Impaired glymphatic system in genetic frontotemporal dementia: a GENFI study.

The glymphatic system is an emerging target in neurodegenerative disorders. Here, we investigated the activity of the glymphatic system in genetic frontotemporal dementia with a diffusion-based technique called diffusion tensor image analysis along the perivascular space. We investigated 291 subjects with symptomatic or presymptomatic frontotemporal dementia (112 with [] expansion, 119 with [] mutations and 60 with [] mutations) and 83 non-carriers (including 50 young and 33 old non-carriers).

The role of zinc and matrix metalloproteinases in myofibrillar protein degradation in critical illness myopathy.

Due to an unexpected activation of different zinc (Zn) transporters in a recent prospective clinical study, we have revisited the role of Zn homeostasis and the activation of matrix metalloproteinases (MMPs) in skeletal muscle exposed to the intensive care unit (ICU) condition (immobilization and mechanical ventilation). ICU patients exposed to 12 days ICU condition were followed longitudinally with six repeated muscle biopsies while they showed a progressive preferential myosin loss, i.e.

The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha.

Background: Acute myeloid leukemia (AML), a malignancy Often resistant to common chemotherapy regimens (Cytarabine (Ara-c) + Daunorubicin (DNR)), is accompanied by frequent relapses. Many factors are involved in causing chemoresistance. Heme Oxygenase-1 (HO-1) and Hypoxia-Inducible Factor 1-alpha (HIF-1α) are two of the most well-known genes, reported to be overexpressed in AML and promote resistance against chemotherapy according to several studies.

Prelude to malignancy: A gene expression signature in normal mammary gland from breast cancer patients suggests pre-tumorous alterations and is associated with adverse outcomes.

Despite advances in early detection and treatment strategies, breast cancer recurrence and mortality remain a significant health issue. Recent insights suggest the prognostic potential of microscopically healthy mammary gland, in the vicinity of the breast lesion. Nonetheless, a comprehensive understanding of the gene expression profiles in these tissues and their relationship to patient outcomes remain missing.

Cortico-cortical transfer of socially derived information gates emotion recognition.

Emotion recognition and the resulting responses are important for survival and social functioning. However, how socially derived information is processed for reliable emotion recognition is incompletely understood. Here, we reveal an evolutionarily conserved long-range inhibitory/excitatory brain network mediating these socio-cognitive processes.

ITGB5 facilitates gastric cancer metastasis by promoting TGFBR2 endosomal recycling.

TGFBR2, a key regulator of the TGFβ signaling pathway, plays a crucial role in gastric cancer (GC) metastasis through its endosomal recycling process. Despite its importance, the mechanisms governing this process remain unclear. Here, we identify integrin β5 (ITGB5) as a critical mediator that promotes TGFBR2 endosomal recycling.

Albuminuria predicts kidney events in IgA nephropathy.

Background & Hypothesis: KDIGO recommends proteinuria <1 g/d as a treatment target in patients with immunoglobulin A nephropathy (IgAN) because of high-risk of progression to kidney failure. However, long-term kidney outcomes in patients with low-grade proteinuria remain insufficiently studied.

Methods: We enrolled patients with biopsy-proven primary IgAN from the Swedish Renal Registry and analyzed associations between urine albumin-to-creatinine ratio (uACR, in categories < 0.

Scalable and efficient DNA sequencing analysis on different compute infrastructures aiding variant discovery.

DNA variation analysis has become indispensable in many aspects of modern biomedicine, most prominently in the comparison of normal and tumor samples. Thousands of samples are collected in local sequencing efforts and public databases requiring highly scalable, portable, and automated workflows for streamlined processing. Here, we present nf-core/sarek 3, a well-established, comprehensive variant calling and annotation pipeline for germline and somatic samples.

Fcγ-Receptor-Independent Controlled Activation of CD40 Canonical Signaling by Novel Therapeutic Antibodies for Cancer Therapy.

The activation of CD40-mediated signaling in antigen-presenting cells is a promising therapeutic strategy to promote immune responses against tumors. Most agonistic anti-CD40 antibodies currently in development require the Fcγ-receptor (FcγR)-mediated crosslinking of CD40 molecules for a meaningful activation of CD40 signaling but have limitations due to dose-limiting toxicities. Here we describe the identification of CD40 antibodies which strongly stimulate antigen-presenting cells in an entirely FcγR-independent manner.

Evaluation of bacterial safety approaches of platelet blood concentrates: bacterial screening and pathogen reduction.

This mini-review analyzed two approaches to screening bacterial contamination and utilizing pathogen reduction technology (PRT) for Platelet concentrates (PCs). While the culture-based method is still considered the gold standard for detecting bacterial contamination in PCs, efforts in the past two decades to minimize transfusion-transmitted bacterial infections (TTBIs) have been insufficient to eliminate this infectious threat. PRTs have emerged as a crucial tool to enhance safety and mitigate these risks.

Extending the phenotypic spectrum assessed by the CDR plus NACC FTLD in genetic frontotemporal dementia.

Introduction: We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD).

Methods: Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD-NM scale. This was assessed in 522 mutation carriers and 310 mutation-negative controls from the Genetic Frontotemporal dementia Initiative (GENFI).

Focal-to-bilateral tonic-clonic seizures and High-grade CMV-infection are poor survival predictors in Tumor-related Epilepsy Adult-type diffuse gliomas-A single-center study and literature review.

Introduction: Previous studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored.

A phenotypic screening approach to target p60AmotL2-expressing invasive cancer cells.

Background: Tumor cells have the ability to invade and form small clusters that protrude into adjacent tissues, a phenomenon that is frequently observed at the periphery of a tumor as it expands into healthy tissues. The presence of these clusters is linked to poor prognosis and has proven challenging to treat using conventional therapies. We previously reported that p60AmotL2 expression is localized to invasive colon and breast cancer cells.

COVID-19 vaccine uptake among young adults: Influence of asthma and sociodemographic factors.

Background: Asthma was initially described as a risk factor for severe coronavirus disease 2019 (COVID-19), but the uptake of COVID-19 vaccine among young adults with asthma is not well studied.

Objective: The aims were to assess COVID-19 vaccine uptake among young adults in general and to explore potential determinants including sociodemographic factors and asthma.

Methods: Participants from the population-based birth cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) were included: 4,064 in the study population, 3,064 in a follow-up at age 24 years, and 2,049 in a COVID-19 follow-up (mean age, 26.

Clinically relevant gene signatures provide independent prognostic information in older breast cancer patients.

Background: The clinical utility of gene signatures in older breast cancer patients remains unclear. We aimed to determine signature prognostic capacity in this patient subgroup.

Methods: Research versions of the genomic grade index (GGI), 70-gene, recurrence score (RS), cell cycle score (CCS), PAM50 risk-of-recurrence proliferation (ROR-P), and PAM50 signatures were applied to 39 breast cancer datasets (N = 9583).

Targeting autophagy as a therapeutic strategy in pediatric acute lymphoblastic leukemia.

Autophagy is activated in response to a variety of stress conditions including anti-cancer therapies, and tumors cells often depend on autophagy for survival. In this study, we have evaluated inhibition of autophagy as therapeutic strategy in acute lymphoblastic leukemia (ALL) in children, both as a single treatment and in combination with glucocorticoid (GC) Dexamethasone (Dexa). Analysis of proteomics and RNA-seq of ALL cell lines and primary samples identified an upregulation of Vps34 and ATG14 proteins and autophagy and lysosomal pathway enrichment in a genetic subgroup with a recurrent t(12;21) translocation.

Combining FAIMS based glycoproteomics and DIA proteomics reveals widespread proteome alterations in response to glycosylation occupancy changes in Neisseria gonorrhoeae.

Protein glycosylation is increasingly recognized as a common protein modification across bacterial species. Within the Neisseria genus O-linked protein glycosylation is conserved yet closely related Neisseria species express O-oligosaccharyltransferases (PglOs) with distinct targeting activities. Within this work, we explore the targeting capacity of different PglOs using Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) fractionation and Data-Independent Acquisition (DIA) to allow the characterization of the impact of changes in glycosylation on the proteome of Neisseria gonorrhoeae.

Prognostic impact of HER2 biomarker levels in trastuzumab-treated early HER2-positive breast cancer.

Background: Overexpression of human epidermal growth factor receptor 2 (HER2) caused by HER2 gene amplification is a driver in breast cancer tumorigenesis. We aimed to investigate the prognostic significance of manual scoring and digital image analysis (DIA) algorithm assessment of HER2 copy numbers and HER2/CEP17 ratios, along with ERBB2 mRNA levels among early-stage HER2-positive breast cancer patients treated with trastuzumab.

Methods: This retrospective study comprised 371 early HER2-positive breast cancer patients treated with adjuvant trastuzumab, with HER2 re-testing performed on whole tumor sections.

Gonadotropin Releasing Hormone agonist (GnRHa) during chemotherapy and post-cancer childbirths - a Nationwide population-based cohort study of 24,922 women diagnosed with cancer in Sweden.

Background: Worldwide, an increasing number of women with cancer are receiving Gonadotropin Releasing Hormone agonist (GnRHa) co-treatment during chemotherapy aiming at ovarian protection. There is divergence among guidelines, and some have recommended GnRHa co-treatment for women with breast cancer, however, the effect of GnRHa on future fertility is uncertain.

Methods: In this population-based cohort study we included all women diagnosed with cancer at ages 15-45 between July 2005 and March 2017 in Sweden, identified in the Swedish Cancer Register.

Dysregulation of micro-RNA 143-3p as a Biomarker of Carotid Atherosclerosis and the Associated Immune Reactions During Disease Progression.

Atherosclerosis commonly remains undiagnosed until disease manifestations occur. The disease is associated with dysregulated micro(mi)RNAs, but how this is linked to atherosclerosis-related immune reactions is largely unknown. A mouse model of carotid atherosclerosis, human APOB100-transgenic Ldlr (HuBL), was used to study the spatiotemporal dysregulation of a set of miRNAs.

The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia.

The immune responses to cancer cells involve both innate and acquired immune cells. In the meantime, the most attention has been drawn to the adaptive immune cells, especially T cells, while, it is now well known that the innate immune cells, especially natural killer (NK) cells, play a vital role in defending against malignancies. While the immune cells are trying to eliminate malignant cells, cancer cells try to prevent the function of these cells and suppress immune responses.