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.

ON-OFF nanopores for optical control of transmembrane ionic communication.

Nanoscale photoswitchable proteins could facilitate precise spatiotemporal control of transmembrane communication and support studies in synthetic biology, neuroscience and bioelectronics. Here, through covalent modification of the α-haemolysin protein pore with arylazopyrazole photoswitches, we produced 'photopores' that transition between iontronic resistor and diode modes in response to irradiation at orthogonal wavelengths. In the diode mode, a low-leak OFF-state nanopore exhibits a reversible increase in unitary conductance of more than 20-fold upon irradiation at 365 nm.

Improving polyketide biosynthesis by rescuing the translation of truncated mRNAs into functional polyketide synthase subunits.

Modular polyketide synthases (mPKSs) are multidomain enzymes in bacteria that synthesize a variety of pharmaceutically important compounds. mPKS genes are usually longer than 10 kb and organized in operons. To understand the transcriptional and translational characteristics of these large genes, here we split the 13-kb busA gene, encoding a 456-kDa three-module PKS for butenyl-spinosyn biosynthesis, into three smaller separately translated genes encoding one PKS module in an operon.

Survival outcomes, multidimensional prediction and subsequent therapy in patients with hormone receptor-positive advanced breast cancer receiving palbociclib: a real-world analysis.

Background: To date, the overall survival (OS) of hormone receptor-positive advanced breast cancer (ABC) treated with palbociclib has not been reported in Chinese patients. It still remains unclear what kind of patients may benefit in OS from palbociclib treatment and what the optimal sequential antineoplastic regimen is for those progressing on palbociclib. Therefore, we aimed to investigate the OS outcome of ABC patients receiving palbociclib, establish a predictive model to identify the potential candidates who may benefit from palbociclib and explore the ideal subsequent treatment strategy after palbociclib.

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

Proteolysis-targeting influenza vaccine strains induce broad-spectrum immunity and in vivo protection.

Generating effective live vaccines from intact viruses remains challenging owing to considerations of safety and immunogenicity. Approaches that can be applied in a systematic manner are needed. Here we created a library of live attenuated influenza vaccines by using diverse cellular E3 ubiquitin ligases to generate proteolysis-targeting (PROTAR) influenza A viruses.

A Serial MRI-based Deep Learning Model to Predict Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

Purpose To develop and evaluate a deep learning-based prognostic model for predicting survival in locoregionally- advanced nasopharyngeal carcinoma (LA-NPC) using serial MRI before and after induction chemotherapy (IC). Materials and Methods This multicenter retrospective study included 1039 LA-NPC patients (779 male, 260 female, mean age 44 [standard deviation: 11]) diagnosed between April 2009 and December 2015. A radiomics- clinical prognostic model (Model RC) was developed using pre-and post-IC MRI and other clinical factors using graph convolutional neural networks (GCN).

High clinical utility of long-read sequencing for precise diagnosis of congenital adrenal hyperplasia in 322 probands.

Background: The molecular genetic diagnosis of congenital adrenal hyperplasia (CAH) is very challenging due to the high homology between the CYP21A2 gene and its pseudogene CYP21A1P.

Methodology: This study aims to assess the clinical efficacy of targeted long-read sequencing (T-LRS) by comparing it with a control method based on the combined assay (NGS, Multiplex ligation-dependent probe amplification and Sanger sequencing) and to introduce T-LRS as a first-tier diagnostic test for suspected CAH patients to improve the precise diagnosis of CAH.

Results: A large cohort of 562 participants including 322 probands and 240 family members was enrolled for the perspective (96 probands) and prospective study (226 probands).

Machine Learning and Computed Tomography Radiomics to Predict Disease Progression to Upfront Pembrolizumab Monotherapy in Advanced Non-Small-Cell Lung Cancer: A Pilot Study.

Background/objectives: Pembrolizumab monotherapy is approved in Canada for first-line treatment of advanced NSCLC with PD-L1 ≥ 50% and no EGFR/ALK aberrations. However, approximately 55% of these patients do not respond to pembrolizumab, underscoring the need for the early intervention of non-responders to optimize treatment strategies. Distinguishing the 55% sub-cohort prior to treatment is a real-world dilemma.

Defecation Site Preferences and Spatial Ecological Segregation of Forest Musk Deer and Siberian Roe Deer in North China.

The forest musk deer () and Siberian roe deer () are browsers with a broad sympatric distribution in North and Southwest China. However, little is known about their spatial utilization of microhabitats and habitats. This study, conducted on Huanglong Mountain in China, analyzed the defecation site distribution, indicating preferences of forest musk deer and Siberian roe deer for their habitat demands.

Systemic Sodium Iodate Injection as a Model for Expanding Geographic Atrophy.

Purpose: Geographic atrophy (GA), an advanced form of dry age-related macular degeneration (AMD), has limited treatment options. This study introduces a novel mouse model featuring an expanding GA patch that can be used to test mechanisms and therapeutics.

Methods: C57Bl/6J male mice (n = 96) aged 9-10 weeks received an intraperitoneal (IP) injection of 20 mg/kg sodium iodate (NaIO3).

Molecular and cellular dynamics of the developing human neocortex.

The development of the human neocortex is highly dynamic, involving complex cellular trajectories controlled by gene regulation. Here we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and the primary visual cortex. These samples span five main developmental stages, ranging from the first trimester to adolescence.

Safety and immunogenicity of an optimized self-replicating RNA platform for low dose or single dose vaccine applications: a randomized, open label Phase I study in healthy volunteers.

Self-replicating RNA (srRNA) technology, in comparison to mRNA vaccines, has shown dose-sparing by approximately 10-fold and more durable immune responses. However, no improvements are observed in the adverse events profile. Here, we develop an srRNA vaccine platform with optimized non-coding regions and demonstrate immunogenicity and safety in preclinical and clinical development.

A Preclinical Immunogenicity Study of the Recombinant Human Papillomavirus Nine-Valent Virus-like Particle Vaccine.

Background: Cervical cancer is associated with persistent infection of high-risk human papillomaviruses (HPVs). Prophylactic HPV vaccines have been recommended and have significant efficacy in preventing cervical cancer. Multivalent HPV vaccines have a better preventative effect on HPV-related diseases.

Novel MRI-based Hyper-Fused Radiomics for Predicting Pathologic Complete Response to Neoadjuvant Therapy in Breast Cancer.

Rationale And Objectives: To propose a novel MRI-based hyper-fused radiomic approach to predict pathologic complete response (pCR) to neoadjuvant therapy (NAT) in breast cancer (BC).

Materials And Methods: Pretreatment dynamic contrast-enhanced (DCE) MRI and ultra-multi-b-value (UMB) diffusion-weighted imaging (DWI) data were acquired in BC patients who received NAT followed by surgery at two centers. Hyper-fused radiomic features (RFs) and conventional RFs were extracted from DCE-MRI or UMB-DWI.

Cerebrospinal fluid proteomics reveals the innate immunity and blood-brain barrier dysregulation in a patient with multidrug-resistant ventriculitis treated with intrathecal and intravenous polymyxin B.

is a major pathogen of nosocomial meningitis and ventriculitis. Due to very limited antibiotic treatment options, polymyxins are often used as a last-line therapy. To optimise polymyxin use in the intraventricular environment, cerebrospinal fluid (CSF) proteomics was employed to investigate host-pathogen-polymyxin interactions in a 69-year-old patient with multidrug-resistant ventriculitis treated with a combination of intrathecal (ITH; 50,000 IU q24h/q48h), intraventricular (IVT; 50,000 IU q48h), and intravenous (500,000 IU, q12h) polymyxin B.

Deficiency of Endothelial Impairs Pulmonary Vascular Angiogenesis and Predisposes Pulmonary Hypertension.

Background: Mechanosensitive Piezo1 channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.

Methods: Endothelial cell (EC)-specific knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.

Real-world evaluation of an evidence-based telemental health program for PTSD symptoms.

Blended care therapy (BCT), which augments live, video-based psychotherapy sessions with asynchronous digital tools, has the potential to increase access to evidence-based treatments for posttraumatic stress disorder (PTSD). However, its effectiveness in diverse, real-world settings is not well-understood. This evaluation aimed to assess clinical outcomes of a BCT program for PTSD symptoms.

Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets.

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic.

Nuclear Medicine Imaging in Epilepsy.

Approximately one-third of patients with focal epilepsy have medically refractory focal epilepsy (MRFE), which significantly impacts their quality of life. Once a seizure focus is identified and determined to be in the noneloquent cortex, it can be surgically resected with the goal of freedom from seizures and minimal neurocognitive deficit. During noninvasive (phase I) presurgical planning, functional (nuclear) imaging and structural imaging are complementary in the accurate localization of the epileptogenic zone (EZ).

Blue Light Damages Retinal Ganglion Cells Via Endoplasmic Reticulum Stress and Autophagy in Chickens.

Purpose: Because chickens have excellent light perception properties, this study focused on investigating whether monochromatic light can cause photodamage in chicken retinal ganglion cells (RGCs).

Methods: Post-hatching day chickens were exposed to four different light-emitting diode light environments for five weeks, respectively, monochromatic blue light (480 nm), green light (560 nm), red light (660 nm), or white light (6000 K). The mechanisms through which monochromatic light influences the structure of the chicken retina were analyzed by detecting the morphological structure of the retina, gene and protein expression levels, and the ultrastructure of the optic nerve.

Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials.

The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.