The biophysical property of the limbal niche maintains stemness through YAP.

The cell fate decisions of stem cells (SCs) largely depend on signals from their microenvironment (niche). However, very little is known about how biochemical niche cues control cell behavior in vivo. To address this question, we focused on the corneal epithelial SC model in which the SC niche, known as the limbus, is spatially segregated from the differentiation compartment.

Ultrasensitive Protein Detection Technologies for Extracellular Vesicle Measurements.

Extracellular vesicles (EVs) are nanoscopic, heterogenous, lipid-rich particles that carry a multitude of cargo biomolecules including proteins, nucleic acids, and metabolites. Although historically EVs were regarded as cellular debris with no intrinsic value, growing understanding of EV biogenesis has led to the realization that EVs facilitate intercellular communication and are sources of liquid biomarkers. EVs can be isolated and analyzed from a wide variety of accessible biofluids for biomarker discovery and diagnostic applications.

Graded BMP signaling within intestinal crypt architecture directs self-organization of the Wnt-secreting stem cell niche.

Signals from the surrounding niche drive proliferation and suppress differentiation of intestinal stem cells (ISCs) at the bottom of intestinal crypts. Among sub-epithelial support cells, deep sub-cryptal CD81 PDGFRA trophocytes capably sustain ISC functions ex vivo. Here, we show that mRNA and chromatin profiles of abundant CD81 PDGFRA mouse stromal cells resemble those of trophocytes and that both populations provide crucial canonical Wnt ligands.

An Optrode Array for Spatiotemporally Precise Large-Scale Optogenetic Stimulation of Deep Cortical Layers in Non-human Primates.

Optogenetics has transformed studies of neural circuit function, but remains challenging to apply in non-human primates (NHPs). A major challenge is delivering intense and spatially precise patterned photostimulation across large volumes in deep tissue. Here, we have developed and validated the Utah Optrode Array (UOA) to meet this critical need.

Cystathionine-γ-lyase overexpression modulates oxidized nicotinamide adenine dinucleotide biosynthesis and enhances neovascularization.

Objective: Hydrogen sulfide is a proangiogenic gas produced primarily by the transsulfuration enzyme cystathionine-γ-lyase (CGL). CGL-dependent hydrogen sulfide production is required for neovascularization in models of peripheral arterial disease. However, the benefits of increasing endogenous CGL and its mechanism of action have not yet been elucidated.

3D CT Urethrography With Cinematic Rendering (3DUG): A New Modality for Evaluation of Complex Urethral Anatomy and Assessment of the Postoperative Phalloplasty Urethra.

Objective: To develop an imaging modality for the postoperative phalloplasty urethra. Despite high urologic complication rates after masculinizing genital surgery, existing methods for postsurgical evaluation after phalloplasty have drawbacks. Fluoroscopic studies like the retrograde urethrogram have limitations like user-dependence and need for meticulous positioning but also are inadequate for the evaluation of the anatomically complex postphalloplasty urethra.

A novel thermoelectric device integrated with a psychophysical paradigm to study pain processing in human subjects.

Introduction: Cerebral projections of nociceptive stimuli are of great interest as targets for neuromodulation in chronic pain. To study cerebral networks involved in processing noxious stimuli, researchers often rely on thermo-nociception to induce pain. However, various limitations exist in many pain-inducing techniques, such as not accounting for individual variations in pain and trial structure predictability.

Fruit and vegetable consumption, pesticide residue intake from consumption of fruits and vegetables, and risk of uterine fibroids.

Objective: To examine the association between consumption of fruits and vegetables and pesticide residue intake from consumption of fruits and vegetables and risk of ultrasound- or hysterectomy-confirmed fibroids. Only a few studies have evaluated the association of fruit and vegetable intake with uterine fibroids, with inconsistent results. No studies have examined pesticide exposure through fruits and vegetables with fibroid risk.

Race and Ethnicity Reporting and Representation in Obstetrics and Gynecology Clinical Trials and Publications From 2007-2020.

Importance: Clinical trials guide evidence-based obstetrics and gynecology (OB-GYN) but often enroll nonrepresentative participants.

Objective: To characterize race and ethnicity reporting and representation in US OB-GYN clinical trials and their subsequent publications and to analyze the association of subspecialty and funding with diverse representation.

Design And Setting: Cross-sectional analysis of all OB-GYN studies registered on ClinicalTrials.

Performance and validation of the Healthy Heart Score model for predicting 12-year cardiovascular mortality in a nationwide Mediterranean population.

Introduction And Objectives: The Healthy Heart Score (HHS) is a lifestyle-based equation for predicting cardiovascular disease (CVD) risk and may serve as a tool in primordial prevention. However, its performance outside North American populations is unknown. This study assessed the performance of the HHS for estimating CVD mortality in the adult population of Spain.

Hidden in plain sight: urinary Cryptococcus neoformans missed by routine diagnostics in a patient with acute leukemia.

Cryptococcuria is a rare manifestation of localized cryptococcal disease. We present a case of Cryptococcus neoformans urinary tract infection in an immunocompromised host missed by routine laboratory workup. The patient had negative blood cultures, a negative serum cryptococcal antigen (CrAg), and "non-Candida yeast" growing in urine culture that was initially dismissed as non-pathogenic.

Chemically stable fluorescent proteins for advanced microscopy.

We report the rational engineering of a remarkably stable yellow fluorescent protein (YFP), 'hyperfolder YFP' (hfYFP), that withstands chaotropic conditions that denature most biological structures within seconds, including superfolder green fluorescent protein (GFP). hfYFP contains no cysteines, is chloride insensitive and tolerates aldehyde and osmium tetroxide fixation better than common fluorescent proteins, enabling its use in expansion and electron microscopies. We solved crystal structures of hfYFP (to 1.

Multiplexed molecular imaging with surface enhanced resonance Raman scattering nanoprobes reveals immunotherapy response in mice multichannel image segmentation.

Visualizing the presence and distribution of multiple specific molecular markers within a tumor can reveal the composition of its microenvironment, inform diagnosis, stratify patients, and guide treatment. Raman imaging with multiple molecularly-targeted surface enhanced Raman scattering (SERS) nanoprobes could help investigate emerging cancer treatments preclinically or enable personalized treatment assessment. Here, we report a comprehensive strategy for multiplexed imaging using SERS nanoprobes and machine learning (ML) to monitor the early effects of immune checkpoint blockade (ICB) in tumor-bearing mice.

Successful Derivation of Hepatoblasts, Cholangiocytes and Hepatocytes from Simian Induced Pluripotent Stem Cells.

The use of primary cells in human liver therapy is limited by a lack of cells. Induced pluripotent stem cells (iPSCs) represent an alternative to primary cells as they are infinitely expandable and can be differentiated into different liver cell types. The aim of our work was to demonstrate that simian iPSCs (siPSCs) could be used as a new source of liver cells to be used as a large animal model for preclinical studies.

Longitudinal association of dietary carbohydrate quality with visceral fat deposition and other adiposity indicators.

Background & Aims: The quality of dietary carbohydrates rather than total carbohydrate intake may determine the accumulation of visceral fat; however, to date, few studies have examined the impact of diet on adiposity using specific imaging techniques. Thus, the aim of this prospective study was to investigate the association between concurrent changes in carbohydrate quality index (CQI) and objectively-quantified adiposity distribution over a year.

Methods: We analyzed a cohort of 1476 participants aged 55-75 years with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus randomized controlled trial.

Clinical Correlates of Placenta Accreta Spectrum Disorder Depending on the Presence or Absence of Placenta Previa: A Systematic Review and Meta-analysis.

Objective: To evaluate whether there are differences in risk factors and maternal outcomes of pregnancies complicated by placenta accreta spectrum depending on the presence or absence of placenta previa.

Data Sources: We performed a systematic search in Medline, EMBASE, ClinicalTrials.gov , and Web of Science from inception through April 25, 2022, without language or date restrictions.

Inflammatory Bowel Disease and Cardiovascular Diseases.

Background: Emerging data showed patients with chronic inflammatory disorders, including inflammatory bowel disease, are more likely to develop atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. This article aims to review the evidence of those associations.

Methods: PubMed was searched from inception to January 2022 using the keywords, including inflammatory bowel diseases, Crohn disease, ulcerative colitis, atherosclerotic cardiovascular disease, coronary artery disease, cardiovascular disease, atrial fibrillation, heart failure, and premature coronary artery disease.

Multiomics assessment of dietary protein titration reveals altered hepatic glucose utilization.

Dietary protein restriction (PR) has rapid effects on metabolism including improved glucose and lipid homeostasis, via multiple mechanisms. Here, we investigate responses of fecal microbiome, hepatic transcriptome, and hepatic metabolome to six diets with protein from 18% to 0% of energy in mice. PR alters fecal microbial composition, but metabolic effects are not transferable via fecal transplantation.

Assessing clinical utility of machine learning and artificial intelligence approaches to analyze speech recordings in multiple sclerosis: A pilot study.

Background: An early diagnosis together with an accurate disease progression monitoring of multiple sclerosis is an important component of successful disease management. Prior studies have established that multiple sclerosis is correlated with speech discrepancies. Early research using objective acoustic measurements has discovered measurable dysarthria.

Odor Enrichment Attenuates the Anesthesia/Surgery-induced Cognitive Impairment.

Objective: To determine the association between olfactory function and cognition in patients and rodents.

Background: Perioperative neurocognitive disorders include delayed neurocognitive recovery (dNCR). The contribution of olfactory function to dNCR remains undetermined.