ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells.

The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.

Relationship Between Pre- and Post-Orchidectomy Serum Dihydrotestosterone and Prostate Cancer Severity in a Cohort of Nigerian Patients.

Introduction: Prostate cancer (PCa) is the commonest urologic cancer worldwide and the leading cause of male cancer deaths in Nigeria. In Nigeria, orchidectomy remains the primary androgen deprivation therapy. Dihydrotestosterone (DHT) is the active prostatic androgen, but its relationship with PCa severity has not been extensively studied in Africa.

Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.

Blood-based epigenome-wide association study and prediction of alcohol consumption.

Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait.

Association of life's essential 8 and inflammatory biomarkers with nutritional anemia in UK adults.

Several modifiable health factors in Life's Essential 8 (LE8) are linked to nutritional anemia and can assess overall cardiovascular health (CVH). This study explored the associations of CVH measured by LE8 score with nutritional anemia and iron deficiency anemia (IDA), including the mediating role of inflammatory biomarkers. This prospective cohort study included 181,069 participants from UK Biobank.

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.

Preoperative anxiety and depression are associated with poorer patient-reported outcomes following total ankle replacements.

Introduction: It is unclear how pre-operative anxiety/depression affects patient reported outcome measures (PROMs) following total ankle replacements (TAR). We investigated the effects of anxiety/depression on PROMs using the Manchester-Oxford Foot Questionnaire (MOXFQ) following TAR.

Methods: PROMs data for primary TAR patients between 2011 and 2022 were extracted from a single-centre regional registry.

Kinetics of recovery and normalization of running biomechanics following aerobic-based exercise-induced muscle damage in recreational male runners.

Objectives: The study aimed to examine the effects of exercise-induced muscle damage on running kinetics.

Design: Twenty-six adult recreational male runners performed 60 min of downhill running (-10 %) at 65 % of maximal heart rate. Running gait changes, systemic and localized muscle damage markers were assessed pre - and post-exercise induced muscle damage protocol.

Exploring the experiences of cognitive symptoms in Long COVID: a mixed-methods study in the UK.

Objective: To explore the lived experiences and extent of cognitive symptoms in Long COVID (LC) in a UK-based sample.

Design: This study implemented a mixed-methods design. Eight focus groups were conducted to collect qualitative data, and the Framework Analysis was used to reveal the experiences and impact of cognitive symptoms.

Matching model with mechanism: Appropriate rodent models for studying various aspects of diabetes pathophysiology.

Many rodent models are available for preclinical diabetes research making it a challenge for researchers to choose the most appropriate one for their experimental question. To aid in this, models have classically been categorized according to which type of diabetes they represent, and further into whether the model is induced, spontaneous or the result of genetic manipulation. This fails to capture the complexity of pathogenesis seen in diabetes in humans.

Coronary CT angiography-guided management of patients with stable chest pain: 10-year outcomes from the SCOT-HEART randomised controlled trial in Scotland.

Background: The Scottish Computed Tomography of the Heart (SCOT-HEART) trial demonstrated that management guided by coronary CT angiography (CCTA) improved the diagnosis, management, and outcome of patients with stable chest pain. We aimed to assess whether CCTA-guided care results in sustained long-term improvements in management and outcomes.

Methods: SCOT-HEART was an open-label, multicentre, parallel group trial for which patients were recruited from 12 outpatient cardiology chest pain clinics across Scotland.

Impact of SARS-CoV-2 spike antibody positivity on infection and hospitalisation rates in immunosuppressed populations during the omicron period: the MELODY study.

Background: In the UK, booster COVID-19 vaccinations have been recommended biannually to people considered immune vulnerable. We investigated, at a population level, whether the absence of detectable anti-SARS-CoV-2 spike protein IgG antibody (anti-S Ab) following three or more vaccinations in immunosuppressed individuals was associated with greater risks of infection and severity of infection.

Methods: In this prospective cohort study using UK national disease registers, we recruited participants with solid organ transplants (SOTs), rare autoimmune rheumatic diseases (RAIRDs), and lymphoid malignancies.

Association of statins use and genetic susceptibility with incidence of Alzheimer's disease.

Background: The effect of statins use on the incidence of Alzheimer's disease (AD) is still under debate, and it could be modified by a series of factors.

Objectives: We aimed to examine the association of statins use with the risk of cognitive impairment and AD, and assess the moderating roles of genetic susceptibility and other individual-related factors.

Design: A longitudinal study was conducted from the UK Biobank where individuals completed baseline surveys (2006-2010) and were followed (mean follow-up period: 9 years).

Associations of early-onset coronary heart disease and genetic susceptibility with incident dementia and white matter hyperintensity: A prospective cohort study.

Background: The associations of early-onset coronary heart disease (CHD) and genetic susceptibility with incident dementia and brain white matter hyperintensity (WMH) remain unclear. Elucidation of this problem could promote understanding of the neurocognitive impact of early-onset CHD and provide suggestions for the prevention of dementia.

Objectives: This study aimed to investigate whether observed and genetically predicted early-onset CHD were related to subsequent dementia and WMH volume.

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.

Monitoring for 5-aminosalicylate nephrotoxicity in adults with inflammatory bowel disease: prognostic model development and validation using data from the Clinical Practice Research Datalink.

Objective: To develop and validate a prognostic model for risk-stratified monitoring of 5-aminosalicylate nephrotoxicity.

Methods: This UK retrospective cohort study used data from the Clinical Practice Research Datalink Aurum and Gold for model development and validation respectively. It included adults newly diagnosed with inflammatory bowel disease and established on 5-aminosalicylic acid (5-ASA) treatment between 1 January 2007 and 31 December 2019.

Ethnic disparities in HbA1c and hypoglycemia among youth with type 1 diabetes: beyond access to technology, social deprivation and mean blood glucose.

Introduction: The UK national pediatric diabetes audit reports higher HbA1c for children and young people (CYP) with type 1 diabetes (T1D) of Black ethnicity compared with White counterparts. This is presumably related to higher mean blood glucose (MBG) due to lower socioeconomic status (SES) and less access to technology. We aimed to determine if HbA1c ethnic disparity persists after accounting for the above variables.

Discontinuous named entities in clinical Text: A systematic literature review.

Objective: Extracting named entities from clinical free-text presents unique challenges, particularly when dealing with discontinuous entities-mentions that are separated by unrelated words. Traditional NER methods often struggle to accurately identify these entities, prompting the development of specialised computational solutions. This paper systematically reviews and presents the methodologies developed for Discontinuous Named Entity Recognition in clinical texts, highlighting their effectiveness and the challenges they face.

Prognostic performance of the two-step clinical care pathway in metabolic dysfunction-associated steatotic liver disease.

Background & Aims: Current guidelines recommend a 2-step approach for risk stratification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or similar second-line tests. This study aimed to examine to prognostic performance of this approach.

Methods: The VCTE-Prognosis Study was a longitudinal study of patients with MASLD who had undergone VCTE examinations at 16 centres from the US, Europe and Asia with subsequent follow-up for clinical events.

Acute angiotensin receptor blockade and mnemonic discrimination in healthy participants.

Background: The renin angiotensin system (RAS) is implicated in various cognitive processes relevant to anxiety. However, the role of the RAS in pattern separation, a hippocampal memory mechanism that enables discrete encoding of similar stimuli, is unclear. Given the proposed role of this mechanism in overgeneralization and the maintenance of anxiety, we explored the influence of the RAS on mnemonic discrimination i.

Atrial fibrillation versus. atrial myopathy in thrombogenesis: Two sides of the same coin?

Atrial fibrillation (AF) and atrial myopathy are recognized contributors to cardiovascular morbidity, particularly ischemic stroke. AF poses an elevated risk of thrombogenesis due to irregular heart rhythm leading to blood stasis and clot formation. Atrial myopathy, marked by structural and functional alterations in the atria, is emerging as a crucial factor influencing thromboembolic events, independently of AF.

Challenges and compromises: Predicting unbound antibody structures with deep learning.

Therapeutic antibodies are manufactured, stored and administered in the free state; this makes understanding the unbound form key to designing and improving development pipelines. Prediction of unbound antibodies is challenging, specifically modelling of the CDRH3 loop, where inaccuracies are potentially worse due to a bias in structural data towards antibody-antigen complexes. This class imbalance provides a challenge for deep learning models trained on this data, potentially limiting generalisation to unbound forms.

Flies as carriers of antimicrobial resistant (AMR) bacteria in Nigerian hospitals: A workflow for surveillance of AMR bacteria carried by arthropod pests in hospital settings.

The dissemination of antimicrobial resistant (AMR) bacteria by flies in hospitals is concerning as nosocomial AMR infections pose a significant threat to public health. This threat is compounded in low- and middle-income countries (LMICs) by several factors, including limited resources for sufficient infection prevention and control (IPC) practices and high numbers of flies in tropical climates. In this pilot study, 1,396 flies were collected between August and September 2022 from eight tertiary care hospitals in six cities (Abuja, Enugu, Kaduna, Kano, Lagos and Sokoto) in Nigeria.