Tuberculosis in otherwise healthy adults with inherited TNF deficiency.

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses.

Next-generation lung cancer pathology: Development and validation of diagnostic and prognostic algorithms.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. In this study, we develop a clinically useful computational pathology platform for NSCLC that can be a foundation for multiple downstream applications and provide immediate value for patient care optimization and individualization. We train the primary multi-class tissue segmentation algorithm on a substantial, high-quality, manually annotated dataset of whole-slide images with lung adenocarcinoma and squamous cell carcinomas.

Relationship Between Endothelial Function, Vital Parameters, and Cognitive Performance in Community Dwellers with Subjective Cognitive Decline: An Observational Study with Six Months Follow Up.

Background: With advancing age, cognitive decline is frequently associated with endothelial dysfunction, but data on vascular performance prior to the onset of mild cognitive impairment (MCI) is scarce.

Objective: To investigate the relationship between endothelial function, vital parameters and cognitive performance in older adults with subjective cognitive decline (SCD).

Methods: Forty-five volunteers aged 65 years and older with SCD underwent comprehensive geriatric assessment-based prognosis evaluation by means of the Multidimensional Prognostic Index (MPI), full neuropsychological examination and peripheral arterial tonometry measurement by means of EndoPAT™2000 to evaluate endothelial flexibility and vital parameters.

Optogenetic induction of mechanical muscle stress identifies myosin regulatory ubiquitin ligase NHL-1 in C. elegans.

Mechanical stress during muscle contraction is a constant threat to proteome integrity. However, there is a lack of experimental systems to identify critical proteostasis regulators under mechanical stress conditions. Here, we present the transgenic Caenorhabditis elegans model OptIMMuS (Optogenetic Induction of Mechanical Muscle Stress) to study changes in the proteostasis network associated with mechanical forces.

Long-Term Effects of the Multicomponent Program BrainProtect on Cognitive Function: One-Year Follow-Up in Healthy Adults.

Background: Age-related neuronal changes impact cognitive integrity, which is a major contributor to health and quality of life. The best strategy to prevent cognitive decline and Alzheimer's disease is still debated.

Objective: To investigate the long-term effects of the eight-week multicomponent training program BrainProtect on cognitive abilities compared to general health counseling (GHC) in cognitively healthy adults in Germany.

Proximity ligation-based sequencing for the identification of human papillomavirus genomic integration sites in formalin-fixed paraffin embedded oropharyngeal squamous cell carcinomas.

Human papillomavirus (HPV) infections are an increasing cause of oropharyngeal squamous cell carcinomas (OPSCC). Integration of the viral genome into the host genome is suggested to affect carcinogenesis, however, the correlation with OPSCC patient prognosis is still unclear. Research on HPV integration is hampered by current integration detection technologies and their unsuitability for formalin-fixed paraffin-embedded (FFPE) tissues.

Geroscience in the continuum from healthy longevity to frailty.

The socioeconomic and technological developments of the past decades have enabled unique progress associated to increased life expectancy and better health for a large part of the world's population; however, multimorbidity, frailty and disability are also on the rise. Geroscience as the new biology of aging is based on the evidence that the main risk factor for noncommunicable chronic diseases (NCD) is the aging process; however, its technology is mostly used for the scientific study of longevity and its interaction with aging medicine and geriatrics is still limited. In this perspective, the need for a tighter exchange between geroscience and geriatrics for longer health span and intrinsic capacity is discussed in the context of existing evidence and knowledge gaps.

NMDtxDB: data-driven identification and annotation of human NMD target transcripts.

The nonsense-mediated RNA decay (NMD) pathway is a crucial mechanism of mRNA quality control. Current annotations of NMD substrate RNAs are rarely data-driven, but use generally established rules. We present a data set with four cell lines and combinations for , , and knockdowns or knockout.

RhoGDI1 regulates cell-cell junctions in polarized epithelial cells.

Cell-cell contact formation of polarized epithelial cells is a multi-step process that involves the co-ordinated activities of Rho family small GTPases. Consistent with the central role of Rho GTPases, a number of Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating proteins (GAPs) have been identified at cell-cell junctions at various stages of junction maturation. As opposed to RhoGEFs and RhoGAPs, the role of Rho GDP dissociation inhibitors (GDIs) during cell-cell contact formation is poorly understood.

Isogenic patient-derived organoids reveal early neurodevelopmental defects in spinal muscular atrophy initiation.

Whether neurodevelopmental defects underlie postnatal neuronal death in neurodegeneration is an intriguing hypothesis only recently explored. Here, we focus on spinal muscular atrophy (SMA), a neuromuscular disorder caused by reduced survival of motor neuron (SMN) protein levels leading to spinal motor neuron (MN) loss and muscle wasting. Using the first isogenic patient-derived induced pluripotent stem cell (iPSC) model and a spinal cord organoid (SCO) system, we show that SMA SCOs exhibit abnormal morphological development, reduced expression of early neural progenitor markers, and accelerated expression of MN progenitor and MN markers.

Profiles of Geriatric Syndromes and Resources in Older Patients with Atrial Fibrillation.

Older patients with nonvalvular atrial fibrillation (AF) are at high risk for frailty and geriatric syndromes (GSs), which modulate their individual prognosis and are therefore relevant for further management. Because few studies have evaluated the geriatric profile of older AF patients, this secondary analysis aims to further characterize the patterns of GSs and geriatric resources (GRs) in AF patients and their association with anticoagulation use. Data from 362 hospitalized patients aged 65 years and older with AF (n = 181, 77.

Definitions and symptoms of the post-COVID syndrome: an updated systematic umbrella review.

Post-COVID syndrome (PCS) describes a persistent complex of symptoms following a COVID-19 episode, lasting at least 4 to 12 weeks, depending on the specific criteria used for its definition. It is often associated with moderate to severe impairments of daily life and represents a major burden for many people worldwide. However, especially during the first two years of the COVID-19 pandemic, therapeutic and diagnostic uncertainties were prominent due to the novelty of the disease and non-specific definitions that overlooked functional deficits and lacked objective assessment.

Inflammatory Cytokine Levels in Patients with Autosomal Dominant Polycystic Kidney Disease.

Key Points: Higher levels of IL-6, IL-8, monocyte chemoattractant protein-1, TNF-, and IFN- in patients with autosomal dominant polycystic kidney disease highlight inflammation's role in disease progression. Elevated inflammatory markers in autosomal dominant polycystic kidney disease could serve as biomarkers for progression and targets for therapy.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic ciliopathy that causes adult-onset progressive renal failure.

Mitochondrial DNA mutations attenuate Bleomycin-induced dermal fibrosis by inhibiting differentiation into myofibroblasts.

Post-mitotic, non-proliferative dermal fibroblasts have crucial functions in maintenance and restoration of tissue homeostasis. They are involved in essential processes such as wound healing, pigmentation and hair growth, but also tumor development and aging-associated diseases. These processes are energetically highly demanding and error prone when mitochondrial damage occurs.

Deep Learning Histology for Prediction of Lymph Node Metastases and Tumor Regression after Neoadjuvant FLOT Therapy of Gastroesophageal Adenocarcinoma.

Background: The aim of this study was to establish a deep learning prediction model for neoadjuvant FLOT chemotherapy response. The neural network utilized clinical data and visual information from whole-slide images (WSIs) of therapy-naïve gastroesophageal cancer biopsies.

Methods: This study included 78 patients from the University Hospital of Cologne and 59 patients from the University Hospital of Heidelberg used as external validation.

Can geroscience be translated into healthcare?

As an introduction to this special issue on geroscience, the present work focuses on the complexity of disentangling biomolecular mechanisms of aging from biopsychosocial causes of accelerated aging. Due to this complexity, the biomolecular aging hallmarks of frailty and multimorbidity as predominant aging phenotypes in geriatrics reflect single aspects of the aging process. A possible approach to facilitate the integration of geroscience into healthcare might be to consider aging as the dynamic ratio between damage accumulation at the molecular and cellular level and resilience as strategies that prevent or repair such damage.