Care home resident identification: A comparison of address matching methods with Natural Language Processing.

Background: Care home residents are a highly vulnerable group, but identifying care home residents in routine data is challenging. This study aimed to develop and validate Natural Language Processing (NLP) methods to identify care home residents from primary care address records.

Methods: The proposed system applies an NLP sequential filtering and preprocessing of text, then the calculation of similarity scores between general practice (GP) addresses and care home registered addresses.

Direct Oral Anticoagulants Versus Warfarin in Patients With Isolated Heparin-Induced Thrombocytopenia or Heparin-Induced Thrombocytopenia With Thrombosis.

No existing studies compare oral anticoagulants to treat heparin-induced thrombocytopenia with or without thrombosis (HIT/HITT). This retrospective study evaluated thrombotic and bleeding outcomes in adults treated for HIT/HITT with a direct oral anticoagulant (DOAC) or warfarin between 2012 and 2023 within the Ochsner Health System. Patients with mechanical heart valves, valvular atrial fibrillation, antiphospholipid syndrome, active malignancy, or venous thromboembolism (VTE) within the previous 6 months were excluded.

Longitudinal genomic surveillance of a UK intensive care unit shows a lack of patient colonisation by multi-drug-resistant Gram-negative bacterial pathogens.

Vulnerable patients in an intensive care unit (ICU) setting are at high risk of infection from bacteria including gut-colonising and species. Complex ICU procedures often depend on successful antimicrobial treatment, underscoring the importance of understanding the extent of patient colonisation by multi-drug-resistant organisms (MDROs) in large UK ICUs. Previous work on ICUs globally uncovered high rates of colonisation by transmission of MDROs, but the situation in UK ICUs is less understood.

Dysregulation of FicD AMPylation causes diabetes by disrupting pancreatic endocrine homeostasis.

Bi-functional enzyme FicD regulates the endoplasmic reticulum chaperone BiP using AMPylation and deAMPylation during ER homeostasis and stress, respectively. Human FicD with an arginine-to-serine mutation disrupts FicD deAMPylation activity resulting in severe neonatal diabetes. We generated the mutation in mice to create a pre-clinical murine model for neonatal diabetes.

5-HT receptors in the nucleus accumbens constrain the rewarding effects of MDMA.

MDMA is a promising adjunct to psychotherapy and has well-known abuse liability, although less than other amphetamine analogs. While the reinforcing dopamine (DA)-releasing properties of MDMA are on par with methamphetamine (METH), MDMA is a far more potent serotonin (5-HT) releaser, via the 5-HT transporter (SERT). MDMA-mediated 5-HT release in a major reward center, the nucleus accumbens (NAc), drives prosocial behaviors via 5-HTR activation.

A reproducible extended ex-vivo normothermic machine liver perfusion protocol utilising improved nutrition and targeted vascular flows.

Background: Normothermic machine perfusion of donor livers has become standard practice in the field of transplantation, allowing the assessment of organs and safe extension of preservation times. Alongside its clinical uses, there has been expanding interest in extended normothermic machine perfusion (eNMP) of livers as a potential vehicle for medical research. Reproducible extended normothermic machine perfusion has remained elusive due to its increased complexity and monitoring requirements.

Cross-species brain-wide mapping reveals a conserved and coordinated network engaged by NAc DBS.

Nucleus accumbens (NAc) deep brain stimulation (DBS) has been increasingly explored as a treatment modality for refractory neuropsychiatric disorders. Uncovering the accumbens network that is engaged by DBS is a critical step forward in understanding how modulating this important node impacts the broader mesocorticolimbic circuit. Using whole-brain clearing and unbiased, brain-wide neural activity mapping, we found that NAc DBS increases neural activity in a coordinated mesocorticolimbic network in mice.

FicD sensitizes cellular response to glucose fluctuations in mouse embryonic fibroblasts.

During homeostasis, the endoplasmic reticulum (ER) maintains productive transmembrane and secretory protein folding that is vital for proper cellular function. The ER-resident HSP70 chaperone, binding immunoglobulin protein (BiP), plays a pivotal role in sensing ER stress to activate the unfolded protein response (UPR). BiP function is regulated by the bifunctional enzyme filamentation induced by cyclic-AMP domain protein (FicD) that mediates AMPylation and deAMPylation of BiP in response to changes in ER stress.

How to build resiliency in autistic individuals: an implication to advance mental health.

Introduction: Individuals on the autism spectrum (ASD) often experience poor mental health and coping strategies compared to their peers due to social exclusion and co-occurring conditions. Resiliency has been identified as a key factor in preventing adverse outcomes and promoting mental health. Therefore, it is important to determine what strategies can be used to build resiliency among autistic individuals.

Anatomic and Functional Outcomes of Vitrectomy for Advanced Retinopathy of Prematurity: A Systematic Review.

The success of vitrectomy in the advanced stages of retinopathy of prematurity (ROP) is defined not only by anatomical results, but also by functional outcomes. Studies have indicated that vitrectomy produces better outcomes when performed at an earlier stage (stage 4 vs. stage 5 ROP).

Diagnosis of Post-Hematopoietic Stem Cell Transplantation Bronchiolitis Obliterans Syndrome in Children: Time for a Rethink?

Hematopoietic stem cell transplantation (HSCT) is undertaken in children with the aim of curing a range of malignant and nonmalignant conditions. Unfortunately, pulmonary complications, especially bronchiolitis obliterans syndrome (BOS), are significant sources of morbidity and mortality post-HSCT. Currently, criteria developed by a National Institutes of Health (NIH) working group are used to diagnose BOS in children post-HSCT.

Detection of Bronchiolitis Obliterans Syndrome after Pediatric Hematopoietic Stem Cell Transplantation: An Official American Thoracic Society Clinical Practice Guideline.

Many children undergo allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignant and nonmalignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common noninfectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent NIH workshop highlighted the need for a standardized approach to post-HSCT monitoring.

Innovations in the care of childhood interstitial lung disease associated with connective tissue disease and immune-mediated disorders.

Childhood interstitial lung disease (chILD) associated with connective tissue and immune mediated disorders is the second most common chILD diagnostic category. As knowledge of the molecular and genetic underpinnings of these rare disorders advances, the recognized clinical spectrum of associated pulmonary manifestations continues to expand. Pulmonary complications of these diseases, including ILD, confer increased risk for morbidity and mortality and contribute to increased complexity for providers tasked with managing the multiple organ systems that can be impacted in these systemic disorders.

FicD regulates adaptation to the unfolded protein response in the murine liver.

The unfolded protein response (UPR) is a cellular stress response that is activated when misfolded proteins accumulate in the endoplasmic reticulum (ER). Regulation of the UPR response must be adapted to the needs of the cell as prolonged UPR responses can result in disrupted cellular function and tissue damage. Previously, we discovered that the enzyme FicD (also known as Fic or HYPE) through its AMPylation and deAMPylation activity can modulate the UPR response via post-translational modification of BiP.

FicD regulates adaptation to the unfolded protein response in the murine liver.

The unfolded protein response (UPR) is a cellular stress response that is activated when misfolded proteins accumulate in the endoplasmic reticulum (ER). The UPR elicits a signaling cascade that results in an upregulation of protein folding machinery and cell survival signals. However, prolonged UPR responses can result in elevated cellular inflammation, damage, and even cell death.

epHero - a tandem-fluorescent probe to track the fate of apoptotic cells during efferocytosis.

The efficient removal of apoptotic cells via efferocytosis is critical for maintaining optimal tissue function. This involves the binding and engulfment of apoptotic cells by phagocytes and the subsequent maturation of the phagosome, culminating in lysosomal fusion and cargo destruction. However, current approaches to measure efferocytosis rely on labelling apoptotic targets with fluorescent dyes, which do not sufficiently distinguish between changes to the engulfment and acidification of apoptotic material.

Synthesis of cationic liposome nanoparticles using a thin film dispersed hydration and extrusion method.

Liposome nanoparticles can carry a wide range of therapeutic molecules including small molecules and nucleic acid-based therapeutics. Potential benefits include translocation across physiological barriers, reduced systemic toxicity, and enhanced pharmacokinetic parameters such as absorption, distribution, selective release and optimal elimination kinetics. Liposome nanoparticles can be generated with a wide range of natural and synthetic lipid-based molecules that confer desirable properties depending on the desired therapeutic application Nel et al (2023), Large (2021), Elkhoury (2020).

Virtual interviews and equity: The pediatric pulmonary fellow perspective.

Background And Objectives: The SARS-CoV-2 pandemic shifted medical training programs to utilize virtual interviews (VIs) starting with the 2020 interview cycle. Fellowship interviews continue in the virtual format. It is unknown how this shift has affected equity for applicants as compared to in-person interviews.

Opioid receptor expressing neurons of the central amygdala gate behavioral effects of ketamine in mice.

Ketamine has anesthetic, analgesic, and antidepressant properties which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. It is unclear whether naltrexone blocks a direct effect of ketamine at ORs, or whether normal functioning of the OR system is required to realize the full antidepressant effects of treatment.

Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear.