake of selenium and cancer risk in a case–control study of 3758 incident cancer cases (i.e., stomach, colon, rectum, lung cancers, and other sites) and 2929 control subjects in Vietnam. Daily intake of selenium was derived from a semiquantitative food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between selenium intake and cancer risk. We observed a U-shaped association between selenium intake and cancer risk. A safe intake ranged from 110.8 to 124.4 µg/day (mean 117.8 µg/day). Compared to individuals with the safe intake of selenium, individuals with the lowest intake (i.e., 27.8–77.2 µg/day) were associated with an increased risk of cancer (OR = 3.78, 95% CI 2.89–4.95) and those with the highest intake (169.1–331.7 µg/day) also had an increased cancer risk (OR = 1.86, 95% CI 1.45–2.39). A U-shaped pattern of association between selenium intake and cancer risk was stronger among participants with body mass index (BMI)

The emergence of multicancer early detection (MCED) tests holds promise for improving early cancer detection and public health outcomes. However, positive MCED test results require confirmation through recommended cancer diagnostic imaging modalities. To address these challenges, we have developed a consultation and work-up protocol for definitive diagnostic results post MCED testing, named SPOT-MAS. Developed through circulating tumor DNA (ctDNA) analysis and in line with professional guidelines and advisory board consensus, this protocol standardizes information to aid general practitioners in accessing, interpreting and managing SPOT-MAS results. Clinical effectiveness is demonstrated through a series of identified cancer cases. Our research indicates that the protocol could empower healthcare professionals to confidently interpret circulating tumor DNA test results for 5 common types of cancer, thereby facilitating the clinical integration of MCED tests.

Objectives Providing clinical performance feedback to physicians is an established method to improve care, but the impact on physician well-being is unclear. This evaluation aimed to better understand physician perspectives on clinical feedback and its potential impact on well-being.Design A qualitative design using semi-structured interviews was undertaken. Data were analysed via consensus coding using an inductive–deductive approach informed by Clinical Performance Feedback Intervention Theory. Findings were used to develop a novel framework describing the relationship between feedback and well-being.Setting Interviews were conducted in a large academic medical centre from June–September 2021.Participants We conducted 25 semi-structured interviews with general outpatient and inpatient paediatricians and internists.Results Physicians felt that feedback supported well-being based on its perceived purpose (intended to promote professional growth vs serving an alternative purpose), which they discerned based on feedback content (aligned with physician priorities vs not aligned), validity (accurate vs inaccurate), actionability (specific vs not, within a physician’s sphere of control vs not) and delivery (supportive vs punitive). The Clinical Performance Feedback Well-Being Model is presented to understand how feedback and recipient variables impact well-being.Conclusions Attention to the process and content of physician clinical performance feedback may advance both the quality of care and physician well-being.

During a 2023 outbreak of Mycoplasma pneumoniae–associated community-acquired pneumonia among children in northern Vietnam, we analyzed M. pneumoniae isolated from nasopharyngeal samples. In almost half (6 of 13) of samples tested, we found known A2063G mutations (macrolide resistance) and a novel C2353T variant on the 23S rRNA gene.

Abstract Fluorescence nanosilica-based cell tracker has been explored and applied in cell biological research. However, the aggregation of these nanoparticles at physiological pH is still the main limitation. In this research, we introduced a novel fluorescence nano-based cell tracker suitable for application in live cells. The silica-coated fluorescein isothiocyanate isomer (FITC-SiO2) nanoparticles (NPs) were modified with carboxymethylsilanetriol disodium salt (FITC-SiO2-COOH), integrating the dianion form of FITC molecules. This nanosystem exhibited superior dispersion in aqueous solutions and effectively mitigated dye leakage. These labeled NPs displayed notable biocompatibility and minimal cytotoxicity in both in vitro and in vivo conditions. Significantly, the NPs did not have negative implications on cell migration or angiogenesis. They successfully penetrated primary fibroblasts, human umbilical vein endothelial cells and HeLa cells in both 2D and 3D cultures, with the fluorescence signal enduring for over 72 h. Furthermore, the NP signals were consistently observed in the developing gastrointestinal tract of live medaka fish larvae for extended periods during phases of subdued digestive activity, without manifesting any apparent acute toxicity. These results underscore the promising utility of FITC-SiO2-COOH NPs as advanced live cell trackers in biological research.

Asthma is characterized by airway obstruction and inflammation, and presents significant diagnostic and treatment challenges. The concept of endotypes has improved understanding of the mechanisms of asthma and has stimulated the development of effective treatment strategies. Sputum profiles may be used to classify asthma into two major inflammatory types: type 2-high (T2H) and type 2-low (T2L) asthma. T2H, characterized by elevated type 2 inflammation, has been extensively studied and several effective biologic treatments have been developed. However, managing T2L is more difficult due to the lack of reliable biomarkers for accurate diagnosis and classification. Additionally, conventional anti-inflammatory therapy does not completely control the symptoms of T2L; therefore, further research is needed to identify effective biologic treatments. This review provides new insights into the clinical characteristics and underlying mechanisms of severe T2L and investigates potential therapeutic approaches to control the disease.

Abstract The design of cereblon-binding molecular glues (MGs) that selectively recruit a desired protein while excluding teratogenic SALL4 is an area of significant interest when designing therapeutic agents. Previous studies show that SALL4 is degraded in the presence of IKZF1 degraders pomalidomide, and to a lesser extent by CC-220. To expand our understanding of the molecular basis for the interaction of SALL4 with cereblon, we performed biophysical and structural studies demonstrating that SALL4 zinc finger domains one and two (ZF1-2) interact with cereblon (CRBN) in a unique manner. ZF1 interacts with the N-terminal domain of cereblon and ZF2 binds as expected in the C-terminal IMiD-binding domain. Both ZF1 and ZF2 contribute to the potency of the interaction of ZF1-2 with CRBN:MG complexes and the affinities of SALL4 ZF1-2 for the cereblon:CC-220 complex are less potent than for the corresponding pomalidomide complex. Structural analysis provides a rationale for understanding the reduced affinity of SALL4 for cereblon in the presence of CC-220, which engages both ZF1 and ZF2. These studies further our understanding of the molecular glue-mediated interactions of zinc finger-based proteins with cereblon and may provide structural tools for the prospective design of compounds with reduced binding and degradation of SALL4.

Abstract An optimized hepatocellular carcinoma (HCC)-targeted methylation next generation sequencing assay was developed to discover HCC-associated methylation markers directly from urine for HCC screening. Urine cell-free DNA (ucfDNA) isolated from a discovery cohort of 31 non-HCC and 30 HCC was used for biomarker discovery, identifying 29 genes with differentially methylated regions (DMRs). Methylation-specific qPCR (MSqPCR) assays were developed to verify the selected DMRs corresponding to 8 genes (GRASP, CCND2, HOXA9, BMP4, VIM, EMX1, SFRP1, and ECE). Using archived ucfDNA, methylation of GRASP, HOXA9, BMP4, and ECE1, were found to be significantly different (p

Abstract Unraveling the molecular mechanisms for COVID-19-associated encephalopathy and its immunopathology is crucial for developing effective treatments. Here, we utilized single-cell transcriptomic analysis and integrated clinical observations and laboratory examination to dissect the host immune responses and reveal pathological mechanisms in COVID-19-associated pediatric encephalopathy. We found that lymphopenia was a prominent characteristic of immune perturbation in COVID-19 patients with encephalopathy, especially those with acute necrotizing encephalopathy (AE). This was characterized a marked reduction of various lymphocytes (e.g., CD8+ T and CD4+ T cells) and significant increases in other inflammatory cells (e.g., monocytes). Further analysis revealed activation of multiple cell apoptosis pathways (e.g., granzyme/perforin-, FAS- and TNF-induced apoptosis) may be responsible for lymphopenia. A systemic S100A12 upregulation, primarily from classical monocytes, may have contributed to cytokine storms in patients with AE. A dysregulated type I interferon (IFN) response was observed which may have further exacerbated the S100A12-driven inflammation in patients with AE. In COVID-19 patients with AE, myeloid cells (e.g., monocytic myeloid-derived suppressor cells) were the likely contributors to immune paralysis. Finally, the immune landscape in COVID-19 patients with encephalopathy, especially for AE, were also characterized by NK and T cells with widespread exhaustion, higher cytotoxic scores and inflammatory response as well as a dysregulated B cell-mediated humoral immune response. Taken together, this comprehensive data provides a detailed resource for elucidating immunopathogenesis and will aid development of effective COVID-19-associated pediatric encephalopathy treatments, especially for those with AE.

Abstract Identification of ventilatory constraint is a key objective of clinical exercise testing. Expiratory flow-limitation (EFL) is a well-known type of ventilatory constraint. However, EFL is difficult to measure, and commercial metabolic carts do not readily identify or quantify EFL. Deep machine learning might provide a new approach for identifying EFL. The objective of this study was to determine if a convolutional neural network (CNN) could accurately identify EFL during exercise in adults in whom baseline airway function varied from normal to mildly obstructed. 2931 spontaneous exercise flow-volume loops (eFVL) were placed within the baseline maximal expiratory flow-volume curves (MEFV) from 22 adults (15 M, 7 F; age, 32 yrs) in whom lung function varied from normal to mildly obstructed. Each eFVL was coded as EFL or non-EFL, where EFL was defined by eFVLs with expired airflow meeting or exceeding the MEFV curve. A CNN with seven hidden layers and a 2-neuron softmax output layer was used to analyze the eFVLs. Three separate analyses were conducted: (1) all subjects (n = 2931 eFVLs, [GRALL]), (2) subjects with normal spirometry (n = 1921 eFVLs [GRNORM]), (3) subjects with mild airway obstruction (n = 1010 eFVLs, [GRLOW]). The final output of the CNN was the probability of EFL or non-EFL in each eFVL, which is considered EFL if the probability exceeds 0.5 or 50%. Baseline forced expiratory volume in 1 s/forced vital capacity was 0.77 (94% predicted) in GRALL, 0.83 (100% predicted) in GRNORM, and 0.69 (83% predicted) in GRLOW. CNN model accuracy was 90.6, 90.5, and 88.0% in GRALL, GRNORM and GRLOW, respectively. Negative predictive value (NPV) was higher than positive predictive value (PPV) in GRNORM (93.5 vs. 78.2% for NPV vs. PPV). In GRLOW, PPV was slightly higher than NPV (89.5 vs. 84.5% for PPV vs. NPV). A CNN performed very well at identifying eFVLs with EFL during exercise. These findings suggest that deep machine learning could become a viable tool for identifying ventilatory constraint during clinical exercise testing.

Abstract Background The incidence and mortality rates of cancer are rapidly increasing worldwide. This study aimed to assess the knowledge of common cancers among new-entry health science students in Japan and Vietnam, thereby providing insights for implementing appropriate medical educational interventions. Methods This cross-sectional study was conducted among new-entry health science students at Hiroshima University, Japan, and the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. A printed predesigned questionnaire consisting of eleven questions was distributed to the participants during the freshmen health screening at the beginning of the academic year to assess their knowledge of cancer. Results A total of 2,748 new-entry health science students participated in the study, including 394 (14.3%) Japanese students and 2,354 (85.7%) Vietnamese students. Most cancer knowledge levels in Japanese students were significantly higher than those in Vietnamese students (p

We report on an outbreak of nongroupable Neisseria meningitidis–associated urethritis, primarily among men who have sex with men in southern Vietnam. Nearly 50% of N. meningitidis isolates were resistant to ciprofloxacin. This emerging pathogen should be considered in the differential diagnosis and management of urethritis.

Abstract Combinations of lifestyle behaviors may lead to different cancer risks. This study aimed to identify the latent classes based on lifestyle behavior trajectories and to investigate the association between these latent classes and cancer risk. Participants in the 2002–2003 National Health Insurance Service general health examination were included. Data on smoking, alcohol drinking, body mass index (BMI), and physical activity measured four times between 2002 and 2009 were analyzed. Incident cancer cases were tracked from 2010 to 2018. Patterns of alcohol drinking, smoking, BMI, and physical activity and latent classes based on trajectories of smoking, alcohol drinking, BMI, and physical activity were identified. Among 2,735,110 adults (1,787,486 men and 947,624 women), 111,218 (69,089 men and 42,129 women) developed incident cancer. Six latent classes of lifestyle behavior were identified, with Class 1 (healthy class) involving only 0.2% of men and 0.5% of women. The highest risk class in males tended to be steady light drinkers and steady moderate smokers, have steady low frequency of physical activity, and be obese. This class showed a 1.47 times higher (95% CI = 1.29–1.69) risk of all cancers than did the healthy class. Among women, there was only an association between the highest risk class (tendency to be non-drinkers, light smokers) and colorectal cancer (HR = 1.70, 95% CI = 1.02–2.83). Only a small percentage of participants maintained a long-term healthy lifestyle. Identifying classes of behavior combinations and their links to cancer development is therefore critical for cancer prevention.

BackgroundPatients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer may have poor prognoses and short overall and disease-free survival. Most previous studies focused on assessing the quality of life and health-state utility of the general population of breast cancer patients. The number of studies for HER2-positive breast cancer patients is negligible. This study investigated the health-state utility and its associated factors among Vietnamese patients with HER2-positive breast cancer.MethodsWe conducted face-to-face interviews with 301 HER2-positive breast cancer patients to collect data. Their health-state utility was measured via the EQ-5D-5L instrument. The Mann-Whitney U and Kruskal-Wallis tests were employed to compare the differences in utility scores between two groups and among three groups or more, respectively. Factors associated with patients' heath-state utility were identified via Tobit regression models.ResultsPain/discomfort (56.1%) and anxiety/depression (39.5%) were the two issues that patients suffered from the most, especially among metastatic breast cancer patients. The severity of distress (depression, anxiety, and stress) in patients was relatively mild. Of 301 patients, their average utility score was 0.86±0.17 (range: 0.03-1.00), and the average EQ-visual analogue scale (VAS) score was 69.12±12.60 (range: 30-100). These figures were 0.79±0.21 and 65.20±13.20 for 102 metastatic breast cancer patients, significantly lower than those of 199 non-metastatic cancer patients (0.89±0.13 and 71.13±11.78) (pConclusionsOur findings showed a significant decrement in utility scores among metastatic breast cancer patients. Patients' health-state utility differed by their demographic characteristics (age, education level, and income) and clinical characteristics (stage of cancer and distress). Their utility scores may support further cost-effectiveness analysis in Vietnam.

IntroductionIn the context of collective efforts taken in Japan to control the spread of COVID-19, the state of emergency and social distancing have caused a negative impact on the mental health of all residents, including foreign communities in Japan. This study aimed to evaluate the level of anxiety and its associated factors among non-Japanese residents residing in Japan during the COVID-19 pandemic.MethodsA web-based survey in 13 languages was conducted among non-Japanese residents living in Japan during the COVID-19 situation. The State-Trait Anxiety Inventory assessed the level of anxiety-State (STAI-S) scores prorated from its six-item version. The multivariable logistic regression using the Akaike Information Criterion (AIC) method was performed to identify the associated factors of anxiety among participants.ResultsFrom January to March 2021, we collected 392 responses. A total of 357 valid responses were analyzed. 54.6% of participants suffered from clinically significant anxiety (CSA). In multivariable logistic model analysis, the CSA status or the high level of anxiety was associated with three factors, including having troubles/difficulties in learning or working, decreased sleep duration, and decreased overall physical health (pConclusionOur study suggests several possible risk factors of anxiety among non-Japanese residents living in Japan undergoing the COVID-19 pandemic, including the troubles or difficulties in learning or working, the decrease in sleep duration, and the decrease in overall physical health.

Convergent extension of the chordamesoderm is the best-examined gastrulation movement in Xenopus. Here we study general features of cell-cell contacts in this tissue by combining depletion of adhesion factors C-cadherin, Syndecan-4, fibronectin, and hyaluronic acid, the analysis of respective contact width spectra and contact angles, and La3+ staining of the pericellular matrix. We provide evidence that like in other gastrula tissues, cell-cell adhesion in the chordamesoderm is largely mediated by different types of pericellular matrix. Specific glycocalyx structures previously identified in Xenopus gastrula tissues are absent in chordamesoderm but other contact types like 10-20 nm wide La3+ stained structures are present instead. Knockdown of any of the adhesion factors reduces the abundance of cell contacts but not the average relative adhesiveness of the remaining ones: a decrease of adhesiveness at low contact widths is compensated by an increase of contact widths and an increase of adhesiveness proportional to width. From the adhesiveness-width relationship, we derive a model of chordamesoderm cell adhesion that involves the interdigitation of distinct pericellular matrix units. Quantitative description of pericellular matrix deployment suggests that reduced contact abundance upon adhesion factor depletion is correlated with excessive accumulation of matrix material in non-adhesive gaps and the loss of some contact types.

In Vietnam, erectile dysfunction (ED) is prevalent and recognized to be associated with mental disorders; however, societal taboos impede a comprehensive understanding of this connection. Our study aims to investigate the factors related to higher levels of anxiety and/or depression (HAD) in individuals with ED. Between November 2022 and March 2023, a face-to-face survey was conducted at the Center for Andrology of Viet Duc University Hospital, involving 390 patients diagnosed with ED. The survey included 51 questions covering general patient information, the International Index of Erectile Function-15 (IIEF-15), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7). The stepwise Akaike Information Criterion (AIC) method was used to identify factors associated with HAD. The study revealed an average age of 37.63 (11.84) years among participants, with a HAD prevalence of 17.69%. Several factors were associated with a higher likelihood of belonging to the HAD group in ED patients. These factors included non-office workers (OR: 1.11; 95% CI: [1.01, 1.21], p = .025), medium and high levels of work-related stress (OR: 1.23; [1.06, 1.44], p = .008; OR: 1.22; [1.04, 1.45], p = .018), multiple shameful experiences related to ED (OR: 1.16; [1.08, 1.25], p < .001), moderate and severe ED (OR: 1.17; [1.03, 1.32], p = .013; OR: 1.31; [1.14, 1.51], p < .001), and dissatisfaction with intercourse skills (OR: 1.09; [1.01, 1.17], p = .028). Our findings suggest a 16% higher likelihood of HAD status in individuals with multiple shameful experiences related to ED, while moderate and severe ED are associated with respective increases of 17% and 31% in the likelihood. These findings emphasize the importance of considering mental health in the care of individuals with ED.

Abstract The SARS-CoV-2 virus has caused a public health crisis globally. Against the backdrop of global resilience, studies have demonstrated the therapeutic value of home gardening as a measure to strengthen human health. However, there is a lack of comparative studies on its benefits across countries. Studies need to examine the role of home gardening in improving public health in various societies to understand and encourage this practice broadly and effectively. We chose Taiwan, Thailand, and Vietnam as case studies, which have suffered substantial pandemic impacts, with millions of infections and thousands of deaths. We explored and compared the perceptions of people on home gardening and its health benefits during the COVID-19 pandemic. We conducted online surveys in three countries between May 1 and September 30, 2022, with a total of 1172 participants. Data were collated on perceived pandemic stress, challenges and solutions in gardening, home gardening intentions, and mental and physical health benefits. In these countries, we found that perceived pandemic stress positively affects home gardening intentions, whereby the motivation of Vietnamese people is the highest. Challenges hinder gardening intentions, while the solutions only positively affect gardening intentions in Taiwan and Vietnam. Home gardening intentions positively affect mental and physical health, whereby there are higher mental health benefits in Taiwanese people than in Thai people. Our findings potentially support public health recovery and promote healthy lifestyles during the COVID-19 pandemic.

Abstract This study examines the dynamic impact of face mask use on both infected cases and fatalities at a global scale by using a rich set of panel data econometrics. An increase of 100% of the proportion of people declaring wearing a mask (multiply by two) over the studied period lead to a reduction of around 12 and 13.5% of the number of Covid-19 infected cases (per capita) after 7 and 14 days respectively. The delay of action varies from around 7 days to 28 days concerning infected cases but is more longer concerning fatalities. Our results hold when using the rigorous controlling approach. We also document the increasing adoption of mask use over time and the drivers of mask adoption. In addition, population density and pollution levels are significant determinants of heterogeneity regarding mask adoption across countries, while altruism, trust in government and demographics are not. However, individualism index is negatively correlated with mask adoption. Finally, strict government policies against Covid-19 have a strong significant effect on mask use.

Abstract Background Meta-analyses are on top of the evidence-based medicine pyramid, yet many of them are not completed after they are begun. Many factors impacting the publication of meta-analysis works have been discussed, and their association with publication likelihood has been investigated. These factors include the type of systematic review, journal metrics, h-index of the corresponding author, country of the corresponding author, funding sources, and duration of publication. In our current review, we aim to investigate these various factors and their impact on the likelihood of publication. A comprehensive review of 397 registered protocols retrieved from five databases was performed to investigate the different factors that might affect the likelihood of publication. These factors include the type of systematic review, journal metrics, h-index of the corresponding author, country of the corresponding author, funding sources, and duration of publication. Results We found that corresponding authors in developed countries and English-speaking countries had higher likelihoods of publication: 206/320 (p = 0.018) and 158/236 (p = 0.006), respectively. Factors affecting publications are the countries of corresponding author (p = 0.033), whether they are from developed countries (OR: 1.9, 95% CI: 1.2–3.1, p = 0.016), from English-speaking countries (OR: 1.8, 95% CI: 1.2–2.7, p = 0.005), update status of the protocol (OR: 1.6, 95% CI: 1.0–2.6, p = 0.033), and external funding (OR: 1.7, 95% CI: 1.1–2.7, p = 0.025). Multivariable regression retains three variables as significant predictors for the publication of a systematic review: whether it is the corresponding author from developed countries (p = 0.013), update status of the protocol (p = 0.014), and external funding (p = 0.047). Conclusion Being on top of the evidence hierarchy, systematic review and meta-analysis are the keys to informed clinical decision-making. Updating protocol status and external funding are significant influences on their publications. More attentions should be paid to the methodological quality of this type of publication.

Abstract This multicentre prospective cohort study aimed to compare the accuracy of the PAASH, WFNS, and Hunt and Hess (H&H) scales in predicting the outcomes of adult patients with aneurysmal SAH presented to three central hospitals in Hanoi, Vietnam, from August 2019 to June 2021. Of 415 eligible patients, 32.0% had a 90-day poor outcome, defined as an mRS score of 4 (moderately severe disability) to 6 (death). The PAASH, WFNS and H&H scales all have good discriminatory abilities for predicting the 90-day poor outcome. There were significant differences in the 90-day mean mRS scores between grades I and II (p = 0.001) and grades II and III (p = 0.001) of the PAASH scale, between grades IV and V (p = 0.026) of the WFNS scale, and between grades IV and V (p

Introduction: In hospitalized patients, atrial fibrillation is the most common arrhythmia, and leading cause of cardio-embolic stroke. Objective: To evaluate the association between N-terminal b-type natriuretic peptide pro (NT-proBNP) and left atrial appendage thrombus in persistent atrial fibrillation patients. Methods: A cross-sectional study, enrolled 139 patients with persistent non-valvular atrial fibrillation. Transthoracic and trans-esophageal echocardiographs were performed in all patients. Results: Mean age was 70.5 ± 10.6 years, 80.6% male. In patients with LAAT, NT-proBNP was positively correlated with left ventricular end diastolic diameter (LVEDD) (r=0.345), left ventricular end-systolic diameter (LVEDS) (r= 0.449), E/e' (r=0.445), and left atrial spontaneous echo contrast (LA SEC) (r=0.478), and negatively correlated with left ventricular ejection fraction (LVEF) (r=-0.473), left atrial strain (r= -0.301), strain rate (r= -0.283), and e'(r= -0.458). In patients without LAAT, NT-proBNP was positively correlated with LVEDD (r= 0.333), LVESD (r= 0.358), E (r= 0.318), E/e' (r= 0.411), left atrial volume index (LAVI) (r= 0.421), and negatively correlated with LVEF (r= -0.307). Plasma NT-proBNP (> 1279 pg/mL) could be used to predict LAAT (AUC= 0.639; Se= 67.7%, Sp= 60.2%). In patients with ejection fraction > 50%, the cutoff value of NT-proBNP to predict LAAT was 1325 pg/mL (AUC= 0.572; Se= 57.9%, Sp= 78.3%). Multiple logistic regression analysis showed that prior stroke, E/e' index, and NT-proBNP correlated with LAAT (r= 0.887; p< 0.001; r= -0.092, p= 0.035 and 0.022; p= 0.004, respectively). Conclusion: Plasma NT-proBNP levels and E/e' index are associated with LAAT in patients with persistent atrial fibrillation.

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening.

Abstract We present an apparatus for attosecond transient-absorption spectroscopy (ATAS) featuring soft-X-ray (SXR) supercontinua that extend beyond 450 eV. This instrument combines an attosecond table-top high-harmonic light source with mid-infrared (mid-IR) pulses, both driven by 1.7–1.9 mJ, sub-11 fs pulses centered at 1.76 $$\upmu$$ μ m. A remarkably low timing jitter of $$\sim$$ ∼ 20 as is achieved through active stabilization of the pump and probe arms of the instrument. A temporal resolution of better than 400 as is demonstrated through ATAS measurements at the argon L $$_{2,3}$$ 2 , 3 -edges. A spectral resolving power of 1490 is demonstrated through simultaneous absorption measurements at the sulfur L $$_{2,3}$$ 2 , 3 - and carbon K-edges of OCS. Coupled with its high SXR photon flux, this instrument paves the way to attosecond time-resolved spectroscopy of organic molecules in the gas phase or in aqueous solutions, as well as thin films of advanced materials. Such measurements will advance the studies of complex systems to the electronic time scale.

Abstract Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of advanced melanoma, but many patients do not respond to ICIs alone, and thus there is need for additional treatment options. Topical immunomodulators such as diphencyprone (DPCP) also have clinical use in advanced melanoma, particularly in the treatment of cutaneous metastases. In a previous report, we characterized the enhanced clinical response to dual agent immunotherapy with pembrolizumab and DPCP in a patient with cutaneous melanoma metastases. To improve mechanistic understanding of this response, we analyzed proteomic data using the Olink immuno-oncology panel of 96 biomarkers from tissue and serum samples of this patient throughout his treatment course. Particular attention was paid to programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and lymphocyte-activation gene 3 (LAG-3) given they are all targeted by ICIs in clinical practice. These proteins were upregulated during the period of DPCP monotherapy, then downregulated during pembrolizumab monotherapy, and then robustly upregulated again during dual therapy. Although not exclusively, the induction of checkpoint inhibitor proteins in the presence of DPCP suggests potential synergy between this agent and ICIs in the treatment of cutaneous melanoma metastases. Large-scale investigation is warranted to further evaluate this potential novel combination therapeutic approach.

Purpose: This narrative review aims to explore the current status of facial scanning technology in the dental field; outlining the history, mechanisms, and current evidence regarding its use and limitations within digital dentistry. Methods: Subtopics within facial scanner technology in dentistry were identified and divided among four reviewers. Electronic searches of the Medline (PubMed) database were performed with the following search terms: facial scanner, dentistry, prosthodontics, virtual patient, sleep apnea, maxillofacial prosthetics, accuracy. For this review only studies or review papers evaluating facial scanning technology for dental or medical applications were included. A total of 44 articles were included. Due to the narrative nature of this review, no formal evidence-based quality assessment was performed and the search was limited to the English language. No further restrictions were applied. Results: The significance, applications, limitations, and future directions of facial scanning technology were reviewed. Specific subtopics include significant history of facial scanner use and development for dentistry, different types and mechanisms used in facial scanning technology, accuracy of scanning technology, use as a diagnostic tool, use in creating a virtual patient, virtual articulation, smile design, diagnosing and treating obstructive sleep apnea, limitations of scanning technology, and future directions with artificial intelligence. Conclusions: Despite limitations in scan quality and software operation, 3D facial scanners are rapid and non-invasive tools that can be utilized in multiple facets of dental care. Facial scanners can serve an invaluable role in the digital workflow by capturing facial records to facilitate interdisciplinary communication, virtual articulation, smile design, and obstructive sleep apnea diagnosis and treatment. Looking into the future, facial scanning technology has promising applications in the fields of craniofacial research, and prosthodontic diagnosis and treatment planning.

Abstract This study presents the Slime Mold Algorithm (SMA) to solve the time—cost—quality trade-off problem in a construction project. The proposed SMA is a flexible and efficient algorithm in exploration and exploitation to reach the best optimal solution to process the input model’s data. This paper aims to discuss and solve the optimization problem and compare the evaluation with other algorithms such as Opposition-based Multiple Objective Differential Evolution, Non-dominated sorting genetic algorithm, Multiple objective particle swarm optimization, Multiple objective differential evolution and Chaotic initialized multiple objective differential evolution (CAMODE) to verify the efficiency and potential of the proposed algorithm. According to the analysis results, the SMA model generated a diversification measure for case studies, producing superior outcomes to those of previous algorithms.

Abstract Background Preterm birth may affect maternal mental health, yet most studies focus on postpartum mental disorders only. We explored the relationship between preterm delivery and the long-term risk of maternal hospitalization for mental illness after pregnancy. Methods We performed a longitudinal cohort study of 1,381,300 women who delivered between 1989 and 2021 in Quebec, Canada, and had no prior history of mental illness. The exposure was preterm birth, including extreme (

Abstract Background We reported that PARP-1 regulates genes whose products are crucial for asthma, in part, by controlling STAT6 integrity speculatively through a calpain-dependent mechanism. We wished to decipher the PARP-1/STAT6 relationship in the context of intracellular trafficking and promoter occupancy of the transcription factor on target genes, its integrity in the presence of calpains, and its connection to autophagy. Methods This study was conducted using primary splenocytes or fibroblasts derived from wild-type or PARP-1−/− mice and Jurkat T cells to mimic Th2 inflammation. Results We show that the role for PARP-1 in expression of IL-4-induced genes (e.g. gata-3) in splenocytes did not involve effects on STAT6 phosphorylation or its subcellular trafficking, rather, it influenced its occupancy of gata-3 proximal and distal promoters in the early stages of IL-4 stimulation. At later stages, PARP-1 was crucial for STAT6 integrity as its inhibition, pharmacologically or by gene knockout, compromised the fate of the transcription factor. Calpain-1 appeared to preferentially degrade JAK-phosphorylated-STAT6, which was blocked by calpastatin-mediated inhibition or by genetic knockout in mouse fibroblasts. The STAT6/PARP-1 relationship entailed physical interaction and modification by poly(ADP-ribosyl)ation independently of double-strand-DNA breaks. Poly(ADP-ribosyl)ation protected phosphorylated-STAT6 against calpain-1-mediated degradation. Additionally, our results show that STAT6 is a bonafide substrate for chaperone-mediated autophagy in a selective and calpain-dependent manner in the human Jurkat cell-line. The effects were partially blocked by IL-4 treatment and PARP-1 inhibition. Conclusions The results demonstrate that poly(ADP-ribosyl)ation plays a critical role in protecting activated STAT6 during Th2 inflammation, which may be synthetically targeted for degradation by inhibiting PARP-1.

OBJECTIVES This study aimed to investigate socioeconomic status (SES)-based inequality in colorectal cancer (CRC) screening in Korea. We assessed whether the rates of opportunistic and organized CRC screening differed according to income and education levels. METHODS We analyzed data from the Korean National Cancer Screening Survey of 27,654 cancer-free individuals, aged 50-74 years, from 2009 to 2021. The weighted cancer screening rates with trends were estimated with the average annual percentage change using joinpoint regression. Inequality was calculated in both relative and absolute terms, based on a Poisson regression model. RESULTS The organized screening rate increased significantly from 22.1% in 2009 to 53.1% in 2020 and 50.6% in 2021, with an average annual change of 8.6% (95% confidence interval [CI], 4.9 to 12.5). In contrast, no significant trend was observed for opportunistic screening. The SES inequality in opportunistic screening uptake was indicated by a slope index of inequality (SII) of 9.74% (95% CI, 6.36 to 13.12), relative index of inequality (RII) of 2.18 (95% CI, 1.75 to 2.70) in terms of education level; and an SII of 7.03% (95% CI, 4.09 to 9.98), RII of 1.81 (95% CI, 1.41 to 2.31) in terms of measured income. Although there was an increasing trend in income inequality, no significant SES inequalities were observed in the overall estimates for organized screening. CONCLUSIONS Organized CRC screening is effective in improving the participation rate, regardless of SES. However, significant inequalities were found in opportunistic screening, suggesting room for improvement in the overall equity of CRC screening.

Summary: Background: Dysregulated inflammatory responses and oxidative stress are key pathogenic drivers of chronic inflammatory diseases such as liver cirrhosis (LC). Regulatory T cells (Tregs) are essential to prevent excessive immune activation and maintain tissue homeostasis. While inflammatory cues are well known to modulate the function and stability of Tregs, the extent to which Tregs are influenced by oxidative stress has not been fully explored. Methods: The phenotypic and functional properties of CD4+CD25+CD127lo/- Tregs isolated from patients with LC were compared to healthy controls (HC). Treg redox state was investigated by characterizing intracellular reactive oxygen species (ROS), NADPH oxidase-2 (Nox2) activity, mitochondrial function, morphology, and nuclear factor-erythroid 2-related factor (Nrf2) antioxidant signalling. The relevance of Nrf2 and its downstream target, Heme-oxygenase-1 (HO-1), in Treg function, stability, and survival, was further assessed using mouse models and CRISPR/Cas9-mediated HO-1 knock-out. Findings: Circulating Tregs from LC patients displayed a reduced suppressive function, correlating with liver disease severity, associated with phenotypic abnormalities and increased apoptosis. Mechanistically, this was linked to a dysregulated Nrf2 signalling with resultant lower levels of HO-1, enhanced Nox2 activation, and impaired mitochondrial respiration and integrity. The functional deficit in LC Tregs could be partially recapitulated by culturing control Tregs in patient sera. Interpretation: Our findings reveal that Tregs rely on functional redox homeostasis for their function, stability, and survival. Targeting Treg specific anti-oxidant pathways may have therapeutic potential to reverse the Treg impairment in conditions of oxidative damage such as advanced liver disease. Funding: This study was funded by the Wellcome Trust (211113/A/18/Z).

Abstract O6-Methylguanine-DNA-methyltransferase (MGMT) promoter methylation was shown in many studies to be an important predictive biomarker for temozolomide (TMZ) resistance and poor progression-free survival in glioblastoma multiforme (GBM) patients. However, identifying the MGMT methylation status using molecular techniques remains challenging due to technical limitations, such as the inability to obtain tumor specimens, high prices for detection, and the high complexity of intralesional heterogeneity. To overcome these difficulties, we aimed to test the feasibility of using a novel radiomics-based machine learning (ML) model to preoperatively and noninvasively predict the MGMT methylation status. In this study, radiomics features extracted from multimodal images of GBM patients with annotated MGMT methylation status were downloaded from The Cancer Imaging Archive (TCIA) public database for retrospective analysis. The radiomics features extracted from multimodal images from magnetic resonance imaging (MRI) had undergone a two-stage feature selection method, including an eXtreme Gradient Boosting (XGBoost) feature selection model followed by a genetic algorithm (GA)-based wrapper model for extracting the most meaningful radiomics features for predictive purposes. The cross-validation results suggested that the GA-based wrapper model achieved the high performance with a sensitivity of 0.894, specificity of 0.966, and accuracy of 0.925 for predicting the MGMT methylation status in GBM. Application of the extracted GBM radiomics features on a low-grade glioma (LGG) dataset also achieved a sensitivity 0.780, specificity 0.620, and accuracy 0.750, indicating the potential of the selected radiomics features to be applied more widely on both low- and high-grade gliomas. The performance indicated that our model may potentially confer significant improvements in prognosis and treatment responses in GBM patients.

Jejunal Dieulafoy lesion (DL) is an exceedingly rare, life-threatening cause of gastrointestinal bleeding. Due to its rarity, intermittent bleeding symptoms that often necessitate prompt clinical intervention, variability in detection and treatment methods, and the risk of rebleeding, this condition frequently presents a diagnostic and therapeutic conundrum. We report a case of severe, intermittent, recurrent hematochezia due to a jejunal DL that was difficult to localize. In this case, the metallic coils used as a radiopaque marker allowed surgeons to accurately identify the bleeding site during intraoperative enteroscopy and successfully manage the lesion with minimally invasive laparoscopic surgery.

Abstract Gastric adenocarcinoma, commonly known as stomach cancer, has a predilection for metastasis to the peritoneum, which portends limited survival. The peritoneal metastatic cascade remains poorly understood, and existing models fail to recapitulate key elements of the interaction between cancer cells and the peritoneal layer. To explore the underlying cellular and molecular mechanisms of peritoneal metastasis, we developed an ex vivo human peritoneal explant model. Fresh peritoneal tissue samples were suspended, mesothelial layer down but without direct contact, above a monolayer of red-fluorescent dye stained AGS human gastric adenocarcinoma cells for 24 h, then washed thoroughly. Implantation of AGS cells within the explanted peritoneum and invasion beyond the mesothelial layer were examined serially using real-time confocal fluorescence microscopy. Histoarchitecture of the explanted peritoneum was preserved over 5 days ex vivo. Both implantation and invasion were suppressed by restoration of functional E-cadherin through stable transfection of AGS cells, demonstrating sensitivity of the model to molecular manipulation. Thus, our ex vivo human peritoneal explant model permits meaningful investigation of the pathways and mechanism that contribute to peritoneal metastasis. The model will facilitate screening of new therapies that target peritoneal dissemination of gastric, ovarian and colorectal cancer.

Patients with severe COVID-19 disease require monitoring with pulse oximetry as a minimal requirement. In many low- and middle- income countries, this has been challenging due to lack of staff and equipment. Wearable pulse oximeters potentially offer an attractive means to address this need, due to their low cost, battery operability and capacity for remote monitoring. Between July and October 2021, Ho Chi Minh City experienced its first major wave of SARS-CoV-2 infection, leading to an unprecedented demand for monitoring in hospitalized patients. We assess the feasibility of a continuous remote monitoring system for patients with COVID-19 under these circumstances as we implemented 2 different systems using wearable pulse oximeter devices in a stepwise manner across 4 departments.

Bacterial leaf blight (BB) of rice, caused by Xanthomonas oryzae pv. oryzae (Xoo), threatens global food security and the livelihood of small-scale rice producers. Analyses of Xoo collections from Asia, Africa and the Americas demonstrated complete continental segregation, despite robust global rice trade. Here, we report unprecedented BB outbreaks in Tanzania. The causative strains, unlike endemic African Xoo, carry Asian-type TAL effectors targeting the sucrose transporter SWEET11a and iTALes suppressing Xa1. Phylogenomics clustered these strains with Xoo from Southern-China. African rice varieties do not carry effective resistance. To protect African rice production against this emerging threat, we developed a hybrid CRISPR-Cas9/Cpf1 system to edit all known TALe-binding elements in three SWEET promoters of the East African elite variety Komboka. The edited lines show broad-spectrum resistance against Asian and African strains of Xoo, including strains recently discovered in Tanzania. The strategy could help to protect global rice crops from BB pandemics.

Objectives To investigate the impact of intracerebral haematoma (ICH) on the outcomes and the factors related to an ICH in patients with aneurysmal subarachnoid haemorrhage (aSAH) in a low- and middle-income country.Design A multicentre prospective cohort study.Setting Three central hospitals in Hanoi, Vietnam.Participants This study included all patients (≥18 years) presenting with aSAH to the three central hospitals within 4 days of ictus, from August 2019 to June 2021, and excluded patients for whom the admission Glasgow Coma Scale was unable to be scored or patients who became lost at 90 days of follow-up during the study.Outcome measures The primary outcome was ICH after aneurysm rupture, defined as ICH detected on an admission head CT scan. The secondary outcomes were 90-day poor outcomes and 90-day death.Results Of 415 patients, 217 (52.3%) were females, and the median age was 57.0 years (IQR: 48.0–67.0). ICH was present in 20.5% (85/415) of patients with aSAH. There was a significant difference in the 90-day poor outcomes (43.5% (37/85) and 29.1% (96/330); p=0.011) and 90-day mortality (36.5% (31/85) and 20.0% (66/330); p=0.001) between patients who had ICH and patients who did not have ICH. The multivariable regression analysis showed that systolic blood pressure (SBP) ≥140 mm Hg (adjusted odds ratio (AOR): 2.674; 95% CI: 1.372 to 5.214; p=0.004), World Federation of Neurosurgical Societies (WFNS) grades II (AOR: 3.683; 95% CI: 1.250 to 10.858; p=0.018) to V (AOR: 6.912; 95% CI: 2.553 to 18.709; p

Introduction Therapeutic hypothermia (TH) became the standard of care treatment for neonates with moderate and severe neonatal encephalopathy (NE) in most industrialized countries about 10 years ago. Although TH is effective in reducing mortality and the incidence of severe developmental disabilities, the recent literature converges in reporting frequent cognitive and behavioural difficulties at school entry in children with NE-TH. Although these challenges are deemed minor compared with cerebral palsy and intellectual disability, their impacts on a child’s self-determination and family’s well-being are quite significant. Therefore, the nature and extent of these difficulties need to be comprehensively described so that appropriate care can be offered.Methods and analysis The current study will be the largest follow-up study of neonates with NE treated with TH to characterize their developmental outcomes and associated brain structural profiles at 9 years of age. Specifically, we will compare executive function, attention, social cognition, behaviour, anxiety, self-esteem, peer problems, brain volume, cortical features, white matter microstructure and myelination between children with NE-TH and matched peers without NE. Associations of perinatal risk factors and structural brain integrity with cognitive, behavioural and psycho-emotional deficits will be evaluated to inform about the potential aggravating and protective factors associated with function.Ethics and dissemination This study is supported by the Canadian Institute of Health Research (202203PJT-480065-CHI-CFAC-168509), and received approval from the Pediatric Ethical Review Board of the McGill University Health Center (MP-37-2023-9320). The study findings will be disseminated in scientific journals and conferences and presented to parental associations and healthcare providers to inform best practices.Trial registration number NCT05756296.

In Vietnam, chest radiography (CXR) is used to refer people for GeneXpert (Xpert) testing to diagnose tuberculosis (TB), demonstrating high yield for TB but a wide range of CXR abnormality rates. In a multi-center implementation study, computer-aided detection (CAD) was integrated into facility-based TB case finding to standardize CXR interpretation. CAD integration was guided by a programmatic framework developed for routine implementation. From April through December 2022, 24,945 CXRs from TB-vulnerable populations presenting to district health facilities were evaluated. Physicians interpreted all CXRs in parallel with CAD (qXR 3.0) software, for which the selected TB threshold score was ≥0.60. At three months, there was 47.3% concordance between physician and CAD TB-presumptive CXR results, 7.8% of individuals who received CXRs were referred for Xpert testing, and 858 people diagnosed with Xpert-confirmed TB per 100,000 CXRs. This increased at nine months to 76.1% concordant physician and CAD TB-presumptive CXRs, 9.6% referred for Xpert testing, and 2112 people with Xpert-confirmed TB per 100,000 CXRs. Our programmatic CAD-CXR framework effectively supported physicians in district facilities to improve the quality of referral for diagnostic testing and increase TB detection yield. Concordance between physician and CAD CXR results improved with training and was important to optimize Xpert testing.

Abstract Complications of portal hypertension can be treated with transjugular intrahepatic portosystemic shunt (TIPS) in selected patients. TIPS dysfunction is a relevant clinical problem. This study investigated the prognostic value of two-dimensional (2D) TIPS geometry for the development of TIPS dysfunction. Three hundred and seven patients undergoing TIPS procedure between 2014 and 2019 were analyzed in this monocentric retrospective study. 2D angiograms from the patients with and without TIPS dysfunction were reviewed to determine geometric characteristics including insertion and curve angles and the location of the stent. Primary outcome was the development of TIPS dysfunction. A total of 70 patients developed TIPS dysfunction and were compared to the dysfunction-free (n = 237) patients. The position of the cranial stent end in the hepatic vein and the persistence of spontaneous portosystemic shunts were significantly associated with the development of TIPS dysfunction. Among significant parameters in univariable regression analysis (portal vein-pressure after TIPS, Child–Pugh Score before TIPS, MELD before TIPS and white blood cell count before TIPS), multivariable models showed cranial stent position (p = 0.027, HR 2.300, 95% CI 1.101–4.806) and SPSS embolization (p = 0.006, HR 0.319, 95% CI 0.140–0.725) as the only predictors of TIPS dysfunction. This monocentric study demonstrates that the position of the cranial stent end is independently associated with the development of TIPS dysfunction. The distance of the cranial stent end to the IVC at the time of TIPS placement should be less than 1 cm in 2D angiography.

Abstract Contrast-rebalanced dichoptic movies have been shown to be an effective binocular treatment for amblyopia in the laboratory. Yet, at-home therapy is a more practical approach. In a randomized clinical trial, we compared dichoptic movies, streamed at-home on a handheld 3D-enabled game console, versus patching as amblyopia treatment. Sixty-five amblyopic children (3–7 years; 20/32–125) were randomly assigned to one of two parallel arms, binocular treatment (3 movies/week) or patching (14 h/week). The primary outcome, change in best corrected visual acuity (BCVA) at the 2-week visit was completed by 28 and 30, respectively. After the primary outcome, both groups of children had the option to complete up to 6 weeks of binocular treatment. At the 2-week primary outcome visit, BCVA had improved in the movie (0.07 ± 0.02 logMAR; p

Abstract The spread of SARS-CoV-2 led to rapid vaccine development. However, there remains considerable vaccine hesitancy in some countries. We investigate vaccine willingness in three nations with very different vaccine histories: Israel, Japan and Hungary. Employing an ecological-systems approach we analyse associations between health status, individual cognitions, norms, trust in government, COVID-19 myths and willingness to be vaccinated, with data from three nationally representative samples (Israel, Jan. 2021, N = 1011; Japan, Feb. 2021, N = 997; Hungary, April 2021, N = 1130). Vaccine willingness was higher in Israel (74%) than Japan (51%) or Hungary (31%). In all three countries vaccine willingness was greatest amongst who would regret not being vaccinated and respondents who trusted their government. Multi-group latent class analysis identified three groups of COVID myths, with particular concern about alteration of DNA (Israel), allergies (Hungary) and infection from the vaccine (Japan). Intervention campaigns should address such cultural myths while emphasising both individual and social benefits of vaccination.

Introduction The lack of definitive means to prevent or treat cognitive impairment or dementia is driving intense efforts to identify causal mechanisms. Recent evidence suggests clinically meaningful declines in cognition might present as early as middle age. Studying cognitive changes in middle adulthood could elucidate modifiable factors affecting later cognitive and health outcomes, yet few cognitive ageing studies include this age group. The purpose of the MidCog study is to begin investigations of less-studied and potentially modifiable midlife determinants of later life cognitive outcomes.Methods and analysis MidCog is a prospective cohort study of adults ages 35–64, with two in-person interviews 2.5 years apart. Data will be collected from interviews, electronic health records and pharmacy fill data. Measurements will include health literacy, self-management skills, cognitive function, lifestyle and health behaviours, healthcare use, health status and chronic disease outcomes. Associations of health literacy and self-management skills with health behaviours and cognitive/health outcomes will be examined in a series of regression models, and moderating effects of modifiable psychosocial factors.Finally, MidCog data will be linked to an ongoing, parallel cohort study of older adults recruited at ages 55–74 in 2008 (‘LitCog’; ages 70–90 in 2023), to explore associations between age, health literacy, self-management skills, chronic diseases, health status and cognitive function among adults ages 35–90.Ethics and dissemination The Institutional Review Board at Northwestern University has approved the MidCog study protocol (STU00214736). Results will be published in peer-reviewed journals and summaries will be provided to the funders of the study as well as patients.

We characterized polysubstance use burden and associations with mental health problems across demographic subgroups of PWH. In 2018-2020, as part of a primary care-based intervention study, PWH in care at three medical centers in Kaiser Permanente Northern California were screened for depression (PHQ-9≥10), anxiety (GAD-2≥3), and substance use (Tobacco, Alcohol, Prescription medication, and other Substance use [TAPS]≥1 per substance). We used Poisson regression to estimate prevalence ratios (PRs) comparing polysubstance use prevalence (TAPS≥1 for ≥2 substances) between PWH with positive screens for depression or anxiety vs. neither, among all PWH, and stratified by race/ethnicity and age (restricted to men), adjusting for sociodemographics, CD4, and HIV load. Screened PWH (N = 2865) included 92% men, 56% White, 19% Black, and 15% Hispanic PWH, with a median age of 55 years. Overall, polysubstance use prevalence was 26.4% (95% CI 24.9%-28.1%). PWH with depression or anxiety (n = 515) had an adjusted polysubstance use PR of 1.26 (1.09-1.46) vs. PWH with neither (n = 2350). Adjusted PRs were 1.47 (1.11-1.96), 1.07 (0.74-1.54), and 1.10 (0.85-1.41) among Black, Hispanic, and White men, respectively. Adjusted PRs did not differ by age group. Interventions should consider jointly addressing mental health and substance use problems and potential drivers, e.g. stigma or socioeconomic factors.

BackgroundEvaluating the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH) who may be at risk of poor outcomes using grading systems is one way to make a better decision on treatment for these patients. This study aimed to compare the accuracy of the modified World Federation of Neurosurgical Societies (WFNS), WFNS, and Hunt and Hess (H&H) Grading Scales in predicting the outcomes of patients with aSAH.MethodsFrom August 2019 to June 2021, we conducted a multicenter prospective cohort study on adult patients with aSAH in three central hospitals in Hanoi, Vietnam. The primary outcome was the 90-day poor outcome, measured by a score of 4 (moderately severe disability) to 6 (death) on the modified Rankin Scale (mRS). We calculated the areas under the receiver operator characteristic (ROC) curve (AUROCs) to determine how well the grading scales could predict patient prognosis upon admission. We also used ROC curve analysis to find the best cut-off value for each scale. We compared AUROCs using Z-statistics and compared 90-day mean mRS scores among intergrades using the pairwise multiple-comparison test. Finally, we used logistic regression to identify factors associated with the 90-day poor outcome.ResultsOf 415 patients, 32% had a 90-day poor outcome. The modified WFNS (AUROC: 0.839 [95% confidence interval, CI: 0.795-0.883]; cut-off value≥2.50; PAUROCConclusionsIn this study, the modified WFNS, WFNS, and H&H scales all had good discriminatory abilities for the prognosis of patients with aSAH. Because of the better effect size in predicting poor outcomes, the modified WFNS scale seems preferable to the WFNS and H&H scales.

Situated in the southern end of the Annamite Mountain Range, Langbiang Plateau is a major biodiversity hotspot of southern Vietnam known for high species diversity and endemicity. To achieve effective conservation, parts of the plateau were designated as the Langbiang Biosphere Reserve, an UNESCO World Network aiming to improve relationships between inhabitants and their environments. Amongst the rich endemic flora of the plateau are three gesneriads ascribed to Primulina, a calciphilous genus with high species diversity in the vast limestone karsts stretching from southern China to northern Vietnam. However, a recent phylogenetic study questioned the generic placement of the Langbiang Primulina, corroborating with observations on the geographical distribution, habitat preference, and phyllotaxy of the three species. Based on phylogenetic analyses of nuclear ITS and plastid trnL-F DNA sequences of a comprehensive sampling covering nearly all genera of the Old World Gesneriaceae, we demonstrate that the three Langbiang Primulina species form a fully supported clade distantly related to other Primulina. As this clade is biogeographically, ecologically, morphologically, and phylogenetically distinct worthy of generic recognition, we propose to name it Langbiangia gen. nov. to highlight the rich and unique biodiversity of the Langbiang Plateau. By means of this taxonomic endeavor, we are hoping to raise the conservation awareness of this biodiversity heritage of southern Vietnam and promote the importance of Langbiang Biosphere Reserve that is crucial for achieving action-oriented global targets of the post-2020 global biodiversity framework (GBF) of the UN Convention on Biological Diversity (CBD)-effective conservation and management of at least 30% of biodiverse terrestrial, inland water, and costal and marine areas by 2030-that has been agreed at the COP15 in Montréal in December 2022.