Graph Neural Network with Two Uplift Estimators for Label-Scarcity Individual Uplift Modeling

Uplift modeling aims to measure the incremental effect, which we call uplift, of a strategy or action on the users from randomized experiments or observational data. Most existing uplift methods only use individual data, which are usually not informative enough to capture the unobserved and complex hidden factors regarding the uplift. Furthermore, uplift modeling scenario usually has scarce labeled data, especially for the treatment group, which also poses a great challenge for model training. Considering that the neighbors' features and the social relationships are very informative to characterize a user's uplift, we propose a graph neural network-based framework with two uplift estimators, called GNUM, to learn from the social graph for uplift estimation. Specifically, we design the first estimator based on a class-transformed target. The estimator is general for all types of outcomes, and is able to comprehensively model the treatment and control group data together to approach the uplift. When the outcome is discrete, we further design the other uplift estimator based on our defined partial labels, which is able to utilize more labeled data from both the treatment and control groups, to further alleviate the label scarcity problem. Comprehensive experiments on a public dataset and two industrial datasets show a superior performance of our proposed framework over state-of-the-art methods under various evaluation metrics. The proposed algorithms have been deployed online to serve real-world uplift estimation scenarios

Effectiveness and safety of anti-BCMA chimeric antigen receptor T-cell treatment in relapsed/refractory multiple myeloma: a comprehensive review and meta-analysis of prospective clinical trials

Background: Chimeric antigen receptor T cells treatment targeting B cell maturation antigen (BCMA) is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) and has demonstrated outstanding outcomes in clinical studies.Objective: The aim of this comprehensive review and meta-analysis was to summarize the effectiveness and safety of anti-BCMA CAR-T treatment for patients with relapsed/refractory multiple myeloma (RRMM). Our research identifies variables influencing outcome measures to provide additional evidence for CAR-T product updates, clinical trial design, and clinical treatment guidance.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard was followed for conducting this comprehensive review and meta-analysis, which was submitted to PROSPERO (CRD42023390037). From the inception of the study until 10 September 2022, PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, and WanFang databases were searched for eligible studies. Stata software (version 16.0) was used to assess effectiveness and safety outcomes.Results: Out of 875 papers, we found 21 relevant trials with 761 patients diagnosed as RRMM and were given anti-BCMA CAR-T treatment. The overall response rate (ORR) for the entire sample was 87% (95% CI: 80–93%) complete response rate (CRR) was 44% (95% CI: 34–54%). The minimal residual disease (MRD) negativity rate within responders was 78% (95% CI: 65–89%). The combined incidence of cytokine release syndrome was 82% (95% CI: 72–91%) and neurotoxicity was 10% (95% CI: 5%–17%). The median progression-free survival (PFS) was 8.77 months (95% CI: 7.48–10.06), the median overall survival (OS) was 18.87 months (95% CI: 17.20–20.54) and the median duration of response (DOR) was 10.32 months (95% CI: 9.34–11.31).Conclusion: According to this meta-analysis, RRMM patients who received anti-BCMA CAR-T treatment have demonstrated both effectiveness and safety. Subgroup analysis confirmed the anticipated inter-study heterogeneity and pinpointed potential factors contributing to safety and efficacy, which may help with the development of CAR-T cell studies and lead to optimized BCMA CAR-T-cell products.Systematic Review Registration:Clinicaltrials.gov, PROSPERO, CRD42023390037

A Bioinspired and Biocompatible ortho-sulfiliminyl phenol Synthesis

Synthetic methods inspired by Nature often offer unique advantages including mild conditions and biocompatibility with aqueous media. Inspired by an ergothioneine biosynthesis protein EgtB, a mononuclear non-haem iron enzyme capable of catalysing the C–S bond formation and sulfoxidation, herein, we discovered a mild and metal-free C–H sulfenylation/intramolecular rearrangement cascade reaction employing an internally oxidizing O–N bond as a directing group. Our strategy accommodates a variety of oxyamines with good site selectivity and intrinsic oxidative properties. Combining an O–N bond with an X–S bond generates a C–S bond and an S¼N bond rapidly. The newly discovered cascade reaction showed excellent chemoselectivity and a wide substrate scope for both oxyamines and sulfenylation reagents. We demonstrated the biocompatibility of the C–S bond coupling reaction by applying a coumarin-based fluorogenic probe in bacterial lysates. Finally, the C–S bond coupling reaction enabled the first fluorogenic formation of phospholipids, which self-assembled to fluorescent vesicles in situ

CONUT score is associated with short-term prognosis in patients with severe acute pancreatitis: a propensity score matching cohort study

BackgroundThe Controlling Nutritional Status (CONUT) score was designed to assess the immune-nutritional status in patients. This study aimed to investigate the role of the CONUT score in the short-term prognosis of severe acute pancreatitis.MethodsThis was a retrospective cohort study. 488 patients with severe acute pancreatitis at the Department of Critical Care Medicine of the West China Hospital of Sichuan University (Chengdu, China) were enrolled in the study. Baseline data were collected from the West China Hospital of Sichuan University database. The primary outcome during follow-up was all-cause mortality. The secondary outcomes were 28 day mortality, renal insufficiency, length of stay (LOS) in the ICU, and length of stay (LOS) in the hospital. Patients were divided into two groups based on a median CONUT score of 7, and baseline differences between the two groups were eliminated by propensity matching. Univariate Cox regression analyses were performed to estimate the association between CONUT score and outcomes. The Kaplan–Meier method was used to estimate the survival rate of patients.ResultsCONUT score was an independent predictor of all-cause mortality (hazard ratio [HR]:2.093; 95%CI: 1.342–3.263; p < 0.001) and 28 day mortality (hazard ratio [HR]:1.813; 95%CI: 1.135–2.896; p < 0.013). CONUT score was not statistically significant in predicting the incidence of renal insufficiency. The high CONUT group had significantly higher all-cause mortality (p < 0.001), and 28 day mortality (p < 0.011) than the low CONUT group.ConclusionThe CONUT score is an independent predictor of short-term prognosis in patients with severe acute pancreatitis, and timely nutritional support is required to reduce mortality in patients with severe acute pancreatitis

Prenatal Diagnosis of Recurrent Distal 1q21.1 Duplication in Three Fetuses With Ultrasound Anomalies

Background: The phenotype of duplication of 1q21.1 region is variable, ranging from macrocephaly, autism spectrum disorder, congenital anomalies, to a normal phenotype. Few cases have been reported in the literature regarding prenatal diagnosis of 1q21.1 duplication syndrome. The current study presents prenatal diagnosis of 1q21.1 duplication syndrome in three fetuses with ultrasound anomalies.Case presentation: Three fetuses from three unrelated families were included in the study. The prenatal routine ultrasound examination showed nasal bone loss in Fetus 1 and Fetus 3, as well as duodenal atresia in Fetus 2. Chromosomal microarray analysis was performed to provide genetic analysis of amniotic fluid and parental blood samples. The CMA results revealed two de novo duplications of 1.34 and 2.69 Mb at distal 1q21.1 region in two fetuses with absent nasal bone, as well as a maternal inherited 1.35-Mb duplication at distal 1q21.1 in one fetus with duodenal atresia.Conclusions: The phenotype of 1q21.1 duplication syndrome in prenatal diagnosis is variable. The fetuses with nasal bone loss or duodenal atresia may be related to 1q21.1 duplication and chromosomal microarray analysis should be performed

Near-Infrared-Emissive AIE Bioconjugates: Recent Advances and Perspectives

Near-infrared (NIR) fluorescence materials have exhibited formidable power in the field of biomedicine, benefiting from their merits of low autofluorescence background, reduced photon scattering, and deeper penetration depth. Fluorophores possessing planar conformation may confront the shortcomings of aggregation-caused quenching effects at the aggregate level. Fortunately, the concept of aggregation-induced emission (AIE) thoroughly reverses this dilemma. AIE bioconjugates referring to the combination of luminogens showing an AIE nature with biomolecules possessing specific functionalities are generated via the covalent conjugation between AIEgens and functional biological species, covering carbohydrates, peptides, proteins, DNA, and so on. This perfect integration breeds unique superiorities containing high brightness, good water solubility, versatile functionalities, and prominent biosafety. In this review, we summarize the recent progresses of NIR-emissive AIE bioconjugates focusing on their design principles and biomedical applications. Furthermore, a brief prospect of the challenges and opportunities of AIE bioconjugates for a wide range of biomedical applications is presented

Learning to Dislike Chocolate: Conditioning Negative Attitudes toward Chocolate and Its Effect on Chocolate Consumption

Evaluative conditioning (EC) procedures can be used to form and change attitudes toward a wide variety of objects. The current study examined the effects of a negative EC procedure on attitudes toward chocolate, and whether it influenced chocolate evaluation and consumption. Participants were randomly assigned to the experimental condition in which chocolate images were paired with negative stimuli, or the control condition in which chocolate images were randomly paired with positive stimuli (50%) and negative stimuli (50%). Explicit and implicit attitudes toward chocolate images were collected. During an ostensible taste test, chocolate evaluation and consumption were assessed. Results revealed that compared to participants in the control condition, participants in the experimental condition showed more negative explicit and implicit attitudes toward chocolate images and evaluated chocolate more negatively during the taste test. However, chocolate consumption did not differ between experimental and control conditions. These findings suggest that pairing chocolate with negative stimuli can influence attitudes toward chocolate, though behavioral effects are absent. Intervention applications of EC provide avenues for future research and practices

Donor/π-Bridge Manipulation for Constructing a Stable NIR-II Aggregation-Induced Emission Luminogen with Balanced Phototheranostic Performance

Taking advantages of the versatile functionality and tunable energy dissipation, aggregation-induced emission lumino-gens (AIEgens) emerge as a rising star to afford multimodal theranostics platform. Nevertheless, the construction of AIE-active phototheranostic agent in the second near-infrared window (NIR-II, 1000−1700 nm) which allows superior resolu-tion and minimized photodamage is still a formidably challenging suffering from the limited candidate of building blocks. Herein, benzo[c]thiophene is innovatively utilized as electron-rich and bulky donor (D)/π-bridge neighboring to the elec-tron acceptor (A), which can enlarge the conjugation length and distort the backbone. By precise D/π-bridge engineering, highly stable NIR-II AIEgen DPBTA-DPTQ NPs with acceptable NIR-II fluorescence quantum yield and excellent photo-thermal conversion efficiency of 40.6% under 808 nm laser irradiation are successfully obtained. Compared with the re-ported NIR-II AIEgens, the exactly spatial conformation of DPBTA-DPTQ is determined for the first time by associating X-ray single crystal diffraction and theoretical simulations, elaborately revealing the relationship between structure and AIE effect/photothermal performance. Extensive in vitro tests demonstrate that DPBTA-DPTQ NPs with good biocom-patibility show efficient photothermal therapeutic effects. Furthermore, their prominent performance on fluorescence-photoacoustic-photothermal trimodal imaging-guided photothermal eradication of tumor is verified in HepG2 and B16-F10 tumor-xenografted mice, demonstrating distinguished cancer theranostic capability