Whole Slide Multiple Instance Learning for Predicting Axillary Lymph Node Metastasis

Breast cancer is a major concern for women's health globally, with axillary lymph node (ALN) metastasis identification being critical for prognosis evaluation and treatment guidance. This paper presents a deep learning (DL) classification pipeline for quantifying clinical information from digital core-needle biopsy (CNB) images, with one step less than existing methods. A publicly available dataset of 1058 patients was used to evaluate the performance of different baseline state-of-the-art (SOTA) DL models in classifying ALN metastatic status based on CNB images. An extensive ablation study of various data augmentation techniques was also conducted. Finally, the manual tumor segmentation and annotation step performed by the pathologists was assessed.Comment: Accepted for MICCAI DEMI Workshop 202

Microbial wars: competition in ecological niches and within the microbiome

Many microbial communities live in highly competitive surroundings, in which the fight for resources determines their survival and genetic persistence. Humans live in a close relationship with microbial communities, which includes the health- and disease-determining interactions with our microbiome. Accordingly, the understanding of microbial competitive activities are essential at physiological and pathophysiological levels. Here we provide a brief overview on microbial competition and discuss some of its roles and consequences that directly affect humans

Elevated temperature and browning increase dietary methylmercury, but decrease essential fatty acids at the base of lake food webs

Climate change scenarios predict increases in temperature and organic matter supply from land to water, which affect trophic transfer of nutrients and contaminants in aquatic food webs. How essential nutrients, such as polyunsaturated fatty acids (PUFA), and potentially toxic contaminants, such as methylmercury (MeHg), at the base of aquatic food webs will be affected under climate change scenarios, remains unclear. The objective of this outdoor mesocosm study was to examine how increased water temperature and terrestrially-derived dissolved organic matter supply (tDOM; i.e., lake browning), and the interaction of both, will influence MeHg and PUFA in organisms at the base of food webs (i.e. seston; the most edible plankton size for zooplankton) in subalpine lake ecosystems. The interaction of higher temperature and tDOM increased the burden of MeHg in seston (< 40 mu m) and larger sized plankton (microplankton; 40-200 mu m), while the MeHg content per unit biomass remained stable. However, PUFA decreased in seston, but increased in microplankton, consisting mainly of filamentous algae, which are less readily bioavailable to zooplankton. We revealed elevated dietary exposure to MeHg, yet decreased supply of dietary PUFA to aquatic consumers with increasing temperature and tDOM supply. This experimental study provides evidence that the overall food quality at the base of aquatic food webs deteriorates during ongoing climate change scenarios by increasing the supply of toxic MeHg and lowering the dietary access to essential nutrients of consumers at higher trophic levels

Elevated temperature and browning increase dietary methylmercury, but decrease essential fatty acids at the base of lake food webs

Climate change scenarios predict increases in temperature and organic matter supply from land to water, which affect trophic transfer of nutrients and contaminants in aquatic food webs. How essential nutrients, such as polyunsaturated fatty acids (PUFA), and potentially toxic contaminants, such as methylmercury (MeHg), at the base of aquatic food webs will be affected under climate change scenarios, remains unclear. The objective of this outdoor mesocosm study was to examine how increased water temperature and terrestrially-derived dissolved organic matter supply (tDOM; i.e., lake browning), and the interaction of both, will influence MeHg and PUFA in organisms at the base of food webs (i.e. seston; the most edible plankton size for zooplankton) in subalpine lake ecosystems. The interaction of higher temperature and tDOM increased the burden of MeHg in seston (\u3c 40 μm) and larger sized plankton (microplankton; 40–200 μm), while the MeHg content per unit biomass remained stable. However, PUFA decreased in seston, but increased in microplankton, consisting mainly of filamentous algae, which are less readily bioavailable to zooplankton. We revealed elevated dietary exposure to MeHg, yet decreased supply of dietary PUFA to aquatic consumers with increasing temperature and tDOM supply. This experimental study provides evidence that the overall food quality at the base of aquatic food webs deteriorates during ongoing climate change scenarios by increasing the supply of toxic MeHg and lowering the dietary access to essential nutrients of consumers at higher trophic levels

Cell Stress – a new journal for cellular pathophysiology

Launched by over a hundred high-carat founding editors, including five Nobel Laureates and more than 30 members of the National Academy of Sciences, Cell Stress emerges as a new online-only journal that focuses on disease-relevant cellular responses to endogenous and exogenous stress. Cell Stress is a peer-reviewed publishing platform for high-impact research in all areas of pathophysiology with a rigorous open access policy that allows maximal visibility and transparency for the publication of excellent science. Cell Stress thus offers readers and experts all over the world a common, peer-reviewed platform to develop and transfer technical and experimental knowledge, to understand cellular and organismal stress and, ultimately, to combat disease

Targeting GATA transcription factors – a novel strategy for anti-aging interventions?

GATA transcription factors (TFs) constitute a conserved family of zinc-finger TFs that fulfill diverse functions across eukaryotes. Accumulating evidence suggests that GATA TFs also play a role in lifespan regulation. In a recent study, we identified a natural polyphenol, 4,4’-dimethoxychalcone (DMC), that extends lifespan depending on reduced activity of distinct GATA TFs. Prolonged lifespan by DMC treatment depends on autophagy, a protective cellular self-cleansing mechanism. In yeast, DMC reduces the activity of the GATA TF Gln3 and, genetic deletion of Gln3 is sufficient to increase autophagy levels during cellular aging. In addition, we observed similar changes in the abundance of several amino acids in the metabolome of DMC-treated and GATA/Gln3 depleted cells. Here, we examine current data on the involvement of GATA TFs in the regulation of autophagy and longevity in different organisms and explore if GATA TFs might be suitable targets for anti-aging interventions

4,4’Dimethoxychalcone: a natural flavonoid that promotes health through autophagy-dependent and -independent effects

The age-induced deterioration of the organism results in detrimental and ultimately lethal pathologies. The process of aging itself involves a plethora of different mechanisms that should be subverted concurrently to delay and/or prevent age- related maladies. We have identified a natural compound, 4,4ʹ-dimethoxychalcone (DMC), which promotes longevity in yeast, worms and flies, and protects mice from heart injury and liver toxicity. Interestingly, both the DMC-mediated lifespan extension and the cardioprotection depend on macroautophagy/autophagy whereas hepatoprotection does not. DMC induces autophagy by inhibiting specific GATA transcription factors (TFs), independently of the TORC1 kinase pathway. The autophagy-independent beneficial effects of DMC might involve its antioxidative properties. DMC treatment results in a phylogenetically conserved, systemic impact on the metabolome, which is most prominently characterized by changes in cellular amino acid composition. Altogether, DMC exerts multiple, geroprotective effects by igniting distinct pathways, and thus represents a potential pharmacological agent that delays aging through multipronged effects

Targeting GATA transcription factors – a novel strategy for anti-aging interventions?

GATA transcription factors (TFs) constitute a conserved family of zinc-finger TFs that fulfill diverse functions across eukaryotes. Accumulating evidence suggests that GATA TFs also play a role in lifespan regulation. In a recent study, we identified a natural polyphenol, 4,4’-dimethoxychalcone (DMC), that extends lifespan depending on reduced activity of distinct GATA TFs. Prolonged lifespan by DMC treatment depends on autophagy, a protective cellular self-cleansing mechanism. In yeast, DMC reduces the activity of the GATA TF Gln3 and, genetic deletion of Gln3 is sufficient to increase autophagy levels during cellular aging. In addition, we observed similar changes in the abundance of several amino acids in the metabolome of DMC-treated and GATA/Gln3 depleted cells. Here, we examine current data on the involvement of GATA TFs in the regulation of autophagy and longevity in different organisms and explore if GATA TFs might be suitable targets for anti-aging interventions

Guidelines and Recommendations on Yeast Cell Death Nomenclature

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research

Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review

Background Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. Methods For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. Results We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m2 in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. Conclusions The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study result