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.

Unveiling the role of miRNAs in Diminished Ovarian Reserve: an in silico network approach.

MicroRNAs (miRNAs) have acquired an increased recognition to unravel the complex molecular mechanisms underlying Diminished Ovarian Reserve (DOR), one of the main responsible for infertility. To investigate the impact of miRNA profiles in granulosa cells and follicular fluid, crucial players in follicle development, this study employed a computational network theory approach to reconstruct potential pathways regulated by miRNAs in granulosa cells and follicular fluid of women suffering from DOR. Available data from published research were collected to create the FGC_MiRNome_MC, a representation of miRNA target genes and their interactions.

Thyroid Hormone Activation Regulates the Crosstalk between Breast Cancer and Mesenchymal Stem Cells.

Background: Thyroid Hormones (THs) critically impact human cancer. Although endowed with both tumor-promoting and inhibiting effects in different cancer types, excess of THs has been linked to enhanced tumor growth and progression. Breast cancer depends on the interaction between bulk tumor cells and the surrounding microenvironment in which mesenchymal stem cells (MSCs) exert powerful pro-tumorigenic activities.

Contribution of Nuclear Fragmentation to Dose and RBE in Carbon-Ion Radiotherapy.

Variable relative biological effectiveness (RBE) of carbon radiotherapy may be calculated using several models, including the microdosimetric kinetic model (MKM), stochastic MKM (SMKM), repair-misrepair-fixation (RMF) model, and local effect model I (LEM), which have not been thoroughly compared. In this work, we compared how these four models handle carbon beam fragmentation, providing insight into where model differences arise. Monoenergetic and spread-out Bragg peak carbon beams incident on a water phantom were simulated using Monte Carlo.

Exploring the Pathophysiology, Diagnosis, and Treatment Options of Multiple Sclerosis.

The complicated neurological syndrome known as multiple sclerosis (MS) is typified by demyelination, inflammation, and neurodegeneration in the central nervous system (CNS). Managing this crippling illness requires an understanding of the complex interactions between neurophysiological systems, diagnostic techniques, and therapeutic methods. A complex series of processes, including immunological dysregulation, inflammation, and neurodegeneration, are involved in the pathogenesis of MS.

Short (2-Hour) Non-Oxygenated End-Ischemic Hypothermic Perfusion Versus Cold Storage in the Setting of Renal Transplantation.

Background: Kidney transplantation (KT) is the most effective treatment for end-stage renal disease. End-ischemic hypothermic machine perfusion (EI-HMP) has emerged as a promising method for preserving grafts before transplantation. This study aimed to compare graft function recovery in KT recipients of deceased brain-death (DBD) grafts preserved with EI-HMP versus static cold storage (SCS).

The Line of Emotion Dysregulation and Need Frustration from Parents to Adolescents: The Role of Parental Psychological Control.

Accumulating evidence, as outlined by Self-Determination Theory (SDT), highlights the crucial role of emotion dysregulation and basic psychological needs in shaping various psychological outcomes. Parental psychological control may play a key role in understanding how these processes develop within the family context. This study aims to examine the intergenerational transmission of basic psychological needs and emotion dysregulation from parents to adolescents, focusing on the indirect association of parental psychological control within this relationship.

Efficacy of Orthognathic Surgery in OSAS Patients: A Systematic Review and Meta-Analysis.

Background: Obstructive sleep apnea syndrome (OSAS) is a prevalent condition characterised by repeated episodes of partial or complete obstruction of the upper airway during sleep, leading to disrupted sleep and associated morbidities. Orthognathic surgery (OGS) has been proposed as a treatment option for OSAS, aimed at anatomically repositioning the maxillofacial structures to alleviate airway obstruction. This systematic review and meta-analysis aimed to evaluate the efficacy of OGS in reducing apnea-hypopnea index (AHI) and Epworth Sleepiness Scale (ESS) scores among OSAS patients.

Real-World Impact of Olaparib Exposure in Advanced Pancreatic Cancer Patients Harboring Germline BRCA1-2 Pathogenic Variants.

Introduction: Pancreatic cancer arising in the context of BRCA predisposition may benefit from poly(ADP-ribose) polymerase inhibitors. We analyzed real-world data on the impact of olaparib on survival in metastatic pancreatic cancer patients harboring germline BRCA mutations in Italy, where olaparib is not reimbursed for this indication.

Methods: Clinico/pathological data of pancreatic cancer patients with documented BRCA1-2 germline pathogenic variants who had received first-line chemotherapy for metastatic disease were collected from 23 Italian oncology departments and the impact of olaparib exposure on overall survival (OS) was analyzed.

Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy.

Objectives: We aim to investigate cognitive phenotype distribution and MRI correlates across pediatric-, elderly-, and adult-onset MS patients as a function of disease duration.

Methods: In this cross-sectional study, we enrolled 1262 MS patients and 238 healthy controls, with neurological and cognitive assessments. A subset of 222 MS patients and 92 controls underwent 3T-MRI scan for brain atrophy and lesion analysis.

Eight Years of Norovirus Surveillance in Urban Wastewater: Insights from Next-Generation.

Human noroviruses (HNoVs) are a leading cause of acute gastroenteritis worldwide, with significant public health implications. In this study, wastewater-based epidemiology (WBE) was used to monitor the circulation and genetic diversity of HNoVs in Rome over an eight-year period (2017-2024). A total of 337 wastewater samples were analyzed using RT-nested PCR and next-generation sequencing (NGS) to identify genogroups GI and GII and their respective genotypes.

Neurotropic Tick-Borne Flavivirus in Alpine Chamois (), Austria, 2017, Italy, 2023.

The European subtype of tick-borne encephalitis virus (TBEV-Eur; species , family ) was the only tick-borne flavivirus present in central Europe known to cause neurologic disease in humans and several animal species. Here, we report a tick-borne flavivirus isolated from Alpine chamois () with encephalitis and attached ticks, present over a wide area in the Alps. Cases were detected in 2017 in Salzburg, Austria, and 2023 in Lombardy and Piedmont, Italy.

Herald Patch as the Only Evidence of Pityriasis Rosea: Clinical, Laboratory and Pathogenetic Features.

Pityriasis rosea (PR) is a self-limited exanthem associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and HHV-7. The disease typically begins with a single erythematous patch on the trunk (herald patch), followed by a secondary eruption of smaller papulosquamous lesions. Rarely, the herald patch may be the only cutaneous manifestation of PR.

Risk of Nipah Virus Seroprevalence in Healthcare Workers: A Systematic Review with Meta-Analysis.

Nipah virus (NiV) is a zoonotic pathogen with the potential to cause human outbreaks with a high case fatality ratio. In this systematic review and meta-analysis, available evidence on NiV infections occurring in healthcare workers (HCWs) was collected and critically appraised. According to the PRISMA statement, four medical databases (PubMed, CINAHL, EMBASE, and Scopus) and the preprint repository medRixv were inquired through a specifically designed searching strategy.

Bronchiolitis Severity Affects Blood Count and Inflammatory Marker Levels: A Real-Life Experience.

Background: Bronchiolitis is the most common cause of lower respiratory tract infection (LRTI) in the first year of life. We analyzed the association between complete blood count (CBC), c-reactive protein (CRP), and novel inflammatory indexes (NLR, PLR, MLR, ELR, LMR, NPR, LPR, LNR, PNR, SII, SIRI) in predicting bronchiolitis severity at hospital admission.

Methods: We retrospectively collected data from 95 infants hospitalized for bronchiolitis in a third-level hospital during three epidemic seasons.

Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries.

Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL's viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL and identified potentially active antiretrovirals in combination among treatment-experienced patients in Cameroon, where NRTIs (3TC) have been the backbone of ART for decades now.

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.

Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic Analysis.

Coronavirus disease 2019 (COVID-19) has been associated with a significant fatality rate and persistent evolution in immunocompromised patients. In this prospective study, we aimed to determine the duration of excretion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 37 Tunisian patients with hematological malignancies (40.5% with lymphoma and 37.

Difference in Optical Coherence Tomography Angiography Parameters After SARS-CoV-2 Infection During the Alpha and Delta Variant Dominance Periods.

The SARS-CoV-2 infection manifests with diverse clinical manifestations, with severity potentially influenced by the viral variant. COVID-19 has also been shown to impact ocular microcirculation in some patients, but whether this effect varies by viral lineage remains unclear. This prospective study compared clinical features and ocular parameters assessed via optical coherence tomography angiography (OCTA) in patients recovering from SARS-CoV-2 infections during the dominance of two distinctive viral lineages, Alpha (B.

Clinical Characteristics and Outcomes in Patients with Chronic HBV Infection and Hospitalized for COVID-19 Pneumonia: A Retrospective Cohort Study.

The effects of a concomitant infection of hepatitis B virus (HBV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still debated, with a recognized major risk of HBV reactivation during immune-suppressive treatments. The aim of this study was to determine the prevalence and predictive factors of HBV reactivation in a cohort of hospitalized patients with coronavirus disease 2019 (COVID-19) and a current or past hepatitis B infection. In a monocentric retrospective observational study, we enrolled all consecutive hospital admitted patients with COVID-19 pneumonia and a positive HBV serology (N = 84) in our Infectious Diseases Unit from April 2021 to December 2023.

Assessing the Burden of Neglected Tropical Diseases in Low-Income Communities: Challenges and Solutions.

Neglected tropical diseases (NTDs) represent a group of chronic and debilitating infections that affect more than one billion people, predominantly in low-income communities with limited health infrastructure. This paper analyzes the factors that perpetuate the burden of NTDs, highlighting how poor health infrastructure, unfavorable socioeconomic conditions and lack of therapeutic resources exacerbate their impact. The effectiveness of current interventions, such as mass drug administration (MDA) programs and improved sanitation, in reducing disease prevalence is examined.

Impact of Age and Sex on Viral Load in Hepatitis C Virus Infection.

The determinants of hepatitis C virus (HCV) viral load remain incompletely understood and may differ in females, who are relatively protected from the consequences of HCV infection during their reproductive years. We aimed to evaluate how age affects the relationship between sex and viral load. = 922 patients (males = 497, median age 62 years), all naïve to direct antiviral agents, were studied.

Biotechnological Phytocomplex of (L.) DC. Enhances Collagen Biosynthesis In Vitro and Improves Skin Elasticity In Vivo.

(L.) DC., commonly known as Japanese pepper, is a deciduous shrub native to East Asia.

Prilling as an Effective Tool for Manufacturing Submicrometric and Nanometric PLGA Particles for Controlled Drug Delivery to Wounds: Stability and Curcumin Release.

Background/objectives: This study investigates for the first time the use of the prilling technique in combination with solvent evaporation to produce nano- and submicrometric PLGA particles to deliver properly an active pharmaceutical ingredient. Curcumin (CCM), a hydrophobic compound classified under BCS (Biopharmaceutics Classification System) class IV, was selected as the model drug.

Methods: Key process parameters, including polymer concentration, solvent type, nozzle size, and surfactant levels, were optimized to obtain stable particles with a narrow size distribution determined by DLS analysis.