Diffusion tensor imaging with free-water correction reveals distinctions between severe and attenuated subtypes in Mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder leading to deleterious brain effects. While animal models suggested that MPS I severely affects white matter (WM), whole-brain diffusion tensor imaging (DTI) analysis was not performed due to MPS-related morphological abnormalities. 3T DTI data from 28 severe (MPS IH, treated with hematopoietic stem cell transplantation-HSCT), 16 attenuated MPS I patients (MPS IA) enrolled under the study protocol NCT01870375, and 27 healthy controls (HC) were analyzed using the free-water correction (FWC) method to resolve macrostructural partial volume effects and unravel differences in DTI metrics accounting for microstructural abnormalities.

A bispecific antibody-drug conjugate targeting pCAD and CDH17 has antitumor activity and improved tumor-specificity.

P-cadherin (pCAD) and LI-cadherin (CDH17) are cell-surface proteins belonging to the cadherin superfamily that are both highly expressed in colorectal cancer. This co-expression profile presents a novel and attractive opportunity for a dual targeting approach using an antibody-drug conjugate (ADC). In this study, we used a unique avidity-driven screening approach to generate pCAD x CDH17 bispecific antibodies that selectively target cells expressing both antigens over cells expressing only pCAD or only CDH17.

Molecular Profiling of Sinonasal Adenoid Cystic Carcinoma: Canonical and Noncanonical Gene Fusions and Mutation.

Adenoid cystic carcinomas (AdCC) of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost universal presence of the gene fusion MYB::NFIB, or less commonly MYBL1::NFIB. Sinonasal AdCC is an aggressive salivary gland malignancy with no effective systemic therapy. Therefore, it is urgent to search for potentially targetable genetic alterations associated with AdCC.

Predicting Antidepressant Treatment Response From Cortical Structure on MRI: A Mega-Analysis From the ENIGMA-MDD Working Group.

Accurately predicting individual antidepressant treatment response could expedite the lengthy trial-and-error process of finding an effective treatment for major depressive disorder (MDD). We tested and compared machine learning-based methods that predict individual-level pharmacotherapeutic treatment response using cortical morphometry from multisite longitudinal cohorts. We conducted an international analysis of pooled data from six sites of the ENIGMA-MDD consortium (n = 262 MDD patients; age = 36.

Spontaneous base flipping helps drive Nsp15's preferences in double stranded RNA substrates.

Coronaviruses evade detection by the host immune system with the help of the endoribonuclease Nsp15, which regulates levels of viral double stranded RNA by cleaving 3' of uridine (U). While prior structural data shows that to cleave double stranded RNA, Nsp15's target U must be flipped out of the helix, it is not yet understood whether Nsp15 initiates flipping or captures spontaneously flipped bases. We address this gap by designing fluorinated double stranded RNA substrates that allow us to directly relate a U's sequence context to both its tendency to spontaneously flip and its susceptibility to cleavage by Nsp15.

The Nonclinical Safety Assessment of a Novel Anti-CEACAM5 Antibody Exatecan Conjugate Predicts a Low Risk for Interstitial Lung Disease (ILD) in Patients-The Putative Mechanism Behind ILD.

The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan.

Pan-phylum genomes of hornworts reveal conserved autosomes but dynamic accessory and sex chromosomes.

Hornworts, one of the three bryophyte phyla, show some of the deepest divergences in extant land plants, with some families separated by more than 300 million years. Previous hornwort genomes represented only one genus, limiting the ability to infer evolution within hornworts and their early land plant ancestors. Here we report ten new chromosome-scale genomes representing all hornwort families and most of the genera.

EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

Characteristics Associated With Early Ileocolonic Resection in Pediatric Crohn's Disease.

Introduction: Pediatric-onset Crohn's disease (CD) has a more severe phenotype than adult-onset, and nearly one-third of pediatric CD patients will require surgical therapy. There is limited data on patient/disease characteristics that are associated with earlier surgical management.

Methods: All pediatric CD patients (<22 yrs) who underwent ileocolectomy from 2005 to 2021 were included.

Quantum Thermodynamics of Nonequilibrium Processes in Lattice Gauge Theories.

A key objective in nuclear and high-energy physics is to describe nonequilibrium dynamics of matter, e.g., in the early Universe and in particle colliders, starting from the standard model of particle physics.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Combined endurance and resistance exercise training in heart failure with preserved ejection fraction: a randomized controlled trial.

Endurance exercise training (ET) is an effective treatment in heart failure with preserved ejection fraction (HFpEF), but the efficacy of resistance training in this patient population has been only scarcely evaluated. In this multicenter, randomized trial, we evaluated the effects of combined endurance and resistance training over 12 months in patients with HFpEF. The primary endpoint was a modified Packer score, including all-cause mortality, hospitalizations classified as potentially related to heart failure or exercise and changes in peak oxygen consumption ( ), diastolic function (E/e'), New York Heart Association (NYHA) class and global self-assessment (GSA).

Importance of reference group selection in the evaluation of cancer incidence.

Elevated cancer incidence has been reported among World Trade Center (WTC)-exposed responders, with some incidence rate ratios (IRRs) varying over time. This study describes the influence that different reference populations have on relative cancer incidence and temporal trends. Participants from the WTC Combined Rescue/Recovery Cohort (n = 65,691) were observed between 1/1/2002 and 12/31/2015 using data obtained from 13 state cancer registries.

Long-term persistence of glycemic dysregulation in patients with a history of pheochromocytoma/paraganglioma.

Context: Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors that frequently produce catecholamines. Catecholamine-induced cardiometabolic complications substantially contribute to increased morbidity and mortality in PPGL patients prior to surgical resection.

Objective: To determine whether markers of elevated cardiometabolic risk persist in patients following PPGL resection.

Assessing environmental gradients in relation to dark CO fixation in estuarine wetland microbiomes.

Unlabelled: The rising atmospheric concentration of CO is a major concern to society due to its global warming potential. In soils, CO-fixing microorganisms are preventing some of the CO from entering the atmosphere. Yet, the controls of dark CO fixation are rarely studied .

Mathematical modelling and analysis for the co-infection of viral and bacterial diseases: a systematic review protocol.

Introduction: Breaking the chain of transmission of an infectious disease pathogen is a major public health priority. The challenges of understanding, describing and predicting the transmission dynamics of infections have led to a wide range of mathematical, statistical and biological research problems. Advances in diagnostic laboratory procedures with the ability to test multiple pathogens simultaneously mean that co-infections are increasingly being detected, yet little is known about the impact of co-infections in shaping the course of an infection, infectivity, and pathogen replication rate.

Interaction of Vitamin D-BODIPY With Fat Cells and the Link to Obesity-associated Vitamin D Deficiency.

Background/aim: Obese individuals often exhibit vitamin D deficiency, potentially due to sequestration in fat cells. Little is known about how vitamin D enters adipocytes and associates with the intracellular lipid droplet.

Materials And Methods: Newly differentiated human and mouse (3T3-L1) adipocytes and primary mouse adipocytes were treated with vitamin D covalently linked to green fluorescent BODIPY (VitD-B) or Green BODIPY (GB) as control.

Self-reported chronic rhinosinusitis diagnoses and symptoms in World Trade Center-exposed and non-World Trade Center-exposed United States firefighters.

Background: Greater World Trade Center (WTC) exposure levels have been associated with chronic rhinosinusitis (CRS) diagnoses and symptoms. We aimed to determine whether self-reported CRS is elevated in WTC-exposed Fire Department of the City of New York (FDNY) firefighters when compared with non-WTC-exposed/non-FDNY firefighters and with the general population.

Methods: The study included male WTC-exposed (N = 7840) and non-WTC-exposed (N = 2771) firefighters who were employed on 9/11/2001 and later completed a health survey.

Spongy-looking microfabrics in the earliest named stromatolite represent deep burial alteration and incipient metamorphism.

The earliest named stromatolite Cryptozoon Hall, 1884 (Late Cambrian, ca. 490 Ma, eastern New York State), was recently re-interpreted as an interlayered microbial mat and non-spiculate (keratosan) sponge deposit. This "classic stromatolite" is prominent in a fundamental debate concerning the significance or even existence of non-spiculate sponges in carbonate rocks from the Neoproterozoic (Tonian) onwards.

Behavior Coding of Adolescent and Therapy Dog Interactions During a Social Stress Task.

Youth mental health interventions incorporating trained therapy animals are increasingly popular, but more research is needed to understand the specific interactive behaviors between participants and therapy dogs. Understanding the role of these interactive behaviors is important for supporting both intervention efficacy and animal welfare and well-being. The goal of this study was to develop ethograms to assess interactive behaviors (including both affiliative and stress-related behaviors) of participants and therapy dogs during a social stress task, explore the relationship between human and dog behaviors, and assess how these behaviors may vary between experimental conditions with varying levels of physical contact with the therapy dog.

Comparison of Alcohol Septal Ablation With Mavacamten in Obstructive Hypertrophic Cardiomyopathy.

Obstructive hypertrophic cardiomyopathy (HCM) is associated with significant morbidity because of left ventricular outflow tract (LVOT) obstruction. Although alcohol septal ablation (ASA) is an established interventional treatment, mavacamten, a novel cardiac myosin inhibitor, has emerged as a noninvasive pharmacologic alternative. Understanding the comparative efficacy of these 2 treatments is important for optimizing patient care.

Development of evidence-based standards for inpatient physiotherapy services: a systematic review and content analysis of clinical practice guidelines.

Objective: Performance standards are critical to service design and quality improvement. There are no published standards defining the care inpatients should receive from physiotherapists in Aotearoa New Zealand. This study aims to explore the potential of using clinical practice guidelines (CPGs) to develop a set of evidence-based standards for physiotherapy in inpatient settings.