Epidermal spongiotic Langerhans cell collections, but not eosinophils, are a clue to the diagnosis of allergic contact dermatitis: A series of 170 clinically- and patch test-confirmed cases.

Background: Allergic contact dermatitis cannot be reliably differentiated from other forms of spongiotic/eczematous dermatitis by histology alone. Textbooks and recent studies have variably supported the specificity of dermal eosinophils, eosinophilic spongiosis, and Langerhans cell collections, among other features.

Objective: To assess which histopathologic features favor a diagnosis of allergic contact dermatitis.

Primary Biliary Cholangitis: personalizing second-line therapies.

Primary biliary cholangitis (PBC) is an enigmatic, autoimmune disease targeting the small intralobular bile ducts resulting in cholestasis and potentially progression to biliary cirrhosis. Primarily affecting middle-aged women, the diagnosis of PBC is typically straightforward, with most patients presenting with cholestatic liver tests and the highly specific antimitochondrial antibody. For decades, the foundational treatment of PBC has been ursodeoxycholic acid, which delays disease progression in most patients but has no impact on PBC symptoms.

The lateral habenula is necessary for maternal behavior in the naturally parturient primiparous mouse dam.

Mammalian parenting is an unusually demanding commitment. How has the reward system been co-opted to ensure parental care? Previous work has implicated the lateral habenula (LHb), an epithalamic nucleus, as a potential intersection of parenting behavior and reward. Here, we examine the role of the LHb in the maternal behavior of naturally parturient primiparous mouse dams.

Natural Language Processing to Identify Infants Aged 90 Days and Younger With Fevers Prior to Presentation.

Objective: Natural language processing (NLP) can enhance research studies for febrile infants by more comprehensive cohort identification. We aimed to refine and validate an NLP algorithm to identify and extract quantified temperature measurements from infants aged 90 days and younger with fevers at home or clinics prior to emergency department (ED) visits.

Patients And Methods: We conducted a cross-sectional study using electronic health record (EHR) data from 17 EDs in 10 health systems that are part of the Pediatric Emergency Care Applied Research Network Registry.

Clinical Course of Isolated Recurrent, Persistent Complex Perianal Fistulas Without Luminal Crohn's Disease: A Multicenter Case Series of 24 Patients.

Background: Isolated complex perianal fistulas, without luminal evidence of inflammatory bowel disease in the gastrointestinal tract, pose diagnostic and treatment dilemmas for gastroenterologists and colorectal surgeons. For patients who develop recurrent complex fistulas, a presumptive diagnosis of Crohn's disease may be made. It is unclear whether these cases of isolated perianal disease in the absence of luminal inflammation truly represent isolated severe cryptoglandular fistulas or rather an early presentation of Crohn's disease.

Transformation of a Testicular Teratoma to an Aggressive Primitive Neuroectodermal Tumor.

We present a case of a 36-year-old male found to have a nonseminomatous germ cell tumor (NSGCT) with alpha-fetoprotein levels (AFP) of 737.9 ng/mL and beta-human chorionic gonadotropin (β-HCG) of 692 IU/mL. Pathology analysis after left orchiectomy showed a mixed germ cell tumor with 20% embryonal carcinoma, 20% yolk sac tumor, and 60% teratoma.

Non-alcohol-related cirrhosis leads to higher 6-week mortality after acute variceal bleeding than alcohol-related cirrhosis.

Introduction: Acute variceal bleeding (AVB) portends significant 6-week mortality in patients with cirrhosis. It remains unclear if the correlation between liver prognostic scores and 6-week mortality are similar across different etiologies of liver cirrhosis, particularly alcohol-related liver disease (ALD) vs. non-alcohol-related liver disease (non-ALD).

Ruxolitinib-dependent reduction of seizure load and duration is accompanied by spatial memory improvement in the rat pilocarpine model of temporal lobe epilepsy.

Molecules with optimized pharmacokinetic properties selectively aimed at the inhibition of STAT3 phosphorylation in brain have recently emerged as potential disease modifying therapies for epilepsy. In the current study, pharmacological inhibition of JAK1/2 with the orally available, FDA-approved drug ruxolitinib, produced nearly complete inhibition of hippocampal STAT3 phosphorylation, and reduced the expression of its downstream target Cyclin D1, when administered to rats 30 ​min and 3 ​h after onset of pilocarpine-induced status epilepticus (SE). This effect was accompanied by significantly shorter seizure duration and lower overall seizure frequency throughout the 4 weeks of EEG recording, but did not completely prevent the development of epilepsy in ruxolitinib-treated male rats.

Childhood adversity and late-life cognitive and brain health in a diverse cohort.

Introduction: Childhood adversity harms neurodevelopment. Literature on late-life brain health is limited, and findings on late-life cognition are mixed.

Methods: Pooling data from Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) and Study of Healthy Aging in African Americans (STAR) cohorts, we assessed the impact of childhood adversity (factor score from seven self-reported items) on (a) executive function and verbal memory decline using linear mixed effects models (n = 2447), (b) structural magnetic resonance imaging (MRI) using linear regression (n = 618), and (c) amyloid positron emission tomography (PET) using generalized linear models (n = 331), all adjusting for early-life demographic and socioeconomic confounders.

The TRIM37 variant rs57141087 contributes to triple-negative breast cancer outcomes in Black women.

Triple-negative breast cancer (TNBC) disproportionately affects younger Black women, who show more aggressive phenotypes and poorer outcomes than women of other racial identities. While the impact of socioenvironmental inequities within and beyond health systems is well documented, the genetic influence in TNBC-associated racial disparities remains elusive. Here, we report that cancer-free breast tissue from Black women expresses TRIM37 at a significantly higher level relative to White women.

The Impact of a Ketogenic Diet on Late-Stage Pancreatic Carcinogenesis in Mice: Efficacy and Safety Studies.

Background: High-fat diets (HFDs) have been associated with an increased risk of pancreatic cancer. In contrast, ketogenic diets (KDs) have been shown to display anti-tumor characteristics. The objective of this work was to evaluate the efficacy of a KD on late-stage pancreatic carcinogenesis in a genetically modified mouse model of pancreatic cancer [LSL-; -Cre (KC) mice], as well as its liver safety, and to compare it to that of an HFD.

Epigenetic Modulations by Microbiome in Breast Cancer.

Recent studies have identified a critical role of the diverse and dynamic microbiome in modulating various aspects of host physiology and intrinsic processes. However, the altered microbiome has also become a hallmark of cancer, which could influence the tumor microenvironment. Aberrations in epigenetic regulation of tumor suppressors, apoptotic genes, and oncogenes can accentuate breast cancer onset and progression.

A developmental biliary lineage program cooperates with Wnt activation to promote cell proliferation in hepatoblastoma.

Cancers evolve not only through the acquisition and clonal transmission of somatic mutations but also by epigenetic mechanisms that modify cell phenotype. Here, we use histology-guided and spatial transcriptomics to characterize hepatoblastoma, a childhood liver cancer that exhibits significant histologic and proliferative heterogeneity despite clonal activating mutations in the Wnt/β-catenin pathway. Highly proliferative regions with embryonal histology show high expression of Wnt target genes, the embryonic biliary transcription factor SOX4, and striking focal expression of the growth factor FGF19.

Measurement Error and Methodologic Issues in Analyses of the Proportion of Variance Explained in Cognition.

Existing studies examining the predictive ability of biomarkers for cognitive outcomes do not account for variance due to measurement error, which could lead to under-estimates of the proportion of variance explained. We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 1084) to estimate the proportion of variance explained by Alzheimer's disease (AD) imaging biomarkers in four cognitive outcomes: memory, executive functioning, language, and visuospatial functioning. We compared estimates from standard models that do not account for measurement error, and multilevel models that do account for measurement error.

Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca and Mg in the formulation.

Oligonucleotide therapeutics (ASOs and siRNAs) have been explored for modulation of gene expression in the central nervous system (CNS), with several drugs approved and many in clinical evaluation. Administration of highly concentrated oligonucleotides to the CNS can induce acute neurotoxicity. We demonstrate that delivery of concentrated oligonucleotides to the CSF in awake mice induces acute toxicity, observable within seconds of injection.