Deep Learning-Based Assessment of Lip Symmetry for Patients With Repaired Cleft Lip.

Objective: Post-surgical lip symmetry assessment is a key indicator of cleft repair success. Traditional methods rely on distances between anatomical landmarks, which are impractical for video analysis and overlook texture and appearance. We propose an artificial intelligence (AI) approach to automate this process, analyzing lateral lip morphology for a quantitative symmetry evaluation.

Oncogenic mutant KRAS inhibition through oxidation at cysteine 118.

Specific reactive oxygen species activate the GTPase Kirsten rat sarcoma virus (KRAS) by reacting with cysteine 118 (C118), leading to an electron transfer between C118 and nucleoside guanosine diphosphate (GDP), which causes the release of GDP. Here, we have mimicked permanent oxidation of human KRAS at C118 by replacing C118 with aspartic acid (C118D) in KRAS to show that oncogenic mutant KRAS is selectively inhibited via oxidation at C118, both in vitro and in vivo. Moreover, the combined treatment of hydrogen-peroxide-producing pro-oxidant paraquat and nitric-oxide-producing inhibitor N(ω)-nitro-l-arginine methyl ester selectively inhibits human mutant KRAS activity by inducing oxidization at C118.

Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease.

Vitronectin (VTN) is an important extracellular matrix protein in tissue remodeling, but its role in COPD is unknown. We show that VTN regulates tissue remodeling through urokinase plasminogen activator (uPA) signaling pathway in COPD. In human COPD airways and bronchoepithelial cells and the airways of mice with cigarette smoke (CS)-induced experimental COPD, VTN protein was not changed, but downstream uPA signaling was altered (increased plasminogen activator inhibitor-1, uPAR) that induced collagen and airway remodeling.

Filarial parasite infection prevalence in field-caught mosquitoes from Connecticut, United States.

Filarial nematodes are parasitic roundworms transmitted by mosquitoes that can cause morbidity and mortality for their human and animal hosts. The filariae community, specifically infection prevalence of heartworm, Dirofilaria immitis (Filarioidea: Onchocercidae) (Leidy), and its primary mosquito vector species, has not been described in Connecticut since 1977. In light of the recent invasion and establishment of an important filariasis vector, Aedes albopictus (Diptera: Culicidae) (Skuse), we used molecular-based sequencing methods to identify filarial species infecting field-caught mosquitoes in Connecticut, United States.

Comparison of Telehealth Versus Face-to-Face Administration of the Oral Trail Making Test in Older Adults with and without Cognitive Impairment: A Brief Report.

Objectives: To examine the performance reliability of the Oral Trail Making Test (OTMT) in face-to-face (FTF) and teleneuropsychology (TeleNP) conditions among older individuals with and without cognitive impairment.

Methods: Two hundred participants (with [n = 81], and without cognitive impairment [n = 119]) completed the OTMT in both conditions, in a counterbalanced design. Paired sample t-tests compared OTMT scores and intra-class correlation coefficients examined the degree of agreement between the two testing conditions for both diagnostic groups.

Separation Surgery Followed by Conformal Postoperative Spine Stereotactic Body Radiation Therapy Does Not Increase Risk of Adjacent Spine Level Progression in the Management of Spine Metastases.

Objectives: To determine if piecemeal separation surgery, in conjunction with smaller treatment volumes utilized with spine stereotactic radiation therapy (S-SBRT), increased the risk of adjacent level progression (ALP).

Methods: We performed a retrospective analysis of a prospectively maintained database of adult spine oncologic patients who underwent SBRT to the spine at University of Michigan from 2010 to 2021. We compared ALP in patients undergoing SBRT who had pretreatment surgery with those who did not.

Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits.

Background: As our understanding of gut microbiota's metabolic impacts on health grows, the interest in engineered probiotics has intensified. This study aimed to engineer the probiotic Escherichia coli Nissle 1917 (EcN) to produce indoleacetic acid (IAA) in response to gut inflammatory biomarkers thiosulfate and nitrate.

Results: Genetic circuits were developed to initiate IAA synthesis upon detecting inflammatory signals, optimizing a heterologous IAA biosynthetic pathway, and incorporating a RiboJ insulator to enhance IAA production.

Documentation of lead exposure-associated comorbidity among 4538 workers in China.

Background: Systematic documentation of morbidity with exposure assessment in a large group of lead (Pb)-exposed workers in China.

Methods: Using the cluster sampling method, Pb-exposed workers were recruited from a factory in the Henan Province, China. The morbidity information and blood lead concentration (BLC) from each worker were collected.

The epidemiology and unmet need of migraine in five european countries: results from the national health and wellness survey.

Background: Despite the high global prevalence, burden, and direct and indicated costs, migraines are often under-diagnosed and undertreated. Understanding the prevalence of migraine and unmet needs is crucial for improving diagnosis and treatment across Europe (EU) countries; however, real-world studies are limited.

Methods: This retrospective cross-sectional survey utilized weighted patient-reported data from the 2020 National Health and Wellness Survey (NHWS) in five EU (5EU) countries (France, Germany, United Kingdom [UK], Italy, and Spain).

Medical Students' Observations of High Value and Potentially Wasteful Care Behaviors Modeled During Clinical Rotations.

Background: Medical student exposure to role-modeling of high-value care (HVC) behaviors may shape professional identity formation and future HVC practices.

Objective: To investigate the frequency and characteristics of HVC role-modeling witnessed by medical students during core clinical rotations.

Design: Cross-sectional survey study.

Perceived Discrimination in the Healthcare Setting and Medical Mistrust: Findings from the Health Information National Trends Survey, 2022.

Background: Perceived discrimination and medical mistrust are barriers to care that impact both individual and population health.

Objective: This study aims to characterize the prevalence of perceived racial or ethnic discrimination in healthcare as well as mistrust in the medical system and explore their associations with race and ethnicity.

Design: Cross-sectional study of nationally representative data from the Health Information National Trends Survey (fielded March-November 2022).

Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial.

Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Intermittent documentation of blood pressure values does not provide comprehensive evaluation of the hemodynamic response during continuous intravenous medication administration.

Blood pressure (BP) is a dynamic measure that is frequently discussed in static terms. There exist many limitations in current documentation systems whereby documented BP values may not be reflective of the dynamic variability of BP. This study used an observational, prospective, non-randomized study design to examine the variability in BP response during intravenous vasoactive medication administration in an intensive care unit setting.

Humanized dual-targeting antibody-drug conjugates specific to MET and RON receptors as a pharmaceutical strategy for the treatment of cancers exhibiting phenotypic heterogeneity.

Cancer heterogeneity, characterized by diverse populations of tumorigenic cells, involves the occurrence of differential phenotypes with variable expressions of receptor tyrosine kinases. Aberrant expressions of mesenchymal-epithelial transition (MET) and recepteur d'origine nantais (RON) receptors contribute to the phenotypic heterogeneity of cancer cells, which poses a major therapeutic challenge. This study aims to develop a dual-targeting antibody-drug conjugate (ADC) that can act against both MET and RON for treating cancers with high phenotypic heterogeneity.

Measurements of groundwater, hydrodynamics, and sand characteristics at a dissipative sea turtle nesting beach.

Beach groundwater and nearshore hydrodynamic data were collected during a field experiment along two dissipative beach transects on Galveston Island, Texas, in the fall of 2023. The monitored beaches serve as nesting habitat for the critically endangered Kemp's ridley sea turtle. Conditions ranged from calm to stormy, with two storms occurring during the experiment, inundating the entire beach up to the dune toe.

GnIH secreted by green light exposure, regulates bone mass through the activation of Gpr147.

Reproductive hormones associated with the hypothalamic-pituitary-gonadal (HPG) axis are closely linked to bone homeostasis. In this study, we demonstrate that Gonadotropin inhibitory hormone (GnIH, one of the key reproductive hormones upstream of the HPG axis) plays an indispensable role in regulating bone homeostasis and maintaining bone mass. We find that deficiency of GnIH or its receptor Gpr147 leads to a significant reduction in bone mineral density (BMD) in mice primarily by enhancement of osteoclast activation in vivo and in vitro.

TRAF2 and RIPK1 redundantly mediate classical NFκB signaling by TNFR1 and CD95-type death receptors.

This study suggests a modified model of TNFR1-induced complex I-mediated NFκB signaling. Evaluation of a panel of five tumor cell lines (HCT116-PIK3CAmut, SK-MEL-23, HeLa-RIPK3, HT29, D10) with TRAF2 knockout revealed in two cell lines (HT29, HeLa-RIPK3) a sensitizing effect for death receptor-induced necroptosis and in one cell line (D10) a mild sensitization for TNFR1-induced apoptosis. TRAF2 deficiency inhibited death receptor-induced classical NFκB-mediated production of IL-8 only in a subset of cell lines and only partly.

Vaccines in a time of global boiling and megacities.

Neglected tropical diseases are accelerating because of climate change and urbanization to create new clusters of vast urban areas beset by poverty and environmental degradation. These hot and contaminated megacities could enable the rise of parasitic and other tropical infections. A new generation of antiparasitic vaccines will be needed.

Durability of response of UGN-101: Longitudinal follow up of multicenter study.

Purpose: UGN-101, a reverse thermal mitomycin gel for upper tract instillation, recently became the first FDA approved treatment for upper tract urothelial carcinoma (UTUC). However, the durability of UGN-101 treatment has not been well described. Here we present long term outcomes from our multi-institutional cohort for patients who initially responded to treatment.

Cross-Cultural Adaptation and Validation of the Central Sensitization Inventory Into Simplified Chinese.

Purpose: To translate the Central Sensitization Inventory from English into simplified Chinese (CSI-sC) and test the psychometric properties of the CSI-sC in patients with chronic pain.

Design: A cross-sectional design was used.

Methods: Cross-cultural adaptation of the CSI-sC was performed following Beaton's guidelines.