Immunotherapy-Resistant Neuropathic Pain and Fatigue Predict Quality-of-Life in Contactin-Associated Protein-Like 2 Antibody Disease.

The long-term clinical outcomes and associated prognostic factors in contactin-associated protein-like 2 (CASPR2)-antibody diseases are unknown. A total of 75 participants with CASPR2 antibodies were longitudinally assessed for disability, quality-of-life, and chronic pain. Although most symptoms improved within 6 months of treatment, neuropathic pain and fatigue were the most immunotherapy refractory, and persisted for up to 6 years.

Differences in gene expression between high and low tolerance rainbow trout (Oncorhynchus mykiss) to acute thermal stress.

Understanding the mechanisms that underlie the adaptive response of ectotherms to rising temperatures is key to mitigate the effects of climate change. We assessed the molecular and physiological processes that differentiate between rainbow trout (Oncorhynchus mykiss) with high and low tolerance to acute thermal stress. To achieve our goal, we used a critical thermal maximum trial in two strains of rainbow trout to elicit loss of equilibrium responses to identify high and low tolerance fish.

Hypoxia promotes tumor immune evasion by suppressing MHC-I expression and antigen presentation.

Hypoxia is a common feature of solid tumors that has previously been linked to resistance to radiotherapy and chemotherapy, and more recently to immunotherapy. In particular, hypoxic tumors exclude T cells and inhibit their activity, suggesting that tumor cells acquire a mechanism to evade T-cell recognition and killing. Our analysis of hypoxic tumors indicates that hypoxia downregulates the expression of MHC class I and its bound peptides (i.

Complex and Dynamic Gene-by-Age and Gene-by-Environment Interactions Underlie Functional Morphological Variation in Adaptive Divergence in Arctic Charr (Salvelinus alpinus).

The evolution of adaptive phenotypic divergence requires heritable genetic variation. However, it is underappreciated that trait heritability is molded by developmental processes interacting with the environment. We hypothesized that the genetic architecture of divergent functional traits was dependent on age and foraging environment.

Evaluating the need for standardised disease manifestation categories in patients infected with the tick-borne encephalitis virus: A Delphi panel.

Categorization systems for tick-borne encephalitis virus (TBEV) infection lack consistency in classifying disease severity. To evaluate the need for a standard, consensus-based categorisation system for TBEV infection across subtypes, we gathered an expert panel of clinicians and scientists with diverse expertise in TBEV infection. Consensus was sought using the Delphi technique, which consisted of 2 web-based survey questionnaires and a final, virtual, consensus-building exercise.

Turns around periodic spatial boundaries facilitate increasing event segmentation over time.

Event segmentation is a neurocognitive process bridging perception and episodic memory. To our knowledge, almost all segmentation work is framed towards humans, yet evolutionarily conserved mechanisms in event cognition exist across species. Here, we addressed segmentation in a way that is applicable to humans and non-human animals, inspired by research in rats; specifically, the fragmentation of grid-cell spatial representations following the insertion of boundaries into an environment (forming a corridor maze).

Context in memory is reconstructed, not encoded.

Context has long been regarded as an important element of long-term memory, and episodic memory in particular. The ability to remember not only the object or focus of a memory but also contextual details allow us to reconstruct integrated representations of events. However, despite its prevalence in the memory literature, context remains difficult to define and identify, with different studies using context to refer to different sets of stimuli or concepts.

Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction.

The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19.

Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer.

Testing for DNA mismatch repair deficiency (MMRd) is recommended for all colorectal cancers (CRCs). Automating this would enable precision medicine, particularly if providing information on etiology not captured by deep learning (DL) methods. We present AIMMeR, an AI-based method for determination of mismatch repair (MMR) protein expression at a single-cell level in routine pathology samples.

Measuring episodic memory and mental time travel: crossing the species gap.

Mental time travel is the projection of the mind into the past or future, and relates to experiential aspects of episodic memory, and episodic future thinking. Framing episodic memory and future thinking in this way causes a challenge when studying memory in animals, where demonstration of this mental projection is prevented by the absence of language. However, there is good evidence that non-human animals pass tests of episodic memory that are based on behavioural criteria, meaning a better understanding needs to be had of the relationship between episodic memory and mental time travel.

Elements of episodic memory: lessons from 40 years of research.

40 years ago, Endel Tulving published his hugely influential (Oxford: Clarendon Press, 1983). For the first time, this discussed the details of episodic memory (i.e.

Utilising accessible and reproducible neurological assessments in clinical studies: Insights from use of the Neurological Impairment Scale in the multi-centre COVID-CNS study.

Reproducible and standardised neurological assessment scales are important in quantifying research outcomes. These scales are often performed by non-neurologists and/or non-clinicians and must be robust, quantifiable, reproducible and comparable to a neurologist's assessment. COVID-CNS is a multi-centre study which utilised the Neurological Impairment Scale (NIS) as a core assessment tool in studying neurological outcomes following COVID-19 infection.

Assessment of long-term psychosocial outcomes in N-methyl-D-aspartate receptor encephalitis - the SAPIENCE study protocol.

Background: N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a rare neurological autoimmune disease with severe neuropsychiatric symptoms during the acute phase. Despite good functional neurological recovery, most patients continue to experience cognitive, psychiatric, psychological, and social impairments years after the acute phase. However, the precise nature and evolving patterns over time of these long-term consequences remain unclear, and their implications for the well-being and quality of life of predominantly young patients have yet to be thoroughly examined.

Primate cerebrospinal fluid CHI3L1 reflects brain TREM2 agonism.

Introduction: Triggering receptor expressed on myeloid cells 2 (TREM2) agonists are being clinically evaluated as disease-modifying therapeutics for Alzheimer's disease. Clinically translatable pharmacodynamic (PD) biomarkers are needed to confirm drug activity and select the appropriate therapeutic dose in clinical trials.

Methods: We conducted multi-omic analyses on paired non-human primate brain and cerebrospinal fluid (CSF), and stimulation of human induced pluripotent stem cell-derived microglia cultures after TREM2 agonist treatment, followed by validation of candidate fluid PD biomarkers using immunoassays.

ANZACS-QI Heart Failure Registry: a new approach using age-stratified sampling of hospital discharges to guide quality improvement (ANZACS-QI 79).

Heart failure is a major healthcare problem in New Zealand. The Acute Decompensated Heart Failure (ADHF) Registry was introduced in 2015, and has identified the need for quality improvement strategies to improve care of patients hospitalised with heart failure. In this paper, we describe the implementation of the revised ANZACS-QI Heart Failure Registry, which has a primary aim to support evidence-based management of and quality improvement measures for patients who are hospitalised with heart failure in New Zealand.

UK research priority setting for childhood neurological conditions.

Aim: To identify research priorities regarding the effectiveness of interventions for children and young people (CYP) with childhood neurological conditions (CNCs). These include common conditions such as epilepsies and cerebral palsy, as well as many rare conditions.

Method: The National Institute for Health and Care Research (NIHR) and the James Lind Alliance (JLA) champion and facilitate priority setting partnerships (PSPs) between patients, caregivers, and clinicians (stakeholders) to identify the most important unanswered questions for research (uncertainties).

Mice integrate conspecific and contextual information in forming social episodic-like memories under spontaneous recognition task conditions.

The ability to remember unique past events (episodic memory) may be an evolutionarily conserved function, with accumulating evidence of episodic-(like) memory processing in rodents. In humans, it likely contributes to successful complex social networking. Rodents, arguably the most used laboratory models, are also rather social animals.

Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer's Disease and Multiple Sclerosis.

Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist antibodies in multiple mixed-sex mouse models of Alzheimer's disease (AD) pathology and remyelination. Receptor activation and downstream signaling are explored in vitro, and active dose ranges are determined in vivo based on pharmacodynamic responses from microglia.

Acquired rifamycin resistance among patients with tuberculosis and HIV in new York City, 2001-2023.

Introduction: Acquired rifamycin resistance (ARR) in tuberculosis (TB) has been associated with HIV infection and can necessitate complicated TB treatment regimens, particularly in people living with HIV (PLWH). This work examines clinical characteristics and treatment outcomes of PLWH who developed ARR from 2001 to 2023 in New York City (NYC) to inform best practices for treating these patients.

Methods: PLWH who developed ARR 2001-2023 were identified from the NYC TB registry.