C-Disentanglement: Discovering Causally-Independent Generative Factors under an Inductive Bias of Confounder

Representation learning assumes that real-world data is generated by a few semantically meaningful generative factors (i.e., sources of variation) and aims to discover them in the latent space. These factors are expected to be causally disentangled, meaning that distinct factors are encoded into separate latent variables, and changes in one factor will not affect the values of the others. Compared to statistical independence, causal disentanglement allows more controllable data generation, improved robustness, and better generalization. However, most existing work assumes unconfoundedness in the discovery process, that there are no common causes to the generative factors and thus obtain only statistical independence. In this paper, we recognize the importance of modeling confounders in discovering causal generative factors. Unfortunately, such factors are not identifiable without proper inductive bias. We fill the gap by introducing a framework entitled Confounded-Disentanglement (C-Disentanglement), the first framework that explicitly introduces the inductive bias of confounder via labels from domain expertise. In addition, we accordingly propose an approach to sufficiently identify the causally disentangled factors under any inductive bias of the confounder. We conduct extensive experiments on both synthetic and real-world datasets. Our method demonstrates competitive results compared to various SOTA baselines in obtaining causally disentangled features and downstream tasks under domain shifts.Comment: accepted to Neurips 202

Association of cumulative monocyte to high-density lipoprotein ratio with the risk of type 2 diabetes: A prospective cohort study

Background: Recent studies have established that monocyte-derived inflammation plays a central role in the pathogenesis of type 2 diabetes mellitus (T2DM). It is unclear whether chronic metabolic inflammation, reflected by the cumulative monocyte to high-density lipoprotein ratio (CumMHR), predisposes the general population to T2DM. Methods: This study included 40,813 participants without diabetes from a real-life, community-based cohort (the Kailuan Study) attending a 2-year cycle of health survey since 2006. Cumulative exposure was obtained from 2006/2007 to 2010/2011. Follow-up started at 2010/2011 and through 2020. Multivariable-adjusted Cox regression models were used to calculate the CumMHR-associated risk of incident T2DM. Results: Over a median follow-up period of 7.98 (IQR: 5.74 – 8.87) years, 4,848 T2DM cases occurred. The CumMHR was positively associated with the risk of incident T2DM after adjusting for age, sex, smoking, drinking habits, physical activities, BMI, triglyceride-glycemia index, log(leukocyte count), log(hsCRP), blood pressure, renal function, and medication uses with adjusted HRs of 1.0 (ref.), 1.18 (1.05 ‒ 1.25), 1.17 (1.07 ‒ 1.27), 1.38 (1.26 ‒ 1.50), respectively, in CumMHR Quartiles 1, 2, 3 and 4. When follow-up ended at 2014/2015, the short-term (4 ‒ year) adjusted T2DM risks in CumMHR Quartiles 2, 3, and 4 were 1.14 (1.01 ‒ 1.29), 1.17 (1.04 ‒ 1.32), 1.40 (1.25 ‒ 1.58), respectively, relative to Quartile 1. A significant interaction between CumMHR and cumulative high-sensitivity C-reactive protein (CumCRP) was observed (P-interaction: 0.0109). The diabetic risk in the highest quartile of CumMHR was higher (1.53 [1.28 ‒ 1.84]) when CumCRP \u3c 1 mg/L, attenuated with increasing CumCRP levels (1 ~ 10 mg/L) and disappeared in CumCRP ≥ 10 mg/L. Hypertension, overweight, or smoking habits further modified the CumMHR-associated diabetic risk. Conclusions: Cumulative MHR may be a promising supplement to hsCRP for more comprehensively assessing the influence of metabolic inflammation on T2DM susceptibility. For primary prevention, targeting high CumMHR, especially in cases at low risk of diabetes defined by traditional risk factors, may further help reduce the diabetic risk

The utility of high-frequency 18 MHz ultrasonography for preoperative evaluation of acral melanoma thickness in Chinese patients

BackgroundDespite the increasing use of preoperative ultrasound evaluation for melanoma, there is limited research on the use of this technique for Acral Melanoma (AM).MethodsThis retrospective study analyzed the electronic medical records of patients who underwent preoperative evaluation for cutaneous melanoma maximum thickness using an 18 MHz probe and histopathological examination between December 2017 and March 2021 at the Department of Dermatology in Xiangya Hospital, Central South University.ResultsA total of 105 patients were included in the study. The mean tumor thickness was 3.9 mm (s.d., 2.3), with 63% of the specimens showing ulceration and 44 patients showing lymph node metastasis. The results showed a good correlation between the high-frequency ultrasonography (HFUS) and histopathological thickness measurements, with a Spearman’s correlation coefficient of 0.83 [(95% CI 0.73–0.90) (P < 0.001)]. The positive predictive value (PPV) of sonography in identifying tumor thickness was also found to be high.ConclusionOur study suggests that high-frequency 18 MHz ultrasonography is an effective tool for the preoperative evaluation of AM thickness. The HFUS measurements correlated well with the histopathological thickness measurements, making it a valuable and reliable method for clinicians to assess the thickness of melanoma lesions preoperatively

Surface Adsorption-Mediated Ultrahigh Efficient Peptide Encapsulation with a Precise Ratiometric Control for Type 1 and 2 Diabetic Therapy

A surface adsorption strategy is developed to enable the engineering of microcomposites featured with ultrahigh loading capacity and precise ratiometric control of co-encapsulated peptides. In this strategy, peptide molecules (insulin, exenatide, and bivalirudin) are formulated into nanoparticles and their surface is decorated with carrier polymers. This polymer layer blocks the phase transfer of peptide nanoparticles from oil to water and, consequently, realizes ultrahigh peptide loading degree (up to 78.9%). After surface decoration, all three nanoparticles are expected to exhibit the properties of adsorbed polymer materials, which enables the co-encapsulation of insulin, exenatide, and bivalirudin with a precise ratiometric control. After solidification of this adsorbed polymer layer, the release of peptides is synchronously prolonged. With the help of encapsulation, insulin achieves 8 days of glycemic control in type 1 diabetic rats with one single injection. The co-delivery of insulin and exenatide (1:1) efficiently controls the glycemic level in type 2 diabetic rats for 8 days. Weekly administration of insulin and exenatide co-encapsulated microcomposite effectively reduces the weight gain and glycosylated hemoglobin level in type 2 diabetic rats. The surface adsorption strategy sets a new paradigm to improve the pharmacokinetic and pharmacological performance of peptides, especially for the combination of peptides.Peer reviewe

Inhibiting Phase Transfer of Protein Nanoparticles by Surface Camouflage-A Versatile and Efficient Protein Encapsulation Strategy

Engineering a system with a high mass fraction of active ingredients, especially water-soluble proteins, is still an ongoing challenge. In this work, we developed a versatile surface camouflage strategy that can engineer systems with an ultrahigh mass fraction of proteins. By formulating protein molecules into nanoparticles, the demand of molecular modification was transformed into a surface camouflage of protein nanoparticles. Thanks to electrostatic attractions and van der Waals interactions, we camouflaged the surface of protein nanoparticles through the adsorption of carrier materials. The adsorption of carrier materials successfully inhibited the phase transfer of insulin, albumin, β-lactoglobulin, and ovalbumin nanoparticles. As a result, the obtained microcomposites featured with a record of protein encapsulation efficiencies near 100% and a record of protein mass fraction of 77%. After the encapsulation in microcomposites, the insulin revealed a hypoglycemic effect for at least 14 d with one single injection, while that of insulin solution was only ∼4 h.Peer reviewe

High drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury

High drug loading improves therapeutic efficacy and reduces side effects in drug delivery. Here, the authors use controlled diffusion of solvents to precipitate drug nanoparticles in polymer particles while the polymer is solidifying and demonstrate the particles for drug delivery in a spinal cord injury model. Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8-63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 mu g) within the limited administration volume (10 mu L) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.Peer reviewe

Pregled AC-DC i DC-DC pretvarača za primjene u LED rasvjeti

High-Brightness Light Emitting Diodes (HB-LEDs) are considered the future trend in lighting not only due to their high efficiency and high reliability, but also due to their other outstanding characteristics: chromatic variety, shock and vibration resistance, etc. Nevertheless, they need the development of new power supplies especially designed for boosting and taking advantage of their aforementioned characteristics. Besides, their behaviour is completely different from the rest of lighting devices and, consequently, it should be also taken into account in the design of the converters used to drive them. As a result, many well-known topologies have been optimized or redesigned in order to be used in LED–lighting applications and many new topologies have come up in the recent years with the same purpose. In this paper, the main HB-LED characteristics will be explained, highlighting how they influence the design of their power supplies. After, the main topologies will be presented from the simplest to the most complex ones, analysing their advantages and disadvantages.Svjetleće diode s visokom razinom svjetline (HB-LED) smatraju se budućim trendom u rasvjeti zahvaljujući ne samo visokom stupnju efikasnosti i pouzdanosti, nego i njihovim izvanrednim svojstvima: raznolikost boja, otpornost na udarce i vibracije i sl. Ipak, s ciljem potpunog iskorištenja prethodno spomenutih svojstava, potrebno je razviti nove, posebno osmišljene izvore napajanja. Osim toga, ponašanje im se posve razlikuje od ostalih tipova rasvjete što je potrebno uzeti u obzir pri projektiranju pretvarača za njihovo napajanje. Kao posljedica toga, mnoge su poznate topologije pretvarača optimirane ili preoblikovane posebno za primjenu u LED rasvjeti, a zadnjih nekoliko godina mnoge nove su se tek pojavile. U ovom članku objašnjena su osnovna HB-LED svojstva naglašavajući njihov utjecaj na razvoj izvora napajanja. Uz to, prikazane su osnovne topologije, od najjednostavnijih do najsloženijih, ujedno analizirajući prednosti i nedostatke pojedinih

Subspace analysis isolation forest for hyperspectral anomaly detection

Since the anomalies are usually “rare and different” in the hyperspectral image scene, they tend to be more easily isolated from the background pixels by appropriate splitting criterion. In view of this, we propose a hyperspectral anomaly detection method based isolation forest (iForest) with subspace analysis. Firstly, orthogonal subspace background suppression and dimension reduction techniques were used to improve the reliability of the isolation tree-splitting criterion. Secondly, the iForest-based detection may produce a number of false alarms since the forest is constructed using the randomly selected pixels in the whole scene. In order to solve this problem, the initial anomaly detection map was refined by local iForest processing. Compared with original iForest method, our approach can not only handle high dimensional problem, but also make full use of the local information. The experiments demonstrate the AUC score have been significantly improved in our approach