Earlier Approaches Research Articles

Relationships between brain structure-function coupling in normal aging and cognition: A cross-ethnicity population-based study

Increased efforts in neuroscience seek to understand how macro-anatomical and physiological connectomes cooperatively work to generate cognitive behaviors. However, the structure-function coupling characteristics in normal aging individuals remain unclear. Here, we developed an index, the Coupling in Brain Structural connectome and Functional connectome (C-BSF) index, to quantify regional structure-function coupling in a large community-based cohort. C-BSF used diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) data from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events study (PRECISE) cohort (2007 individuals, age: 61.15 ± 6.49 years) and the Sydney Memory and Ageing Study (MAS) cohort (254 individuals, age: 83.45 ± 4.33 years). We observed that structure-function coupling was the strongest in the visual network and the weakest in the ventral attention network. We also observed that the weaker structure-function coupling was associated with increased age and worse cognitive level of the participant. Meanwhile, the structure-function coupling in the visual network was associated with the visuospatial performance and partially mediated the connections between age and the visuospatial function. This work contributes to our understanding of the underlying brain mechanisms by which aging affects cognition and also help establish early diagnosis and treatment approaches for neurological diseases in the elderly.

Sensitive phenotyping of serum extracellular vesicles on a SERS-microfluidic platform for early-stage clinical diagnosis of ovarian carcinoma

Ovarian carcinoma (OvCa) poses a severe threat to women's health due to its high mortality rate and lack of efficient early diagnosis approach. There is evidence to suggest that nanosized small extracellular vesicles (sEVs) which carrying cell-specific components from OvCa can serve as potential diagnostic biomarkers. Herein, we reported a Surface-enhanced Raman Scattering (SERS)-multichannel microchip for sEVs (S-MMEV) assay to investigate the phenotype changes of sEVs. The microchip composed of seven microchannels, which enabled the parallel detection of multiple biomarkers to improve the detection accuracy. Using SERS probes conjugated with antibodies recognizing different biomarkers including ubiquitous EV biomarkers (i.e., tetraspanins; CD9, CD81) and putative OvCa tumor biomarkers (i.e. EpCAM, CD24, CA125, EGFR), we successfully analyzed the phenotypic changes of sEVs and accurately differentiated OvCa patients from healthy controls, even at early stage (I-II), with high sensitivity, high specificity and an area under the curve value of 0.9467. Additionally, the proposed approach exhibited higher sensitivity than conventional methods, demonstrating the efficiency of precise detection from cell culture and clinical samples. Collectively, the developed EV phenotyping approach S-MMEV could serve as a potential tool to achieve the early clinical diagnosis of OvCa for further precise diagnosis and personal treatment monitoring.

Bruxismo del sueño en el paciente infantil: revisión narrativa de la literatura.

Introduction: Sleep bruxism is a parafunctional activity in which clenching and/or grinding of teeth occurs in both the paediatric and adult population. Objective: To gather the most current knowledge available on the causes, diagnosis and treatment of sleep bruxism in children in order to facilitate the dentist and/or paediatric dentist's identification and appropriate management in daily clinical practice. Material and methods: An electronic bibliographic search of articles published in English between 1986 and 2023 on sleep bruxism in children under 14 years of age was carried out. Thirty-six articles were selected. Results: The prevalence of sleep bruxism in children ranges from 5 to 46%. Of multifactorial aetiology, its clinical manifestations are both intraoral and extraoral. Diagnosis in most cases is not easy and must be made by assessing not only its consequences but also the aetiological elements involved. Comprehensive treatment always requires an early and multidisciplinary approach combining psychological and dental techniques. The available evidence does not support the use of rigid splints in children. Conclusion: Current knowledge on sleep bruxism in children aims to focus on early diagnosis and aetiological treatment, but further studies are still needed to achieve a standardised and protocolised early diagnosis that will help clinicians' decision-making and improve the patient's quality of life in the short, medium and long term.

After Restructuring: Understanding Religion, Nonreligion, and Spirituality in the Twenty-First Century

Abstract The Restructuring of American Religion (1988) provided a still-influential framework for the study of American religion that centered the emergence, after World War II, of a left–right religio-political divide driving mobilization around conflicts understood as moral. But in the last 30 years, the landscape of American religion has been transformed by decline in commitment to mainstream religious institutions, especially white Christian ones, and by the emergence of large groups of Americans who are religiously indifferent or who embrace spirituality or nonreligion. A new framework is needed to account for this transformed landscape. This framework must avoid problems characteristic of earlier approaches by conceiving of morals and interests as mutually constitutive, centering whiteness, racialization, and the defense of heteropatriarchy in explaining religio-political conflict, integrating the study of nonreligion and spirituality and religion, and analyzing not only decline in religious commitment but the changing meaning of religious identity in a transformed landscape.

Outcome of early detection approach in control of breast, cervical, and oral cancer: Experience from a rural cancer center in India.

In low- and middle-income countries most of the cancer patients attend the hospital at a late stage and treatment completion of these cases is challenging. The early detection program (EDP), in rural areas of Punjab state, India was initiated to identify breast, cervical, and oral cancer at an early stage by raising awareness and providing easy access to diagnosis and treatment. A total of 361 health education programs and 99 early detection clinics were organized. The symptomatic and self-interested (non-symptomatic individuals who opted for screening) cases visited the detection clinic. They were screened for breast, cervical, and/or oral cancer. Further diagnosis and treatment of screen-positive cases were carried out at Homi Bhabha Cancer Hospital (HBCH), Sangrur. Community leaders and healthcare workers were involved in all the activities. The EDP, Sangrur removed barriers between cancer diagnosis and treatment with the help of project staff. From 2019 to 2023, a total of 221,317 populations were covered. Symptomatic and self-interested individuals attended the breast (1627), cervical (1601), and oral (1111) examinations. 46 breast (in situ-4.3%; localized-52.2%), 9 cervical (localized-77.8%), and 12 oral (localized-66.7%) cancer cases were detected, and treatment completion was 82.6%, 77.8%, and 50.0%, respectively. We compared cancer staging and treatment completion of cases detected through EDP with the cases attended HBCH from Sangrur district in 2018; the difference between two groups is statistically significant. Due to the early detection approach, there is disease down-staging and improvement in treatment completion. This approach is feasible and can be implemented to control these cancers in low- and middle-income countries.

Low dose lenalidomide versus placebo in non-transfusion dependent patients with low risk, del(5q) myelodysplastic syndromes (SintraREV): a randomised, double-blind, phase 3 trial

Lenalidomide is the standard of care for patients who are transfusion dependent with chromosome 5q deletion (del[5q]) myelodysplastic syndromes. In the SintraREV trial, we aimed to investigate whether an early intervention of low lenalidomide doses for 2 years could delay transfusion dependency in patients with anaemia who were not transfusion dependent. This randomised, double-blind, phase 3 trial, was conducted at 22 sites (University Hospitals) in Spain, France, and Germany. Eligible patients were aged 18 years or older diagnosed with low-risk or intermediate-1-risk del(5q) myelodysplastic syndromes with non-transfusion-dependent anaemia (according to the IPSS), were erythropoietin-stimulating agents naive, and had an ECOG performance status of 2 or less. Patients were randomly assigned (2:1) by means of a telephone system to receive lenalidomide 5 mg daily in 28-day cycles versus placebo for 2 years. The primary endpoint was time to transfusion dependency based on blinded independent central review. Analysis were by intent-to-treat (ITT) and evaluable population. Safety analyses included all participants who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov (NCT01243476) and EudraCT (2009-013619-36) and is complete. Between Feb 15, 2010, and Feb 21, 2018, 61 patients were randomly assigned to receive lenalidomide (n=40; two did not receive treatment) or placebo (n=21). The median age was 72·2 (IQR 65·4-81·9) years, 50 (82%) patients were female, and 11 (18%) were male. The median follow-up time was 60·6 (IQR 32·1-73·9) months. Regarding primary endpoint, median time to transfusion dependency was not reached (95% CI not applicable) in the lenalidomide group versus 11·6 months (95% CI 0·00-30·11) in the placebo group (p=0·0027). Lenalidomide significantly reduced the risk of transfusion dependency by 69·8% (hazard ratio 0·302, 95% CI 0·132-0·692; p=0·0046). The most frequent treatment-related adverse event was neutropenia, occurring in 24 (63%) of 38 patients in the lenalidomide group (grade 3 and 4 in 17 [45%] patients and one [3%], respectively) and in four (19%) of 21 patients in the placebo group (grade 3 in one [5%] patient). Thrombocytopenia was detected in seven (18%) of 38 patients receiving lenalidomide (grade 3 in two [5%] patients). Regarding the non-haematological toxicity, skin disorders (rash nine [23%] of 38 patients) were the most frequently described toxicities among patients receiving lenalidomide, being grade 3 in one (3%) of 38 patients. 19 serious adverse events were reported in 13 patients, 18 in the lenalidomide group and one in the placebo group, five of which were potentially related to the study drug. No treatment-related deaths were identified. An early approach with low doses of lenalidomide across two years delays the time to transfusion dependency and improves the rate and quality of the responses, with a manageable safety profile in patients who are non-transfusion dependent with del(5q) low-risk myelodysplastic syndromes. Bristol Myers Squibb.

365. METHYLATION BIOMARKERS TO STRATIFY BARRETT’S ESOPHAGUS PATIENTS PROGRESSING AND NON-PROGRESSING TO ESOPHAGEAL ADENOCARCINOMA

Abstract Background Over the last forty years, North America and Europe have witnessed a notable surge in cases of esophageal adenocarcinoma (EAC). This malignancy typically arises from Barrett esophagus (BE), a condition characterized by the replacement of normal squamous epithelium with specialized metaplastic cells. Our study aims to identify specific methylation markers capable of distinguishing between BE patients that will and will not progress to EAC. Methods We conducted differential expression analysis on RNASeq public dataset GSE210647 to distinguish BE progressors from non-progressors. Reads were aligned to hg38 genome using STAR aligner, normalized and analyzed with DESeq2. Significant genes were selected by |log2 fold change| ≥ 0.2 and padj < 0.01. GO, pathway enrichment, and transcription factor (TF) network analyses were performed to uncover biological disparities. Integration with previous methylation data (N.R. Dehkordi et al., 292. Specific methylation markers associated with changes in gene expression distinguish EAC and sub-types of BE patients, ISDE 2023) allowed the identification of overlapping biomarkers, aiding in better discrimination between the two groups. Results Differential expression analysis of GSE210647 identified 2261 significative DEGs between BE progressors and non-progressors. Pathway enrichment analysis in BE progressors revealed significant associations with cellular morphogenesis and reprogramming, alongside the induction of the bile acid pathway, known for its implications in invasiveness and cancer stem cell expansion. TF network analysis identified key regulators such as TBX20, FOXS1, and ZNF454, shedding light on their roles in esophageal carcinogenesis. Among the 505 CpG markers acquired in prior analyses, 127 genomic regions were linked with overexpressed genes either in progressors or in non-progressors BE patients. Leveraging this marker panel, BE samples were stratified into discrete subtypes, aligning either with normal esophageal tissue or EAC, and suggesting a potential stratification by disease progression. Conclusions The integration of expression and methylation analyses allows the identification of key genomic and epigenomic loci able to distinguish BE patients progressing or not-progressing towards EAC. The identified biomarkers are pivotal for personalized risk assessment and for the design of targeted interventions, holding promises for enhanced surveillance protocols, refined early EAC detection approaches, and improved therapeutic strategies aimed at mitigating the risk of EAC development in BE population.

The Burden of Chronic Diseases with the Status of Family Medical History Among Older Adults in India.

This study aims to assess and compare the prevalence of chronic diseases by the first-degree Family Medical History (FMH) and also explores the relationship between FMH and selected Non-communicable diseases (NCDs) among older adults in India. The present study collated secondary data from the Longitudinal Ageing Study in India (LASI, 2017-18). The eligible respondents for the analysis of this study were aged 45years and above, where the final study sample consistedof 65,562 older adults across all Indian states and union territories. The LASI dataset collected responses onself-reported diseases: Hypertension, Stroke, Heart disease, Cancer, and Diabetes. These diseases have a high prevalence among the population and are considered in the present study. Along with disease status, respondents' first-degree relatives FMH were used to fulfil the objective. Descriptive statistical analysis and multiple logistic regression techniques were used to accomplish the objectives analysis. This approach was chosen due to the binary nature of our primary dependent variables. The study found that the prevalence of selected NCDs was considerably higher among older adults with FMH than those without FMH. It revealed that NCDs and the status of FMH of parents and siblings were significantly associated. Based on the multivariate-adjusted model, we foundsignificantly higher odds for developing the NCDs when the respondents have FMH among at least one of the first-degree relative. The likelihood among those with FMHof having hypertension (AOR: 2.058), diabetes (AOR: 2.94), heart diseases (AOR: 2.39), stroke (AOR: 1.62) and cancer (AOR: 2.32) was higher compared to no FMH of respective diseases. Similarly, significant associations were observed according to the different stratification of the number offirst-degree relatives FMH. The present study demonstrated that first-degree relatives FMH is indeed a dominant associated risk factor for chronic disease among the older adults of India. This study supports the promotion of a disease history tool for chronic disease prevention and early detection approaches as a valuable measure of NCD risk. Public health practitioners can take several steps to access FMH and incorporate FMH into public health programs for the screening of the risk population.

Effect of Delayed Parathyroidectomy on Risk of Future Cardiovascular and Nephrolithiasis Interventions in Adults with Primary Hyperparathyroidism [Original Study

To determine whether the timing of parathyroid surgery impacts the risk of renal stone retreatment and cardiovascular interventions. Long-term, untreated primary hyperparathyroidism is associated with significant morbidity including nephrolithiasis and cardiovascular disease. We conducted a Population-based Cohort study of New York and California state-wide data from 2000-2020. Adult patients who underwent renal stone treatment and subsequently diagnosed with primary hyperparathyroidism (pHPT) and underwent parathyroidectomy (PTX) were included. Patients were excluded if PTX was prior to index stone procedure, they underwent second stone treatment within 6 months, with stage V CKD, with secondary or tertiary hyperparathyroidism, with prior kidney transplant or hemodialysis, or with prior cancer diagnosis. Rate of renal stone retreatment and cardiovascular interventions after PTX in pHPT patients with nephrolithiasis who underwent parathyroid surgery at ≤ 2 years and >2 years after index stone procedure was measured. We identified 2,093 patients who underwent first-time stone treatment and subsequent PTX. The median time to PTX was 560 days (IQR 187-1477) and follow-up was 7.4 years (IQR 4.5-13.1). Delaying PTX for more than 2 years increased the risk of renal stone retreatment by 59% (HR 1.59; P<0.001), increased the risk of experiencing coronary disease or associated interventions by 118% (HR=2.18; P=0.01), and increased the risk of experiencing an overall cardiovascular event by 52% (HR 1.52; P<0.01). In symptomatic pHPT, delaying PTX significantly increases the risk of requiring future stone retreatment and cardiac/vascular surgical interventions. This highlights the importance of early surgical referral and multidisciplinary approaches to optimize outcomes and resource utilization in pHPT.

Early Oral Feeding is Safe and Comfortable in Patients with Gastric Cancer Undergoing Radical Total Gastrectomy

Data supporting the safety and clinical efficacy of early oral feeding (EOF) after total gastrectomy are limited. The aim of this prospective randomized controlled study was to explore the safety and clinical efficacy of two early enteral nutrition approaches for gastric cancer patients after radical total gastrectomy. The EOF group had faster postoperative recovery of intestinal function than the enteral tube feeding (ETF) group. The times to first flatus and first defecation were shorter in the EOF group (p < 0.05). In addition, the EOF protocol effectively avoided abdominal distension (p < 0.05). The hospitalization cost of the EOF group was lower than that of the ETF group (p < 0.05). Moreover, oral nutrition satisfied the physiological need for oral intake. People were more satisfied with EOF (p < 0.01). Furthermore, it is worth noting that compared with ETF, EOF did not increase the risk of anastomotic complications such as leakage and bleeding. Most obviously, EOF not only avoided the risk of complications during tube insertion, but also avoided the discomfort experience of nasal feeding tube. In summary, compared with ETF, EOF promotes early bowel recovery effectively without increasing the risk of postoperative complications. It is safe and comfortable for gastric cancer patients undergoing radical total gastrectomy.

“Unless you’ve got a conviction, there’s not much you can do”: Rethinking long-term disruption and exit strategy in RASSO investigations

Purpose This paper aims to evaluate how five Operation Soteria Bluestone (OSB) participating forces integrated principles of procedural justice and proactive disruption of offending into their investigations, specifically during the closing stages of a case when considering exit strategy and longer-term prevention. Design/methodology/approach A mixed-methods approach was taken, including 32 semi-structured interviews with officers and 59 case reviews of recent rape and serious sexual offences (RASSO). Data analysis methods included qualitative thematic analysis of interviews, while data from reviewed case logs was extracted and analysed using a bespoke case review tool. Findings Increased workloads, preparation of evidence and relational/communication difficulties with the crown prosecution service (CPS) were identified as barriers to implementing long-term disruption options. Dedicated resourcing, training and support are needed to promote suspect-focused investigative strategy and wider uptake of long-term disruption methods. Early investigative approach was also found to have “snowball” effects on suspect exit strategy, with initial lack of suspect focus and preoccupation with victim credibility, impeding consideration of long-term disruption and safeguarding options. Findings also point to a disparity between promising practice in relation to procedural justice for victims and (a relative lack of) proactive policing of repeat suspects. Originality/value The study represents a novel contribution to research on policing RASSO, illustrating the scale and nature of the obstacles to changing how these offences are investigated, even when under intense scrutiny from policy makers. It also highlights how increased organisational investment and support is linked to positive changes in practice in some forces.

Proposed Supercluster-Based UMBBFS Routing Protocol for Emergency Message Dissemination in Edge-RSU for 5G VANET

Vehicular ad hoc networks (VANETs) can bolster road safety through the proactive dissemination of emergency messages (EMs) among vehicles, effectively reducing the occurrence of traffic-related accidents. It is difficult to transmit EMs quickly and reliably due to the high-speed mobility of VANET and the attenuation of the wireless signal. However, poor network design and high vehicle mobility are the two most difficult problems that affect VANET’s network performance. The real-time traffic situation and network dependability will also be significantly impacted by route selection and message delivery. Many of the current works have undergone studies focused on forwarder selection and message transmission to address these problems. However, these earlier approaches, while effective in forwarder selection and routing, have overlooked the critical aspects of communication overhead and excessive energy consumption, resulting in transmission delays. To address the prevailing challenges, the proposed solutions use edge computing to process and analyze data locally from surrounding cars and infrastructure. EDGE-RSUs are positioned by the side of the road. In intelligent transportation systems, this lowers latency and enhances real-time decision-making by employing proficient forwarder selection techniques and optimizing the dissemination of EMs. In the context of 5G-enabled VANET, this paper introduces a novel routing protocol, namely, the supercluster-based urban multi-hop broadcast and best forwarder selection protocol (UMB-BFS). The improved twin delay deep deterministic policy gradient (IT3DPG) method is used to select the target region for emergency message distribution after route selection. Clustering is conducted using modified density peak clustering (MDPC). Improved firefly optimization (IFO) is used for optimal path selection. In this way, all emergency messages are quickly disseminated to multiple directions and also manage the traffic in VANET. Finally, we plotted graphs for the following metrics: throughput (3.9 kbps), end-to-end delay (70), coverage (90%), packet delivery ratio (98%), packet received (12.75 k), and transmission delay (57 ms). Our approach’s performance is examined using numerical analysis, demonstrating that it performs better than the current methodologies across all measures.

Depressive symptom clusters and biomarkers of monocyte activation, inflammation, and coagulation in people with HIV and depression.

We assess associations of somatic and cognitive/affective depressive symptom clusters with monocyte activation (soluble (s)CD14, sCD163), systemic inflammation (interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)), and coagulation (D-dimer, fibrinogen) in people with HIV (PWH) on suppressive antiretroviral therapy with depression. Utilizing baseline data from a randomized controlled trial, we found no significant associations in linear regression models examining individual depressive symptom clusters; however, models examining both clusters simultaneously showed that the somatic cluster was positively associated with inflammation biomarkers, while the cognitive/affective cluster was negatively associated with inflammation and coagulation biomarkers (suggesting a cooperative suppression effect). Our findings indicate a differential association with depressive symptom clusters and biological mechanisms underlying cardiovascular disease (CVD) in HIV, which may be driven by unique components of each depressive symptom cluster. This line of research could identify subgroups of PWH with depression at elevated CVD risk needing early CVD prevention approaches. Supported by R01 HL126557.

Endoscopic techniques for early diagnosis of cloacal pathologies and sex determination in blue spotted tree monitor (Varanus macraei) and Cuming’s water monitor (Varanus cumingi)

This article attempts to present, for the first time, the usefulness and feasibility of using endoscopic techniques in the cloacal region of Varanus cumingi and Varanus macraei. This method can serve both diagnostic and therapeutic purposes, as well as offering an early approach to sex determination through the observation of the urodeum which in males ends in a blind end while in females it consists of two ostia which represent the outlets of the oviducts. In this context, commonly employed sex determination techniques, such as post-cloacal spur detection, have shown unreliability. The study involved the examination of ten specimens, approximately one year old, from a private breeding farm, following a complete clinical evaluation to confirm their general state of health. All subjects underwent sedation, which allowed the evaluation of anatomical structures, the health status of the cloaca and the determination of sex. This study and its findings may provide a critical basis for addressing population declines of these species, particularly for V. macraei, which has already been classified as ‘endangered’ by the IUCN.

Nutritional Management and Physical Activity in the Treatment of Sarcopenic Obesity: A Review of the Literature.

The prevalence of sarcopenic obesity among adults aged ≥65 years is increasing worldwide. It is a condition that describes the concomitant presence of sarcopenia and obesity, but it appears to be associated with greater increases in the risks for disability, morbidity, and mortality than the two conditions combined. The current review aims to summarize the available literature data on the effectiveness of lifestyle modification for the management of this high-risk geriatric syndrome. We conducted a comprehensive search across multiple databases, including PubMed, Scopus, Web of Science, and Cochrane Library, for publications published from January 1950 to June 2024. The detection of early preventive and therapeutic approaches to combat sarcopenic obesity is essential for healthy aging. There is ample evidence that suggests that poor dietary habits and physical inactivity are the main reasons for the development of sarcopenic obesity and should thus be the main targets for intervention. In the absence of effective pharmacological interventions, the best effect on sarcopenic obesity is achieved by combination with proper dietary intervention and regular physical activity according to the individual's health condition. Further research is needed to discover the most effective strategy for the prevention and treatment of sarcopenic obesity, as well as potential pharmacological options to improve muscle mass and function in older populations with physical restrictions.

Machine learning-assisted label-free colorectal cancer diagnosis using plasmonic needle-endoscopy system

Early and accurate detection of colorectal cancer (CRC) is critical for improving patient outcomes. Existing diagnostic techniques are often invasive and carry risks of complications. Herein, we introduce a plasmonic gold nanopolyhedron (AuNH)-coated needle-based surface-enhanced Raman scattering (SERS) sensor, integrated with endoscopy, for direct mucus sampling and label-free detection of CRC. The thin and flexible stainless-steel needle is coated with polymerized dopamine, which serves as an adhesive layer and simultaneously initiates the nucleation of gold nanoparticle (AuNP) seeds on the needle surface. The AuNP seeds are further grown through a surface-directed reduction using Au ions-hydroxylamine hydrochloride solution, resulting in the formation of dense AuNHs. The formation mechanism of AuNHs and the layered structure of the plasmonic needle-based SERS (PNS) sensor are thoroughly analyzed. Furthermore, a strong field enhancement of the PNS sensor is observed, amplified around the edges of the polyhedral shapes and at nanogap sites between AuNHs. The feasibility of the PNS sensor combined with endoscopy system is further investigated using mouse models for direct colonic mucus sampling and verifying noninvasive label-free classification of CRC from normal controls. A logistic regression-based machine learning method is employed and successfully differentiates CRC and normal mice, achieving 100% sensitivity, 93.33% specificity, and 96.67% accuracy. Moreover, Raman profiling of metabolites and their correlations with Raman signals of mucus samples are analyzed using the Pearson correlation coefficient, offering insights for identifying potential cancer biomarkers. The developed PNS-assisted endoscopy technology is expected to advance the early screening and diagnosis approach of CRC in the future.

Machine learning-driven diagnosis of multiple sclerosis from whole blood transcriptomics

Multiple sclerosis (MS) is a neurological disorder characterized by immune dysregulation. It begins with a first clinical manifestation, a clinically isolated syndrome (CIS), which evolves to definite MS in case of further clinical and/or neuroradiological episodes. Here we evaluated the diagnostic value of transcriptional alterations in MS and CIS blood by machine learning (ML).Deep sequencing of more than 200 blood RNA samples comprising CIS, MS and healthy subjects, generated transcriptomes that were analyzed by the binary classification workflow to distinguish MS from healthy subjects and the Time-To-Event pipeline to predict CIS conversion to MS along time. To identify optimal classifiers, we performed algorithm benchmarking by nested cross-validation with the train set in both pipelines and then tested models generated with the train set on an independent dataset for final validation.The binary classification model identified a blood transcriptional signature classifying definite MS from healthy subjects with 97% accuracy, indicating that MS is associated with a clear predictive transcriptional signature in blood cells. When analyzing CIS data with ML survival models, prediction power of CIS conversion to MS was about 72% when using paraclinical data and 74.3% when using blood transcriptomes, indicating that blood-based classifiers obtained at the first clinical event can efficiently predict risk of developing MS.Coupling blood transcriptomics with ML approaches enables retrieval of predictive signatures of CIS conversion and MS state, thus introducing early non-invasive approaches to MS diagnosis.

Impact of the First Twenty-Four-Hour Area Under the Concentration-Time Curve/Minimum Inhibitory Concentration of Vancomycin on Treatment Outcomes in Patients With Methicillin-Resistant Staphylococcus aureus Bacteremia.

Vancomycin regimens are designed to achieve an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) ratio ranging between 400 and 600 µg·h/mL in the steady state. However, in cases of critical infections such as bacteremia requiring an early treatment approach, the clinical course may be affected by the AUC/MIC before reaching the steady state, that is, the AUC/MIC values 24 h after the first dose (first 24-h AUC/MIC). This study evaluated the relationship between the first 24-h AUC/MIC and the clinical course of methicillin-resistant Staphylococcus aureus (MRSA) infection. We retrospectively reviewed the records of patients with MRSA bacteremia in a university hospital between 2015 and 2022. The first 24-h AUC/MIC cutoff was set at 300 µg·h/mL based on the results of early response, and eligible patients were divided into groups with a first 24-h AUC/MIC either < 300 µg·h/mL (< 300 group, n = 32) or ≥ 300 µg·h/mL (≥ 300 group, n = 38). The primary endpoint was the rate of treatment efficacy, and the secondary endpoints were time to clinical and bacteriological improvement and 30-day survival rate. Treatment efficacy and 30-day survival rates were not significantly different between the two groups (78.1% vs. 79.0%, P = 0.933 and 83.9% vs. 87.2%, P = 0.674, respectively). Among patients who showed treatment efficacy, the median time to clinical and bacteriological improvement was 11.5 days and 8.0 days in the < 300 and ≥ 300 groups, respectively; compared to the ≥ 300 group, the < 300 group had a significantly longer time to improvement (P = 0.001). The first 24-h AUC/MIC had no effect on the treatment efficacy and 30-day survival rates. However, the time to clinical and bacteriological improvement was significantly prolonged in the < 300 group, indicating that the first 24-h AUC/MIC does not affect the rate of therapeutic efficacy but may affect the treatment period.

Prognosis of Dementia Using Early Fusion Approach with Digital Clock Drawing and Trail-Making Tests

Prognosis of Dementia Using Early Fusion Approach with Digital Clock Drawing and Trail-Making Tests

Inequitable access to mental healthcare for socially excluded adolescents.

Adolescence is a critical period for mental health and social exclusion, a key social determinant of mental health. Early intervention approaches are key to mitigating the impact of mental ill-health during adolescence, however social exclusion can create additional barriers to accessing care. We aimed to better understand help-seeking experiences of adolescents facing co-occurring social exclusion and mental ill-health, including sources of support, barriers and preferences for service provision. Cross-sectional data were analysed, from the 2022 Mission Australia Youth Survey (N = 18,800). Adolescents aged 15 to 19 years were recruited from around Australia, through schools, community organisations and digital platforms. Indices of four domains of social exclusion (housing, finances, relational and education/employment) were created using existing Youth Survey variables, and supplemented with demographic characteristics, psychological distress and help-seeking behaviours (perceived need, mental health supports, barriers to access and preferences). Relationships between social exclusion domains, mental health concerns and help-seeking behaviours were explored using logistic regression models. A total of 9,743 young people reported having needed mental health support, yet only 58.1% reportedly sought support (n = 5,565). Social exclusion domains were associated with different help-seeking behaviours: housing challenges with higher help-seeking (OR = 1.28; 95% CI [1.15, 1.42]); relational difficulties and edu-employment issues with lower (OR = 0.75; 95% CI [0.68, 0.83] and OR = 0.82; 95% CI [0.75, 0.89]). Stigma, confidentiality concerns, cost and not knowing where to seek help were common barriers to help-seeking; those experiencing social exclusion more likely to report these. Participants reported a strong preference for face-to-face support. This study highlights the additional needs and challenges faced by adolescents dealing with both social exclusion and mental ill-health. With greater barriers to help-seeking, concerted efforts are needed to reduce stigma, improve mental health literacy and increase access to trusted information sources. Further initiatives should focus on structural factors that socially exclude young people and exacerbate inequitable access to mental healthcare.