The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

Protocol for identifying Dicer as dsRNA binding and cleaving reagent in response to transfected dsRNA.

Mammalian Dicer has been proved to be functional on double-stranded RNAs (dsRNAs) and involved in antiviral immunity or immune regulation. Here, we present a protocol for identifying Dicer as a dsRNA binding and cleaving factor to transfected dsRNA in cell lines, based on small RNA sequencing (RNA-seq) and dsRNA-immunoprecipitation (dsRNA-IP). We detail both experimental processes and analysis on small RNA-seq data.

Identification of GBN5 as a molecular biomarker of pan-cancer species by integrated multi-omics analysis.

Introduction: We conducted a panoramic analysis of GBN5 expression and prognosis in 33 cancers, aiming to deepen the systematic understanding of GBN5 in cancer.

Materials And Methods: We employed a multi-omics approach, including transcriptomic, genomic, proteomic, single-cell cytomic, spatial transcriptomic, and genomic data, to explore the prognostic value and potential oncogenic mechanisms of GBN5 across pan-cancers from multiple perspectives.

Results: We found that GBN5 was differentially expressed in multiple tumors and showed early diagnostic value.

Computed tomography-based nomogram for estimating progression-free survival probability in bladder cancer patients undergoing partial cystectomy.

Purpose: To establish a prognostic model to estimate progression-free survival (PFS) probability in bladder cancer (BCa) patients undergoing partial cystectomy.

Material And Methods: Consecutive patients who underwent partial cystectomy between August 2012 and April 2021 were enrolled. The primary endpoint was PFS during the follow-up.

Evaluation value of contrast enhanced ultrasound quantitative parameters in ischemic-type biliary lesions after liver transplantation-a prospectively study.

Purpose: To explore the evaluation value of contrast enhanced ultrasound (CEUS) quantitative parameters in ischemic-type biliary lesions after liver transplantation to assist its early-diagnosis.

Methods: Patients who underwent liver transplantation and intravenous CEUS at Beijing Friendship Hospital, Capital Medical University from June 25, 2020 to December 28, 2022 and were diagnosed with Ischemic-type biliary lesions (ITBLs) by Magnetic Resonance Cholangiopancreatography (MRCP) or Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiography (PTC) were prospectively enrolled. SonoLiver software was used to quantitatively analyze the contrast images, transplanted livers with normal biliary tracts as the control group.

Prediction of main pancreatic duct involvement in intraductal papillary mucinous neoplasms on magnetic resonance imaging.

Purpose: To evaluate the measurement of main pancreatic duct (MPD) diameter on MRI for predicting MPD involvement in intraductal papillary mucinous neoplasms (IPMN).

Methods: This retrospective study included 595 patients with surgically confirmed IPMN who underwent preoperative MRI from 2015 to 2022. Three independent readers measured the maximum MPD diameter on two-dimensional axial and coronal T2-weighted imaging.

Factors influencing diagnostic yield in ultrasound-guided omental biopsies: insights from a retrospective study.

Purpose: To evaluate the safety, diagnostic accuracy, and factors influencing the diagnostic yield of ultrasound (US)-guided omental biopsies.

Materials And Methods: This retrospective study included 109 patients who underwent US-guided omental biopsies between June 2020 and June 2024. Pre-biopsy diagnostic images (CT, MRI, or [18 F]FDG PET/CT) were reviewed.

Risk of clinically significant prostate cancer undercategorized by multiparametric magnetic resonance imaging.

Background: To investigative potential clinicopathological characteristics and imaging-related risk factors of clinically significant prostate cancer (csPCa) undercategorized in patients with negative or equivocal MRI.

Methods: This retrospective study included 581 patients with pathologically confirmed csPCa (Gleason score ≥ 3 + 4), including 108 undercategorized csPCa and 473 detected csPCa. All patients underwent multiparametric MRI (mpMRI).

Spectral CT radiomics features of the tumor and perigastric adipose tissue can predict lymph node metastasis in gastric cancer.

Objectives: To develop a nomogram based on the radiomics features of tumour and perigastric adipose tissue adjacent to the tumor in dual-layer spectral detector computed tomography (DLCT) for lymph node metastasis (LNM) prediction in gastric cancer (GC).

Methods: A retrospective analysis was conducted on 175 patients with gastric adenocarcinoma. They were divided into training cohort (n = 125) and validation cohort (n = 50).

Usefulness of urinary biomarker-based risk score and multiparametric MRI for clinically significant prostate cancer detection in biopsy-naïve patients.

Objectives: This study aimed to investigate the accuracy of multiparametric magnetic resonance imaging (mpMRI), genetic urinary test (GUT), and prostate cancer prevention trial risk calculator version 2.0 (PCPTRC2) for the clinically significant prostate cancer (csPCa) diagnostic in biopsy-naïve patients.

Materials And Methods: In a single center study between 2021 and 2024 participants underwent prostate mpMRI, GUT, and ultrasound (US) guided biopsy.

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.

High Modified 5 Factor Frailty Index is Associated With Worse PROMs and Decreased Return to Activities After 1 or 2 Level MI-TLIF.

Study Design: Retrospective cohort study.

Objective: Frailty is defined as a state of minimal "physiologic reserve." The modified 5 factor frailty index (mFI-5) is a recently proposed metric for assessing frailty and has been previously studied as a predictor of morbidity and mortality.

Task activation results in regional C-lactate signal increase in the human brain.

Hyperpolarized-C magnetic resonance imaging (HP-C MRI) was used to image changes in C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain C-pyruvate, C-lactate and C-bicarbonate production was imaged in healthy volunteers (N = 6, ages 24-33) for the two conditions using two separate hyperpolarized C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation.

A-kinase anchor protein 12 promotes oligodendrogenesis and cognitive recovery in carbon monoxide therapy for traumatic brain injury.

Therapeutic drug development for central nervous system injuries, such as traumatic brain injury (TBI), presents significant challenges. TBI results in primary mechanical damage followed by secondary injury, leading to cognitive dysfunction and memory loss. Our recent study demonstrated the potential of carbon monoxide-releasing molecules (CORMs) to improve TBI recovery by enhancing neurogenesis.

Virtual screening: hope, hype, and the fine line in between.

Introduction: Technological advancements in virtual screening (VS) have rapidly accelerated its application in drug discovery, as reflected by the exponential growth in VS-related publications. However, a significant gap remains between the volume of computational predictions and their experimental validation. This discrepancy has led to a rise in the number of unverified 'claimed' hits which impedes the drug discovery efforts.

2024 White Paper on Recent Issues in Bioanalysis: Three Way-Cross Validation; Urine Clinical Analysis; Automated Methods; Regulatory Queries on Plasma Protein Binding; Automated Biospecimen Management; ELN Migration; Ultra-Sensitivity Mass Spectrometry ( - Recommendations on Advanced Strategies for Mass Spectrometry Assays, Chromatography, Sample Preparation and BMV/Regulated Bioanalysis - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

2024 White Paper on Recent Issues in Bioanalysis: Evolution of Immunogenicity Assessment beyond ADA/NAb; Regulated Genomic/NGS Assays; Hypersensitivity Reactions; Minimum Noise Reduction; False Positive Range; Modernized Vaccine Approaches; NAb/TAb Correlation - Recommendations on Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy, Vaccine; Biotherapeutics Immunogenicity Assessment & Clinical Relevance - Regulatory Agencies' Input on Immunogenicity/Technologies of Biotherapeutics, Gene, Cell & Vaccine Therapies).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

2024 White paper on recent issues in bioanalysis: Impact of LDT in US and IVDR in EU; AI/ML for High Parameter Flow Cytometry; The rise of Olink Technology; CDx for AAV Gene Therapies; Integrative Bioanalysis by Multiple Platforms; Super Sensitive ADA/NAb LBA ( - Recommendations on Advanced Strategies for Biomarkers, IVD/CDx Assays (BAV), Cell Based Assays (CBA), and Ligand-Binding Assays (LBA) - Regulatory Agencies' Input on Biomarkers, IVD/CDx, and Biomarker Assay Validation).

The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Analysis of "Dose Accuracy and Reliability of a Connected Insulin Pen System".

In an article in the , Backfish and coauthors examined the dose accuracy and reliability of the Tempo Pen and Tempo Smart Button connected insulin pen system. This study sponsored by Eli Lilly and Company found that this system met the International Organization for Standardization 11608-1:2014 requirements for dose accuracy at a range of doses, as well as the data transfer requirements after all injections. While these results are very encouraging, they were based on simulated human factors data while data from a human factors validation study where individuals successfully dialed and administered correct doses was not reported.

Probability of Achieving Bone Mineral Density Treatment Goals with Denosumab Treatment in Postmenopausal Women with Osteoporosis.

Bone mineral density (BMD) levels achieved on osteoporosis treatment are predictive of subsequent fracture risk, and T-score > -2.5 has been proposed as a minimum treatment target for women with osteoporosis. Knowing the likelihood of attaining target T-scores with different medications for different baseline BMD levels can help determine appropriate initial treatment for individual patients.

The experiences of speech-language pathologists when collaborating with spoken language interpreters, multilingual families, and their children with hearing loss.

Purpose: The parents of children who are deaf or hard-of-hearing may require a spoken language interpreter to access early-intervention services. This research sought to describe speech-language pathologists' perspectives regarding collaboration with interpreters in this space.

Method: Twenty-seven speech-language pathologists working in Australia completed a cross-sectional mixed-method online survey.

Interferon-Stimulated Genes and Immune Metabolites as Broad-Spectrum Biomarkers for Viral Infections.

The type I interferon (IFN-I) response is a critical component of the immune defense against various viral pathogens, triggering the expression of hundreds of interferon-stimulated genes (ISGs). These ISGs encode proteins with diverse antiviral functions, targeting various stages of viral replication and restricting infection spread. Beyond their antiviral functions, ISGs and associated immune metabolites have emerged as promising broad-spectrum biomarkers that can differentiate viral infections from other conditions.

Flunarizine as a Candidate for Drug Repurposing Against Human Pathogenic Mammarenaviruses.

Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome.

Expanding the Diversity of : A Novel Genus from .

Six novel phages belonging to the family were isolated using as a host. Phages MuffinTheCat, Badulia, DesireeRose, Bee17, SCoupsA, and LuzDeMundo were purified from environmental samples by students participating in the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) program at Alliance University, New York. The phages have linear dsDNA genomes 15,438-15,636 bp with 112-120 bp inverted terminal repeats.