The effect of active exoskeleton support with different lumbar-to-hip support ratios on spinal musculoskeletal loading and lumbar kinematics during lifting.

While active back-support exoskeletons can reduce mechanical loading of the spine, current designs include only one pair of actuated hip joints combined with a rigid structure between the pelvis and trunk attachments, restricting lumbar flexion and consequently intended lifting behavior. This study presents a novel active exoskeleton including actuated lumbar and hip joints as well as subject-specific exoskeleton control based on a real-time active low-back moment estimation. We evaluated the effect of exoskeleton support with different lumbar-to-hip (L/H) support ratios on spine loading, lumbar kinematics, and back muscle electromyography (EMG).

Metastatic conjunctival melanoma: a multicentre international study.

Background: To reveal clinical findings related to metastatic conjunctival melanoma.

Methods: 10 ophthalmic oncology centres (9 countries and 4 continents) shared data to create a large clinical case series. The main outcome measures were the incidence and cumulative risk of systemic metastasis, study mortality rates and Kaplan-Meier patient mortality after developing conjunctival melanoma metastasis.

Benefit of adjuvant chemotherapy on recurrence free survival per consensus molecular subtype in stage III colon cancer.

The consensus molecular subtype (CMS) classification divides colon tumors into four subtypes holding promise as a predictive biomarker. However, the effect of adjuvant chemotherapy on recurrence free survival (RFS) per CMS in stage III patients remains inadequately explored. With this intention, we selected stage III colon cancer (CC) patients from the MATCH cohort (n = 575) and RadboudUMC (n = 276) diagnosed between 2005 and 2018.

Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's disease.

APOE4 is the strongest genetic risk factor for Alzheimer's disease (AD), with increased odds ratios in female carriers. Targeting amyloid plaques shows modest improvement in male non-APOE4 carriers. Leveraging single-cell transcriptomics across APOE variants in both sexes, multiplex flow cytometry and validation in two independent cohorts of APOE4 female carriers with AD, we identify a new subset of neutrophils interacting with microglia associated with cognitive impairment.

Radiotherapy induces persistent innate immune reprogramming of microglia into a primed state.

Over half of patients with brain tumors experience debilitating and often progressive cognitive decline after radiotherapy treatment. Microglia, the resident macrophages in the brain, have been implicated in this decline. In response to various insults, microglia can develop innate immune memory (IIM), which can either enhance (priming or training) or repress (tolerance) the response to subsequent inflammatory challenges.

Can intermittent changes in trunk extensor muscle length delay muscle fatigue development?

Muscle length changes may evoke alternating activity and consequently reduce local fatigue and pain during prolonged static bending. The aim of this study was to assess whether a postural intervention involving intermittent trunk extensor muscle length changes (INTERMITTENT) can delay muscle fatigue during prolonged static bending when compared to a near-isometric condition (ISOMETRIC) or when participants were allowed to voluntarily vary muscle length (VOLUNTARY). These three conditions were completed by 11 healthy fit male participants, in three separate sessions of standing with 30 ± 3 degrees trunk inclination until exhaustion.

The Complexity of Shapes: How the Circularity of Tumor Nodules Affects Prognosis in Colorectal Cancer.

The current stratification of tumor nodules in colorectal cancer (CRC) staging is subjective and leads to high interobserver variability. In this study, the objective assessment of the shape of lymph node metastases (LNMs), extranodal extension (ENE), and tumor deposits (TDs) was correlated with outcomes. A test cohort and a validation cohort were included from 2 different institutions.

Trunk extensor muscle endurance and its relationship to action potential conduction velocity and spectral parameters estimated using high-density electromyography.

Trunk extensor muscle fatigue typically manifests as a decline in spectral content of surface electromyography. However, previous research on the relationship of this decline with trunk extensor muscle endurance have shown inconsistent results. The decline of spectral content mainly reflects the decrease in average motor unit action potential conduction velocity (CV).

Exposure to inclined trunk postures in surgical staff.

In surgical staff, low-back pain (LBP) is prevalent and prolonged trunk inclination is hypothesized to be one of its potential causes. The aim of this study was to evaluate the magnitude and duration of trunk inclination in the sagittal plane of surgical assistants during surgical procedures. The three-dimensional trunk orientation was measured in 91 surgical assistants across four medical facilities during surgical procedures using an inertial measurement unit on the thorax.

Transcriptomics and proteomics reveal distinct biology for lymph node metastases and tumour deposits in colorectal cancer.

Both lymph node metastases (LNMs) and tumour deposits (TDs) are included in colorectal cancer (CRC) staging, although knowledge regarding their biological background is lacking. This study aimed to compare the biology of these prognostic features, which is essential for a better understanding of their role in CRC spread. Spatially resolved transcriptomic analysis using digital spatial profiling was performed on TDs and LNMs from 10 CRC patients using 1,388 RNA targets, for the tumour cells and tumour microenvironment.

APOE4 impairs the microglial response in Alzheimer's disease by inducing TGFβ-mediated checkpoints.

The APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). The contribution of microglial APOE4 to AD pathogenesis is unknown, although APOE has the most enriched gene expression in neurodegenerative microglia (MGnD). Here, we show in mice and humans a negative role of microglial APOE4 in the induction of the MGnD response to neurodegeneration.

The effect of back muscle fatigue on EMG and kinematics based estimation of low-back loads and active moments during manual lifting tasks.

This study investigated the effects of back muscle fatigue on the estimation of low-back loads and active low-back moments during lifting, using an EMG and kinematics based model calibrated with data from an unfatigued state. Fourteen participants performed lifting tasks in unfatigued and fatigued states. Fatigue was induced through semi-static forward bending.

Pseudobudding: ruptured glands do not represent true tumor buds.

Tumor budding (TB) is a strong biomarker of poor prognosis in colorectal cancer and other solid cancers. TB is defined as isolated single cancer cells or clusters of up to four cancer cells at the invasive tumor front. In areas with a large inflammatory response at the invasive front, single cells and cell clusters surrounding fragmented glands are observed appearing like TB.

Computer-Assisted Diagnosis of Lymph Node Metastases in Colorectal Cancers Using Transfer Learning With an Ensemble Model.

Screening of lymph node metastases in colorectal cancer (CRC) can be a cumbersome task, but it is amenable to artificial intelligence (AI)-assisted diagnostic solution. Here, we propose a deep learning-based workflow for the evaluation of CRC lymph node metastases from digitized hematoxylin and eosin-stained sections. A segmentation model was trained on 100 whole-slide images (WSIs).

Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions.

Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS-induced by limited bedding and nesting material during the first week of life (postnatal days [P]2-9) on microglial (i) morphology; (ii) hippocampal gene expression; and (iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice.

Characterizing microglial gene expression in a model of secondary progressive multiple sclerosis.

Multiple sclerosis (MS) is the most common inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. Chronic-relapsing experimental autoimmune encephalomyelitis (crEAE) in Biozzi ABH mice is an experimental model of MS. This crEAE model is characterized by an acute phase with severe neurological disability, followed by remission of disease, relapse of neurological disease and remission that eventually results in a chronic progressive phase that mimics the secondary progressive phase (SPEAE) of MS.

Neurovascular dysfunction in GRN-associated frontotemporal dementia identified by single-nucleus RNA sequencing of human cerebral cortex.

Frontotemporal dementia (FTD) is the second most prevalent form of early-onset dementia, affecting predominantly frontal and temporal cerebral lobes. Heterozygous mutations in the progranulin gene (GRN) cause autosomal-dominant FTD (FTD-GRN), associated with TDP-43 inclusions, neuronal loss, axonal degeneration and gliosis, but FTD-GRN pathogenesis is largely unresolved. Here we report single-nucleus RNA sequencing of microglia, astrocytes and the neurovasculature from frontal, temporal and occipital cortical tissue from control and FTD-GRN brains.

Low back muscle action potential conduction velocity estimated using high-density electromyography.

While a decreasing spectral content of surface electromyography reflects low back muscle fatigue development, reliability of these decreases may be insufficient. Decreasing frequency content is largely determined by decreasing average motor unit action potential conduction velocities (CV), which is considered a more direct measure of muscle fatigue development. However, for the low back muscles it has been proven difficult to identify propagating potentials and consequently estimate the CV.

Indirect determination of biochemistry reference intervals using outpatient data.

The aim of this study was to determine reference intervals in an outpatient population from Vall d'Hebron laboratory using an indirect approach previously described in a Dutch population (NUMBER project). We used anonymized test results from individuals visiting general practitioners and analysed during 2018. Analytical quality was assured by EQA performance, daily average monitoring and by assessing longitudinal accuracy between 2018 and 2020 (using trueness verifiers from Dutch EQA).

Epigenetic regulation of innate immune memory in microglia.

Background: Microglia are the tissue-resident macrophages of the CNS. They originate in the yolk sac, colonize the CNS during embryonic development and form a self-sustaining population with limited turnover. A consequence of their relative slow turnover is that microglia can serve as a long-term memory for inflammatory or neurodegenerative events.

Outcome Measures of New Technologies in Uveal Melanoma: Review from the European Vision Institute Special Interest Focus Group Meeting.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. New diagnostic procedures and basic science discoveries continue to change our patient management paradigms. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "Outcome Measures of New Technologies in Uveal Melanoma," addressing the latest advances in UM, starting with genetic developments, then moving on to imaging and treatment of the primary tumor, as well as to investigating the most recent developments in treating metastases, and eventually taking care of the patient's well-being.

Immunophenotypic Analysis of Acute Megakaryoblastic Leukemia: A EuroFlow Study.

Acute megakaryoblastic leukemia (AMKL) is a rare and heterogeneous subtype of acute myeloid leukemia (AML). We evaluated the immunophenotypic profile of 72 AMKL and 114 non-AMKL AML patients using the EuroFlow AML panel. Univariate and multivariate/multidimensional analyses were performed to identify most relevant markers contributing to the diagnosis of AMKL.