Exposomics: a review of methodologies, applications, and future directions in molecular medicine.

The exposome is the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Exposomics is the emerging field of research to measure and study the totality of the exposome. Exposomics can assist with molecular medicine by furthering our understanding of how the exposome influences cellular and molecular processes such as gene expression, epigenetic modifications, metabolic pathways, and immune responses.

Preclinical use of a clinically-relevant scAAV9/SUMF1 vector for the treatment of multiple sulfatase deficiency.

Background: Multiple Sulfatase Deficiency (MSD) is a rare inherited lysosomal storage disorder characterized by loss of function mutations in the SUMF1 gene that manifests as a severe pediatric neurological disease. There are no available targeted therapies for MSD.

Methods: We engineered a viral vector (AAV9/SUMF1) to deliver working copies of the SUMF1 gene and tested the vector in Sumf1 knock out mice that generally display a median lifespan of 10 days.

A genome-wide atlas of human cell morphology.

A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries.

Black-vs-white racial disparities in 30-day outcomes following primary and revisional metabolic and bariatric surgery: a MBSAQIP database analysis.

Background: Previous studies have demonstrated Black-vs-White disparities in postoperative outcomes following primary metabolic and bariatric surgery (MBS). With the rising prevalence of MBS, it is important to examine racial disparities using quality indicators in primary and revisional procedures. This study explores Black-vs-White disparities in postoperative outcomes following primary and revisional MBS.

Short-term outcomes of mesh-suture repair in the treatment of ventral hernias: a single-center study.

Background: Defect closure with mesh suture is a novel technique for hernia repair. Originally described as the construction of lightweight macroporous polypropylene mesh strips as a suture material, it is now available as an FDA-approved product. Mesh suture better distributes tensile forces and reduces fascial tearing compared to traditional suture but requires less implanted material and tissue dissection compared to planar mesh.

A systematic review of portable technologies for the early assessment of motor development in infants.

Early screening and evaluation of infant motor development are crucial for detecting motor deficits and enabling timely interventions. Traditional clinical assessments are often subjective, without fully capturing infants' "real-world" behavior. This has sparked interest in portable, low-cost technologies to objectively and precisely measure infant motion at home, with a goal of enhancing ecological validity.

Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis.

No therapy has been shown to reduce the risk of major adverse liver outcomes (MALO) in patients with cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). The Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) observational study compared the effects of metabolic surgery and nonsurgical treatment in patients with obesity and compensated histologically proven MASH-related cirrhosis. Using a doubly robust estimation methodology to balance key baseline characteristics between groups, the time-to-incident MALO was compared between 62 patients (68% female) who underwent metabolic surgery and 106 nonsurgical controls (71% female), with a mean follow-up of 10.

Age-related p53 SUMOylation accelerates senescence and tau pathology in Alzheimer's disease.

Aging is a major risk factor for Alzheimer's disease (AD). With the prevalence of AD increased, a mechanistic linkage between aging and the pathogenesis of AD needs to be further addressed. Here, we report that a small ubiquitin-related modifier (SUMO) modification of p53 is implicated in the process which remarkably increased in AD patient's brain.

RECQL4 requires PARP1 for recruitment to DNA damage, and PARG dePARylation facilitates its associated role in end joining.

RecQ helicases, highly conserved proteins with pivotal roles in DNA replication, DNA repair and homologous recombination, are crucial for maintaining genomic integrity. Mutations in RECQL4 have been associated with various human diseases, including Rothmund-Thomson syndrome. RECQL4 is involved in regulating major DNA repair pathways, such as homologous recombination and nonhomologous end joining (NHEJ).

Comparison of aesthetic perception and acceptability of silver diamine fluoride staining between Spanish and Italian parents.

Assessing parental aesthetic acceptability of Silver Diamine Fluoride (SDF) staining is crucial for its potential implementation in paediatric dentistry in different regions. This study aimed to compare aesthetic perceptions and acceptance of SDF staining between Spanish and Italian parents, and assess weather acceptability is influenced by location, child's cooperation, or demographic background. A cross-sectional comparative study was conducted among Spanish and Italian parents at three university dental clinics, using a validated Italian version of the questionnaire "Parental perceptions of Silver Diamine Fluoride Dental Color Changes".

Social epidemiology of early adolescent nutrition.

Background: This study aimed to investigate associations between sociodemographic factors and dietary intake among a diverse population of early adolescents ages 10-13 years in the United States.

Methods: We examined data from the Adolescent Brain Cognitive Development (ABCD) Study in Year 2 (2018-2020, ages 10-13 years, N = 10,280). Multivariable linear regression models were conducted to estimate the adjusted associations between sociodemographic factors (age, sex, race and ethnicity, household income, parental education) and dietary intake of various food groups, measured by the Block Kids Food Screener.

Long-term burden of body mass index since childhood and impaired physical performance in midlife.

Background: The impact of long-term burden of body mass index (BMI) since childhood on physical performance in midlife remains unclear. We aimed to investigate the association between cumulative exposure to BMI since childhood and midlife physical performance by using data from the Bogalusa Heart Study (BHS).

Methods: This longitudinal study consisted of 749 participants (aged 37.

International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma.

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies.

Multistage deep learning methods for automating radiographic sharp score prediction in rheumatoid arthritis.

The Sharp-van der Heijde score (SvH) is crucial for assessing joint damage in rheumatoid arthritis (RA) through radiographic images. However, manual scoring is time-consuming and subject to variability. This study proposes a multistage deep learning model to predict the Overall Sharp Score (OSS) from hand X-ray images.

Characteristics and paleoclimate significance of authigenic ferrimagnetic minerals in the Xuancheng red earth, southern China.

Soil magnetic records in Quaternary red earth (QRE) deposits contain a valuable record of paleoclimate information, providing insights into controls on Earth's climate system in the past and potentially helping to predict its response to perturbations in the future. Here, analysis of the environmental magnetism and mineralogy of the Xuancheng QRE (Anhui Province, South China) shows that magnetic variation was strongly linked to production of authigenic ferrimagnetic minerals such as maghemite. Fine-grained maghemite formed during the weathering-related transformation of iron-bearing illite to vermiculite, generating aggregates of vermiculite or mixed-layer illite-vermiculite.

The role of homogenization cycles and Poloxamer 188 on the quality of mitochondria isolated for use in mitochondrial transplantation therapy.

Mitochondrial transplantation (MTx) offers a promising therapeutic approach to mitigate mitochondrial dysfunction in conditions such as ischemia-reperfusion (IR) injury. The quality and viability of donor mitochondria are critical to MTx success, necessitating the optimization of isolation protocols. This study aimed to assess a rapid mitochondrial isolation method, examine the relationship between mitochondrial size and membrane potential, and evaluate the potential benefits of Poloxamer 188 (P-188) in improving mitochondrial quality during the isolation process.

Developing anti-TDE vaccine for sensitizing cancer cells to treatment and metastasis control.

Tumor-derived exosomes (TDEs) mediate oncogenic communication, which modifies target cells to reinforce a tumor-promoting microenvironment. TDEs support cancer progression by suppressing anti-tumor immune responses, promoting metastasis, and conferring drug resistance. Thus, targeting TDEs could improve the efficacy of anti-cancer treatments and control metastasis.

A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer.

While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on "bystander" genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed.

Simultaneous aerobic and anaerobic respiration in hot spring chemolithotrophic bacteria.

Aerobic and anaerobic organisms and their functions are spatially or temporally decoupled at scales ranging from individual cells to ecosystems and from minutes to hours. This is due to competition for energy substrates and/or biochemical incompatibility with oxygen (O). Here we report a chemolithotrophic Aquificales bacterium, Hydrogenobacter, isolated from a circumneutral hot spring in Yellowstone National Park (YNP) capable of simultaneous aerobic and anaerobic respiration when provided with hydrogen (H), elemental sulfur (S), and O.

Who is American? A comprehensive analysis of the American = White/Foreign = Asian stereotype (2007-2023).

Against the backdrop of increasing ethnic diversity in the U.S., we replicate, extend, and challenge previous examinations of the American = White/Foreign = Asian stereotype in the largest sample to date (N = 666,623 respondents) over 17 years (2007-2023).

Optimal life-cycle adaptation of coastal infrastructure under climate change.

Climate change-related risk mitigation is typically addressed using cost-benefit analysis that evaluates mitigation strategies against a wide range of simulated scenarios and identifies a static policy to be implemented, without considering future observations. Due to the substantial uncertainties inherent in climate projections, this identified policy will likely be sub-optimal with respect to the actual climate trajectory that evolves in time. In this work, we thus formulate climate risk management as a dynamic decision-making problem based on Markov Decision Processes (MDPs) and Partially Observable MDPs (POMDPs), taking real-time data into account for evaluating the evolving conditions and related model uncertainties, in order to select the best possible life-cycle actions in time, with global optimality guarantees for the formulated optimization problem.

GPX modulation promotes regenerative axonal fusion and functional recovery after injury through PSR-1 condensation.

Axonal fusion represents an efficient way to recover function after nerve injury. However, how axonal fusion is induced and regulated remains largely unknown. We discover that ferroptosis signaling can promote axonal fusion and functional recovery in C.