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.

Review of upper extremity passive joint impedance identification in people with Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) progressively leads to loss of limb function due to muscle weakness. The incurable nature of the disease shifts the focus to improving quality of life, including assistive supports to improve arm function. Over time, the passive joint impedance (Jimp) of people with DMD increases.

Peroral Endoscopic myotomy (POEM) in pediatric achalasia: a retrospective cohort on institutional experience and quality of life.

Background: Achalasia is a rare esophageal motility disorder with an estimated annual incidence of 1-5/100.000 and a mean age at diagnosis > 50 years of age. Only a fraction of the patients has an onset during childhood (estimated incidence of 0.

Self-sampling and self-testing for HIV at a commercial and community-based test provider in the Netherlands: user preferences and usability.

HIV self-sampling and -testing (HIVSS/ST) reduces testing barriers and potentially reaches populations who may not test otherwise. In the Netherlands, at-home HIV tests became commercially available around 2016, but data on user experiences are limited. This study aimed to explore characteristics of users and their experiences with HIVSS/ST.

A participatory needs assessment to map the system dynamics of overweight related behaviours of 10-14-year-old adolescents living in an underserved neighbourhood in Amsterdam, the Netherlands.

Background: Developing interventions along with the population of interest using systems thinking is a promising method to address the underlying system dynamics of overweight. The purpose of this study is twofold: to gain insight into the perspectives of adolescents regarding: (1) the system dynamics of energy balance-related behaviours (EBRBs) (physical activity, screen use, sleep behaviour and dietary behaviour); and (2) underlying mechanisms and overarching drivers of unhealthy EBRBs.

Methods: We conducted Participatory Action Research (PAR) to map the system dynamics of EBRBs together with adolescents aged 10-14 years old living in a lower socioeconomic, ethnically diverse neighbourhood in Amsterdam East, the Netherlands.

Relationship between plasma urea and copeptin in response to arginine stimulation in healthy adults, patients with vasopressin deficiency and primary polydipsia.

Background: Arginine infusion stimulates copeptin secretion, a surrogate marker of arginine vasopressin (AVP), thereby serving as a diagnostic test in the differential diagnosis of suspected AVP deficiency (AVP-D). Yet, the precise mechanism underlying the stimulatory effect of arginine on the vasopressinergic system remains elusive. Arginine plays a significant role in the urea cycle and increases the production of urea.

Unveiling the relation between swallowing muscle mass and skeletal muscle mass in head and neck cancer patients.

Purpose: Sarcopenia, characterized by loss of skeletal muscle mass (SMM) and strength, often leads to dysphagia in the elderly. This condition can also worsen treatment outcomes in head and neck cancer (HNC) patients, who are susceptible to swallowing difficulties. This study aimed to establish the correlation between swallowing muscle mass (SwMM) and SMM in HNC patients.

The Hsf1-sHsp cascade has pan-antiviral activity in mosquito cells.

Aedes mosquitoes transmit pathogenic arthropod-borne (arbo) viruses, putting nearly half the world's population at risk. Blocking virus replication in mosquitoes is a promising approach to prevent arbovirus transmission, the development of which requires in-depth knowledge of virus-host interactions and mosquito immunity. By integrating multi-omics data, we find that heat shock factor 1 (Hsf1) regulates eight small heat shock protein (sHsp) genes within one topologically associated domain in the genome of the Aedes aegypti mosquito.

Osilodrostat improves blood pressure and glycemic control in patients with Cushing's disease: a pooled analysis of LINC 3 and LINC 4 studies.

Purpose: To evaluate the effect of osilodrostat and hypercortisolism control on blood pressure (BP) and glycemic control in patients with Cushing's disease.

Methods: Pooled analysis of two Phase III osilodrostat studies (LINC 3 and LINC 4), both comprising a 48-week core phase and an optional open-label extension. Changes from baseline in systolic and diastolic BP (SBP and DBP), fasting plasma glucose (FPG), and glycated hemoglobin (HbA) were evaluated during osilodrostat treatment in patients with/without hypertension or diabetes at baseline.

Asymptomatic female softball pitchers have altered hip morphology and cartilage composition.

Few studies have explored hip morphology and cartilage composition in female athletes or the impact of asymmetric repetitive loading, such as occurs during softball pitching. The current cross-sectional study assessed bilateral bony hip morphology on computed tomography imaging in collegiate-level softball pitchers ('Pitch1', n = 25) and cross-country runners ('Run', n = 13). Magnetic resonance imaging was used to assess cartilage relaxation times in a second cohort of pitchers ('Pitch2', n = 10) and non-athletic controls ('Con', n = 4).

Early identification of dropouts during the special forces selection program.

Recruits are exposed to high levels of psychological and physical stress during the special forces selection period, resulting in dropout rates of up to 80%. To identify who likely drops out, we assessed a group of 249 recruits, every week of the selection program, on their self-efficacy, motivation, experienced psychological and physical stress, and recovery. Using linear regression as well as state-of-the-art machine learning techniques, we aimed to build a model that could meaningfully predict dropout while remaining interpretable.

Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.

Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.

Anthracyclines disaggregate and restore mutant p63 function: a potential therapeutic approach for AEC syndrome.

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) syndrome is a rare genetic disorder caused by mutations in the TP63 gene, which encodes a transcription factor essential for epidermal gene expression. A key feature of AEC syndrome is chronic skin erosion, for which no effective treatment currently exists. Our previous studies demonstrated that mutations associated with AEC syndrome lead to p63 protein misfolding and aggregation, exerting a dominant-negative effect.

Revealing microRNA regulation in single cells.

MicroRNAs (miRNAs) are key regulators of gene expression and control cellular functions in physiological and pathophysiological states. miRNAs play important roles in disease, stress, and development, and are now being investigated for therapeutic approaches. Alternative processing of miRNAs during biogenesis results in the generation of miRNA isoforms (isomiRs) which further diversify miRNA gene regulation.

Genome-wide association study on chronic postsurgical pain in the UK Biobank.

Background: Chronic postsurgical pain (CPSP) persists beyond the expected healing period after surgery, imposing a substantial burden on overall patient well-being. Unfortunately, CPSP often remains underdiagnosed and undertreated. To better understand the mechanism of CPSP development, we aimed to identify genetic variants associated with CPSP.

Protocol for a systematic review and individual participant data meta-analysis for risk factors for lung cancer in individuals with lung nodules identified by low-dose CT screening.

Background: Worldwide, lung cancer (LC) is the second most frequent cancer and the leading cause of cancer related mortality. Low-dose CT (LDCT) screening reduced LC mortality by 20-24% in randomised trials of high-risk populations. A significant proportion of those screened have nodules detected that are found to be benign.

Physical compatibility of insulin aspart, lidocaine, alprostadil and vancomycin with individualised two-in-one parenteral nutrition used in the neonatal intensive care unit.

Objectives: Critically ill newborn infants often require simultaneous administration of multiple intravenous (IV) solutions through the same catheter lumen, making compatibility of these solutions crucial in neonatal intensive care units (NICUs). This study aimed to investigate the physical compatibility of insulin aspart, lidocaine, alprostadil and vancomycin with individualised two-in-one parenteral nutrition (PN).

Methods: The study was conducted at the hospital pharmacy's drug compounding facility of the University Medical Centre Utrecht.

The effect of sleep disturbances on the incidence of dementia for varying lag times.

Background: Few studies have addressed the association of sleep disturbances with incident dementia with long lag times. We add to this literature by investigating how lag times varying from 2.2 to 23.

Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study.

Objectives: To evaluate the potential of clinical factors, ultrasound findings, serum autoantibodies, and serum cytokine and chemokine profiles as predictors of clinical outcomes in rheumatoid arthritis (RA).

Patients And Methods: We included 200 patients with RA treated with biological and targeted synthetic disease-modifying antirheumatic drugs in a prospective multicentre ultrasound cohort study. Their serum levels of multiple cytokines and chemokines, rheumatoid factors, and serum autoantibodies (anti-cyclic citrullinated peptide-2 (anti-CCP2) and anti-carbamylated protein antibodies) were measured at baseline, 3 months and 12 months.

Acute on chronic stress fracture after a medial malleolar osteotomy following osteochondral lesion of the talus treatment.

A patient in his 40s presented at the outpatient clinic with sudden pain and swelling over his medial malleolus, 16 weeks after he had undergone osteoperiosteal autografting with a medial malleolar osteotomy for his tertiary osteochondral lesion of the talus. Postoperatively, the patient was treated using the regular evidence-based rehabilitation protocol of 5 weeks of non-weight-bearing and 5 weeks of partial weight-bearing. However, after the confirmed radiological union the patient experienced an acute on chronic stress fracture through the osteotomy line.

Accurate urine sodium measurements at home using Point of Care Testing in patients with Short Bowel Syndrome.

Background And Aims: Measurement of the urine sodium concentration (USC) is a simple procedure that in many patients adequately indicates their hydration status. This is of particular importance in patients suffering from short bowel syndrome (SBS), who may very rapidly dehydrate and are at risk for permanently compromising their kidney function. A point of care test (POCT) that allows reliable measurement of USC would enable these patients to effectively evaluate their sodium- and water balance in the at home setting, thereby avoiding hospital visits and delayed test results.

Classification of Fibro-osseous Tumors in the Craniofacial Bones using DNA Methylation and Copy Number Alterations.

Fibro-osseous tumors of the craniofacial bones are a heterogeneous group of lesions comprising cemento-osseous dysplasia (COD), cemento-ossifying fibroma (COF), juvenile trabecular ossifying fibroma (JTOF), psammomatoid ossifying fibroma (PsOF), fibrous dysplasia (FD), and low-grade osteosarcoma (LGOS) with overlapping clinicopathological features. However, their clinical behavior and treatment differ significantly, underlining the need for accurate diagnosis. Molecular diagnostic markers exist for subsets of these tumors, including GNAS mutations in FD, SATB2 fusions in PsOF, mutations involving the RAS-MAPK signaling pathway in COD, and MDM2 amplification in LGOS.

Multimodal strategies for the implementation of infection prevention and control (IPC) interventions - update of a systematic review for the WHO guidelines on core components of IPC programmes at the facility level.

Background: Healthcare-associated infections (HAIs) remain a significant challenge worldwide, and the use of multimodal strategies is recommended by the World Health Organization (WHO) to enhance infection prevention.

Objectives: To update the systematic review on facility-level infection prevention and control (IPC) interventions on the WHO Core Component of using multimodal strategies.

Methods: Data Sources: Medline (via PubMed), EMBASE, CINAHL, and the Cochrane library.