Dysregulation of synaptic transcripts underlies network abnormalities in ALS patient-derived motor neurons.

Amyotrophic lateral sclerosis (ALS) is characterized by dysfunction and loss of upper and lower motor neurons. Several studies have identified structural and functional alterations in the motor neurons before the manifestation of symptoms, yet the underlying cause of such alterations and how they contribute to the progressive degeneration of affected motor neuron networks remain unclear. Importantly, the short and long-term spatiotemporal dynamics of neuronal network activity make it challenging to discern how ALS-related network reconfigurations emerge and evolve.

Inducible, but not constitutive, pancreatic isoforms are regulated by intestinal microbiota and pancreatic diseases.

The / gene locus encodes for a conserved family of potent antimicrobial but also pancreatitis-associated proteins. Here we investigated whether family members differ in their baseline expression levels and abilities to be regulated in the pancreas and gut upon perturbations. We found, in human and mouse, pancreas and gut differed in / isoform levels and preferences, with duodenum most resembling the pancreas.

A spectroscopic analysis code for spatially resolved x-ray absorption data from the COAX platform.

Sophisticated tools such as computer vision techniques in combination with 1D lineout type analyses have been used in automating the analysis of spectral data for high energy density (HED) plasmas. Standardized automation can solve the problems posed by the complexity of HED spectra and the quantity of data. We present a spectroscopic code written for automated and streamlined analysis of spatially resolved x-ray absorption data from the COAX platform on Omega-60.

European Association of Hospital Pharmacists (EAHP) guidance on the pharmacy handling of in vivo gene therapy medicinal products.

Gene therapy is becoming increasingly prevalent, with new gene therapy medicinal products (GTMPs) being approved for use every year. Hospital pharmacists are expected to prepare and dispense these products, but there is substantial heterogeneity in the availability of up-to-date, practical guidance at a national level in Europe. Many institutions have no or very limited experience in handling GTMPs.

Comparing forced-choice and single-stimulus personality scores on a level playing field: A meta-analysis of psychometric properties and susceptibility to faking.

Forced-choice (FC) personality assessments have shown potential in mitigating the effects of faking. Yet despite increased attention and usage, there exist gaps in understanding the psychometric properties of FC assessments, and particularly when compared to traditional single-stimulus (SS) measures. The present study conducted a series of meta-analyses comparing the psychometric properties of FC and SS assessments after placing them on an equal playing field-by restricting to only studies that examined matched assessments of each format, and thus, avoiding the extraneous confound of using comparisons from different contexts (Sackett, 2021).

Disrupting and diversifying the values, voices and governance principles that shape biodiversity science and management.

With climate, biodiversity and inequity crises squarely upon us, never has there been a more pressing time to rethink how we conceptualize, understand and manage our relationship with Earth's biodiversity. Here, we describe governance principles of 17 Indigenous Nations from the Northwest Coast of North America used to understand and steward relationships among all components of nature, including humans. We then chart the colonial origins of biodiversity science and use the complex case of sea otter recovery to illuminate how ancestral governance principles can be mobilized to characterize, manage and restore biodiversity in more inclusive, integrative and equitable ways.

Utilisation and time to performance of diagnostic imaging in patients admitted to Danish emergency departments: a nationwide register-based study from 2007 to 2017.

Objectives: To describe the development of diagnostic imaging utilisation in Denmark from 2007 to 2017, coinciding with a major national reform of the emergency healthcare system.

Design: Nationwide descriptive register-based study.

Setting: All public hospitals in Denmark.

Selective inhibition of excitatory synaptic transmission alters the emergent bursting dynamics of neural networks.

Neurons connect to each other and form neural networks that display emergent electrophysiological activity. This activity begins as spontaneous uncorrelated firing in the early phase of development, and as functional excitatory and inhibitory synapses mature, the activity typically emerges as spontaneous network bursts. Network bursts are events of coordinated global activation among many neurons interspersed with periods of silencing and are important for synaptic plasticity, neural information processing, and network computation.

Patient and family perceptions of the provision of medicines as part of virtual outpatient consultations for children during COVID-19 pandemic.

Objectives: To evaluate (1) views and perceptions of patients/parents/carers and healthcare professionals on the medicines optimisation (MO) process following virtual outpatient clinic (VOC) during the COVID-19 pandemic and (2) the processes introduced at this time, identifying areas for improvements and suggest potential solutions.

Design: A mixed-methods service evaluation using qualitative and quantitative methods of the MO pathway in children aged 0-18 years following VOC across three specialist children's units.Semi-structured interviews were conducted over the telephone with the participants exploring their experiences and categorised into themes.

Kir4.1 is specifically expressed and active in non-myelinating Schwann cells.

Non-myelinating Schwann cells (NMSC) play important roles in peripheral nervous system formation and function. However, the molecular identity of these cells remains poorly defined. We provide evidence that Kir4.

Independent Validation and Assay Standardization of Improved Metabolic Biomarker Signature to Differentiate Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis.

Background & Aims: Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%.

Soybean Yield Formation Physiology - A Foundation for Precision Breeding Based Improvement.

The continued improvement of crop yield is a fundamental driver in agriculture and is the goal of both plant breeders and researchers. Plant breeders have been remarkably successful in improving crop yield, as demonstrated by the continued release of varieties with improved yield potential. This has largely been accomplished through performance-based selection, without specific knowledge of the molecular mechanisms underpinning these improvements.

Measurement specificity with modern methods: Using dimensions, facets, and items from personality assessments to predict performance.

The use of personality measures to predict work-related outcomes has been of great interest over the past several decades. The present study used machine learning (ML) to examine the optimal level in the personality hierarchy to use in developing predictive algorithms. This issue was examined in a sample of incumbent police officers (N = 1,043) who completed a multifaceted personality measure and were rated on their job performance.

Sequential Organ Failure Assessment Score Grouping Should Not Be the Primary Determinant of Allocation of Ventilators During a Pandemic.

The coronavirus-19 (COVD-19) pandemic has resulted in strains on critical care resources throughout the world. Existing and newly developed guidelines for the allocation of scarce resources, including ventilators, frequently use the Sequential Organ Failure Assessment (SOFA) score for prognostic determination. This article will outline how SOFA scores were neither designed nor tested for this purpose and why guidelines based upon SOFA score groupings do not conform to ethical principles and community values.

Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Developing biomarkers for early detection and chemotherapeutic response prediction is crucial to improve the dismal prognosis of PDAC patients. However, molecular cancer signatures based on transcriptome analysis do not reflect intratumoral heterogeneity.

A minigene DNA vaccine encoding peptide epitopes derived from Galectin-1 has protective antitumoral effects in a model of neuroblastoma.

We recently identified Galectin-1 (Gal-1), a β-galactoside-binding lectin, as a novel immune regulator in neuroblastoma (NB). Here, we characterized the tolerogenic function of Gal-1 within the CD8 T cell compartment and further evaluated its relevance as an antigen for effective DNA vaccination against NB in a mouse model. NB cells with Gal-1 knockdown (NXS-2L) exhibited significantly reduced tumor growth compared to NXS-2 NB cells.

Criticality, Connectivity, and Neural Disorder: A Multifaceted Approach to Neural Computation.

It has been hypothesized that the brain optimizes its capacity for computation by self-organizing to a critical point. The dynamical state of criticality is achieved by striking a balance such that activity can effectively spread through the network without overwhelming it and is commonly identified in neuronal networks by observing the behavior of cascades of network activity termed "neuronal avalanches." The dynamic activity that occurs in neuronal networks is closely intertwined with how the elements of the network are connected and how they influence each other's functional activity.

Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects.

Objective: Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to organ dysfunction, chronic pain, an increased risk for pancreatic cancer and considerable morbidity. Due to a lack of specific biomarkers, diagnosis is based on symptoms and specific but insensitive imaging features, preventing an early diagnosis and appropriate management.

Design: We conducted a type 3 study for multivariable prediction for individual prognosis according to the TRIPOD guidelines.

Assessment of Self-Efficacy as a Way to Help Identify Cancer Patients Who Might Benefit from Self-Help Group Attendance?

Participating in patient self-help groups is highly recommended to patients in cancer care. Yet, engagement is relatively rare. A total of 253 patients participated in our study conducted as a paper-and-pencil questionnaire.

Feasibility of developing children's Pill School within a UK hospital.

Objective: We assessed the feasibility of introducing an intervention (children's Pill School-PS) within a UK hospital to provide swallowing training for children, identified the proportion of children who can be switched from oral liquid medicines to pills and assessed children/parents' opinions about the PS training.

Methods: 30 inpatient children (aged 3-18 years; taking oral liquid medicines; their liquid medications assessed suitable for switching to pills; can (and their parents) speak/understand English were included. Training sessions were delivered using hard sweets of different sizes.

Developing new models of care at speed: learning from healthcare redesign for children with COVID-related multisystem inflammation.

This article describes the rapid, system-wide reconfiguration of local and network services in response to the newly described paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) (also known as multisystem inflammatory syndrome in children). Developing the model of care for this novel disease, whose natural history, characteristics and treatment options were still unclear, presented distinct challenges.We analyse this redesign through the lens of healthcare management science, and outline transferable principles which may be of specific and urgent relevance for paediatricians yet to experience the full impact of the COVID-19 pandemic; and more generally, for those developing a new clinical service or healthcare operating model to manage the sudden emergence of any unanticipated clinical entity.

Evidence for person-centred care in chronic wound care: A systematic review and recommendations for practice.

Background: Chronic wounds affect an estimated 2.21 per 1000 population. They are a significant source of morbidity and affect individuals physically, psychologically, socially and financially.

Use of compression therapy to treat lower limb wounds across Europe: a scoping review protocol.

Introduction: Poor lower wound care is an avoidable patient harm. Compression therapy is an effective way of treating non-ischaemic lower limbs wounds, but it is not always used appropriately. There are many guidelines which set out how compression therapy should be used, but there is dearth of evidence about how it is actually used at a population level across Europe.