Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep-learning Based Pathological Assessment of Frozen Procurement Kidney Biopsies Predicts Graft Loss and Guides Organ Utilization: A Large-scale Retrospective Study

Background Lesion scores on procurement donor biopsies are commonly used to guide organ utilization. However, frozen sections present challenges for histological scoring, leading to inter- and intra-observer variability and inappropriate discard. Methods We constructed deep-learning based models to recognize kidney tissue compartments in H&E stained sections from procurement biopsies performed at 583 hospitals nationwide in year 2011-2020. The models were trained and tested respectively on 11473 and 3986 images sliced from 100 slides. We then extracted whole-slide abnormality features from 2431 kidneys, and correlated with pathologists’ scores and transplant outcomes. Finally, a Kidney Donor Quality Score (KDQS) incorporating digital features and the Kidney Donor Profile Index (KDPI) was derived and used in combination with recipient demographic and peri-transplant characteristics to predict graft loss or assist organ utilization. Results Our model accurately identified 96% and 91% of normal/sclerotic glomeruli respectively; 94% of arteries/arterial intimal fibrosis regions; 90% of tubules. Three whole-slide features (Sclerotic Glomeruli%, Arterial Intimal Fibrosis%, and Interstitial Fibrosis%) demonstrated strong correlations with corresponding pathologists’ scores (n=2431), but had superior associations with post-transplant eGFR (n=2033) and graft loss (n=1560). The combination of KDQS and other factors predicted 1- and 4-year graft loss (discovery: n=520, validation: n=1040). Finally, by matching 398 discarded kidneys due to “biopsy findings” to transplanted population, the matched transplants from discarded KDQS<4 group (110/398, 27.6%) showed similar graft survival rate to unmatched transplanted kidneys (2-, 5-year survival rate: 97%, 86%). KDQS ≥ 7 (37/398, 9.3%) and 1-year survival model score ≥ 0.55 were determined to identify possible discards (PPV=0.92). Conclusion This deep-learning based approach provides automatic and reliable pathological assessment of procurement kidney biopsies, which could facilitate graft loss risk stratification and organ utilization. Translational Statement This deep-learning based approach provides rapid but more objective, sensitive and reliable assessment of deceased-donor kidneys before transplantation, and improves the prognostic value of procurement biopsies, thus could potentially reduce inappropriate discard and stratify patients needing monitoring or preventative measures after transplantation. The pipeline can be integrated into various types of scanners and conveniently generates report after slide scanning. Such report can be used in conjunction with pathologists’ report or independently for centers lacking renal pathologists.
Opi1-mediated transcriptional modulation orchestrates genotoxic stress response in budding yeast

In budding yeast, the transcriptional repressor Opi1 regulates phospholipid biosynthesis by repressing expression of genes containing inositol-sensitive upstream activation sequences (UASINO). Upon genotoxic stress, cells activate the DNA Damage Response (DDR) to coordinate a complex network of signaling pathways aimed at preserving genomic integrity. Here, we reveal that Opi1 is important to modulate transcription in response to genotoxic stress. We find that cells lacking Opi1 exhibit hypersensitivity to genotoxins, along with a delayed G1 to S-phase transition and decreased gamma-H2A levels. Transcriptome analysis using RNA-seq reveals that Opi1 plays a central role in modulating essential biological processes during genotoxic stress induced by methyl methanesulfonate, including repression of phospholipid biosynthesis and transduction of mating signaling. Moreover, Opi1 induces sulfate assimilation and amino acid metabolic processes, such as arginine and histidine biosynthesis and glycine catabolism. Furthermore, we observe increased mitochondrial DNA instability in opi1Δ cells upon MMS treatment. Notably, we show that constitutive activation of the transcription factors Ino2-Ino4 is responsible for genotoxin sensitivity in Opi1-deficient cells, and the production of inositol pyrophosphates by Kcs1 counteracts Opi1 function specifically during MMS-induced genotoxic stress. Overall, our findings highlight Opi1 as a critical sensor of genotoxic stress in budding yeast, orchestrating gene expression to facilitate appropriate DNA damage response.
Actin and microtubules position stress granules

Membraneless organelles, composed of protein and nucleic acids, alter the biochemical and physical landscape of the cell. While specific membraneless organelles are found in stereotypical locations, little is known about the physical mechanisms that guide their positioning. Here, we investigate how stress granules, a type of cytoplasmic membraneless organelle, establish their stereotypical perinuclear positioning. We find that actin and microtubules play complementary roles. Lamellar actin confines stress granules, and its retrograde flow drives them toward the cell center. Microtubules, in turn, adhere to stress granules through capillary interactions, which tend to concentrate stress granules in micro-tubule rich regions near the nucleus. Similar physical mechanisms are likely to play a role in the positioning of other membraneless organelles.
Catastrophic health expenditure of households with hypertension: a comparative study in China

Objectives The aim of this study was to understand the impact of multimorbidity on catastrophic health expenditures for people with hypertension. Methods Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) in 2018, 8,342 adults were included in our analysis. Propensity score matching method was used to compare the risk of catastrophic health expenditures between the hypertension patients (treatment group) and those without any chronic disease (control group) in middle-aged and older adults. Patients with hypertension were also divided into two groups: only hypertension and multimorbidity. Results Hypertension increased the likelihood of CHE by 11.3% in older adults. Further analysis showed that hypertension alone does not increase the risk of CHE, and the risk of CHE in hypertension patients with multimorbidity was 12.9% higher than those without chronic disease. Conclusion Our study highlights the importance of healthy management of patients with only hypertension and preventing them from developing multimorbidity.
Genomic Assessment of Enterobacter mori AYS9: A Potential Plant Growth-Promoting Drought-Resistant Rhizobacteria

Drought stress poses a serious danger to agricultural production. Recent studies have revealed that most of the chemical methods used in the mitigation of its effects on plant production pose a serious threat to humans and the environment. Therefore, the demand for ecologically friendly solutions to ensure the security of the world’s food supply has increased as a result. Plant growth-promoting rhizobacteria (PGPR) treatment may be advantageous in this situation. Enterobacter mori is a promising rhizobacteria in this regard. However, information on the genome analysis of E. mori linked to the rhizosphere soil of the sorghum plant has not been extensively studied. In this study, we present a genomic lens into functional attributes of E. mori AYS9 isolated from sorghum plants, as well as assess its drought tolerance and plant growth-promoting potentials. Our results showed the drought tolerance and plant growth-promoting potentials of the AYS9. Whole genome sequencing (WGS) results revealed that the genome yielded 4,852,175 bp sequence reads, an average read length of 151 bp, 1,845,357 bp genome size, 67 tRNAs, 3 rRNAs, and a G + C content of 55.5%. The functional genes identified in the genome were linked to processes including phosphate solubilization, iron transport, hormone regulation, nitrogen fixation, and resistance to oxidative and osmotic stress. Also, secondary metabolites supporting bacterial biocontrol properties against phytopathogens, and abiotic stress such as aerobactin-type non-ribosomal peptide siderophore, Stewartan-type ladderane, and Colicin type NRPS were discovered in the AYS9 genome. Our findings however establish that the intricate metabolic pathways mediated by the projected new genes in the bacterial genome may offer a genetic foundation for future understanding of rhizosphere biology and the diverse roles that these genes play in plant development and health.
Learning the heterogeneous representation of brain's structure from serial SEM images using a masked autoencoder

Introduction The exorbitant cost of accurately annotating the large-scale serial scanning electron microscope (SEM) images as the ground truth for training has always been a great challenge for brain map reconstruction by deep learning methods in neural connectome studies. The representation ability of the model is strongly correlated with the number of such high-quality labels. Recently, the masked autoencoder (MAE) has been shown to effectively pre-train Vision Transformers (ViT) to improve their representational capabilities. Methods In this paper, we investigated a self-pre-training paradigm for serial SEM images with MAE to implement downstream segmentation tasks. We randomly masked voxels in three-dimensional brain image patches and trained an autoencoder to reconstruct the neuronal structures. Results and discussion We tested different pre-training and fine-tuning configurations on three different serial SEM datasets of mouse brains, including two public ones, SNEMI3D and MitoEM-R, and one acquired in our lab. A series of masking ratios were examined and the optimal ratio for pre-training efficiency was spotted for 3D segmentation. The MAE pre-training strategy significantly outperformed the supervised learning from scratch. Our work shows that the general framework of can be a unified approach for effective learning of the representation of heterogeneous neural structural features in serial SEM images to greatly facilitate brain connectome reconstruction.
HIF and MYC signaling in adrenal neoplasms of the neural crest: implications for pediatrics

Pediatric neural crest-derived adrenal neoplasms include neuroblastoma and pheochromocytoma. Both entities are associated with a high degree of clinical heterogeneity, varying from spontaneous regression to malignant disease with poor outcome. Increased expression and stabilization of HIF2α appears to contribute to a more aggressive and undifferentiated phenotype in both adrenal neoplasms, whereas MYCN amplification is a valuable prognostic marker in neuroblastoma. The present review focuses on HIF- and MYC signaling in both neoplasms and discusses the interaction of associated pathways during neural crest and adrenal development as well as potential consequences on tumorigenesis. Emerging single-cell methods together with epigenetic and transcriptomic analyses provide further insights into the importance of a tight regulation of HIF and MYC signaling pathways during adrenal development and tumorigenesis. In this context, increased attention to HIF-MYC/MAX interactions may also provide new therapeutic options for these pediatric adrenal neoplasms.
Genetic insights into immune mechanisms of Alzheimer’s and Parkinson’s disease

Microglia, the macrophages of the brain, are vital for brain homeostasis and have been implicated in a broad range of brain disorders. Neuroinflammation has gained traction as a possible therapeutic target for neurodegeneration, however, the precise function of microglia in specific neurodegenerative disorders is an ongoing area of research. Genetic studies offer valuable insights into understanding causality, rather than merely observing a correlation. Genome-wide association studies (GWAS) have identified many genetic loci that are linked to susceptibility to neurodegenerative disorders. (Post)-GWAS studies have determined that microglia likely play an important role in the development of Alzheimer’s disease (AD) and Parkinson’s disease (PD). The process of understanding how individual GWAS risk loci affect microglia function and mediate susceptibility is complex. A rapidly growing number of publications with genomic datasets and computational tools have formulated new hypotheses that guide the biological interpretation of AD and PD genetic risk. In this review, we discuss the key concepts and challenges in the post-GWAS interpretation of AD and PD GWAS risk alleles. Post-GWAS challenges include the identification of target cell (sub)type(s), causal variants, and target genes. Crucially, the prediction of GWAS-identified disease-risk cell types, variants and genes require validation and functional testing to understand the biological consequences within the pathology of the disorders. Many AD and PD risk genes are highly pleiotropic and perform multiple important functions that might not be equally relevant for the mechanisms by which GWAS risk alleles exert their effect(s). Ultimately, many GWAS risk alleles exert their effect by changing microglia function, thereby altering the pathophysiology of these disorders, and hence, we believe that modelling this context is crucial for a deepened understanding of these disorders.
Prevention is better than cure: why early interventions for insomnia and chronic pain during adolescence should be a priority

COPYRIGHT © 2023 Arnison. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Prevention is better than cure: why early interventions for insomnia and chronic pain during adolescence should be a priority
Properties of the Threshold Method on a Radar Rain Cluster Basis

Abstract The average rain rate 〈R〉 is estimated with radar data at the radar beam height by measuring the fractional area F(τ) of pixels above a preset rain-rate threshold τ. This work applies the “threshold method” to smaller areas. The threshold method typically requires large observing areas (104 km2–105 km2) to achieve good sampling of a well-behaved probability density function (PDF) of rain rate. The present work, however, shows that the threshold method can be applied to smaller observing areas (103 km2) when fractional area is calculated on a rain cluster, or rain cell, defined as a connected set of rainy pixels. The results show general agreement with those reported by other authors. The slope of the 〈R〉–F(τ) regression line relation Ŝ(τ), is approximately linear with the threshold τ. Seasonal values of Ŝ(τ) are obtained by applying the method to seasonally grouped months of radar data from areas surrounding Paris, France, during 1994. Since measuring fractional area on a cell basis allows one to.
N-linoleyltyrosine resisted the growth of non-small cell lung cancer cells via the regulation of CB1 and CB2 involvement of PI3K and ERK pathways

Background: N-linoleyltyrosine (NITyr), one of the anandamide analogs, exerts activity via the endocannabinoid receptors (CB1 and CB2), which showed anti-tumor effects in various tumors. Therefore, we speculated that NITyr might show anti-non-small cell lung cancer (NSCLC) effects via the CB1 or CB2 receptor. The purpose of the investigation was to reveal the anti-tumor ability of NITyr on A549 cells and its mechanisms. Methods: The viability of A549 cells was measured by MTT assay, and the cell cycle and apoptosis were both examined by flow cytometry; in addition, cell migration was tested by wound healing assay. Apoptosis-related markers were measured by immunofluorescence. The downstream signaling pathways (PI3K, ERK, and JNK) of CB1 or CB2 were examined through Western blotting. The expressions of CB1 and CB2 were detected by immunofluorescence. Finally, the AutoDock software was used to validate the binding affinity between the targets, such as CB1 and CB2, with NITyr. Results: We found that NITyr inhibited cell viability, hindered the cell cycle, resulted in apoptosis, and inhibited migration. The CB1 inhibitor, AM251, and the CB2 inhibitor, AM630, weakened the aforementioned phenomenon. The immunofluorescence assay suggested that NITyr upregulated the expression of CB1 and CB2. Western blot analysis indicated that NITyr upregulated the expression of p-ERK, downregulated the expression of p-PI3K, and did not affect p-JNK expression. In conclusion, NITyr showed a role in inhibiting NSCLC through the activation of CB1 and CB2 receptors involved in PI3K and ERK pathways.
Fast strain mapping in abdominal aortic aneurysm wall reveals heterogeneous patterns

Abdominal aortic aneurysm patients are regularly monitored to assess aneurysm development and risk of rupture. A preventive surgical procedure is recommended when the maximum aortic antero-posterior diameter, periodically assessed on two-dimensional abdominal ultrasound scans, reaches 5.5 mm. Although the maximum diameter criterion has limited ability to predict aneurysm rupture, no clinically relevant tool that could complement the current guidelines has emerged so far. In vivo cyclic strains in the aneurysm wall are related to the wall response to blood pressure pulse, and therefore, they can be linked to wall mechanical properties, which in turn contribute to determining the risk of rupture. This work aimed to enable biomechanical estimations in the aneurysm wall by providing a fast and semi-automatic method to post-process dynamic clinical ultrasound sequences and by mapping the cross-sectional strains on the B-mode image. Specifically, the Sparse Demons algorithm was employed to track the wall motion throughout multiple cardiac cycles. Then, the cyclic strains were mapped by means of radial basis function interpolation and differentiation. We applied our method to two-dimensional sequences from eight patients. The automatic part of the analysis took under 1.5 min per cardiac cycle. The tracking method was validated against simulated ultrasound sequences, and a maximum root mean square error of 0.22 mm was found. The strain was calculated both with our method and with the established finite-element method, and a very good agreement was found, with mean differences of one order of magnitude smaller than the image spatial resolution. Most patients exhibited a strain pattern that suggests interaction with the spine. To conclude, our method is a promising tool for investigating abdominal aortic aneurysm wall biomechanics as it can provide a fast and accurate measurement of the cyclic wall strains from clinical ultrasound sequences.
Incidence of harmful algal blooms in pristine subtropical ocean: a satellite remote sensing approach (Jeju Island)

Despite the increasing numbers of red tide events in the pristine subtropical ocean, a paucity of previous observations has limited understanding of harmful algae in the seas around the Korean Peninsula. Therefore, using six years (2012–2017) of Geostationary Ocean Color Imager (GOCI) satellite data, we characterized the red tides around Jeju Island, a volcanic island located near the paths of the Jeju Warm Current and Tsushima Warm Current, using the Normalized Red Tide Index (NRTI) method. The seawater around Jeju Island has for a long time been considered to be very clear, with relatively low suspended particulate matter concentrations and few harmful algae. Nonetheless, the satellite-based NRTI detection method used in this study detected and supported the existence of red tides in the coastal region around Jeju Island. Analysis of the red tide distribution showed that red tide first began to appear near the western coast of Jeju Island, then developed in the northern and eastern coastal regions, and finally vanished in the eastern coastal region. The monthly averages of the NRTI demonstrated a bloom event from April to May in every year. Additional fall blooms were detected in August–September, particularly in 2013 and 2016. The NRTI revealed strong interannual variations. The longest blooms occurred in 2015, and the most comprehensive and strongest event occurred in the spring of 2016. The latter three years (2015–2017) had much higher NRTI than the former three years (2012–2014). The probability of red tide occurrence at a given point during the 6-year study period revealed spatial differences. Relatively high probability of 0.3–0.5 was determined along the northern coastal region, whereas low probability of less than 0.2 was found along the southern region. Ground truth data also showed more frequent observations and higher red tide cell densities along the northern coast. Changes in NRTI in spring are positively correlated with changes in ENSO indices in winter. This study is the first to use a satellite-based approach with a vast long-term satellite database to elucidate the existence and probability of red tides near Jeju Island. We anticipate that this study will provide a useful strategy for remote monitoring of harmful algal blooms over wide regions using optical data.
Eye-tracking technology and the dynamics of natural gaze behavior in sports: an update 2016–2022

Updating and complementing a previous review on eye-tracking technology and the dynamics of natural gaze behavior in sports, this short review focuses on the progress concerning researched sports tasks, applied methods of gaze data collection and analysis as well as derived gaze measures for the time interval of 2016–2022. To that end, a systematic review according to the PRISMA guidelines was conducted, searching Web of Science, PubMed Central, SPORTDiscus, and ScienceDirect for the keywords: eye tracking, gaze behavio*r, eye movement, and visual search. Thirty-one studies were identified for the review. On the one hand, a generally increased research interest and a wider area of researched sports with a particular increase in official’s gaze behavior were diagnosed. On the other hand, a general lack of progress concerning sample sizes, amounts of trials, employed eye-tracking technology and gaze analysis procedures must be acknowledged. Nevertheless, first attempts to automated gaze-cue-allocations (GCA) in mobile eye-tracking studies were seen, potentially enhancing objectivity, and alleviating the burden of manual workload inherently associated with conventional gaze analyses. Reinforcing the claims of the previous review, this review concludes by describing four distinct technological approaches to automating GCA, some of which are specifically suited to tackle the validity and generalizability issues associated with the current limitations of mobile eye-tracking studies on natural gaze behavior in sports.