Single-input polarization-sensitive optical coherence tomography through a catheter.

Intravascular polarimetry with catheter-based polarization-sensitive optical coherence tomography (PS-OCT) complements the high-resolution structural tomograms of OCT with morphological contrast available through polarimetry. Its clinical translation has been complicated by the need for modification of conventional OCT hardware to enable polarimetric measurements. Here, we present a signal processing method to reconstruct the polarization properties of tissue from measurements with a single input polarization state, bypassing the need for modulation or multiplexing of input states.

Explainable Risk Prediction of Post-Stroke Adverse Mental Outcomes Using Machine Learning Techniques in a Population of 1780 Patients.

Post-stroke depression and anxiety, collectively known as post-stroke adverse mental outcome (PSAMO) are common sequelae of stroke. About 30% of stroke survivors develop depression and about 20% develop anxiety. Stroke survivors with PSAMO have poorer health outcomes with higher mortality and greater functional disability.

In Vitro Susceptibility to Ceftazidime-Avibactam and Comparator Antimicrobial Agents of Carbapenem-Resistant Enterobacterales Isolates.

The emergence of carbapenem-resistant Enterobacterales (CRE) has been recognized as a significant concern globally. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor that has demonstrated activity against isolates producing class A, C, and D β-lactamases. Here-in, we evaluated the in vitro activity of CZA and comparator antimicrobial agents against 858 CRE isolates, arising from the Southeast Asian region, collected from a large tertiary hospital in Singapore.

Bessel Beams in Ophthalmology: A Review.

The achievable resolution of a conventional imaging system is inevitably limited due to diffraction. Dealing with precise imaging in scattering media, such as in the case of biomedical imaging, is even more difficult owing to the weak signal-to-noise ratios. Recent developments in non-diffractive beams such as Bessel beams, Airy beams, vortex beams, and Mathieu beams have paved the way to tackle some of these challenges.

The Pathogenesis of Systemic Sclerosis: The Origin of Fibrosis and Interlink with Vasculopathy and Autoimmunity.

Systemic sclerosis (SSc) is an autoimmune disease associated with increased mortality and poor morbidity, impairing the quality of life in patients. Whilst we know that SSc affects multiple organs via vasculopathy, inflammation, and fibrosis, its exact pathophysiology remains elusive. Microvascular injury and vasculopathy are the initial pathological features of the disease.

Neurodegenerative Diseases: Molecular Mechanisms and Therapies.

Neurodegenerative diseases are characterized by the progressive degeneration or death of neurons in the central or peripheral nervous system [...

Economic Evaluations of Imaging Biomarker-Driven Companion Diagnostics for Cancer: A Systematic Review.

Introduction: There is a boom in imaging biomarker-driven companion and complementary diagnostics (CDx) for cancer, which brings opportunity for personalized medicine. Whether adoption of these technologies is likely to be cost-effective is a relevant question, and studies on this topic are emerging. Despite the growing number of economic evaluations, no review of the methods used, quality of reporting, and potential risk of bias has been done.

Group Model Building on causes and interventions for falls in Singapore: insights from a systems thinking approach.

Background: Falls in older adults are the result of a complex web of interacting causes, that further results in other physical, emotional, and psychological sequelae. A conceptual framework that represents the reciprocal dynamics of these causal factors can enable clinicians, researchers, and policymakers to clarify goals in falls intervention in older adults.

Methods: A Group Model Building (GMB) exercise was conducted with researchers and clinicians from academic units and public healthcare institutes in Singapore.

Febrile infants risk score at triage (FIRST) for the early identification of serious bacterial infections.

We aimed to derive the Febrile Infants Risk Score at Triage (FIRST) to quantify risk for serious bacterial infections (SBIs), defined as bacteremia, meningitis and urinary tract infections. We performed a prospective observational study on febrile infants < 3 months old at a tertiary hospital in Singapore between 2018 and 2021. We utilized machine learning and logistic regression to derive 2 models: FIRST, based on patient demographics, vital signs and history, and FIRST + , adding laboratory results to the same variables.

Role of dopamine in the pathophysiology of Parkinson's disease.

A pathological feature of Parkinson's disease (PD) is the progressive loss of dopaminergic neurons and decreased dopamine (DA) content in the substantia nigra pars compacta in PD brains. DA is the neurotransmitter of dopaminergic neurons. Accumulating evidence suggests that DA interacts with environmental and genetic factors to contribute to PD pathophysiology.

DARESOME enables concurrent profiling of multiple DNA modifications with restriction enzymes in single cells and cell-free DNA.

5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the most abundant DNA modifications that have important roles in gene regulation. Detailed studies of these different epigenetic marks aimed at understanding their combined effects and dynamic interconversion are, however, hampered by the inability of current methods to simultaneously measure both modifications, particularly in samples with limited quantities. We present DNA analysis by restriction enzyme for simultaneous detection of multiple epigenomic states (DARESOME), an assay based on modification-sensitive restriction digest and sequential tag ligation that can concurrently perform quantitative profiling of unmodified cytosine, 5mC, and 5hmC in CCGG sites genome-wide.

Degradation of methylation signals in cryopreserved DNA.

Background: Blood-based DNA methylation has shown great promise as a biomarker in a wide variety of diseases. Studies of DNA methylation in blood often utilize samples which have been cryopreserved for years or even decades. Therefore, changes in DNA methylation associated with long-term cryopreservation can introduce biases or otherwise mislead methylation analyses of cryopreserved DNA.

Cooperative regulation of coupled oncoprotein synthesis and stability in triple-negative breast cancer by EGFR and CDK12/13.

Evidence has long suggested that epidermal growth factor receptor (EGFR) may play a prominent role in triple-negative breast cancer (TNBC) pathogenesis, but clinical trials of EGFR inhibitors have yielded disappointing results. Using a candidate drug screen, we identified that inhibition of cyclin-dependent kinases 12 and 13 (CDK12/13) dramatically sensitizes diverse models of TNBC to EGFR blockade. This combination therapy drives cell death through the 4E-BP1-dependent suppression of the translation and translation-linked turnover of driver oncoproteins, including MYC.

Dysregulated COMT Expression in Fragile X Syndrome.

Transcriptional and proteomics analyses in human fragile X syndrome (FXS) neurons identified markedly reduced expression of COMT, a key enzyme involved in the metabolism of catecholamines, including dopamine, epinephrine and norepinephrine. FXS is the most common genetic cause of intellectual disability and autism spectrum disorders. COMT encodes for catechol-o-methyltransferase and its association with neuropsychiatric disorders and cognitive function has been extensively studied.

Emerging systemic therapy options beyond CDK4/6 inhibitors for hormone receptor-positive HER2-negative advanced breast cancer.

Endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is currently the standard first-line treatment for most patients with hormone receptor (HR) positive, human epidermal growth factor receptor (HER2) negative advanced breast cancer. However, resistance to ET and CDK4/6i inevitably ensues. The optimal post-progression treatment regimens and their sequencing continue to evolve in the rapidly changing treatment landscape.

Exploiting frequent and specific expression of PRL3 in pediatric solid tumors for first-in-child use of PRL3-zumab humanized antibody.

Phosphatase of regenerating liver 3 (PRL3) is a specific tumor antigen overexpressed in a broad range of adult cancer types. However, its physiological expression in pediatric embryonal and mesenchymal tumors and its association with clinical outcomes in children is unknown. We sought to profile the expression of PRL3 in pediatric tumors in relation to survival outcomes, expression of angiogenesis markers, and G-protein-coupled receptor (GPCR)-mitogen-activated protein kinase (MAPK) signaling targets.

A wild boar cathelicidin peptide derivative inhibits severe acute respiratory syndrome coronavirus-2 and its drifted variants.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a clear threat to humanity. It has infected over 200 million and killed 4 million people worldwide, and infections continue with no end in sight. To control the pandemic, multiple effective vaccines have been developed, and global vaccinations are in progress.

-encoded microprotein mitoregulin regulates fatty acid metabolism at the mitochondrial outer membrane.

encodes a microprotein first identified as Mitoregulin (MTLN), where it was reported to localize to the inner membrane of mitochondria to regulate fatty acid oxidation and oxidative phosphorylation. These initial discoveries were followed by reports with differing findings about its molecular functions and submitochondrial localization. To clarify the apparent discrepancies, we constructed multiple orthogonal methods of determining the localization of MTLN, including split GFP-based reporters that enable efficient and reliable topology analyses for microproteins.

Use of immobilisation bra for daily setup of patients with pendulous breasts undergoing radiotherapy.

Purpose: A feasibility study to evaluate the Chabner XRT® Radiation Bra (CIVCO Radiotherapy & Qfix, Coralville, IA, USA) as a customised immobilisation device for patients with pendulous breasts undergoing radiotherapy was conducted.

Methods: A total of 34 patients with large pendulous breasts were fitted with the Chabner XRT® Radiation Bra during RT. A mixed-method questionnaire was administered to both radiation therapists (RTTs) and patients.

Unveiling the Influence of Tumor Microenvironment and Spatial Heterogeneity on Temozolomide Resistance in Glioblastoma Using an Advanced Human In Vitro Model of the Blood-Brain Barrier and Glioblastoma.

Glioblastoma (GBM) is the most common primary malignant brain cancer in adults with a dismal prognosis. Temozolomide (TMZ) is the first-in-line chemotherapeutic; however, resistance is frequent and multifactorial. While many molecular and genetic factors have been linked to TMZ resistance, the role of the solid tumor morphology and the tumor microenvironment, particularly the blood-brain barrier (BBB), is unknown.

The BCKDK inhibitor BT2 is a chemical uncoupler that lowers mitochondrial ROS production and lipogenesis.

Elevated levels of branched chain amino acids (BCAAs) and branched-chain α-ketoacids (BCKAs) are associated with cardiovascular and metabolic disease, but the molecular mechanisms underlying a putative causal relationship remain unclear. The branched-chain ketoacid dehydrogenase kinase (BCKDK) inhibitor BT2 is often used in preclinical models to increase BCAA oxidation and restore steady-state BCAA and BCKA levels. BT2 administration is protective in various rodent models of heart failure and metabolic disease, but confoundingly, targeted ablation of in specific tissues does not reproduce the beneficial effects conferred by pharmacologic inhibition.