G2C: A Generator-to-Classifier Framework Integrating Multi-Stained Visual Cues for Pathological Glomerulus Classification

Pathological glomerulus classification plays a key role in the diagnosis of nephropathy. As the difference between different subcategories is subtle, doctors often refer to slides from different staining methods to make decisions. However, creating correspondence across various stains is labor-intensive, bringing major difficulties in collecting data and training a vision-based algorithm to assist nephropathy diagnosis. This paper provides an alternative solution for integrating multi-stained visual cues for glomerulus classification. Our approach, named generator-to-classifier (G2C), is a two-stage framework. Given an input image from a specified stain, several generators are first applied to estimate its appearances in other staining methods, and a classifier follows to combine visual cues from different stains for prediction (whether it is pathological, or which type of pathology it has). We optimize these two stages in a joint manner. To provide a reasonable initialization, we pre-train the generators in an unlabeled reference set under an unpaired image-to-image translation task, and then fine-tune them together with the classifier. We conduct experiments on a glomerulus type classification dataset collected by ourselves (there are no publicly available datasets for this purpose). Although joint optimization slightly harms the authenticity of the generated patches, it boosts classification performance, suggesting more effective visual cues are extracted in an automatic way. We also transfer our model to a public dataset for breast cancer classification, and outperform the state-of-the-arts significantly.Comment: Accepted by AAAI 201

Counting triangles in graphs without vertex disjoint odd cycles

Given two graphs $H$ and $F$, the maximum possible number of copies of $H$ in an $F$-free graph on $n$ vertices is denoted by $\mathrm{ex}(n, H, F)$. Let $(\ell+1) \cdot F$ denote $\ell+1$ vertex disjoint copies of $F$. In this paper, we determine the exact value of $\mathrm{ex}(n, C_3, (\ell+1)\cdot C_{2k+1})$ and its extremal graph, which generalizes some known results

Two stability theorems for Kℓ+1r\mathcal{K}_{\ell + 1}^{r}-saturated hypergraphs

An $\mathcal{F}$-saturated $r$-graph is a maximal $r$-graph not containing any member of $\mathcal{F}$ as a subgraph. Let $\mathcal{K}_{\ell + 1}^{r}$ be the collection of all $r$-graphs $F$ with at most $\binom{\ell+1}{2}$ edges such that for some $\left(\ell+1\right)$-set $S$ every pair $\{u, v\} \subset S$ is covered by an edge in $F$. Our first result shows that for each $\ell \geq r \geq 2$ every $\mathcal{K}_{\ell+1}^{r}$-saturated $r$-graph on $n$ vertices with $t_{r}(n, \ell) - o(n^{r-1+1/\ell})$ edges contains a complete $\ell$-partite subgraph on $(1-o(1))n$ vertices, which extends a stability theorem for $K_{\ell+1}$-saturated graphs given by Popielarz, Sahasrabudhe and Snyder. We also show that the bound is best possible. Our second result is motivated by a celebrated theorem of Andr\'{a}sfai, Erd\H{o}s and S\'{o}s which states that for $\ell \geq 2$ every $K_{\ell+1}$-free graph $G$ on $n$ vertices with minimum degree $\delta(G) > \frac{3\ell-4}{3\ell-1}n$ is $\ell$-partite. We give a hypergraph version of it. The \emph{minimum positive co-degree} of an $r$-graph $\mathcal{H}$, denoted by $\delta_{r-1}^{+}(\mathcal{H})$, is the maximum $k$ such that if $S$ is an $(r-1)$-set contained in a edge of $\mathcal{H}$, then $S$ is contained in at least $k$ distinct edges of $\mathcal{H}$. Let $\ell\ge 3$ be an integer and $\mathcal{H}$ be a $\mathcal{K}_{\ell+1}^3$-saturated $3$-graph on $n$ vertices. We prove that if either $\ell \ge 4$ and $\delta_{2}^{+}(\mathcal{H}) > \frac{3\ell-7}{3\ell-1}n$; or $\ell = 3$ and $\delta_{2}^{+}(\mathcal{H}) > 2n/7$, then $\mathcal{H}$ is $\ell$-partite; and the bound is best possible. This is the first stability result on minimum positive co-degree for hypergraphs

Picking transplant glomerulopathy out of the CAN: evidence from a clinico-pathological evaluation

Abstract Background Since the term chronic allograft nephropathy (CAN) was removed from the Banff scheme in 2005, transplant glomerulopathy (TG) has been regarded as a clinicopathological entity that is one of the major causes of graft loss. To assess the distinction between CAN and TG, we performed a comprehensive evaluation comparing TG with traditional CAN. Methods We compared the clinicopathological features of 43 cases of TG with 43 matched cases of non-TG CAN (non-TG group) after renal transplantation. TG was diagnosed by light microscopy based on the double contours of the glomerular basement membranes, and the Banff 97 classification system was used to score TG severity (cg0-3). Results Compared to the control group, we found a significantly higher incidence of positivity for human leukocyte antigen class-I and II antibodies, a higher incidence of hepatitis C virus (HCV) infection, and poorer graft survival in TG patients. Clinically, TG was associated with a higher prevalence of proteinuria, hematuria, anaemia and hypoalbuminemia. Histologically, TG strongly correlated with antibody related microcirculatory injuries, including glomerulitis, peritubular capillaritis and peritubular capillary (PTC) C4d deposition. Interestingly, the TG patients showed a significantly higher incidence of IgA deposition than the control patients. C4d-positive TG was correlated with higher TG and PTC scores, and PTC C4d deposition was correlated with a more rapid progression to graft dysfunction. TG accompanied by HCV infection was associated with heavier proteinuria, higher TG and C4d scores, and poorer graft survival. Conclusions TG presents clinicopathological features that are distinct from non-TG cases and leads to poorer outcomes. PTC C4d deposition is related to a more rapid progression to graft loss, suggesting ongoing antibody reactivity. HCV-positive TG is a more severe sub-entity, that requires further investigation. </jats:sec

Adverse Effects of Simulated Hyper- and Hypo-Phosphatemia on Endothelial Cell Function and Viability

Dysregulation of phosphate homeostasis as occurs in chronic kidney disease is associated with cardiovascular complications. It has been suggested that both hyperphosphatemia and hypophosphatemia can cause cardiovascular disease. The molecular mechanisms by which high or low serum phosphate levels adversely affect cardiovascular function are poorly understood. The purpose of this study was to explore the mechanisms of endothelial dysfunction in the presence of non-physiologic phosphate levels.We studied the effects of simulated hyper- and hypophosphatemia in human umbilical vein endothelial cells in vitro. We found both simulated hyperphosphatemia and hypophosphatemia decrease eNOS expression and NO production. This was associated with reduced intracellular calcium, increased protein kinase C β2 (PKCβ2), reduced cell viability, and increased apoptosis. While simulated hyperphosphatemia was associated with decreased Akt/p-Akt, Bcl-xl/Bax ratios, NFkB-p65 and p-Erk abundance, simulated hypophosphatemia was associated with increased Akt/p-Akt and Bcl-xl/Bax ratios and p-Mek, p38, and p-p38 abundance.This is the first demonstration of endothelial dysfunction with hypophosphatemia. Our data suggests that both hyperphosphatemia and hypophosphatemia decrease eNOS activity via reduced intracellular calcium and increased PKCβ2. Hyperphosphatemia also appears to reduce eNOS transcription via reduced signaling through PI3K/Akt/NF-kB and MAPK/NF-kB pathways. On the other hand, hypophosphatemia appears to activate these pathways. Our data provides the basis for further studies to elucidate the relationship between altered phosphate homeostasis and cardiovascular disease. As a corollary, our data suggests that the level of phosphate in the culture media, if not in the physiologic range, may inadvertently affect experimental results

Regulation of MUTYH, a DNA Repair Enzyme, in Renal Proximal Tubular Epithelial Cells

MUTYH is a DNA repair enzyme that initiates a base excision repair (BER) by recognizing and removing 8-Oxoguanine (8-oxoG) and its paired adenine. We demonstrated that both TGF-β1 and H2O2 treatment led to an increased 8-oxoG in cultured human proximal tubule epithelial (HK-2) cells, while the former induced epithelial-mesenchymal transition and the latter caused cell apoptosis. Without stimulation, HK-2 cells showed MUTYH expression in mitochondria. TGF-β1 triggered a transient upregulation of mitochondrial MUTYH and induced the expression of nuclear isoforms, while H2O2 showed no role on MUTYH expression. Ureteral obstruction (UUO) mice exhibited high 8-oxoG reactivity with tubulointerstitial lesions. After obstruction, the MUTYH expression was increased only in tubules at day 3 and decreased with obvious tubular atrophy at day 10. Particularly, MUTYH was primarily located in normal tubular cytoplasm with a dominant mitochondrial form. A few cells with nuclear MUTYH expression were observed in the fibrotic interstitium. We confirmed that increased MUTYH expression was upregulated and positively correlated with the severity of kidney fibrosis. Thus, renal fibrosis caused a cell-type-specific and time-dependent response of oxidative DNA repairs, even within the same tissues. It suggests that intervention of MUTYH might be effective for therapies

The possible mechanisms of ferroptosis in sepsis-associated acquired weakness

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and its morbidity and mortality rates are increasing annually. It is an independent risk factor for intensive care unit-acquired weakness (ICU-AW), which is a common complication of patients in ICU. This situation is also known as sepsis-associated acquired weakness (SAW), and it can be a complication in more than 60% of patients with sepsis. The outcomes of SAW are often prolonged mechanical ventilation, extended hospital stays, and increased morbidity and mortality of patients in ICUs. The pathogenesis of SAW is unclear, and an effective clinical treatment is not available. Ferroptosis is an iron-dependent type of cell death with unique morphological, biochemical, and genetic features. Unlike other forms of cell death such as autophagy, apoptosis, and necrosis, ferroptosis is primarily driven by lipid peroxidation. Cells undergo ferroptosis during sepsis, which further enhances the inflammatory response. This process leads to increased cell death, as well as multi-organ dysfunction and failure. Recently, there have been sporadic reports suggesting that SAW is associated with ferroptosis, but the exact pathophysiological mechanisms remain unclear. Therefore, we reviewed the possible pathogenesis of ferroptosis that leads to SAW and offer new strategies to prevent and treat SAW

Cardiometabolic index as a predictor of major adverse cardiovascular events in atrial fibrillation: insights from a community-based cohort

BackgroundThe cardiometabolic index, a composite indicator integrating central obesity and lipid abnormalities, has demonstrated predictive value in several cardiovascular diseases. However, its role in predicting major adverse cardiovascular events among patients with atrial fibrillation remains underexplored.MethodsIn this single-center retrospective cohort study, 192 atrial fibrillation (AF) patients under management at the Jinyang Community Health Service Center in Pudong, Shanghai, from January 2022 to January 2024 were enrolled. Patients were stratified into tertiles based on baseline cardiometabolic index (CMI). The primary endpoint was major adverse cardiovascular events (MACE), comprising cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for worsening heart failure, and coronary revascularization due to unstable angina or ischemic events. Multivariable Cox proportional hazards models were used to assess the independent association between CMI and MACE. Kaplan–Meier curves and Log-rank tests were applied to compare event incidence across groups. Restricted cubic spline analysis examined potential nonlinearity. An extreme gradient boosting model was developed to evaluate predictive performance, with SHapley Additive exPlanations used to assess variable importance. Subgroup analyses were conducted to evaluate the consistency of CMI’s predictive value across different clinical populations. The median follow-up duration was 664 days (interquartile range: 384–900 days), estimated using the reverse Kaplan–Meier method.ResultsMACE incidence increased significantly with rising CMI levels. Compared to the low CMI group, the high CMI group had a significantly higher risk of MACE (HR = 5.56, 95% CI: 1.48 – 20.90, P = 0.011). Kaplan–Meier analysis showed significant differences in cumulative incidence among the three groups (Log-rank P &lt; 0.001). restricted cubic spline (RCS) modeling revealed a nonlinear positive association, with a sharp increase in MACE risk above a CMI threshold of approximately 0.85 (P for nonlinearity &lt; 0.001). The Extreme Gradient Boosting (XGBoost) model achieved a C-index of 0.737 in the test set, with SHapley Additive exPlanations (SHAP) analysis ranking CMI as the fourth most influential predictor, following age, left atrial diameter, and left ventricular ejection fraction. Subgroup analyses suggested that the predictive value of CMI was particularly evident in patients without chronic kidney disease and those without prior catheter ablation.ConclusionElevated CMI is independently associated with increased MACE risk in patients with atrial fibrillation and demonstrates a nonlinear dose–response relationship. As a simple, accessible metabolic indicator, CMI shows promise for improving cardiovascular risk identification and guiding personalized management—especially in high-risk AF patients without overt metabolic dysfunction

Contemporary survival and anticoagulation of patients with atrial fibrillation: A community based cohort study in China

BackgroundsThe understanding of death in patients with atrial fibrillation (AF) in China is limited. This study aimed to assess the contemporary survival of AF patients in China and to explore risk factors for deaths.MethodsThis was a prospective community-based cohort study including 559 AF patients, who were followed-up from July 2015 to December 2020.ResultsDuring 66-month follow-up, there were 200 deaths (56.5% cardiovascular, 40.0% non-cardiovascular, and 3.5% unknown causes) among 559 AF patients with the median age of 76 years. The top three causes of death were heart failure (33.0%), ischemic stroke (17.0%) and cancer (16.5%). Multivariate Cox regression analysis indicated baseline variables positively associated with all-cause death were age (HR: 1.10, 95% CI: 1.08–1.13), AF subtype (HR: 1.37, 95% CI: 1.08–1.73), prior myocardial infarction (HR: 3.40, 95% CI: 1.48–7.78), previous tumor (HR: 2.61, 95% CI: 1.37–4.98), hypoglycemic therapy at baseline (HR: 1.81, 95% CI: 1.13–2.91), but body weight (HR: 0.98, 95% CI: 0.97–1.00) and use of calcium channel blocker (CCB) (HR: 0.62, 95% CI: 0.41–0.95) played a protective role to all-cause death. Of patients who were alive at the end of follow-up, 24.0% were on oral anticoagulants (OAC) alone, 4.5% on dual antithrombotic therapy, 33.1% on antiplatelet agents alone and 38.4% weren't on any antithrombotic medication.ConclusionIschemic stroke still remains one of the leading causes of death and OAC is seriously underused in AF patients in China. Independent risk factors for death are age, AF subtype, previous tumor, prior myocardial infarction, hypoglycemic therapy, low body weight and no CCB use.Clinical Trial Registrationhttp://www.chictr.org.cn/ (ChiCTR-ICR-15007036)