Sub-Microliter H Magnetic Resonance Spectroscopy for In Vivo High-Spatial Resolution Metabolite Quantification in the Mouse Brain.

Proton magnetic resonance spectroscopy (MRS) offers a non-invasive, repeatable, and reproducible method for in vivo metabolite profiling of the brain and other tissues. However, metabolite fingerprinting by MRS requires high signal-to-noise ratios for accurate metabolite quantification, which has traditionally been limited to large volumes of interest, compromising spatial fidelity. In this study, we introduce a new optimized pipeline that combines LASER MRS acquisition at 11.

Cultural Differences in Visual Attention Emerge in Infancy.

East Asians are more likely than North Americans to attend to visual scenes holistically, focusing on the relations between objects and their background rather than isolating components. This cultural difference in context sensitivity-greater attentional allocation to the background of an image or scene-has been attributed to socialization, yet it is unknown how early in development it appears, and whether it is moderated by social information. We employed eye-tracking to investigate context-sensitivity in 15-month-olds in Japan (n = 45) and the United States (n = 52).

Response to neoadjuvant chemotherapy leads to better survival outcomes in upper tract urothelial carcinoma.

Objectives: To evaluate the benefit of neoadjuvant chemotherapy (NAC) for patients with high-risk upper tract urothelial carcinoma (UTUC) using a large, well-curated multi-institutional database.

Patients And Methods: This study was a multi-institutional retrospective analysis conducted by the UTUC Collaborative Network (UCAN), combining data from 2276 patients with UTUC who underwent radical nephroureterectomy at seven high-volume tertiary care centres in the United States. The UCAN data were analysed to evaluate the impact of response to NAC on survival outcomes in patients with UTUC.

Examining eating pathology and psychosocial functioning across subjective eating disorder recovery stages in sexual and gender minority individuals.

Subjective eating disorder (ED) recovery has important clinical relevance. However, studies have focused on the perspectives of cisgender heterosexual individuals, which is notable given that sexual and gender minority (SGM) people often describe feelings misrepresented by prevailing ED conceptualizations. We examined eating pathology and psychosocial functioning across subjective recovery stages in SGM individuals ( = 196).

A Novel Screening System to Characterize and Engineer Quorum Quenching Lactonases.

N-acyl l-homoserine lactones are signaling molecules used by numerous bacteria in quorum sensing. Some bacteria encode lactonases, which can inactivate these signals. Lactonases were reported to inhibit quorum sensing-dependent phenotypes, including virulence and biofilm.

Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.

Background: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

Methods: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk.

Estimation of factorial expressions and its improvement through calibration: A replication and extension of Tversky and Kahneman (1973).

Fifty years ago, Tversky and Kahneman (Cognitive Psychology, 5[2], 207-232, 1973) reported that people's speeded estimations of 8 × 7 × 6 × 5 × 4 × 3 × 2 × 1 were notably higher than their estimations for the equivalent expression in the opposite order, 1 × 2 × 3 × 4 × 5 × 6 × 7 × 8 (Median = 2,250 vs. 512, respectively). On top of this order effect, both groups grossly underestimated the correct value (40,320).

Adherence to multi-target stool DNA testing for colorectal cancer screening in the United States.

Purpose: Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA and is highly preventable, with early screening vital for improving outcomes. This study aimed to evaluate adherence rates of multi-target stool DNA (mt-sDNA) testing, following updated guidelines recommending screening starting at age 45.

Methods: This retrospective cohort study used aggregated data from Exact Sciences Laboratories LLC, examining new users (first-time testers) aged 45-85 with commercial, Medicare, or Medicaid insurance who received mt-sDNA test kits (point-of-care) between January 1, 2023, and June 1, 2023.

Soil Nitrogen Supply Exerts Largest Influence on Leaf Nitrogen in Environments with the Greatest Leaf Nitrogen Demand.

Accurately representing the relationships between nitrogen supply and photosynthesis is crucial for reliably predicting carbon-nitrogen cycle coupling in Earth System Models (ESMs). Most ESMs assume positive correlations amongst soil nitrogen supply, leaf nitrogen content, and photosynthetic capacity. However, leaf photosynthetic nitrogen demand may influence the leaf nitrogen response to soil nitrogen supply; thus, responses to nitrogen supply are expected to be the largest in environments where demand is the greatest.

A Phase II Trial of Onapristone and Fulvestrant for Patients With ER+ and HER2- Metastatic Breast Cancer.

Background: The SMILE study is a multi-institutional phase II clinical trial to determine the efficacy and safety of an antiprogestin, onapristone, in combination with fulvestrant as second-line therapy for patients with ER+, PgR+/-, HER2- metastatic breast cancer. This study was terminated early and herein, we report patient characteristics, and outcomes.

Methods: Eligibility criteria included disease progression on ≥2 lines of prior therapy, ECOG performance status ≤ 2, measurable disease per RECIST 1.

Guidance on the assessment of the functionality of biomaterials for periodontal tissue regeneration: Methodologies and testing procedures.

Innovative biomaterials and tissue engineering strategies show great promise in regenerating periodontal tissues. This guidance provides an overview and detailed recommendations for evaluating the biological functionality of these new biomaterials in vitro, focusing on mineralization, immunomodulatory effects, cellular differentiation, and angiogenesis. Additionally, it discusses the use of in vivo experimental models that mimic periodontitis and scrutinizes methods such as osteogenic differentiation, immunomodulation, and anti-inflammatory responses to assess the effectiveness of these biomaterials in promoting periodontal tissue reconstruction.

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies.

Estradiol Levels are Differentially Associated with Pulse Wave Velocity in Trauma-exposed Premenopausal Women with and without PTSD.

Arterial stiffness is a well-known risk factor for cardiovascular disease. Although estradiol (E2) is known to be cardioprotective, the available data point to a growing cardiovascular disease risk in women before menopause due to post-traumatic stress disorder (PTSD). The present study aimed to investigate the effects of E2 on arterial compliance in trauma-exposed premenopausal women, with and without a clinical diagnosis PTSD.

A high throughput assay for phosphoribosylformylglycinamidine synthase.

Metabolic reprogramming of purine biosynthesis is a hallmark of cancer metabolism and represents a critical vulnerability. The enzyme phosphoribosylformylglycinamidine synthase (PFAS) catalyzes the fourth step in de novo purine biosynthesis and has been demonstrated to be prognostic for survival of liver cancer. Despite the importance of this protein as a drug target, there are no known specific inhibitors of PFAS activity.

Low baseline IsoPSA Index is associated with a Prolonged Low Risk of Clinically Significant Prostate Cancer Diagnosis in Men with an Elevated PSA.

Objective: To compare the rate of diagnosing clinically significant prostate cancer (csPCa) in men with elevated PSA stratified by baseline IsoPSA Index, thus assessing IsoPSA's intermediate-term predictive ability for csPCa.

Material And Methods: Single-center retrospective review of consecutive patients (n=1578) who underwent IsoPSA testing from November 2016-August 2022. Data dichotomized into patients with low(≤6) and high IsoPSA Indices (>6).

Eliminating osmotic stress during cryoprotectant loading: A mathematical investigation of solute-solvent transport.

Osmotic stresses during cryoprotectant loading induce changes in cellular volume, leading to membrane damage or even cell death. Appropriate model-guided mitigation of these osmotic gradients during cryoprotectant loading is currently lacking, but would be highly beneficial in reducing viability loss during the loading process. To address this need, we reformulate the two-parameter formalism described by Jacobs and Stewart for cryoprotectant loading under the constraint of constant cell volume.

Tail Anchored protein insertion mediated by CAML and TRC40 links to neuromuscular function in mice.

Motor neuron diseases, such as amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy, involve loss of muscle control resulting from death of motor neurons. Although the exact pathogenesis of these syndromes remains elusive, many are caused by genetically inherited mutations. Thus, it is valuable to identify additional genes that can impact motor neuron survival and function.

Exploring the impact of grazing on fecal and soil microbiome dynamics in small ruminants in organic crop-livestock integration systems.

In integrated crop-livestock systems, livestock graze on cover crops and deposit raw manure onto fields to improve soil health and fertility. However, enteric pathogens shed by grazing animals may be associated with foodborne pathogen contamination of produce influenced by fecal-soil microbial interactions. We analyzed 300 fecal samples (148 from sheep and 152 from goats) and 415 soil samples (272 from California and 143 from Minnesota) to investigate the effects of grazing and the presence of non-O157 Shiga toxin-producing Escherichia coli (STEC) or generic E.

The Coexistence of Carotico-Clinoid Foramen and Interclinoidal Osseous Bridge: An Anatomo-Radiological Study With Surgical Implications.

Background And Objectives: The coexistence of complete carotico-clinoid bridge (CCB), an ossification between the anterior (ACP) and the middle clinoid (MCP), and an interclinoidal osseous bridge (ICB), between the ACP and the posterior clinoid (PCP), represents an uncommonly reported anatomic variant. If not adequately recognized, osseous bridges may complicate open or endoscopic surgery, along with the pneumatization of the ACP, especially when performing anterior or middle clinoidectomies.

Methods: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines, a systematic scoping review was conducted up to June 5, 2023.

Results of 331 Two-Stage Exchanges for PJI Following THA: Low Reinfection and Mechanical Failure Rates at 10 Years.

Background: The relative advantages and disadvantages of 2-stage versus 1-stage management of infection following total hip arthroplasty (THA) are the current subject of intense debate. To understand the merits of each approach, detailed information on the short and, importantly, longer-term outcomes of each must be known. The purpose of the present study was to assess the long-term results of 2-stage exchange arthroplasty following THA in one of the largest series to date.

An epiallele of a gene encoding a PfkB-type carbohydrate kinase affects plant architecture in maize.

Plant architecture greatly contributes to grain yield, but the epigenetic regulation of plant architecture remains elusive. Here, we identified the maize (Zea mays L.) mutant plant architecture 1 (par1), which shows reduced plant height, shorter and narrower leaves, and larger leaf angles than the wild type.

Assessing the impact of messages about reduced nicotine cigar products among people who use little cigar and cigarillo: Insights from a discrete choice experiment.

Introduction: The U.S. Food and Drug Administration's (FDA) pursuit of a low nicotine standard for cigarettes raises concerns that a focus on cigarettes may encourage people to use other combusted tobacco products, undermining the policy's effectiveness.

Metabolically Stable Adenylation Inhibitors of Biotin Protein Ligase as Antibacterial Agents.

The antibacterial agent Bio-AMS is metabolized in vivo through hydrolysis of the central acyl-sulfamide linker leading to high clearance and release of a moderately cytotoxic metabolite . Herein, we disclose analogues designed to prevent the metabolism of the central acyl-sulfamide moiety through steric hindrance or attenuation of the acyl-sulfamide electrophilicity. was identified as a metabolically stable analogue with a single-digit nanomolar dissociation constant for biotin protein ligase (BPL) and minimum inhibitory concentrations (MICs) against and ranging from 0.