Combined biochemical profiling and DNA sequencing in the expanded newborn screening for inherited metabolic diseases: the experience in an Italian reference center.

Background: Newborn screening (NBS) programs have significantly improved the health and outcomes of patients with inherited metabolic disorders (IMDs). Methods based on liquid chromatography/mass spectrometry (LC-MS/MS) analysis are viewed worldwide as the gold standard procedure for the expanded NBS programs for these disorders. Advanced molecular technologies point to genomic sequencing as an alternative and feasible strategy for the screening of genetic diseases, including IMDs.

Peripheral blood miRNAs are associated with airflow below threshold in children with asthma.

Background: MicroRNAs (miRNAs) are crucial post-transcriptional regulators involved in inflammatory diseases, such as asthma. Poor lung function and airflow issues in childhood are linked to the development of chronic obstructive pulmonary disease (COPD) in adulthood.

Methods: We analyzed small RNA-Seq data from 365 peripheral whole blood samples from the Genetics of Asthma in Costa Rica Study (GACRS) for association with airflow levels measured by FEV1/FVC.

Referral for Diabetes Self-Management Education and Support in Adult Primary Care: An Integrative Review.

Aims: The purpose of this integrative review was to identify effective diabetes self-management education and support for increasing adult primary care referrals, participation rates and improving health outcomes for persons with diabetes.

Design: Integrative review.

Methods: A systematic literature search of PubMed/MEDLINE, Embase and CINAHL was performed by applying the PRISMA guidelines.

Multiple Lurias. Reconstructing Alexander Romanovich's Life-Writing.

While widely considered Alexander Luria's (1902-1977) autobiography, The Making of Mind. A Personal Account of Soviet Psychology, published posthumously in 1979, is not a true autobiography but rather an autobiography with heterobiographic elements. However, the largely overlooked Spanish book, Mirando hacia atrás.

Uniform volumetric single-cell processing for organ-scale molecular phenotyping.

Extending single-cell analysis to intact tissues while maintaining organ-scale spatial information poses a major challenge due to unequal chemical processing of densely packed cells. Here we introduce Continuous Redispersion of Volumetric Equilibrium (CuRVE) in nanoporous matrices, a framework to address this challenge. CuRVE ensures uniform processing of all cells in organ-scale tissues by perpetually maintaining dynamic equilibrium of the tissue's gradually shifting chemical environment.

Genome-wide association analysis of composite sleep health scores in 413,904 individuals.

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches.

Antimicrobial Resistance in Curable Sexually Transmitted Infections.

Purpose Of Review: Antimicrobial resistance in sexually transmitted infections (STIs) has become an urgent global public health threat, raising the specter of untreatable infections. This review summarizes the determinants of resistance among the five most common curable STIs Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Treponema pallidum, and Trichomonas vaginalis, as well as strategies to mitigate the spread of resistance.

Recent Findings: Genetic mutations are key drivers of resistance for N.

Accuracy of GFAP and UCH-L1 in predicting brain abnormalities on CT scans after mild traumatic brain injury: a systematic review and meta-analysis.

Purpose: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. In recent years, blood biomarkers including glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have shown a promising ability to detect head CT abnormalities following TBI. This review aims to combine the existing research on GFAP and UCH-L1 biomarkers and examine how well they can predict abnormal CT results after mild TBI.

Association between exposure to particulate matter and heart rate variability in vulnerable and susceptible individuals.

Particulate matter (PM) exposure can reduce heart rate variability (HRV), a cardiovascular health marker. This study examines PM (aerodynamic diameters <1 μm), PM (≥1 μm and <2.5 μm), and PM (≥2.

Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3).

Dual anti-CTLA-4 and anti-PD-1 blockade in metastatic basal cell carcinoma.

We report the basal cell cancer (BCC) cohort of the SWOG/NCI 1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART), a phase II prospective, multicenter basket trial of nivolumab and ipilimumab. The primary endpoint was objective response rate (ORR) (RECIST v1.1).

Transforming diagnosis through artificial intelligence.

Artificial intelligence (AI) is increasingly permeating the fabric of medicine, but getting full benefits will likely require fundamental changes in practice. Accepting this will be challenging for many clinicians. However, it may be necessary to ensure that AI’s ambitious promises translate into real-life improvement.

Transposon mediated functional genomic screening for BRAF inhibitor resistance reveals convergent Hippo and MAPK pathway activation events.

Genotype-informed anticancer therapies such as BRAF inhibitors can show remarkable clinical efficacy in BRAF-mutant melanoma; however, drug resistance poses a major hurdle to successful cancer treatment. Many resistance events to targeted therapies have been identified, suggesting a complex path to improve therapeutics. Here, we showed the utility of a piggyBac transposon activation mutagenesis screen for the efficient identification of genes that are resistant to BRAF inhibition in melanoma.

V3+ extends the V3 framework to ensure user-centricity and scalability of sensor-based digital health technologies.

We propose the addition of usability validation to the extended V3 framework, now "V3+", and describe a pragmatic approach to ensuring that sensor-based digital health technologies can be used optimally at scale by diverse users. Alongside the original V3 components (verification; analytical validation; clinical validation), usability validation will ensure user-centricity of digital measurement tools, paving the way for more inclusive, reliable, and trustworthy digital measures within clinical research and clinical care.

Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation.

Many essential proteins require pyridoxal 5'-phosphate, the active form of vitamin B6, as a cofactor for their activity. These include enzymes important for amino acid metabolism, one-carbon metabolism, polyamine synthesis, erythropoiesis, and neurotransmitter metabolism. A third of all mammalian pyridoxal 5'-phosphate-dependent enzymes are localized in the mitochondria; however, the molecular machinery involved in the regulation of mitochondrial pyridoxal 5'-phosphate levels in mammals remains unknown.

A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

Using artificial intelligence to optimize anti-seizure treatment and EEG-guided decisions in severe brain injury.

Electroencephalography (EEG) is invaluable in the management of acute neurological emergencies. Characteristic EEG changes have been identified in diverse neurologic conditions including stroke, trauma, and anoxia, and the increased utilization of continuous EEG (cEEG) has identified potentially harmful activity even in patients without overt clinical signs or neurologic diagnoses. Manual annotation by expert neurophysiologists is a major resource limitation in investigating the prognostic and therapeutic implications of these EEG patterns and in expanding EEG use to a broader set of patients who are likely to benefit.

Age Self Care-Resilience, a medical group visit program targeting pre-frailty: A mixed methods pilot clinical trial.

Background: Pre-frailty is highly prevalent and multimodal lifestyle interventions are effective for preventing transition to frailty. However, little is known about the potential for medical group visits (MGV) to prevent frailty progression.

Objectives: To assess the feasibility and acceptability of the MGV Age Self Care-Resilience.

Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis.

Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population.

Methods: We conducted a systematic review and individual participant data meta-analysis.

Clinical outcomes of patients with unsuccessful mechanical thrombectomy versus best medical management of medium vessel occlusion stroke in the middle cerebral artery territory.

Background: Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown.

Methods: This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021.

US children from non-English-speaking households are less likely to undergo vision testing.

Purpose: To investigate the association between primary household language and vision testing among children living in the United States from 2016 to 2020.

Methods: This analysis used data for children aged 3-17 years from the National Survey of Children's Health (NSCH), combining survey responses from 2016 to 2020. Primary household language and whether vision testing occurred were determined by survey responses.

Implantable Cardioverter-Defibrillators and Cardiovascular Resynchronization Therapy with Left Ventricular Assist Devices: A MOMENTUM 3 Trial Analysis.

Background: The benefit of implantable cardioverter-defibrillators (ICD) and cardiovascular resynchronization therapy (CRT-D) in patients supported with a HeartMate 3 left ventricular assist device (LVAD) remains uncertain.

Methods: An analysis of the MOMENTUM 3 randomized clinical trial and the first 1000 patients in the Continued Access Protocol trial. Patients were divided into three groups based on the presence of ICD and/or CRT-D: No device (n=153, 11%), ICD only (n=699, 50.