C0C^{0}-regularity for solutions of elliptic equations with distributional coefficients

In this paper, the continuity of solutions for elliptic equations in divergence form with distributional coefficients is considered. Inspired by the discussion on necessary and sufficient conditions for the form boundedness of elliptic operators by Maz'ya and Verbitsky (Acta Math., 188, 263-302, 2002 and Comm. Pure Appl. Math., 59, 1286-1329, 2006), we propose two kinds of sufficient conditions, which are some Dini decay conditions and some integrable conditions named Kato class or $K^{1}$ class, to show that the weak solution of the Schr\"{o}dinger type elliptic equation with distributional coefficients is continuous and give an almost optimal priori estimate. These estimates can clearly show that how the coefficients and nonhomogeneous terms influence the regularity of solutions. The $\ln$-Lipschitz regularity and H\"{o}lder regularity are also obtained as corollaries which cover the classical De Giorgi's H\"{o}lder estimates

Rethinking Multi-Interest Learning for Candidate Matching in Recommender Systems

Existing research efforts for multi-interest candidate matching in recommender systems mainly focus on improving model architecture or incorporating additional information, neglecting the importance of training schemes. This work revisits the training framework and uncovers two major problems hindering the expressiveness of learned multi-interest representations. First, the current training objective (i.e., uniformly sampled softmax) fails to effectively train discriminative representations in a multi-interest learning scenario due to the severe increase in easy negative samples. Second, a routing collapse problem is observed where each learned interest may collapse to express information only from a single item, resulting in information loss. To address these issues, we propose the REMI framework, consisting of an Interest-aware Hard Negative mining strategy (IHN) and a Routing Regularization (RR) method. IHN emphasizes interest-aware hard negatives by proposing an ideal sampling distribution and developing a Monte-Carlo strategy for efficient approximation. RR prevents routing collapse by introducing a novel regularization term on the item-to-interest routing matrices. These two components enhance the learned multi-interest representations from both the optimization objective and the composition information. REMI is a general framework that can be readily applied to various existing multi-interest candidate matching methods. Experiments on three real-world datasets show our method can significantly improve state-of-the-art methods with easy implementation and negligible computational overhead. The source code will be released.Comment: RecSys 202

Equivariant Contrastive Learning for Sequential Recommendation

Contrastive learning (CL) benefits the training of sequential recommendation models with informative self-supervision signals. Existing solutions apply general sequential data augmentation strategies to generate positive pairs and encourage their representations to be invariant. However, due to the inherent properties of user behavior sequences, some augmentation strategies, such as item substitution, can lead to changes in user intent. Learning indiscriminately invariant representations for all augmentation strategies might be suboptimal. Therefore, we propose Equivariant Contrastive Learning for Sequential Recommendation (ECL-SR), which endows SR models with great discriminative power, making the learned user behavior representations sensitive to invasive augmentations (e.g., item substitution) and insensitive to mild augmentations (e.g., featurelevel dropout masking). In detail, we use the conditional discriminator to capture differences in behavior due to item substitution, which encourages the user behavior encoder to be equivariant to invasive augmentations. Comprehensive experiments on four benchmark datasets show that the proposed ECL-SR framework achieves competitive performance compared to state-of-the-art SR models. The source code is available at https://github.com/Tokkiu/ECL.Comment: Accepted by RecSys 202

Associations of metabolic dysfunction-associated fatty liver disease and hepatic fibrosis with bone mineral density and risk of osteopenia/osteoporosis in T2DM patients

BackgroundExisting evidence on the associations of liver steatosis and fibrosis with bone mineral density (BMD) and risk of osteopenia/osteoporosis was limited with conflicting results. We aimed to evaluate the associations of metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatic fibrosis with BMD and risk of osteopenia/osteoporosis in type 2 diabetes mellitus (T2DM) patients.MethodsBaseline information of an ongoing cohort of 249 T2DM patients in Xiamen, China was analyzed. MAFLD was defined as the presence of hepatic steatosis [diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score >60] for T2DM patients. BMD was measured using dual-energy x-ray absorptiometry at total lumbar (L2–4), femur neck (FN), and total hip (TH) and was categorized as normal (T ≥ −1.0), osteopenia (−2.5 < T < −1.0), or osteoporosis (T ≤ −2.5) according to its minimum T-score.ResultsAmong the 249 T2DM patients, prevalence rates of MAFLD, osteopenia, and osteoporosis were 57.8%, 50.6%, and 17.7%, respectively. Patients with MAFLD had significantly higher BMD T-scores of L2–4, FN, and TH and the minimum as well as lower prevalence of osteoporosis than patients without MAFLD. Hepatic steatosis indices, including FLI score, fatty liver (FLI ≥ 60 or hepatic ultrasonography scanning), and MAFLD, were significantly and positively associated with all T-scores, while hepatic fibrosis index and FIB-4 score, but not NAFLD fibrosis score (NFS), were negatively associated with all T-scores. MAFLD was significantly associated with the decreased risk of osteopenia/osteoporosis and osteoporosis with unadjusted odds ratios (ORs) (95% CI) of 0.565 (0.324–0.987) and 0.434 (0.224–0.843) (both p-values < 0.05), respectively. As for liver fibrosis, FIB-4 score, but not NFS, was significantly associated with elevated risk of osteoporosis with an unadjusted OR (95% CI) per SD increase of FIB-4 score of 1.446 (1.080–1.936, p-value = 0.013). Adjusting for potential confounding variables, especially body mass index, in the multivariable regression analyses, all associations of hepatic steatosis and fibrosis indices with BMD and risk of osteopenia/osteoporosis were not statistically significant.ConclusionMAFLD and hepatic fibrosis were not significantly associated with BMD and risk of osteopenia/osteoporosis independent of obesity. Nevertheless, screening and management of MAFLD and osteopenia/osteoporosis were still important for the prevention of fracture in T2DM patients

Platelet-rich fibrin as an autologous biomaterial for bone regeneration: mechanisms, applications, optimization

Platelet-rich fibrin, a classical autologous-derived bioactive material, consists of a fibrin scaffold and its internal loading of growth factors, platelets, and leukocytes, with the gradual degradation of the fibrin scaffold and the slow release of physiological doses of growth factors. PRF promotes vascular regeneration, promotes the proliferation and migration of osteoblast-related cells such as mesenchymal cells, osteoblasts, and osteoclasts while having certain immunomodulatory and anti-bacterial effects. PRF has excellent osteogenic potential and has been widely used in the field of bone tissue engineering and dentistry. However, there are still some limitations of PRF, and the improvement of its biological properties is one of the most important issues to be solved. Therefore, it is often combined with bone tissue engineering scaffolds to enhance its mechanical properties and delay its degradation. In this paper, we present a systematic review of the development of platelet-rich derivatives, the structure and biological properties of PRF, osteogenic mechanisms, applications, and optimization to broaden their clinical applications and provide guidance for their clinical translation

The Motion of An Inv Nodal Cilium: a Realistic Model Revealing Dynein-Driven Ciliary Motion with Microtubule Mislocalization

Background/Aims: Nodal cilia that rotate in the ventral node play an important role in establishing left-right asymmetry during embryogenesis; however, inv mutant cilia present abnormal movement and induce laterality defects. The mechanism of their motility, which is regulated by dynein activation and microtubule arrangement, has not been fully understood. This study analyzed the dynein-triggered ciliary motion in the abnormal ultrastructure of the inv mutant, aiming to quantitatively evaluate the influence of microtubule mislocalization on the movement of the cilium. Methods: We established a realistic 3-D model of an inv mutant cilium with an ultrastructure based on tomographic datasets generated by ultra-high voltage electron microscopy. The time-variant activation of the axonemal dynein force was simulated by pairs of point loads and embedded at dynein-mounted positions between adjacent microtubule doublets in this mathematical model. Utilizing the finite element method and deformable grid, the motility of the mutant cilium that is induced by various dynein activation hypotheses was investigated and compared to experimental observation. Results: The results indicate that for the inv mutant, simulations of the ciliary movement with the engagement of dyneins based on the distance-controlled pattern in the partially activation scenario are broadly consistent with the observation; the shortening of the microtubules induces smaller movement amplitudes, while the angles of the mislocalized microtubules affect the pattern of the ciliary movement, and during the ciliary movement, the microtubules swing and twist in the mutant ciliary body. Conclusion: More generally, this study implies that dynein engagement is sensitive to subtle geometric changes in the axoneme, and thus, this geometry greatly influences the integrity of a well-formed ciliary rotation

Seizure and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Encephalomyelitis in a Retrospective Cohort of Chinese Patients

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody associated encephalomyelitis is increasingly being considered a distinct disease entity, with seizures and encephalopathy commonly reported. We investigated the clinical features of MOG-IgG positive patients presenting with seizures and/or encephalopathy in a single cohort.Methods: Consecutive patients with suspected idiopathic inflammatory demyelinating diseases were recruited from a tertiary University hospital in Guangdong province, China. Subjects with MOG-IgG seropositivity were analyzed according to whether they presented with or without seizure and/or encephalopathy.Results: Overall, 58 subjects seropositive for MOG-IgG were analyzed, including 23 (40%) subjects presenting with seizures and/or encephalopathy. Meningeal irritation (P = 0.030), fever (P = 0.001), headache (P = 0.001), nausea, and vomiting (P = 0.004) were more commonly found in subjects who had seizures and/or encephalopathy, either at presentation or during the disease course. Nonetheless, there was less optic nerve (4/23, 17.4%, P = 0.003) and spinal cord (6/16, 37.5%, P = 0.037) involvement as compared to subjects without seizures or encephalopathy. Most MOG encephalomyelitis subjects had cortical/subcortical lesions: 65.2% (15/23) in the seizures and/or encephalopathy group and 50.0% (13/26) in the without seizures or encephalopathy group. Cerebrospinal fluid (CSF) leukocytes were elevated in both groups. Subgroup analysis showed that 30% (7/23) MOG-IgG positive subjects with seizures and/or encephalopathy had been misdiagnosed for central nervous system infection on the basis of meningoencephalitis symptoms and elevated CSF leukocytes (P = 0.002).Conclusions: Seizures and encephalopathy are not rare in MOG encephalomyelitis, and are commonly associated with cortical and subcortical brain lesions. MOG-encephalomyelitis often presents with clinical meningoencephalitis symptoms and abnormal CSF findings mimicking central nervous system infection in pediatric and young adult patients

Differential Effects of HIF-1 Inhibition by YC-1 on the Overall Outcome and Blood-Brain Barrier Damage in a Rat Model of Ischemic Stroke

Hypoxia-inducible factor 1 (HIF-1) is a master regulator of cellular adaptation to hypoxia and has been suggested as a potent therapeutic target in cerebral ischemia. Here we show in an ischemic stroke model of rats that inhibiting HIF-1 and its downstream genes by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) significantly increases mortality and enlarges infarct volume evaluated by MRI and histological staining. Interestingly, the HIF-1 inhibition remarkably ameliorates ischemia-induced blood-brain barrier (BBB) disruption determined by Evans blue leakage although it does not affect brain edema. The result demonstrates that HIF-1 inhibition has differential effects on ischemic outcomes and BBB permeability. It indicates that HIF-1 may have different functions in different brain cells. Further analyses show that ischemia upregulates HIF-1 and its downstream genes erythropoietin (EPO), vascular endothelial growth factor (VEGF), and glucose transporter (Glut) in neurons and brain endothelial cells and that YC-1 inhibits their expression. We postulate that HIF-1-induced VEGF increases BBB permeability while certain other proteins coded by HIF-1's downstream genes such as epo and glut provide neuroprotection in an ischemic brain. The results indicate that YC-1 lacks the potential as a cerebral ischemic treatment although it confers certain protection to the cerebral vascular system