Anti-CTLA4 treatment reduces lymphedema risk potentially through a systemic expansion of the FOXP3 T population.

Secondary lymphedema is a common sequel of oncologic surgery and presents a global health burden still lacking pharmacological treatment. The infiltration of the lymphedematous extremities with CD4T cells influences lymphedema onset and emerges as a promising therapy target. Here, we show that the modulation of CD4FOXP3CD25regulatory T (T) cells upon anti-CTLA4 treatment protects against lymphedema development in patients with melanoma and in a mouse lymphedema model.

Fast activity chirp patterns in focal seizures from patients and animal models.

Time-frequency analysis of focal seizure electroencephalographic signals performed with depth electrodes in human temporal lobe structures has revealed the occurrence at onset of oscillations at approximately 30-100 Hz that feature a monotonic rapid decay in frequency content. This seizure onset pattern, referred to as chirp, has been identified as a highly specific and sensitive marker of focal seizures that are characterized by low-voltage fast activity. We report that this chirp pattern is also observed in animal models of temporal lobe epilepsy in both in vivo and in vitro preparations.

Temporal genomic analysis of homogeneous tumor models reveals key regulators of immune evasion in melanoma.

Low intra-tumor heterogeneity (ITH) correlates with increased patient survival and immunotherapy response. However, even highly homogeneous tumors are variably aggressive, and the immunological factors impacting aggressiveness remain understudied. Here, we analyzed the mechanisms underlying immune escape in murine tumors with low ITH.

TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.

The TGFβ signaling pathway is known for its pleiotropic functions in a plethora of biological processes. In melanoma, TGFβ signaling promotes invasiveness and metastasis formation. However, its involvement in the response to therapy is controversial.

A Roadmap of Noninstitutional Living Options for People with Dementia: "Don't Fence Me In".

Canadians overwhelmingly do not want to live in long-term care institutions (LTCIs) when they age; yet many end up there for lack of home care, because family care partners burn out, or because they and their professional advisors are unaware of alternatives to institutions. Not only is institutional dementia care riven with problems, it segregates disabled people, thereby abrogating human rights. Because systemic ageism and ableism cloud seniors' care, institutions remain the default option for Canadians with dementia.

Decoupling of Tree-Ring Cellulose δO and δH Highlighted by Their Contrasting Relationships to Climate and Tree Intrinsic Variables.

Oxygen (δO) and hydrogen (δH) stable isotope ratios are tightly coupled in precipitation and, albeit damped, in leaf water, but are often decoupled in tree-ring cellulose. The environmental and physiological conditions in which this decoupling occurs are not yet well understood. We investigated the relationships between δO and δH and tree-ring width (TRW), tree crown volume, tree age and climate in silver fir and Douglas-fir and found substantial differences between δO and δH.

No Future Growth Enhancement Expected at the Northern Edge for European Beech due to Continued Water Limitation.

With ongoing global warming, increasing water deficits promote physiological stress on forest ecosystems with negative impacts on tree growth, vitality, and survival. How individual tree species will react to increased drought stress is therefore a key research question to address for carbon accounting and the development of climate change mitigation strategies. Recent tree-ring studies have shown that trees at higher latitudes will benefit from warmer temperatures, yet this is likely highly species-dependent and less well-known for more temperate tree species.

Cardiovascular diseases in Quebec health administrative databases: missing diagnoses and underestimation of the number of cases in a 28-year prospective cohort.

Introduction: Cardiovascular disease (CVD) surveillance in Quebec and the rest of Canada is carried out using health administrative databases, which in Quebec includes the physician claims database. The presence of billing claims without diagnoses can lead to the number of CVD cases being underestimated. The purpose of this study is to estimate the proportion of CVD diagnoses and CVD cases that may be missing from these databases.

Psoriasis localization patterns in the Swiss Psoriasis Registry (SDNTT) over 11 years: an analysis by sex and age.

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT.

Distinct Variations in Gene Expression and Cell Composition across Lichen Planus Subtypes.

Lichen planus (LP) is a highly prevalent inflammatory skin disease. While various clinical subtypes have been defined, detailed comparisons of these variants are lacking. This study aimed to elucidate differences in gene expression and cellular composition across LP subtypes.

A rapid review protocol of physiotherapy and occupational therapy telerehabilitation to inform ethical and equity concerns.

Background: Telerehabilitation (TR) has emerged as a feasible and promising approach for delivering rehabilitation services remotely, utilizing technology to bridge the gap between healthcare providers and patients. As new modalities of virtual care and health technologies continue to emerge, it is crucial to stay informed about the growing landscape of virtual care to ensure that telehealth service delivery is ethical and equitable, and improves the quality of services and patient outcomes.

Objective: The primary objective of this article is to present the protocol of a rapid review to examine the equity-related aspects surrounding the implementation of TR.

A targetable type III immune response with increase of IL-17A expressing CD4 T cells is associated with immunotherapy-induced toxicity in melanoma.

Immune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine and chemokine assays from serum at baseline and at the adverse event onset indicated aberrant T cell activity with differential expression of type I and III immune signatures. This was in line with the finding of an increase in the proportion of CD4 T cells with IL-17A expression at the adverse event onset in the peripheral blood using flow cytometry.

Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells.

Publisher Correction: LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition.

[Image: see text]

Low concentration dimethyl sulfoxide (DMSO) modulates epileptiform synchronization in the 4-aminopyridine in vitro model.

Dimethyl sulfoxide (DMSO) is commonly used to dissolve water-insoluble drugs due to its dipolar and aprotic properties. It also serves as a vehicle in many pharmacological studies. However, it has been reported that DMSO can induce seizures in human patients, lower seizure threshold in vivo, and modulate ion receptors activities in vitro.

The genetic evolution of acral melanoma.

Acral melanoma is an aggressive type of melanoma with unknown origins. It is the most common type of melanoma in individuals with dark skin and is notoriously challenging to treat. We examine exome sequencing data of 139 tissue samples, spanning different progression stages, from 37 patients.

Frequency-dependent seizure-suppressing effects of optogenetic activation of septal inhibitory cells in mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) is characterized by recurring focal seizures that arise from limbic areas and are often refractory to pharmacological interventions. We have reported that optogenetic stimulation of PV-positive cells in the medial septum at 0.5 Hz exerts seizure-suppressive effects.

Monitoring melanoma patients on treatment reveals a distinct macrophage population driving targeted therapy resistance.

Resistance to targeted therapy remains a major clinical challenge in melanoma. To uncover resistance mechanisms, we perform single-cell RNA sequencing on fine-needle aspirates from resistant and responding tumors of patients undergoing BRAFi/MEKi treatment. Among the genes most prominently expressed in resistant tumors is POSTN, predicted to signal to a macrophage population associated with targeted therapy resistance (TTR).

COL10A1 expression distinguishes a subset of cancer-associated fibroblasts present in the stroma of high-risk basal cell carcinoma.

Background: Basal cell carcinoma (BCC) is the most frequently diagnosed skin cancer and the most common malignancy in humans. Different morphological subtypes of BCC are associated with a low or high risk of recurrence and aggressiveness, but the underlying biology of how the individual subtypes arise remains largely unknown. As the majority of BCCs appear to arise from mutations in the same pathway, we hypothesized that BCC development, growth and invasive potential is also influenced by the tumour microenvironment and, in particular, by cancer-associated fibroblasts (CAFs) and the factors they secrete.

Triple-isotope analysis in tree-ring cellulose suggests only moderate effects of tree species mixture on the climate sensitivity of silver fir and Douglas-fir.

Disentangling the factors influencing the climate sensitivity of trees is crucial to understanding the susceptibility of forests to climate change. Reducing tree-to-tree competition and mixing tree species are two strategies often promoted to reduce the drought sensitivity of trees, but it is unclear how effective these measures are in different ecosystems. Here, we studied the growth and physiological responses to climate and severe droughts of silver fir and Douglas-fir growing in pure and mixed conditions at three sites in Switzerland.

The laminar position, morphology, and gene expression profiles of cortical astrocytes are influenced by time of birth from ventricular/subventricular progenitors.

Astrocytes that reside in superficial (SL) and deep cortical layers have distinct molecular profiles and morphologies, which may underlie specific functions. Here, we demonstrate that the production of SL and deep layer (DL) astrocyte populations from neural progenitor cells in the mouse is temporally regulated. Lineage tracking following in utero and postnatal electroporation with PiggyBac (PB) EGFP and birth dating with EdU and FlashTag, showed that apical progenitors produce astrocytes during late embryogenesis (E16.

Ictal activity is sustained by the estrogen receptor β during the estrous cycle.

Catamenial epilepsy, defined as a periodicity of seizure exacerbation during the menstrual cycle, affects up to 70 % of epileptic women. Seizures in these patients are often non-responsive to medication; however, our understanding of the relation between menstrual cycle and seizure generation (i.e.