and Beyond: Impact on Therapeutic Choices Across Cancer.

Background: Identifying patients with gm is crucial to facilitate screening strategies, preventive measures and the usage of targeted therapeutics in their management. This review examines the evidence for the latest predictive and therapeutic approaches in -associated cancers.

Clinical Description: Data supports the use of adjuvant olaparib in patients with gm high-risk HER2-negative breast cancer.

Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines.

Machine Learning-Based Prediction for High Health Care Utilizers by Using a Multi-Institutional Diabetes Registry: Model Training and Evaluation.

Background: The cost of health care in many countries is increasing rapidly. There is a growing interest in using machine learning for predicting high health care utilizers for population health initiatives. Previous studies have focused on individuals who contribute to the highest financial burden.

Trends in fluid overload-related hospitalisations among patients with diabetes mellitus The impact of chronic kidney disease.

Introduction: Fluid overload is a known complication in patients with diabetes mellitus, particularly those with cardiovascular and/or chronic kidney disease (CKD). This study investigates the impact of fluid overload on healthcare utilisation and its association with diabetes-related complications.

Method: Electronic medical records from the SingHealth Diabetes Registry (2013-2022) were analysed.

Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype.

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine.

Singapore's experience in managing the COVID-19 pandemic: Key lessons from the ground.

Singapore managed the COVID-19 pandemic in the past three years and gleaned valuable lessons on patient management when the public healthcare system was inundated with COVID-19 patients. There were several initiatives, which included setting up of community treatment facilities to help hospitals manage in-patient loads that did not require acute monitoring, leveraging telemedicine, and developing heuristics to sort patients based on their clinical disposition to various care pathways and to effectively manage patients of different medical needs. These initiatives were implemented in the second year of the epidemic in 2021 and did not include the dormitory-based migrant workers and migrant workers in the construction, maritime and production sectors who were under the care of the Assurance, Care and Engagement Group (ACE) in the Ministry of Manpower that had its own set of treatment management measures.

Sleep spindle architecture associated with distinct clinical phenotypes in older adults at risk for dementia.

Sleep spindles are a hallmark of non-REM sleep and play a fundamental role in memory consolidation. Alterations in these spindles are emerging as sensitive biomarkers for neurodegenerative diseases of ageing. Understanding the clinical presentations associated with spindle alterations may help to elucidate the functional role of these distinct electroencephalographic oscillations and the pathophysiology of sleep and neurodegenerative disorders.

Development and validation of an artificial intelligence based screening tool for detection of retinopathy of prematurity in a South Indian population.

Purpose: The primary objective of this study was to develop and validate an AI algorithm as a screening tool for the detection of retinopathy of prematurity (ROP).

Participants: Images were collected from infants enrolled in the KIDROP tele-ROP screening program.

Methods: We developed a deep learning (DL) algorithm with 227,326 wide-field images from multiple camera systems obtained from the KIDROP tele-ROP screening program in India over an 11-year period.

Possibly pathogenic bacteria in aerosols and foams as a result of aeration remediation in a polluted urban waterway.

Newtown Creek is a tributary of the Hudson River Estuary. It has a legacy of both industrial pollution and sewage pollution and has been designated a Superfund site. To ameliorate the chronically low levels of dissolved oxygen detected in the Creek, the New York City Department of Environmental Protection has been installing aerators.

Abnormal higher-order network interactions in Parkinson's disease visual hallucinations.

Visual hallucinations in Parkinson's disease can be viewed from a systems-level perspective, whereby dysfunctional communication between brain networks responsible for perception predisposes a person to hallucinate. To this end, abnormal functional interactions between higher-order and primary sensory networks have been implicated in the pathophysiology of visual hallucinations in Parkinson's disease, however the precise signatures remain to be determined. Dimensionality reduction techniques offer a novel means for simplifying the interpretation of multidimensional brain imaging data, identifying hierarchical patterns in the data that are driven by both within- and between-functional network changes.

Parallel processing relies on a distributed, low-dimensional cortico-cerebellar architecture.

A characteristic feature of human cognition is our ability to 'multi-task'-performing two or more tasks in parallel-particularly when one task is well learned. How the brain supports this capacity remains poorly understood. Most past studies have focussed on identifying the areas of the brain-typically the dorsolateral prefrontal cortex-that are required to navigate information-processing bottlenecks.

Knowledge, attitudes, and perceptions of hidradenitis suppurativa among young adults in Singapore.

Background: The prevalence of hidradenitis suppurativa (HS) is 0.00033% to 4.10% globally.

A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies.

Background: Phosphatase of regenerating liver-3 (PRL-3) is involved in cellular processes driving metastasis, cell proliferation, invasion, motility and survival. It has been shown to be upregulated and overexpressed in cancer tissue, in contrast to low or no expression in most normal tissue. PRL3-zumab is a first-in-class humanized antibody that specifically binds to PRL-3 oncotarget with high affinity and has been shown to reduce tumor growth and increase survival.

Using the Johns Hopkins ACG Case-Mix System for population segmentation in a hospital-based adult patient population in Singapore.

Objective: Population health management involves risk characterisation and patient segmentation. Almost all population segmentation tools require comprehensive health information spanning the full care continuum. We assessed the utility of applying the ACG System as a population risk segmentation tool using only hospital data.

Composing games into complex institutions.

Game theory is used by all behavioral sciences, but its development has long centered around the economic interpretation of equilibrium outcomes in relatively simple games and toy systems. But game theory has another potential use: the high-level design of large game compositions that express complex architectures and represent real-world institutions faithfully. Compositional game theory, grounded in the mathematics underlying programming languages, and introduced here as a general computational framework, increases the parsimony of game representations with abstraction and modularity, accelerates search and design, and helps theorists across disciplines express real-world institutional complexity in well-defined ways.

Searching for common ground.

The conserved coronavirus fusion peptide is a target of broadly neutralizing antibodies.

Associations Between Mean HbA1c, HbA1c Variability, and Both Mortality and Macrovascular Complications in Patients with Diabetes Mellitus: A Registry-Based Cohort Study.

Background: We investigate the association between mean HbA1c, HbA1c variability, and all-cause mortality and diabetes-related macrovascular complications in patients with diabetes.

Methods: We performed a retrospective cohort study using patients present in the Singapore Health Services diabetes registry (SDR) during 2013 to 2014. We assessed mean HbA1c using three models: a baseline mean HbA1c for 2013-14, the mean across the whole follow-up period, and a time-varying yearly updated mean.

Comparative Assessment of the Binding and Neutralisation Activity of Bispecific Antibodies Against SARS-CoV-2 Variants.

Background: Neutralising antibodies against SARS-CoV-2 are a vital component in the fight against COVID-19 pandemic, having the potential of both therapeutic and prophylactic applications. Bispecific antibodies (BsAbs) against SARS-CoV-2 are particularly promising, given their ability to bind simultaneously to two distinct sites of the receptor-binding domain (RBD) of the viral spike protein. Such antibodies are complex molecules associated with multi-faceted mechanisms of action that require appropriate bioassays to ensure product quality and manufacturing consistency.

Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.

The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike.

Clinical informatics training in medical school education curricula: a scoping review.

Objectives: This scoping review evaluates the existing literature on clinical informatics (CI) training in medical schools. It aims to determine the essential components of a CI curriculum in medical schools, identify methods to evaluate the effectiveness of a CI-focused education, and understand its delivery modes.

Materials And Methods: This review was informed by the methodological guidance of the Joanna Briggs Institute.