Early transcriptomic changes at the skin interface during Powassan virus transmission by ticks.

Introduction: Powassan virus (POWV), a vector-borne pathogen transmitted by ticks in North America, is the causative agent of Powassan encephalitis. As obligate hematophagous organisms, ticks transmit pathogens like POWV at the tick bite site, specifically during the initial stages of feeding. Tick feeding and salivary factors modulate the host's immunological responses, facilitating blood feeding and pathogen transmission.

Inpp5e Is Critical for Photoreceptor Outer Segment Maintenance.

In humans, inositol polyphosphate-5-phosphatase e (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. In mice, mutations cause a spectrum of brain, kidney, and other anomalies and prevent the formation of photoreceptor outer segments. To further explore the function of Inpp5e in photoreceptors, we generated conditional and inducible knockouts of mouse Inpp5e where the gene was deleted either during outer segment formation or after outer segments were fully formed.

Impact of cariprazine on body weight and blood pressure among adults with bipolar I disorder, schizophrenia, or major depressive disorder in a real-world setting.

Background: Atypical antipsychotics are a common treatment for serious mental illness, but many are associated with adverse effects, including weight gain and cardiovascular issues, and real-world experience may differ from clinical trial data. Cariprazine has previously demonstrated a favorable safety and tolerability profile in clinical trials. Here, we evaluated the effects of cariprazine on body weight and blood pressure for bipolar I disorder (BP-I), schizophrenia, or as adjunctive treatment for major depressive disorder (MDD) using real-world data.

Are Randomized Trials Better? Comparison of Baseline Covariate Balance of a Propensity Score-Balanced Lumbar Spine IDE Trial and Comparable RCTs.

Study Design: Prospective Observational Propensity Score.

Objectives: Randomization may lead to bias when the treatment is unblinded and there is a strong patient preference for treatment arms (such as in spinal device trials). This report describes the rationale and methods utilized to develop a propensity score (PS) model for an investigational device exemption (IDE) trial (NCT03115983) to evaluate decompression and stabilization with an investigational dynamic sagittal tether (DST) vs decompression and Transforaminal Lumbar Interbody Fusion (TLIF) for patients with symptomatic grade I lumbar degenerative spondylolisthesis with spinal stenosis.

Resonances of Feeling Alone: A Systematic Review Unveiling Older Persons' Loneliness and Its Mechanisms in Residential Care Facilities.

Aim: To review older persons' lived experiences and perceptions of loneliness in residential care facilities and characterise mechanisms underlying their experiences through a comprehensive loneliness model.

Design: A systematic review synthesising qualitative research on the experiences of loneliness among older people living in residential care facilities.

Methods: This review followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines with quality appraisal conducted using the Critical Appraisal Skills Programme checklist.

Therapeutic outcomes and safety of radiofrequency ablation for primary papillary thyroid carcinoma: A game-changing meta-analysis.

Background: Radiofrequency ablation (RFA) is an emerging treatment option for small, low-risk papillary thyroid carcinoma (PTC). This systematic review and meta-analysis aimed to evaluate and compare the efficacy and safety profiles of RFA for primary T1a vs. T1b PTC.

Pericytes mediate neuroinflammation via Fli-1 in endotoxemia and sepsis in mice.

Background: Sepsis-associated encephalopathy (SAE) often results from neuroinflammation. Recent studies have shown that brain platelet-derived growth factor receptor β (PDGFRβ) cells, including pericytes, may act as early sensors of infection by secreting monocyte chemoattractant protein-1 (MCP-1), which transmits inflammatory signals to the central nervous system. The erythroblast transformation-specific (ETS) transcription factor Friend leukemia virus integration 1 (Fli-1) plays a critical role in inflammation by regulating the expression of key cytokines, including MCP-1.

Evolutionary and Structural Insights into the RNA Polymerase I A34 Protein Family: A Focus on Intrinsic Disorder and Phase Separation.

Background: Eukaryotic RNA polymerase I consists of 12 or 11 core subunits and three dissociable subunits, Rrn3, A34, and A49. The A34 and A49 subunits exist as a heterodimer. In silico analysis of the A34 family of transcription factors demonstrates a commonly shared domain structure despite a lack of sequence conservation, as well as N-terminal and C-terminal disordered regions.

Understanding the Impact of Obesity on Liver Transplant Outcomes: A Comprehensive Analysis.

Background: The purpose of this investigation is to assess how effective it is to exclude individuals from the liver transplant (LT) using the body mass index (BMI) as a criterion.

Methods And Materials: A retrospective longitudinal analysis of patients with liver transplant outcomes from January 2001 to May 2020 was conducted using the United Network for Organ Sharing (UNOS) database.

Results: A total of 118,486 LT cases included in the study.

A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis.

Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population.

Methods: We conducted a systematic review and individual participant data meta-analysis.

Prevalence of Autoimmune Diseases in Patients Treated With Immune Checkpoint Inhibitors: An Epidemiological Study Using A Global Network of Health Care Organizations.

Objective: Evaluate prevalence of new onset autoimmune conditions (ACs) after commencement of immune checkpoint inhibitors (ICIs).

Methods: This retrospective observational study was done using TriNetX. Patients with neoplasm for which ICIs were approved were stratified into two groups based on ICI use.

The Role of WDR77 in Cancer: More Than a PRMT5 Interactor.

WD repeat domain 77 protein (WDR77), a WD-40 domain-containing protein, is a crucial regulator of cellular pathways in cancer progression. While much of the past research on WDR77 has focused on its interaction with PRMT5 in histone methylation, WDR77's regulatory functions extend beyond this pathway, influencing diverse mechanisms such as mRNA translation, chromatin assembly, cell cycle regulation, and apoptosis. WDR77 is a key regulator of cell cycle progression, regulating the transition from the G1 phase.

Know Your ABCs: Discovery, Differentiation, and Targeting of T-Bet+ B Cells.

Since their first description in 2008, T-bet+ B cells have emerged as a clinically important B cell subset. Now commonly known as ABCs (Age-associated B Cells), they are uniquely characterized by their expression of the transcription factor T-bet. Indeed, this singular factor defines this B cell subset.

Revisiting motor unit recruitment to TMS in amyotrophic lateral sclerosis: cortical inhibition is retained during voluntary contractions.

Transcranial magnetic stimulation (TMS) has been used for many years to study the pathophysiology of amyotrophic lateral sclerosis (ALS). Based on single- or dual-pulse TMS and EMG and/or single motor unit (MU) recordings, many groups have described a loss of central inhibition as an early marker of ALS dysfunction, reflecting a state of cortical 'hyperexcitability'. This conclusion is not without its detractors, however, leading us to reexamine this issue using 4-pulse TMS, shown previously to be more effective for testing central motor pathway functional integrity.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Aminocholestane and Aminoandrostane Inhibitors of the SH2 Domain-Containing Inositol 5'-Phosphatase (SHIP).

The SH2-containing inositol phosphatase (SHIP) has become an actively researched therapeutic target for a number of disorders, including Alzheimer's Disease, Graft-vs-Host disease, obesity and cancer. Analogs of the aminosteroid SHIP inhibitor 3a-aminocholestane (3AC) have been synthesized and tested. Analogs with improved water solubility have been identified.

Psychiatric, Neurological, and Somatic Comorbidities in Intermittent Explosive Disorder.

Importance: Intermittent explosive disorder (IED) is an understudied psychiatric condition marked by impulsive aggression and poorly regulated emotional control, often resulting in interpersonal and societal consequences. Better understanding of comorbidities can improve screening, diagnosis, and treatment.

Objective: To investigate the prevalence of IED and its associations with psychiatric, neurological, and somatic disorders.

Impact of cell plasticity on prostate tumor heterogeneity and therapeutic response.

Epithelial-mesenchymal transition (EMT) is a dynamic process of lineage plasticity in which epithelial cancer cells acquire mesenchymal traits, enabling them to metastasize to distant organs. This review explores the current understanding of how lineage plasticity and phenotypic reprogramming drive prostate cancer progression to lethal stages, contribute to therapeutic resistance, and highlight strategies to overcome the EMT phenotype within the prostate tumor microenvironment (TME). Emerging evidence reveals that prostate tumor cells can undergo lineage switching, adopting alternative growth pathways in response to anti-androgen therapies and taxane-based chemotherapy.

Lymphocytic Gastritis in a Patient With Microscopic Colitis: A Case Report.

Lymphocytic gastritis (LG) is a rare form of gastritis characterized by lymphocytosis in the gastric mucosa, while microscopic colitis (MC) is the chronic inflammatory disease of the large intestine with lymphocytic or collagenous colitis as two distinct histologic forms. These lymphocytic disorders of the gastrointestinal tract (GIT) have various associations, commonly gluten-sensitive enteropathy, infection and while others are less commonly associated. We report a case of a 24-year-old patient with concomitant lymphocytic gastritis and microscopic colitis diagnosed via histopathologic analysis of tissue specimens from stomach and colon.

Prognostic Indicators and Comparative Treatment Outcomes in High-Risk Thyroid Cancer with Laryngotracheal Invasion.

Background: Laryngotracheal invasion occurs in a subset of patients with well-differentiated thyroid cancer (WDTC) and is associated with a poor prognosis. We aimed to analyze patterns and predictors/outcomes related to this high-risk manifestation.

Methods: This population-based analysis utilized the Surveillance, Epidemiology, and End Results (SEER) registry (2000 to 2015) to identify WDTC patients.

The Impact of Learning Curve on Robotic Living Donor Nephrectomy Outcomes: Retrospective Analysis.

Background: We aimed to investigate the outcome of patients after RDN at different time points.

Methods: We studied the outcomes of 77 living robotic living donor nephrectomies (RDN). Donors were separated into three groups: learning curve period (LCP), stabilisation period (SP), and teaching period (TP).

Monoclonal nanobodies alter the activity and assembly of the yeast vacuolar H-ATPase.

The vacuolar ATPase (V-ATPase; VV) is a multi-subunit rotary nanomotor proton pump that acidifies organelles in virtually all eukaryotic cells, and extracellular spaces in some specialized tissues of higher organisms. Evidence suggests that metastatic breast cancers mislocalize V-ATPase to the plasma membrane to promote cell survival and facilitate metastasis, making the V-ATPase a potential drug target. We have generated a library of camelid single-domain antibodies (Nanobodies; Nbs) against lipid-nanodisc reconstituted yeast V-ATPase V proton channel subcomplex.