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.

From Vision to Reality: The EU's Pharmaceutical Reforms and the Path to Improved Access.

Disparities in access to oncology medicines in European Union (EU) member states can impact patient outcomes profoundly, with availability and timely access varying significantly across and within member states. This paper discusses the intersection of the new European Health Technology Assessment Regulation (HTAR), the provisions of the proposed pharmaceutical legislation and their potential impacts on access to oncology medicines across EU member states. The HTAR, seeking to standardise the clinical evaluation of new medicines, has the potential to streamline the evaluation process but also risks oversimplifying diverse national healthcare needs.

Unmet clinical needs in women with polycystic ovary syndrome regarding fertility and obesity: a cross-sectional study from the patient's perspective.

Purpose: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, often leading to anovulatory infertility. Obesity exacerbates the reproductive, metabolic and psychological features of PCOS, making fertility treatment and patient satisfaction difficult. Despite guidelines from the European Society of Human Reproduction and Embryology (ESHRE) emphasizing lifestyle modifications and specific treatments, there remains a significant gap in adherence to these guidelines by both healthcare providers and patients.

Which patients with negative PSMA-PET imaging can safely avoid biopsy for prostate cancer? a novel step towards PSMA-based biopsy-free strategy.

Purpose: This study aimed to identify if a subset of men can safely avoid or delay prostate biopsy based on negative results of prostate-specific membrane antigen positron emission tomography (PSMA-PET).

Materials And Methods: Among 341 consecutive cases in a prospective biopsy cohort (NCT05073653), 111 treatment-naïve men with negative PSMA-PET (PRIMARY-score 1/2) were included. All participants underwent PSMA-PET and histopathological examinations.

A generalized structured coalescent for purifying selection without recombination.

Purifying selection is a critical factor in shaping genetic diversity. Current theoretical models mostly address scenarios of either very weak or strong selection, leaving a significant gap in our knowledge. The effects of purifying selection on patterns of genomic diversity remain poorly understood when selection against deleterious mutations is weak to moderate, particularly when recombination is limited or absent.

Cranioplasty infection in porous hydroxyapatite: Potential antibacterial properties.

Introduction: Intensive research is dedicated to the development of novel biomaterials and medical devices to be used as grafts in reconstructive surgery, with the purpose of enhancing their therapeutic effectiveness, safety, and durability. A variety of biomaterials, from autologous bone to polymethylmetacrylate, polyether ether ketone, titanium, and calcium-based ceramics are used in cranioplasty. Porous hydroxyapatite (PHA) is reported as a possible material for bone reconstruction, with good signs of biocompatibility, osteoconductive and osteointegrative properties.

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.

Self-reported health status of patients with acute retinal ischemia and stroke related hemianopia.

Background: We aimed to assess impairments on health-related quality of life, and mental health resulting from Retinal artery occlusion (RAO) with monocular visual field loss and posterior circulation ischemic stroke (PCIS) with full or partial hemianopia using patient-reported outcome measures (PROMs).

Methods: In a prospective study, consecutive patients with acute RAO on fundoscopy and PCIS on imaging were recruited during their surveillance on a stroke unit over a period of 15 months. Baseline characteristics were determined from medical records and interviews.

Fenestrated Anaconda Endograft for the Treatment of Complex Aortic Aneurysms: Systematic Review and Meta-Analysis.

Purpose: To perform a systematic review and meta-analysis of the outcomes of Anaconda fenestrated endograft for the treatment of complex abdominal aortic aneurysms (cAAA).

Material And Methods: A systematic search of all the literature reported until May 2024 was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The pooled 30-day mortality rate, technical success rate, reintervention rate as well as bridging stent occlusion rate, and corresponding 95% confidence intervals (CIs) were estimated using fixed or random effect methods.

A Comprehensive Weightbearing Computed Tomography Study on Patients With Hallux Valgus: Exploring Multiplanar Deformity Interrelationships.

Background: Hallux valgus (HV) is a complex, multiplanar deformity. In this study, we examined the interrelationships between various components of this deformity using weightbearing computed tomography (WBCT). We hypothesized that the severity of traditional axial plane deformities would correlate with malpositioning of the metatarsosesamoid complex, first-ray coronal rotational deformity, and malalignment of the hindfoot and midfoot.

Patterns of Treatment and Real-World Outcomes of Patients With Non-small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations Receiving Mobocertinib: The EXTRACT Study.

Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.

Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).

Validity of non-traditional measures of obesity compared to total body fat across the life course: A systematic review and meta-analysis.

IntroductionTraditional obesity measures including body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio have limitations. The primary objective of this study was to identify and review the validity of non-traditional obesity measures, using measures of total body fat as the reference standard, that have been used across multiple life stages. MethodsWe conducted a systematic review and searched MEDLINE, Embase, and PsycINFO.

Feline Papillomatosis.

Different types of feline papillomaviruses (PVs) are associated with a variety of skin lesions and neoplasia, such as papillomas and cell carcinomas, but the virus can also be found in healthy skin. In this review, the European Advisory Board on Cat Diseases (ABCD), a scientifically independent board of veterinary experts on feline infectious diseases from 11 European Countries, discusses the current knowledge of feline PV infections. Cats most likely become infected through lesions or abrasions of the skin.

Viral Hepatitis B and Its Implications for Public Health in DR Congo: A Systematic Review.

The prevalence of hepatitis B virus infection remains high in the Democratic Republic of Congo (DRC), constituting a public health problem in view of the fatal complications it causes, notably cirrhosis and hepatocellular carcinoma. The aim of this study was to provide an overview of the situation of viral hepatitis B in the DRC and in particular its implications for public health. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) group guidelines.

Visual Acuity Outcomes and Influencing Factors in a Cohort of UK Real-World Diabetic Macular Oedema Patients During the First Two Years of Anti-VEGF Treatment.

Background/objectives: The visual acuity (VA) outcomes after the first and second years of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular oedema (DMO) were evaluated, and the factors associated with treatment success were investigated.

Methods: Using Medisoft electronic medical records (UK), this retrospective cohort study analysed VA outcomes, changes, and determinants in DMO patients at year 1 and year 2 after initial anti-VEGF injection. Descriptive analysis examined baseline demographics and clinical characteristics, while regression models were used to assess associations between these factors and changes in VA.

Maternal and Infant Characteristics and Pumping Profiles of Women That Predominantly Pump Milk for Their Infants.

Background: Whilst it is inconvenient and time-intensive, predominantly (PP) and exclusively pumping (EP) mothers rely on breast expression to provide milk for their infants and to ensure continued milk supply, yet these populations are poorly understood.

Methods: We assessed and characterised Western Australian PP mothers ( = 93) regarding 24 h milk production (MP) and infant milk intake and demographics, perinatal complications and breastfeeding difficulties, the frequencies of which were compared with published general population frequencies. Pumping efficacy and milk flow parameters during a pumping session in PP mothers ( = 32) were compared with those that pump occasionally (reference group, = 60).

Associations with Taste, Diet, and Health in an Italian Population.

Background/objectives: The SNP has previously been associated with sweet taste, diet, and health status, although never comprehensively in a single study. Also, associations between and sweet taste might be body mass index (BMI)-dependent. Therefore, this study aimed to conduct a comprehensive investigation of and sweet taste intensity and liking, food liking, and diet and health status whilst considering BMI.

Cross-National Survey About Nutrition and Nutrition Communication Among Older Adults Aged 60 Years and Above.

The global population is undergoing a significant demographic shift characterised by an increasing proportion of older individuals. Healthy aging has become a priority for personal well-being and sustainable healthcare systems, with nutrition playing a pivotal role. However, the rise in non-communicable diseases (NCDs), malnutrition, and a shift in eating behaviour underscore the need for tailored, effective nutrition communication strategies.

Vitamin Metabolism and Its Dependency on Genetic Variations Among Healthy Adults: A Systematic Review for Precision Nutrition Strategies.

Background/objectives: In recent years, there has been a growing interest in precision nutrition and its potential for disease prevention. Differences in individual responses to diet, especially among populations of different ancestry, have underlined the importance of understanding the effects of genetic variations on nutrient intake (nutrigenomics). Since humans generally cannot synthesize essential vitamins, the maintenance of healthy bodily functions depends on dietary vitamin intake.

The Role of Light Irradiation and Dendrimer Generation in Directing Electrostatic Self-Assembly.

pH-responsive polyamidoamine (PAMAM) dendrimers are used as well-defined building blocks to design light-switchable nano-assemblies in solution. The complex interplay between the photoresponsive di-anionic azo dye Acid Yellow 38 (AY38) and the cationic PAMAM dendrimers of different generations is presented in this study. Electrostatic self-assembly involving secondary dipole-dipole interactions provides well-defined assemblies within a broad size range (10 nm-1 μm) with various shapes.

Molecular Epidemiology, Drug-Resistant Variants, and Therapeutic Implications of Hepatitis B Virus and Hepatitis D Virus Prevalence in Nigeria: A National Study.

Information on circulating HBV (sub-)genotype, variants, and hepatitis D virus (HDV) coinfection, which vary by geographical area, is crucial for the efficient control and management of HBV. We investigated the genomic characteristics of HBV (with a prevalence of 8.1%) and the prevalence of HDV in Nigeria.

A Case of Dibothriocephalosis () from Iseo Lake (Northern Italy): An Update on a Persistent Sanitary Issue.

Dibothriocephalosis is a fish-borne parasitic zoonosis that is caused by tapeworms of the (syn. ) genus. This paper describes a human case of dibothriocephalosis associated with the consumption of a presumably infected fish, prepared at a restaurant near Iseo Lake (northern Italy).

A Transformer Encoder Approach for Localization Reconstruction During GPS Outages from an IMU and GPS-Based Sensor.

Accurate localization is crucial for numerous applications. While several methods exist for outdoor localization, typically relying on GPS signals, these approaches become unreliable in environments subject to a weak GPS signal or GPS outage. Many researchers have attempted to address this limitation, primarily focusing on real-time solutions.

Mid- to Long-Term Outcomes of Two-Stage Revision Arthroplasty for Periprosthetic Joint Infection of the Shoulder.

: Periprosthetic joint infection (PJI) after shoulder arthroplasty is often treated with a two-stage approach, but the data on the mid- to long-term outcomes remain scarce. This study aimed to evaluate the clinical outcomes of two-stage revision arthroplasty for shoulder PJI with a minimum follow-up of five years. : This retrospective study identified 59 shoulders in 58 patients who underwent the first stage of a two-stage revision arthroplasty for shoulder PJI at our institution between 2007 and 2018.