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We studied a community cluster of 25 mpox cases in Vietnam caused by emerging monkeypox virus sublineage C.1 and imported into Vietnam through 2 independent events; 1 major cluster carried a novel APOBEC3-like mutation. Three patients died; all had advanced HIV co-infection. Viral evolution and its potential consequences should be closely monitored.

Abstract The aquaporin-4 (AQP4) water channel is essential in neurofluid dynamics. AQP4 loss impairs solute exchange between the cerebrospinal fluid (CSF) and interstitial fluid (ISF). However, whether AQP4 expression affects solute clearance from the CSF space to the extracranial space remains unclear. This study aimed to investigate this using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) following the intrathecal administration of gadolinium-based contrast agents (GBCAs) to AQP4 knockout (KO) rats. AQP4 KO rats showed reduced efflux of intrathecal GBCAs to the extracranial spaces through CSF drainage pathways and increased retention of intrathecal GBCAs in the CSF space compared with the controls. These results suggest that AQP4 loss impairs solute clearance from the CSF space to the extracranial spaces via the CSF drainage pathways. This study revealed a close relationship between AQP4 expression and CSF solute clearance, contributing to a better understanding of the function of AQP4 in neurofluid dynamics.

Abstract Adaptive microlearning has emerged as a crucial approach for enhancing the working skills of in-service personnel. This study introduces the design and development of an innovative adaptive microlearning (AML) system and investigates its effectiveness compared to a conventional microlearning (CML) system. The main distinguishing feature of an AML system from a CML system is its adaptive features that tailor the learning experience to individual needs, including personalized content delivery, real-time feedback, and adaptive learning paths. A quasi-experimental study involving 111 in-service personnel (NAML = 56, NCML = 55) was conducted. ANCOVA results confirmed that the AML system significantly reduced unnecessary cognitive load due to inappropriate instructional design (mean difference of -20.02, p

Abstract Contrary to expert readers, children learning to read have limited ability to preprocess letters in parafoveal vision. Parafoveal letters induce crowding cost: the features of neighboring letters interfere with target letter identification. We longitudinally studied the weight of parafoveal cost and benefit in two group of children (N = 42), during their first school year (Group 1) and at the end of second school year (Groupe 2). Using a novel digit-tracking method, a blurred text was presented and rendered unblurred by touching the screen, allowing the user to discover a window of visible text as the finger moved along it. We compared two conditions: (1) a large window, where crowding was enhanced by the presence of parafoveal information; (2) a small window, where crowding was suppressed by blurred parafoveal information. Finger kinematics were simultaneously recorded. We found that at the beginning of first-grade, digital fixations - brief slowing or stopping of the finger on a specific point - are significantly longer in the large compared to the small window condition, as parafoveal crowding increases text processing difficulty. This effect diminishes and disappears at the end of second-grade as reading performance improves. In the large window condition, longer digital saccades - rapid movements of the finger changing position - appear by the end of first grade suggesting that parafoveal exposure become more beneficial than harmful when children acquire basic reading skills. Our results show that in beginning readers, crowding has a cognitive cost that interfere with the speed of the learning reading process. Our findings are relevant to the field of education by showing that visual crowding in first grade should not be underestimated.

Abstract Recent advances in studies exploring the roles of extracellular vesicles (EVs) in viral transmission and replication have illuminated hepatotropic viruses, such as hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV). While previous investigations have uncovered these viruses’ ability to exploit cellular EV pathways for replication and transmission, most have focused on the impacts of exosomal pathways. With an improved understanding of EVs, four main subtypes, including exosomes, microvesicles, large oncosomes, and apoptotic bodies, have been categorized based on size and biogenic pathways. However, there remains a noticeable gap in comprehensive reviews summarizing recent findings and outlining future perspectives for EV studies related to hepatotropic viruses. This review aims to consolidate insights into EV pathways utilized by hepatotropic viruses, offering guidance for the future research direction in this field. By comprehending the diverse range of hepatotropic virus-associated EVs and their role in cellular communication during productive viral infections, this review may offer valuable insights for targeting therapeutics and devising strategies to combat virulent hepatotropic virus infections and the associated incidence of liver cancer.

Product design and attractiveness are pivotal factors that determine people’s positive reactions when viewing a product and may eventually affect their purchasing choices. Comprehending how people assess product design is crucial. Various studies have explored the link between product attractiveness and consumer behavior, but these were predominantly behavioral studies that offered limited insight into the neural processes underlying perceptions of product attractiveness. Gaining a deeper understanding of these neural mechanisms is valuable, as it enables the formulation of more objective design guidelines based on brain activity, enhancing product appeal and, ultimately, spurring consumer purchases. In our study, we sought to (1) elucidate the neural network engaged when individuals evaluate highly attractive product images, (2) delineate the neural network activated during the evaluation of less attractive product images, and (3) contrast the differences in neural networks between evaluations of highly and less attractive images. We utilized fMRI to investigate the neural activation patterns elicited by viewing product images of varying attractiveness levels. The results indicated distinct neural activations in response to the two types of attractive images. Highly attractive product images elicited activity in the anterior cingulate cortex (ACC) and the occipital pole, whereas less attractive product images stimulated the insula and the inferior frontal gyrus (IFG). The findings of this project provide some of the first insights of its kind and valuable insights for future product design, suggesting that incorporating more positive and rewarding elements could enhance product appeal. This research elucidates the neural correlates of people’s responses to product attractiveness, revealing that highly attractive designs activate reward-related brain regions, while less attractive designs engage areas associated with emotional processing. These findings offer a neuroscientific basis for further studies on developing design strategies that align with consumers’ innate preferences, potentially transforming product design and marketing practices. By leveraging this knowledge, designers can craft products that not only meet functional needs but also resonate more deeply on an esthetic level, thereby enhancing consumer engagement and purchase likelihood.

Abstract Children with developmental coordination disorder (DCD) display difficulties in perception-action coupling when engaging in tasks requiring predictive timing. We investigated the influence of awareness on auditory-motor adjustments to small and large rhythmic perturbations in the auditory sequence to examine whether children synchronize their movements automatically or through planning and whether those adjustments occur consciously or subconsciously. Electroencephalography (EEG) was used to assess functional connectivity patterns underlying different adjustment strategies. Thirty-two children aged 7–11 participated, including children with DCD and their typically developing (TD) peers with and without musical training. All children automatically adjusted their motor responses to small rhythmic perturbations by employing the anticipatory mode, even when those changes were consciously undetectable. Planned adjustments occurred only when children consciously detected large fluctuations (Δ 20%), which required a shift from predictive to reactive strategies. Compared to TD peers, children with DCD showed reduced interhemispheric connectivity during planned adjustments and displayed similar neural patterns regardless of task constraints. Notably, they benefited from rhythmic entrainment despite having increased variability and lower perceptual acuity. Musical training was associated with enhanced auditory-perceptual timing, reduced variability, and increased interhemispheric coherence. These insights are important for the therapeutic application of auditory/rhythm-based interventions in children with DCD.

Abstract In this paper, we study the formation of optical bistability (OB) and optical multistability (OM) in a degenerate four-level atomic system by an external magnetic field that is excited by a probe laser field, a coupling laser field and a signal laser field. The coupling field can cause electromagnetically induced transparency (EIT) for the probe field in the atomic medium, while the signal field and/or external magnetic field can switch between single-EIT and two-EIT regimes. Based on these properties, OB and OM effects can be formed at two different frequency regions of the probe field (two channels). By adjusting the magnetic field or the intensity and the frequency of laser fields, the threshold intensity and the width of OB or OM can also be changed simply. The model can be useful for experimental observations and applications in modern photonic devices.

Abstract Atopic dermatitis (AD) is a chronic, allergic inflammatory skin disorder that lacks a definite cure. Using a mouse DNCB-induced AD-like skin lesions model, this study evaluated the potential therapeutic utility of tHGA as an oral and topical treatment for AD. Male BALB/c mice were sensitised and challenged with 1% and 0.5% DNCB on their shaved dorsal skin. Mice in the treatment group were administered tHGA (20, 40, and 80 mg/kg) orally three times per week for 2 weeks, or tHGA (0.2%, 1%, and 5%) topically once daily for 12 days. On day 34, the mice were euthanized, and blood and dorsal skin samples were obtained for analysis. All doses of orally and topically administered tHGA significantly improved scratching, epidermal thickness, blood eosinophilia and mast cell infiltration. There was a minor discrepancy between the two routes of administration, with orally treated tHGA showing significant reductions in Scoring of Atopic Dermatitis (SCORAD), tissue eosinophil infiltration, serum IgE and skin IL-4 levels with treatment of 40 and 80 mg/kg tHGA, whereas topically applied tHGA showed significant reductions in all dosages. These findings suggest that tHGA exhibited therapeutic potential for AD as both oral and topical treatment ameliorates AD-like symptoms in the murine model.

Abstract Muscle ultrasound has been shown to be a valid and safe imaging modality to assess muscle wasting in critically ill patients in the intensive care unit (ICU). This typically involves manual delineation to measure the rectus femoris cross-sectional area (RFCSA), which is a subjective, time-consuming, and laborious task that requires significant expertise. We aimed to develop and evaluate an AI tool that performs automated recognition and measurement of RFCSA to support non-expert operators in measurement of the RFCSA using muscle ultrasound. Twenty patients were recruited between Feb 2023 and July 2023 and were randomized sequentially to operators using AI (n = 10) or non-AI (n = 10). Muscle loss during ICU stay was similar for both methods: 26 ± 15% for AI and 23 ± 11% for the non-AI, respectively (p = 0.13). In total 59 ultrasound examinations were carried out (30 without AI and 29 with AI). When assisted by our AI tool, the operators showed less variability between measurements with higher intraclass correlation coefficients (ICCs 0.999 95% CI 0.998–0.999 vs. 0.982 95% CI 0.962–0.993) and lower Bland Altman limits of agreement (± 1.9% vs. ± 6.6%) compared to not using the AI tool. The time spent on scans reduced significantly from a median of 19.6 min (IQR 16.9–21.7) to 9.4 min (IQR 7.2–11.7) compared to when using the AI tool (p

Abstract Visual assessment, while the primary method for pigmentation and erythema evaluation in clinical practice, is subjective, time-consuming, and may lead to variability in observations among clinicians. Objective and quantitative techniques are required for a precise evaluation of the disease's severity and the treatment's efficacy. This research examines the precision and utility of a newly developed skin imaging system in assessing pigmentation and erythema. Sixty participants were recruited, and their facial images were analyzed with the new OBSERV 520 x skin imaging system, compared to DERMACATCH for regional analysis and VISIA for full-face examination. The degree of skin pigmentation was clinically graded using the MASI scores evaluated by dermatologists. The data revealed positive correlations between the novel skin imaging system and the two conventional instruments in quantifying pigmentation and erythema, whether in regional or full-face analysis. Furthermore, the new skin imaging system positively correlated with the clinical MASI scores (r = 0.4314, P

Abstract While studies have suggested increased risks of severe COVID-19 infection in chronic obstructive pulmonary disease (COPD), the persistent and delayed consequences of COVID-19 infection on patients with COPD upon recovery remain unknown. A prospective clinical study was conducted in Hong Kong to investigate the persistent and delayed outcomes of patients with COPD who had COVID-19 infection of different severity (mild-moderate COVID-19 and severe COVID-19), compared with those who did not. Chinese patients with COPD ≥ 40 years old were recruited from March to September 2021. They were prospectively followed up for 24.9 ± 5.0 months until 31st August 2023. The primary outcome was the deterioration in COPD control defined as the change in mMRC dyspnea scale. The secondary outcomes included the change in exacerbation frequency and non-COVID-19 respiratory mortality (including death from COPD exacerbation or bacterial pneumonia). 328 patients were included in the analysis. Patients with mild-moderate and severe COVID-19 infection had statistically significant increased risks of worsening of mMRC dyspnoea scale by increase in 1 score from baseline to follow-up with adjusted odds ratios of 4.44 (95% CI = 1.95–10.15, p

Introduction Home-based, virtually-supported care models may represent the most efficient and scalable approach to delivering prehabilitation services. However, virtual approaches to prehabilitation are understudied. This manuscript describes the protocol for an internal pilot randomised controlled trial of a virtually-delivered, multimodal prehabilitation intervention.Methods and analysis We will conduct a pragmatic, individual patient, internal pilot randomised controlled trial of home-based, virtually supported, multimodal prehabilitation compared with standard perioperative care in adults undergoing elective, inpatient thoracic, abdominal, pelvic and vascular surgery at five Canadian hospitals. Participants will be partially blinded; clinicians and outcome assessors will be fully blinded. The intervention consists of 3–12 weeks of a home-based, multimodal (exercise, nutrition and psychosocial support) prehabilitation programme supported through an online platform. The primary feasibility outcomes and their progression targets are (1) monthly recruitment of>6 participants at each centre, (2) intervention adherence of>75%, (3) retention of>90% of participants at the patient-reported primary outcome point of 30-days after surgery and (4) elicitation of patient, clinician and researcher-identified barriers to our pragmatic trial. A sample size of 144 participants will be adequate to estimate recruitment, adherence and retention rates with acceptable precision. All participants will be followed to either death or up to 1 year. As an internal pilot, if no substantive changes to the trial or intervention design are required, pilot participant outcome data will migrate, unanalysed by allocation, to the future full-scale trial.Ethics and dissemination Ethical approval has been granted by Clinical Trials Ontario (Project ID: 4479) and our ethics review board (Protocol Approval #20230399–01T). Results will be disseminated through presentations at scientific conferences, peer-reviewed publications, partner organisations and engagement of social and traditional media.Trial registration number ClinicalTrials.gov identifier NCT06042491. Protocol, V.1.2, dated 6 June 2024.

Introduction The Longan fruit tree of the Vietnam Mekong Delta is grown in raised beds to improve water drainage during the rainy season and can live as long as 100 years. Objective This research explores the extent to which the soil microorganisms as well as soil physical and chemical properties of these raised beds degrade over a period of 60 years under traditional management practices. Materials and Methods Raised bed topsoil samples at depths of 0–20 cm were obtained from four different Longan orchards raised bed age groups: group 1) 15–25 years (L1–L5); group 2) 26–37 years (L6–L10); group 3) 38–45 years (L11–L15); and group 4) 46–60 years. Soil biological properties were tested for nitrogen-fixing bacteria, phosphorus solubilizing bacteria, potassium solubilizing bacteria, calcium solubilizing bacteria and silicate solubilizing bacteria, β-glucosidase, urease, phosphomonoesterase, and phytase. Soil samples were also tested for moisture content, soil texture, soil porosity, and bulk density as well as soil chemical properties including pH, electrical conductivity (EC), soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), available nitrogen (NH4+, NO3−), available phosphorus (AP), exchangeable potassium (K+), exchangeable calcium (Ca2 +), available silicate (SiO2), available copper (Cu), zinc (Zn), boron (B) and manganese (Mn). Key findings: The results showed that soil moisture, soil porosity, sand content, SOM, TP, TK, available P, exchangeable Ca2 +, available Si, nitrogen fixing bacteria number, β-glucosidase, urease, phosphomonoesterase, and phytase gradually and significantly decreased in the raised bed soil as the Longan orchard increased in age. Pearson correlation analysis between the ages of Longan orchards and soil properties revealed that raised bed ages were positively correlated with soil bulk density, but negatively correlated with soil moisture content, soil porosity, SOM, TN, β-glucosidase, urease, phosphomonoesterase, and phytase. Principal component analysis (PCA) showed Longan yields had a positive correlation with available NO3− but negative correlation with NFB, exchangeable Ca2 +, pH, and available B. These findings reveal that traditional long-term management of Longan trees in raised beds significantly reduce soil organic matter, moisture content, porosity, and soil fertility with impacts on soil microbial numbers and activity within raised bed soils. Future Directions This suggests that more sustainable management practices, such as mulch and cover crops that decrease soil compaction and increase soil organic matter, improve soil porosity, total N, and feed soil microorganisms that are critical to nutrient cycling are needed to improve raised bed soil quality.

Objective: Nutrition interventions delivered through food pantries could reduce health disparities for people experiencing food insecurity. We identified clients’ preferences for cuisines, nutrition interventions, and outcomes and whether preferences differ for subpopulations. Methods: Cross-sectional study at a large pantry in Dallas, Texas (N = 200). Survey collected from February-May 2023 on demographics, cuisine preferences, nutrition intervention preferences, and outcomes clients hope to achieve when changing lifestyle (weight loss, feeling comfortable in clothes, feeling good about diet, wellbeing). A subsample (N = 130) had height and weight measured. We tested whether food security and BMI (categorical) were associated with intervention or outcome preferences using IBM SPSS Statistics (Version 29) to conduct analysis of variance. Results: Top-rated cuisines were Mexican, Chinese, Italian. Participants reported a desire for interventions implemented through the pantry reflected by high Nutrition Intervention Index scores. The highest rated intervention was bringing more healthy food into the pantry and lowest rated was restricting unhealthy donations.Overall wellbeing was the most important outcome and weight loss the least important.Neither food security nor BMI were associated with desire for interventions. All outcomes were rated in a similar pattern, though people with obesity and overweight rated weight loss as more important than people with normal weight. Conclusions: Most participants demonstrated a strong desire for healthier, ethnically diverse options, and nutrition interventions delivered through the pantry. Our findings explore cuisines and outcomes preferred by people that use food pantries which can guide researchers, clinicians, and non-profit organizations in planning and promotion of nutrition programs for pantry clients.

Objective This study aims to explore the associated impairments of cerebral palsy (CP) and their correlates among children with CP in Vietnam.Design Descriptive cross-sectional study using hospital-based surveillance.Setting National Children’s Hospital, Hanoi, Vietnam between June and November 2017.Participants 765 children with CP were recruited.Outcome measures We assessed clinical characteristics of CP, associated impairments (epilepsy, intellectual, visual, hearing, speech impairments) and their correlates. We performed descriptive analyses (median, IQR and proportion). χ2 test and Fisher’s exact test were used for categorical variables. Univariate logistic regression and multivariate logistic regression models were established and associated impairments were included as independent variables.Results The median age of children was 1.7 years (IQR=2.7). Quadriplegia was the predominant subtype (69.5%) and 46.5% were at Gross Motor Function Classification System level IV–V. Of children, 76.3% had ≥one associated impairment, most commonly speech or intellectual impairments (59.1% and 57.8%, respectively). Severity of motor impairment, type of CP, maternal and perinatal factors (eg, gestational age, perinatal asphyxia, timing of injury causing CP) were associated with greater risk of associated impairments.Conclusion Children with CP have a high burden of associated impairments. Findings from our study will inform the development and implementation of appropriate screening and interventions and reduce the long-term adverse effects of these impairments on individuals with CP and their socioeconomic impact.

BackgroundEarly neurodevelopmental risks, compounded with traumatic medical experiences, contribute to emotional and behavioral challenges in as many as 1 in 2 children with congenital heart disease (CHD). Parents report a strong need for supports; yet, there remains a lack of accessible, evidence-based behavioral interventions available for children with CHD and their families. I-InTERACT-North is a web-based stepped-care mental health program designed to support family well-being and reduce behavioral concerns through positive parenting for children with early medical complexity. In previous pilot studies, the program was effective in increasing positive parenting skills and decreasing child behavior problems, with high parent-reported acceptability. This paper presents the protocol for the first randomized study of stepped-care parent support for families of children with CHD. ObjectiveThis study will involve a single-site, 2-arm, single-blind randomized controlled trial to evaluate (1) the feasibility and acceptability of a web-based stepped-care parent support program (I-InTERACT-North) and (2) the effectiveness of the program in enhancing positive parenting skills and reducing behavioral concerns among families of children with CHD. MethodsFamilies will be randomized (1:1) to either receive treatment or continue with care as usual for 12 months. Randomization will be stratified by child’s sex assigned at birth and baseline parent-reported child behavior intensity. Primary outcomes include positive parenting skills and child behavior at baseline, 3 months, 6 months, and 12 months. Secondary outcomes include parental mental health, quality of life, service usage, and feasibility including program reach and adherence. A sample size of 244 families will provide >95% power to detect an effect size of d=0.64. Based on attrition data from pilot studies, a target of 382 families will be enrolled. Parent reports of acceptability, adoption, and suggested adaptability of the program will be examined using cross-case thematic analyses. Primary efficacy analysis will be conducted using an intent-to-treat approach. Generalized estimating equations will be used to examine changes in positive parenting. Child behavior, quality of life, and parent mental health will be tested with repeated-measures analyses. Additional sensitivity and replication analyses will also be carried out. ResultsRecruitment began in February 2024, and recruitment and follow-up will continue until January 2029. We anticipate results in late 2029. ConclusionsThis study aims to test the effectiveness of I-InTERACT-North web-based stepped-care parent support in improving positive parenting skills and reducing child behavior problems in families of children with CHD compared with a care as usual control group. Results will inform future clinical implementation and expansion of this program among families of children with early medical conditions. Trial RegistrationClinicalTrials.gov NCT06075251; https://clinicaltrials.gov/study/NCT06075251 International Registered Report Identifier (IRRID)DERR1-10.2196/64216

Objetivo: Demostrar la estabilidad de la punta nasal en el tiempo con el uso de silicona tallada en pacientes con déficit de estabilidad de la punta nasal, rinoplastia estética previa y manipulación del tabique nasal. Materiales y métodos: Estudio de intervención, analítico, descriptivo, donde se empleó la técnica de reconstrucción de estabilización de punta nasal. Se realizó en una clínica privada en la ciudad de Lima-Perú durante el año 2022. Se tomaron en cuenta 22 casos de pacientes, cuyas edades fluctuaban entre 30 y 55 años, quienes presentaron inestabilidad de punta, rinoplastia previa y tabique nasal manipulado, sin comorbilidades. Los pacientes fueron evaluados en el primer, tercer y sexto mes y al año tras la reconstrucción y estabilización de la punta nasal. Se realizó un muestreo no probabilístico. No se trabajó con una muestra, ya que se consideró el total de pacientes que cumplían con los criterios de inclusión. A todos los participantes se les realizó la técnica quirúrgica con silicona tallada. Resultados: Con la técnica quirúrgica empleada utilizando silicona tallada, se observó menor sangrado y menos hematomas. En la revisión, al año de la cirugía, se evidenció que la técnica mantuvo características similares en el tiempo, tanto en la alineación como en la altura de la punta nasal; se evidenció un caso de extrusión de la lámina de silicona como complicación luego de traumatismo por caída de un paciente. Conclusiones: La silicona tiene una gran aceptación como material utilizado para el perfilamiento facial, con un amplio uso en la rinoplastia. En nuestro estudio se ha demostrado que el soporte de la punta nasal que brinda es perdurable en el tiempo. Esta es una alternativa viable en rinoplastias que no cuenten con cartílago autólogo o en las que se busque una alternativa al uso del cartílago costal. La silicona, al ser un material sintético disponible, fácilmente moldeable y que no se reabsorbe, es una alternativa útil que acorta el tiempo operatorio y mantiene la proyección de punta.

Objectives The objective of this study was to examine the psychometric properties of the Chinese version of the Academic Self-Efficacy Scale (ASES-C) and confirm its measurement invariance across gender identities. Methods In this study, 502 university students (29.68% male, 70.32% female) with a mean age of 19.93 years (SD = 1.64) voluntarily participated. The Academic Self-Efficacy Scale (ASE) was utilized as a unidimensional measure of students’ learning efficacy. The English version of ASES was translated into Chinese using a forward-backward translation procedure. Confirmatory factor analysis (CFA) and invariance testing were conducted with the single-factor model of ASES. Composite reliability (CR) and internal consistency were calculated based on Cronbach’s alpha. Results Upon re-specification of the model, CFA results for the hypothesized single-factor model with eight items indicated an acceptable fit (CFI = 0.959, TLI = 0.943, SRMR = 0.036, RMSEA = 0.065). Cronbach’s alpha and CR values were 0.785 and 0.880, respectively. Multi-group CFA results demonstrated measurement equivalence for the Chinese version of ASES across gender identities. The findings supported the measurement invariance of ASES-C for both male and female participants. Conclusion The ASES-C, consisting of one factor and eight items, is a reliable instrument for assessing Chinese university students’ self-efficacy in learning. Furthermore, it is suitable for making meaningful comparisons across gender identities.

Humans make irrational decisions in the presence of irrelevant distractor options. There is little consensus on whether decision making is facilitated or impaired by the presence of a highly rewarding distractor, or whether the distractor effect operates at the level of options’ component attributes rather than at the level of their overall value. To reconcile different claims, we argue that it is important to consider the diversity of people’s styles of decision making and whether choice attributes are combined in an additive or multiplicative way. Employing a multi-laboratory dataset investigating the same experimental paradigm, we demonstrated that people used a mix of both approaches and the extent to which approach was used varied across individuals. Critically, we identified that this variability was correlated with the distractor effect during decision making. Individuals who tended to use a multiplicative approach to compute value, showed a positive distractor effect. In contrast, a negative distractor effect (divisive normalisation) was prominent in individuals tending towards an additive approach. Findings suggest that the distractor effect is related to how value is constructed, which in turn may be influenced by task and subject specificities. This concurs with recent behavioural and neuroscience findings that multiple distractor effects co-exist.

The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolonged ISR activation perturbs cell function and may contribute to neurodegeneration. DNL343 is an investigational CNS-penetrant small-molecule ISR inhibitor designed to activate the eukaryotic initiation factor 2B (eIF2B) and suppress aberrant ISR activation. DNL343 reduced CNS ISR activity and neurodegeneration in a dose-dependent manner in two established in vivo models – the optic nerve crush injury and an eIF2B loss of function (LOF) mutant – demonstrating neuroprotection in both and preventing motor dysfunction in the LOF mutant mouse. Treatment with DNL343 at a late stage of disease in the LOF model reversed elevation in plasma biomarkers of neuroinflammation and neurodegeneration and prevented premature mortality. Several proteins and metabolites that are dysregulated in the LOF mouse brains were normalized by DNL343 treatment, and this response is detectable in human biofluids. Several of these biomarkers show differential levels in CSF and plasma from patients with vanishing white matter disease (VWMD), a neurodegenerative disease that is driven by eIF2B LOF and chronic ISR activation, supporting their potential translational relevance. This study demonstrates that DNL343 is a brain-penetrant ISR inhibitor capable of attenuating neurodegeneration in mouse models and identifies several biomarker candidates that may be used to assess treatment responses in the clinic.

We report on a 2023 outbreak of severe hand, foot, and mouth disease in southern Vietnam caused by an emerging lineage of enterovirus A71 subgenogroup B5. Affected children were significantly older than those reported during previous outbreaks. The virus should be closely monitored to assess its potential for global dispersal.

Abstract Circulating tumor cells (CTCs) have gathered attention as a biomarker for carcinomas. However, CTCs in sarcomas have received little attention. In this work, we investigated cell surface proteins and antibody combinations for immunofluorescence detection of sarcoma CTCs. A microfluidic device that combines filtration and immunoaffinity using gangliosides 2 and cell surface vimentin (CSV) antibodies was employed to capture CTCs. For CTC detection, antibodies against cytokeratins 7 and 8 (CK), pan-cytokeratin (panCK), or a combination of panCK and CSV were used. Thirty-nine blood samples were collected from 21 patients of various sarcoma subtypes. In the independent samples study, samples were subjected to one of three antibody combination choices. Significant difference in CTC enumeration was found between CK and panCK + CSV, and between panCK and panCK + CSV. Upon stratification of CK + samples, those of metastatic disease had a higher CTC number than those of localized disease. In the paired samples study involving cytokeratin-positive sarcoma subtypes, using panCK antibody detected more CTCs than CK. Similarly, for osteosarcoma, using panCK + CSV combination resulted in a higher CTC count than panCK. This study emphasized deliberate selection of cell surface proteins for sarcoma CTC detection and subtype stratification for studying cancers as heterogeneous as sarcomas.

Abstract Background The duplex kidney is one of the common congenital anomalies of the kidney and urinary tract. We present two cases of renal tumor accompanied with ipsilateral duplex kidney. The image of the tumor, renal artery system and collecting system were rendered by AI software (Fujifilm’s Synapse® AI Platform) to support the diagnosis and surgical planning. Case presentation Two Vietnamese patients (a 45-year-old man and a 54-year-old woman) with incidental cT1 renal cell carcinoma (RCC) were confirmed to have ipsilateral duplex kidneys by 3D reconstruction AI technique. One patient had a Renal score 9ah tumor of left kidney while the other had a Renal score 9 × tumor of right kidney in which a preoperative CT scan failed to identify a diagnosis of duplex kidney. Using the Da Vinci platform, we successfully performed robotic partial nephrectomy without any damage to the collecting system in both cases. Conclusion RCC with duplex kidneys is a rare condition. By utilizing a novel AI reconstruction technique with adequate information, two patients with RCC in duplex kidneys were successfully performed robotic partial nephrectomy without complication.

Abstract The intricate currents of the Northwest Pacific Ocean, with strong manifestations along the westside rim, connect tropical and subtropical gyres and significantly influence East Asian and global climates. The El Niño/Southern Oscillation (ENSO) originates in the tropical Pacific Ocean and disrupts this ocean circulation system. However, the spatiotemporal dependence of the impact of ENSO events has yet to be elucidated because of the complexities of both ENSO events and circulation systems, as well as the increased availability of observational data. We thus combined altimeter and drifter observations to demonstrate the distinct tropical and subtropical influences of the circulation system on ENSO diversity. During El Niño years, the North Equatorial Current, North Equatorial Countercurrent, Mindanao Current, Indonesian Throughflow, and the subtropical Kuroshio Current and its Extension region exhibit strengthening, while the tropical Kuroshio Current weakens. The tropical impact is characterized by sea level changes in the warm pool, whereas the subtropical influence is driven by variations in the wind stress curl. The tropical and subtropical influences are amplified during the Centra Pacific El Niño years compared to the Eastern Pacific El Niño years. As the globe warms, these impacts are anticipated to intensify. Thus, strengthening observation systems and refining climate models are essential for understanding and projecting the enhancing influences of ENSO on the Northwest Pacific Oceanic circulation.

Abstract Background Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). Methods This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. Results Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p

Abstract SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages’ role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

Abstract Genome-wide sequencing and genetic matchmaker services are propelling a new era of genotype-driven ascertainment of novel genetic conditions. The degree to which reported phenotype data in discovery-focused studies address informational priorities for clinicians and families is unclear. We identified reports published from 2017 to 2021 in 10 genetics journals of novel Mendelian disorders. We adjudicated the quality and detail of the phenotype data via 46 questions pertaining to six priority domains: (I) Development, cognition, and mental health; (II) Feeding and growth; (III) Medication use and treatment history; (IV) Pain, sleep, and quality of life; (V) Adulthood; and (VI) Epilepsy. For a subset of articles, all subsequent published follow-up case descriptions were identified and assessed in a similar manner. A modified Delphi approach was used to develop consensus reporting guidelines, with input from content experts across four countries. In total, 200 of 3243 screened publications met inclusion criteria. Relevant phenotypic details across each of the 6 domains were rated superficial or deficient in >87% of papers. For example, less than 10% of publications provided details regarding neuropsychiatric diagnoses and “behavioural issues”, or about the type/nature of feeding problems. Follow-up reports (n = 95) rarely contributed this additional phenotype data. In summary, phenotype information relevant to clinical management, genetic counselling, and the stated priorities of patients and families is lacking for many newly described genetic diseases. The PHELIX (PHEnotype LIsting fiX) reporting guideline checklists were developed to improve phenotype reporting in the genomic era.

Abstract Background Hyperthyroidism is frequently under-recognized and leads to heart failure and mortality. Timely identification of high-risk patients is a prerequisite to effective antithyroid therapy. Since the heart is very sensitive to hyperthyroidism and its electrical signature can be demonstrated by electrocardiography, we developed an artificial intelligence model to detect hyperthyroidism by electrocardiography and examined its potential for outcome prediction. Methods The deep learning model was trained using a large dataset of 47,245 electrocardiograms from 33,246 patients at an academic medical center. Patients were included if electrocardiograms and measurements of serum thyroid-stimulating hormone were available that had been obtained within a three day period. Serum thyroid-stimulating hormone and free thyroxine were used to define overt and subclinical hyperthyroidism. We tested the model internally using 14,420 patients and externally using two additional test sets comprising 11,498 and 596 patients, respectively. Results The performance of the deep learning model achieves areas under the receiver operating characteristic curves (AUCs) of 0.725–0.761 for hyperthyroidism detection, AUCs of 0.867–0.876 for overt hyperthyroidism, and AUC of 0.631–0.701 for subclinical hyperthyroidism, superior to a traditional features-based machine learning model. Patients identified as hyperthyroidism-positive by the deep learning model have a significantly higher risk (1.97–2.94 fold) of all-cause mortality and new-onset heart failure compared to hyperthyroidism-negative patients. This cardiovascular disease stratification is particularly pronounced in subclinical hyperthyroidism, surpassing that observed in overt hyperthyroidism. Conclusions An innovative algorithm effectively identifies overt and subclinical hyperthyroidism and contributes to cardiovascular risk assessment.

Introduction Breastfeeding is associated with many health benefits for both women and their newborns. Exclusive breastfeeding has been recommended for at least 6 months to optimise infant growth, development and health. In addition to standard care, community-based peer support is recommended to help mothers improve breastfeeding. A recent survey reveals that the rate of exclusive breastfeeding at 6 months post partum in Hong Kong is low, and half of all breastfeeding mothers never exclusively breastfeed. Taking into account the local practice for women to stay home during the first month post partum and social isolation during and post-COVID-19 pandemic, a home-based peer support programme with the aid of Zoom or Facetime is proposed. This study aims to evaluate the effectiveness of a home-based breastfeeding peer support programme in improving breastfeeding practices and achieving exclusive breastfeeding rate among women with low breastfeeding self-efficacy.Methods and analysis The study is a two-armed randomised control trial and will include a total of 442 participants. Potential cases will be recruited and screened at four postnatal wards in Hong Kong public hospital. Eligible and consented cases will be randomly allocated into intervention or control groups at a 1:1 ratio. Control group (n=221) will receive standard care, while the intervention group (n=221) will receive home-based peer support as well as standard care. Trained peer counsellors will provide breastfeeding-related support through Zoom or Facetime at 10 days and 1 month post partum. Telephone follow-ups will be conducted at 1 month, 2 months, 3 months and 6 months post partum. Breastfeeding status, mother’s breastfeeding self-efficacy and postpartum depression will be assessed and compared between the two arms.Ethics and dissemination The study has been reviewed and approved by the Institutional Review Board of the University of Hong Kong and Hospital Authority Hong Kong West Cluster (UW 20-564). The findings will be updated in trial registries and disseminated in peer-reviewed journals and academic conferences.Trial registration number NCT04621266.

Introduction: Frailty has an important impact on the health outcomes of older patients, and frailty screening is recommended as part of perioperative evaluation. The Hospital Frailty Risk Score (HFRS) is a validated tool that highlights frailty risk using 109 International Classification of Diseases, 10th revision (ICD-10) codes. In this study, we aim to compare HFRS to the Charlson Comorbidity Index (CCI) and validate HFRS as a predictor of adverse outcomes in Asian patients admitted to surgical services. Method: A retrospective study of electronic health records (EHR) was undertaken in patients aged 65 years and above who were discharged from surgical services between 1 April 2022 to 31 July 2022. Patients were stratified into low (HFRS 15) risk of frailty. Results: Those at high risk of frailty were older and more likely to be men. They were also likely to have more comorbidities and a higher CCI than those at low risk of frailty. High HFRS scores were associated with an increased risk of adverse outcomes, such as mortality, hospital length of stay (LOS) and 30-day readmission. When used in combination with CCI, there was better prediction of mortality at 90 and 270 days, and 30-day readmission. Conclusion: To our knowledge, this is the first validation of HFRS in Singapore in surgical patients and confirms that high-risk HFRS predicts long LOS (≥7days), increased unplanned hospital readmissions (both 30-day and 270-day) and increased mortality (inpatient, 10-day, 30-day, 90-day, 270-day) compared with those at low risk of frailty.

Abstract Hypertension (HTN) affects over 1.2 billion individuals worldwide and is defined as systolic blood pressure (BP) ≥ 140 mmHg and diastolic BP ≥ 90 mmHg. Hypertension is also considered a high risk factor for cerebrovascular diseases, which may lead to vascular cognitive impairment (VCI). VCI is associated with executive dysfunction and is also a transitional stage between hypertension and vascular dementia. Hence, it is essential to establish a reliable approach to diagnosing the severity of VCI. In 28 HTN (51–83 yrs; 18 males, 10 females) and 28 healthy controls (HC) (51–75 yrs; 7 males, 21 females), we investigated which regions demonstrate alterations in the resting-state functional connectome due to vascular cognitive impairment in HTN by using the amplitude of the low-frequency fluctuations (ALFF), regional homogeneity (ReHo), graph theoretical analysis (GTA), and network-based statistic (NBS) methods. In the group comparison between ALFF/ReHo, HTN showed reduced spontaneous activity in the regions corresponding to vascular or metabolic dysfunction and enhanced brain activity, mainly in the primary somatosensory cortex and prefrontal areas. We also observed cognitive dysfunction in HTN, such as executive function, processing speed, and memory. Both the GTA and NBS analyses indicated that the HTN demonstrated complex local segregation, worse global integration, and weak functional connectivity. Our findings show that resting-state functional connectivity was altered, particularly in the frontal and parietal regions, by hypertensive individuals with potential vascular cognitive impairment.

Abstract Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay’s effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher’s syndrome, Leber’s congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.

Abstract Introduction In this case report, we demonstrate our technique of a retroperitoneal laparoscopic heminephrectomy for a T1b right hilar tumor in a horseshoe kidney. Case presentation A 77-year-old Vietnamese woman presented to the hospital because of right flank pain. On presentation, her serum creatinine was 0.86 mg/dL and glomerular filtration rate was 65.2 mL/minute/1.73 m2. According to her renal scintigraphy, glomerular filtration rates of the right and left moieties were 24.2 and 35.5 mL/minute, respectively. Computed tomography imaging demonstrated a 5.5 × 5.0 cm solid hilar mass with a cT1bN0M0 tumor stage was in the right moiety. After discussion, the patient elected a minimally invasive surgery to treat her malignancy. The patient was placed in a flank position. We used Gaur’s balloon technique to create the retroperitoneal working space, and four trocar ports were planned for operation. Three arteries were dissected, including two arteries feeding the right moiety, one artery feeding the isthmus, and one vein, which was clipped and divided by Hem-o-lok. The isthmusectomy was performed with an Endostapler. Consequently, the ureter was clipped and divided. Finally, the whole right segment of the horseshoe kidney was mobilized and taken out via the flank incision. Results The total operative time was 250 min with an estimated blood loss of 200 mL. The patient's serum creatinine after surgery was 1.08 mg/dL, and glomerular filtration rate was 49.47 mL/minute/1.73 m2. The patient was discharged on postoperative day #4 without complication. Final pathologic examination of the tumor specimen revealed a Fuhrman grade II clear cell renal cell carcinoma, capsular invasion, with negative surgical margins. After a three-month follow-up, the serum creatinine was 0.95 mg/dL, and glomerular filtration rate was 57.7 mL/minute/1.73 m2. Local recurrence or metastasis was not detected by follow-up computed tomography imaging. Conclusions Retroperitoneal laparoscopic heminephrectomy is a safe and feasible technique for patients with renal cell carcinoma in a horseshoe kidney and may be particularly useful in low income settings without access to robotic technology.

Many types of RNA viruses, including the hepatitis C virus (HCV), activate autophagy in infected cells to promote viral growth and counteract the host defense response. Autophagy acts as a catabolic pathway in which unnecessary materials are removed via the lysosome, thus maintaining cellular homeostasis. The HCV non-structural 5A (NS5A) protein is a phosphoprotein required for viral RNA replication, virion assembly, and the determination of interferon (IFN) sensitivity. Recently, increasing evidence has shown that HCV NS5A can induce autophagy to promote mitochondrial turnover and the degradation of hepatocyte nuclear factor 1 alpha (HNF-1α) and diacylglycerol acyltransferase 1 (DGAT1). In this review, we summarize recent progress in understanding the detailed mechanism by which HCV NS5A triggers autophagy, and outline the physiological significance of the balance between host–virus interactions.

Abstract Current evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can remain suspended spread in aerosols for longer period of time under poorly ventilated indoor setting. To minimize spreading, application of antiviral filter to capture infectious aerosols and to inactivate SARS-CoV-2 can be a promising solution. This study aimed to develop a method to assess simultaneously the filtration and removal efficiency of aerosolized pseudo-type SARS-CoV-2 using a vertical-type wind tunnel with relatively high face velocity (1.3 m/s). Comparing with the untreated spunlace non-woven filter, the C-POLAR™ treated filter increased the filtration efficiency from 74.2 ± 11.5% to 97.2 ± 1.7%, with the removal efficiency of 99.4 ± 0.051%. The results provided not only solid evidence to support the effectiveness of the cationic polymeric coated filter in fighting against the SARS-CoV-2 pandemic, but also a method to test viral filtration and removal efficiency under relative fast air velocity and with a safer environment to the operators.

Summary: Background: Gut dysbiosis is present in chronic hepatitis B virus (HBV) infection. In this study, we integrated microbiome and metabolome analysis to investigate the role of gut microbiome in virological response to nucleos(t)ide analogues (NAs) treatment. Methods: Chronic HBV patients were prospectively recruited for steatosis and fibrosis assessments via liver elastography, with full-length 16S sequencing performed to identify the compositional gut microbiota differences. Fasting plasma bile acids were quantified by liquid chromatography-tandem mass spectrometry. Findings: All patients (n = 110) were characterized into three distinct microbial clusters by their dominant genus: c-Bacteroides, c-Blautia, and c-Prevotella. Patients with c-Bacteroides had a higher plasma ursodeoxycholic acids (UDCA) level and an increase in 7-alpha-hydroxysteroid dehydrogenase (secondary bile acid biotransformation) than other clusters. In NAs-treated patients (n = 84), c-Bacteroides was associated with higher odds of plasma HBV-DNA undetectability when compared with non-c-Bacteroides clusters (OR 3.49, 95% CI 1.43–8.96, p = 0.01). c-Blautia was positively associated with advanced fibrosis (OR 2.74, 95% CI 1.09–7.31, p = 0.04). No such associations were found in treatment-naïve patients. Increased Escherichia coli relative abundance (0.21% vs. 0.03%, p = 0.035) was found in on-treatment patients (median treatment duration 98.1 months) with advanced fibrosis despite HBV DNA undetectability. An enrichment in l-tryptophan biosynthesis was observed in patients with advanced fibrosis, which exhibited a positive correlation with Escherichia coli. Interpretation: Collectively, unique bacterial signatures, including c-Bacteroides and c-Blautia, were associated with virological undetectability and fibrosis evolution during NAs therapy in chronic HBV, setting up intriguing possibilities in optimizing HBV treatment. Funding: This study was supported by the Guangdong Natural Science Fund (2019A1515012003).

Introduction Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose–response nature of any identified association, to inform future hypertension management.Methods and analysis The study will use data from 2 of Australia’s largest cohort studies; the Australian Longitudinal Study on Women’s Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004–2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used.Ethics and dissemination Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings.Trial registration number NCT05972785.

Abstract Social anxiety and paranoia often co-occur and exacerbate each other. While loneliness and negative schemas contribute to the development of social anxiety and paranoia separately, their role in the development of the two symptoms co-occurring is rarely considered longitudinally. This study examined the moment-to-moment relationship between social anxiety and paranoia, as well as the effects of loneliness and negative schemas on both experiences individually and coincidingly. A total of 134 non-clinical young adults completed experience sampling assessments of momentary social anxiety, paranoia, and loneliness ten times per day for six consecutive days. Participants’ negative-self and -other schemas were assessed with the Brief Core Schema Scale. Dynamic structural equation modelling revealed a bidirectional relationship between social anxiety and paranoia across moments. Loneliness preceded increases in both symptoms in the next moment. Higher negative-self schema was associated with a stronger link from paranoia to social anxiety; whereas higher negative-other schema was associated with a stronger link from social anxiety to paranoia. Our findings support the reciprocal relationship between social anxiety and paranoia. While loneliness contributes to the development of social anxiety and paranoia, negative self and other schemas appear to modify the relationships between the two symptoms.

Abstract This study aims to provide in vitro and in vivo data to support the utilization of antinuclear antibodies (ANAs) as novel tools for the diagnosis and treatment of prostate cancers. The hematological, biochemical, and histological toxicities of ANAs were assessed at the doses of 5 and 50 μg per mouse. Radiolabeling study was then conducted with ANA and 131I using the chloramine T method, and the biodistribution and treatment efficacy were subsequently investigated in a PC3 xenograft model. No changes in clinical behavior or signs of intoxication, necrosis, or malignancy were observed in ANA-treated mice. 131I-ANA was obtained in very high yield and radiochemical purity, at 94.97 ± 0.98% and 98.56 ± 0.29%, respectively. They achieved immunoreactivity fraction of 0.841 ± 0.17% with PC-3 cells. Levels of radiolabeled ANAs were 1.15–10.14 times higher in tumor tissues than in other examined organs at 24 h post-injection. The tumor growth inhibition rates were 28.33 ± 5.01% in PC3 xenografts mice treated with 131I-ANAs compared with controls and a nearly twofold improvement in median survival was observed. These results demonstrate that radioimmunotherapy of radiolabeled natural ANAs may be an effective treatment for prostate tumors.

Abstract This study identifies seasonally-reversed trends in Kuroshio strength and sea surface temperatures (SSTs) within the western North Pacific (WNP) since the 1990s, specifically in the 22° N–28° N region. These trends are characterized by increases during summer and decreases during winter. The seasonally-reversed trends are a result of the asymmetric responses of the WNP to a shift towards the positive phase of the Atlantic multidecadal oscillation (AMO) around the same period. The positive AMO induces an anomalous descent over the North Pacific during summer, leading to the direct strengthening of the gyre. However, during winter, it triggers an anomalous descent over the tropical Pacific, which excites a poleward wavetrain impacting the WNP and causing gyre weakening. The associated responses of the East Asian monsoon and China Coastal Current contribute to the observed seasonally-reversed SST trends. It is noteworthy that the seasonally-reversed trends in gyre strength and SSTs are predominantly observed north of 20° N in the WNP. This limitation arises because the anomalous cyclone within the winter poleward wavetrain is located north of this latitude boundary. Specifically, the clearest trends in gyre strength are observed in the northern segment of the Kuroshio, while the manifestation of SST trends in the Taiwan Strait could potentially be attributed to the influence and enhancement of the East Asian monsoon and the China Coastal Current. Due to the limited length of observational data, statistical significance of some of the signals discussed is rather limited. A CESM1 pacemaker experiments is further conducted to confirm the asymmetric responses of the North Pacific to the AMO between the summer and winter seasons.

Abstract Toll-like receptor (TLR) agonists improve vaccine immunogenicity and efficacy, but they are currently unlicensed as adjuvants in influenza vaccines. This study aimed to investigate whether a combination of monophosphoryl lipid A (MPL, a TLR4 agonist) and polyriboinosinic polyribocytidylic acid (poly I:C, a TLR3 agonist) can enhance the protective efficacy of an inactivated A/Puerto Rico/8/1934 (A/PR8) H1N1 influenza vaccine against homologous influenza infection and minimize illness outcomes. Results showed that combination MPL and poly I:C adjuvanted influenza vaccination increased the production of antigen-specific antibodies, decreased the levels of cytokines and cellular infiltrates at the infection sites, and induced significant memory T and B cell responses in mice. The results of this study suggest that the combination of MPL and poly I:C can be developed into a possible adjuvant for enhancing the efficacy of influenza vaccines.

Abstract Background Variability and inaccuracies in the diagnosis of prostate cancer, and the risk of complications from invasive tests, have been extensively reported in the research literature. To address this, the use of artificial intelligence (AI) has been attracting increased interest in recent years to improve the diagnostic accuracy and objectivity. Although AI literature has reported promising results, further research is needed on the identification of evidence gaps that limit the potential adoption in prostate cancer screening practice. Methods A systematic electronic search strategy will be used to identify peer-reviewed articles published from inception to the date of searches and indexed in CINAHL, IEEE Xplore, MEDLINE, Scopus, and Web of Science Core Collection databases. Registries including Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP) will be searched for unpublished studies, and experts were invited to provide suitable references. The research and reporting will be based on Cochrane recommendations and PRISMA guidelines, respectively. The screening and quality assessment of the articles will be conducted by two of the authors independently, and conflicts will be resolved by a third author. Discussion This systematic review will summarise the use of AI techniques to predict the need for prostate biopsy based on clinical and demographic indicators, including its diagnostic accuracy and readiness for adoption in clinical practice. Systematic review registration PROSPERO CRD42022336540

Abstract It is challenging to regenerate periodontal tissues fully. We have previously reported a heparan sulfate variant with enhanced affinity for bone morphogenetic protein-2, termed HS3, that enhanced periodontal tissue regeneration in a rodent model. Here we seek to transition this work closer to the clinic and investigate the efficacy of the combination HS3 collagen device in a non-human primate (NHP) periodontitis model. Wire-induced periodontitis was generated in ten Macaca fascicularis, and defects were treated with Emdogain or collagen (CollaPlug) loaded with (1) distilled water, (2) HS low (36 µg of HS3), or (3) HS high (180 µg of HS3) for 3 months. At the endpoint, microscopic assessment showed significantly less epithelial down-growth, greater alveolar bone filling, and enhanced cementum and periodontal ligament regeneration following treatment with the HS-collagen combination devices. When evaluated using a periodontal regeneration assessment score (PRAS) on a scale of 0–16, collagen scored 6.78 (± 2.64), Emdogain scored 10.50 (± 1.73) and HS low scored 10.40 (± 1.82). Notably, treatment with HS high scored 12.27 (± 2.20), while healthy control scored 14.80 (± 1.15). This study highlights the efficacy of an HS-collagen device for periodontal regeneration in a clinically relevant NHP periodontitis model and warrants its application in clinical trials.

Abstract Signatures of immune dysregulation as clinical biomarker for psychosis have remained unclear. We aimed to compare the Neutrophil-to-lymphocyte ratio (NLR) of patients with acute non-affective first-episode psychosis (FEP) with healthy controls after accounting for emotional states. We also explored the associations of NLR with symptom severity, onset profile and cognitive functions. The NLR was enumerated from complete blood count taken within a week of assessment. All FEP patients were rated on the Positive and Negative Syndrome Scale (PANSS) and the Clinician Global Impression-Severity (CGI-S) with verbal memory and executive functions assessed with the Cambridge Neuropsychological Test Automated Battery. Prevailing emotional state was measured with Beck Depression Inventory-II and Beck Anxiety Inventory. Out of seventy-nine consecutive FEP patients presenting to the study site, twenty-seven subjects were eligible and recruited. Twenty-seven age-/sex-matched controls were recruited. FEP patients had an NLR of 1.886 over the controls after accounting for scores on emotional states. The NLR of FEP patients was positively associated with CGI-S scores, PANSS positive symptom, disorganization and excitation scores. There was no significant correlation between NLR with the duration of untreated psychosis and cognitive performances. These findings support using NLR as a clinical biomarker in FEP, purporting further prospective study to measure NLR changes in the course of treatment.

Abstract Background Rosai–Dorfman disease is a rare benign histiocytic disorder characterized in most cases by painless cervical adenopathy. Less than 10% of extranodal cases involve bony lesions. Primary bone Rosai–Dorfman disease in the absence of nodal disease is extremely rare. Case presentation A 48 year-old Caucasian male presented with progressive right-sided otalgia, tinnitus, vertigo, and hearing loss. A right temporal bone lytic lesion was detected on diagnostic imaging. Resection of the lesion and histopathological examination revealed Rosai–Dorfman disease. Conclusions Rosai–Dorfman disease primary bone lesions are an atypical presentation of a rare disease. This is the second reported case of Rosai–Dorfman disease arising within the temporal bone. This case study reveals that Rosai–Dorfman disease should be considered for patients presenting with inflammatory/lytic lesions of the temporal bone, in cases where infection and malignancy have been excluded.