The Impact of Family History on Clinical Presentation and Biologic Treatment Response in Patients with Psoriasis: A Multicenter Prospective Cohort Study.

Background: Family history (FH) of psoriasis has been implicated as a risk factor for developing psoriasis. However, whether FH also carries information on clinical presentation and treatment response to biological agents in patients with psoriasis remains unclear.

Objective: This prospective, multicenter observational study aimed to analyze the clinical presentation and efficacy differences between patients with psoriasis with and without a FH.

Concomitant Chronic Lateral Ankle Instability Affects Postoperative Functional Outcomes in Patients With Osteochondral Lesions of the Talus but Does Not Affect Cartilage Repair After Restoration of Ankle Stability.

Purpose: To investigate the effect of concomitant chronic lateral ankle instability (CLAI) on postoperative clinical outcomes in patients with osteochondral lesions of the talus (OLTs).

Methods: Patients who underwent surgery for OLTs between January 2018 and May 2022 were retrospectively evaluated. OLT patients underwent debridement, microfracture, or bone grafting, whereas patients with concomitant CLAI underwent lateral ligament repair or reconstruction.

Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer.

The efficacy of immunotherapy for estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC) has not been proven. We conduct a phase 1b/2 trial to assess the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with premenopausal ER+/HER2- MBC who had failed one to two lines of hormone therapy (HT) without chemotherapy. The primary endpoint of progression-free survival rate at 8 months (i.

Targeting P4HA1 promotes CD8 T cell progenitor expansion toward immune memory and systemic anti-tumor immunity.

Successful immunotherapy relies on both intratumoral and systemic immunity, which is yet to be achieved for most patients with cancer. Here, we identify P4HA1, encoding prolyl 4-hydroxylase 1, as a crucial regulator of CD8 T cell differentiation strongly upregulated in tumor-draining lymph nodes (TDLNs) and hypoxic tumor microenvironment. P4HA1 accumulates in mitochondria, disrupting the tricarboxylic acid (TCA) cycle through aberrant α-ketoglutarate and succinate metabolism, promoting mitochondria unfitness and exhaustion while suppressing progenitor expansion.

Cardiovascular Events Associated with CDK4/6 Inhibitors: A Safety Meta-Analysis of Randomized Controlled Trials and a Pharmacovigilance Study of the FAERS Database.

Background: CDK4/6 inhibitors are highly valued, but the incidence of cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors is not clear.

Objective: Our aim was therefore to assess the risk of developing CVAEs associated with CDK4/6 inhibitors, by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), along with a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database.

Methods: Eligible CVAEs were extracted from the ClinicalTrials.

Dexmedetomidine Regulates Macrophage Phenotype Remodeling Through AMPK/SIRT1 to Alleviate Inflammatory Mediators and Lung Injury.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality in the intensive care unit (ICU) and can cause excessive inflammation. Dexmedetomidine (DEX) is a drug that exerts anti-inflammatory effects. Identifying the anti-inflammatory mechanism of DEX in the context of ALI/ARDS possesses potential significance for the prevention and treatment of ARDS.

Exploring the valleytronic, optical, and piezoelectric properties of Janus MoBXY (X = N, P; Y = S, Se, Te) monolayers for multifunctional applications.

Inspired by recent studies on MoS and MoSiN, we propose and investigate Janus MoBXY (X = N, P; Y = S, Se, Te) monolayers, which exhibit robust dynamic and thermal stabilities. Our findings reveal that all these monolayers are semiconductors, with MoBNS and MoBPTe exhibiting direct band gaps at the K/K' points, resulting in degenerate valleys and significant valley spin splitting (VSS) in the valence band. Notably, Berry curvatures at K and K' points, with opposite signs, suggest potential for inducing the valley Hall effect (VHE).

Mutant-selective AKT inhibition through lysine targeting and neo-zinc chelation.

Somatic alterations in the oncogenic kinase AKT1 have been identified in a broad spectrum of solid tumours. The most common AKT1 alteration replaces Glu17 with Lys (E17K) in the regulatory pleckstrin homology domain, resulting in constitutive membrane localization and activation of oncogenic signalling. In clinical studies, pan-AKT inhibitors have been found to cause dose-limiting hyperglycaemia, which has motivated the search for mutant-selective inhibitors.

Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging.

To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging.

A Nomogram for the Prediction of Invasiveness in Invasive Pulmonary Adenocarcinoma on the Basis of Multimodal PET/CT Parameters.

Objective: We investigated the value of PET/CT-based multimodal parameters in predicting the degree of differentiation and epidermal growth factor receptor (EGFR) mutations in invasive lung adenocarcinoma (ILA) and assessed the correlation between PET/CT-based multimodal parameters and Ki67.

Methods: We retrospectively collected 113 patients with ILA who underwent PET/CT examination, and differences in PET/CT multimodal parameters between different differentiation groups were analyzed. Binary logistic regression was used to establish a multiparameter model for predicting EGFR mutation, and ROC curve was used to compare the diagnostic efficiency.

Large-scale map of RNA-binding protein interactomes across the mRNA life cycle.

mRNAs interact with RNA-binding proteins (RBPs) throughout their processing and maturation. While efforts have assigned RBPs to RNA substrates, less exploration has leveraged protein-protein interactions (PPIs) to study proteins in mRNA life-cycle stages. We generated an RNA-aware, RBP-centric PPI map across the mRNA life cycle in human cells by immunopurification-mass spectrometry (IP-MS) of ∼100 endogenous RBPs with and without RNase, augmented by size exclusion chromatography-mass spectrometry (SEC-MS).

Enhanced Optoelectronic Performance of p-WSe/ReWMoS Heterojunction.

Stacking of van der Waals (vdW) heterostructures and chemical element doping have emerged as crucial methods for enhancing the performance of semiconductors. This study proposes a novel strategy for modifying heterostructures by codoping MoS with two elements, Re and W, resulting in the construction of a ReWMoS/WSe heterostructure for the preparation of photodetectors. This approach incorporates multiple strategies to enhance the performance, including hybrid stacking of materials, type-II band alignment, and regulation of element doping.

Target engagement and immunogenicity of an active immunotherapeutic targeting pathological α-synuclein: a phase 1 placebo-controlled trial.

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF).

Breast Cancer: Multi-b-Value Diffusion Weighted Habitat Imaging in Predicting Pathologic Complete Response to Neoadjuvant Chemotherapy.

Rationale And Objectives: The aim of this study was to ascertain whether the utilization of multiple b-value diffusion-weighted habitat imaging, a technique that depicts tumor heterogeneity, could aid in identifying breast cancer patients who would derive substantial benefit from neoadjuvant chemotherapy (NAC).

Materials And Methods: This prospective study enrolled 143 women (II-III breast cancer), who underwent multi-b-value diffusion-weighted imaging (DWI) in 3-T magnetic resonance (MR) before NAC. The patient cohort was partitioned into a training set (consisting of 100 patients, of which 36 demonstrated a pathologic complete response [pCR]) and a test set (featuring 43 patients, 16 of whom exhibited pCR).

Development and Validation of a Supplementary Grading Scale for Outcomes of Brainstem Cavernous Malformations.

Background: Surgical risk assessment is intriguing for clinical decision-making of brainstem cavernous malformation (BSCM) treatment. While the BSCM grading scale, encompassing size, developmental venous anomaly, crossing axial midpoint, age, and timing of intervention, is increasingly utilized, the clinical relevance of neurological fluctuation and recurrent hemorrhage has not been incorporated. This study aimed to propose a supplementary grading scale with enhanced predictive efficacy.

Seizure, Motor, and Cognitive Outcomes After Epilepsy Surgery for Patients With Sturge-Weber Syndrome: Results From a Multicenter Study.

Background And Objectives: Surgery is widely performed for refractory epilepsy in patients with Sturge-Weber syndrome (SWS), but reports on its effectiveness are limited. This study aimed to analyze seizure, motor, and cognitive outcomes of surgery in these patients and to identify factors associated with the outcomes.

Methods: This was a multicenter retrospective observational study using data from patients with SWS and refractory epilepsy who underwent epilepsy surgery between 2000 and 2020 at 16 centers throughout China.

Right Ventricular Strain Derived from Cardiac MRI Feature Tracking for the Diagnosis and Prognosis of Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose To demonstrate the myocardial strain characteristics of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), based on revised Task Force Criteria (rTFC), and to explore the prognostic value of strain analysis in ARVC. Materials and Methods This retrospective study included 247 patients (median age, 38 years [IQR, 28-48 years]; 167 male, 80 female) diagnosed with ARVC, based on rTFC, between 2014 and 2018. Patients were divided into "possible" ( =25), "borderline" ( = 40), and "definite" ( = 182) ARVC groups following rTFC.

Distinctive Pattern of Metal Deposition in Neurologic Wilson Disease: Insights From 7T Susceptibility-Weighted Imaging.

Background And Objectives: Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD.

PDZ-Binding Kinase, a Novel Regulator of Vascular Remodeling in Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH) is high blood pressure in the lungs that originates from structural changes in small resistance arteries. A defining feature of PAH is the inappropriate remodeling of pulmonary arteries (PA) leading to right ventricle failure and death. Although treatment of PAH has improved, the long-term prognosis for patients remains poor, and more effective targets are needed.

LTK mutations responsible for resistance to lorlatinib in non-small cell lung cancer harboring CLIP1-LTK fusion.

The CLIP1-LTK fusion was recently discovered as a novel oncogenic driver in non-small cell lung cancer (NSCLC). Lorlatinib, a third-generation ALK inhibitor, exhibited a dramatic clinical response in a NSCLC patient harboring CLIP1-LTK fusion. However, it is expected that acquired resistance will inevitably develop, particularly by LTK mutations, as observed in NSCLC induced by oncogenic tyrosine kinases treated with corresponding tyrosine kinase inhibitors (TKIs).

Rupture-Related Features of Cerebral Arteriovenous Malformations and Their Utility in Predicting Hemorrhage.

Background: Evaluating rupture risk in cerebral arteriovenous malformations currently lacks quantitative hemodynamic and angioarchitectural features necessary for predicting subsequent hemorrhage. We aimed to derive rupture-related hemodynamic and angioarchitectural features of arteriovenous malformations and construct an ensemble model for predicting subsequent hemorrhage.

Methods: This retrospective study included 3 data sets, as follows: training and test data sets comprising consecutive patients with untreated cerebral arteriovenous malformations who were admitted from January 2015 to June 2022 and a validation data set comprising patients with unruptured arteriovenous malformations who received conservative treatment between January 2009 and December 2014.