Enhancing Recommender Systems with Causal Inference Methodologies

In the current era of data deluge, recommender systems (RSs) are widely recognized as one of the most effective tools for information filtering. However, traditional RSs are founded on associational relationships among variables rather than causality, meaning they are unable to determine which factors actually affect user preference. In addition, the algorithm of conventional RS continues to recommend similar items to users, resulting in user aesthetic fatigue and ultimately the loss of customer sources. Moreover, the generation of recommendations could be biased by the confounding effect, leading to inaccurate results. To tackle this series of challenges, causal inference for recommender systems (CI for RSs) has emerged as a new area of study. In this paper, we present four different propensity score estimation methods, namely hierarchical Poisson factorization (HPF), logistic regression, non-negative matrix factorization (NMF), and neural networks (NNs), and five causal effect estimation methods, namely linear regression, inverse probability weighting (IPW), zero-inflated Poisson (ZIP) regression, zero-inflated Negative Binomial (ZINB) regression, and doubly robust (DR) estimation. Additionally, we propose a new algorithm for parameter estimation based on the concept of alternating gradient descent (AGD). Regarding the study's reliability and precision, it will be evaluated on two distinct categories of datasets. Our research demonstrates that the causal RS can correctly infer causality from user and item characteristics to the final rating with an accuracy of 96%. Moreover, according to the de-confounded and de-biased recommendations, ratings can be increased by an average of 1.6 points (out of 4) for the Yahoo! R3 dataset and 1.2 points (out of 2) for the Restaurant and Consumer data

Analyses of domains and domain fusions in human proto-oncogenes

Background: Understanding the constituent domains of oncogenes, their origins and their fusions may shed new light about the initiation and the development of cancers. Results: We have developed a computational pipeline for identification of functional domains of human genes, prediction of the origins of these domains and their major fusion events during evolution through integration of existing and new tools of our own. An application of the pipeline to 124 well-characterized human oncogenes has led to the identification of a collection of domains and domain pairs that occur substantially more frequently in oncogenes than in human genes on average. Most of these enriched domains and domain pairs are related to tyrosine kinase activities. In addition, our analyses indicate that a substantial portion of the domain-fusion events of oncogenes took place in metazoans during evolution. Conclusion: We expect that the computational pipeline for domain identification, domain origin and domain fusion prediction will prove to be useful for studying other groups of genes. Originally published BMC Bioinformatics, Vol. 10, No. 88, Mar 200

Evaluation of pharmacokinetics and toxicology of biosimilar APZ001 antibody in Macaca cynomolgus

Purpose: To compare the pharmacokinetics of APZ001 antibody with those of cetuximab (Erbitux®) and to evaluate the toxicology of the former.Methods: To evaluate cetuximab’s biosimilar APZ001, Crl:CD1(ICR) (CD-1) mice and Macaca fascicularis (cynomolgus monkey) were chosen for the studies on acute toxicity, chronic toxicity, pharmacokinetics in chronic toxicity and immunogenicity toxicity. The study also compared the pharmacokinetic parameters of APZ001 with those of cetuximab upon single and multiple drug administrations in cynomolgus monkeys.Results: Pharmacokinetic parameters including maximum concentration (Cmax) and time to attain maximum drug concentration (Tmax), clearance rate and apparent volume of distribution of APZ001 were compared with those of cetuximab in both single and multiple administration studies. Difference of pharmacokinetics from weekly administration of APZ001 and cetuximab in cynomolgus monkeys was insignificant (p > 0.05), with relative bioavailability of 116.9 %. Both APZ001-treated and cetuximabtreated CD-1 mice showed the same level of food intake and body weight. Hematological and serological data were similar from APZ001 antibody and cetuximab treatments, so were the acute and chronic toxicity. Weekly transfusion of APZ001 did not alter its pharmacokinetic parameters. The administered drug was hardly detected in the serum in the 31st and 37th week of recovery; no accumulation of drug was observed upon withdrawal.Conclusion: APZ001 has extremely similar characteristics as cetuximab in terms of pharmacokinetics and toxicity.Keywords: Cetuximab, Pharmacokinetics, Acute toxicity, Chronic toxicity, Immunogenicity, Biosimila

A self-adaptive frequency response compensation method for a TIADC system

Time interleaving is one of the most efficient techniques employed in high-speed sampling systems. However, the frequency response mismatch among different channels will create distortion tones that degrade the system performance. In this paper, a selfadaptive frequency response mismatch compensation method is presented, where the design of compensation filter is optimized with a self-adapting strategy. This digital postprocessing technique realizes the compensation of frequency response effectively and also the increase of the digital bandwidth of the acquisition system. MATLAB-based simulation and an actual two-channel acquisition system test verify the effectiveness of the algorithm

Double lung transplantation for end-stage Kartagener syndrome: A case report and literature review

Kartagener syndrome (KS) is an autosomal recessive disorder characterized by situs inversus, paranasal sinusitis and bronchiectasis. We report the successful use of double lung transplant (DLTx) to treat end-stage KS. A 49-year-old Han woman was admitted to Renmin Hospital (Wuhan University, China) in September 2017 with a ≥15 year history of chronic productive cough that had worsened during the past year. Clinical examination and imaging investigations revealed respiratory failure and situs inversus consistent with KS. The patient was successfully treated with DLTx involving bilateral bronchial anastomoses. DLTx is a feasible treatment option for end-stage KS

The Hera orebody: a complex distal (Au–Zn–Pb–Ag–Cu) skarn in the Cobar Basin of central New South Wales, Australia

The Hera Au–Pb–Zn–Ag deposit in the southeastern Cobar Basin of central New South Wales preserves calc-silicate veins and remnant sandstone/carbonate-hosted skarn within a reduced anchizonal Siluro-Devonian turbidite sequence. The skarn orebody distribution is controlled by a long-lived, basin margin fault system, that has intersected a sedimentary horizon dominated by siliciclastic turbidite, with lesser gritstone and thick sandstone intervals, and rare carbonate-bearing stratigraphy. Foliation (S1) envelopes the orebody and is crosscut by a series of late-stage east–west and north–south trending faults. Skarn at Hera displays mineralogical zonation along strike, from southern spessartine–grossular–biotite–actinolite-rich associations, to central diopside-rich–zoisite–actinolite/tremolite–grossular-bearing associations, through to the northern most tremolite–anorthite-rich (garnet-absent) association in remnant carbonate-bearing lithologies and sandstone horizons; the northern lodes also display zonation down dip to garnet present associations. High-T, prograde skarn assemblages rich in pyroxene and garnet are pervasively replaced by actinolite/tremolite–biotite-rich retrograde skarn which coincides with the main pulse of sulfide mineralization. The dominant sulfides are high-Fe–Mn sphalerite–galena–non-magnetic high-Fe pyrrhotite–chalcopyrite; pyrite, arsenopyrite; scheelite (low Mo) is locally abundant. The distribution of metals in part mimics the changing gangue mineralogy, with Au concentrated in the southern and lower northern lode systems and broadly inverse concentrations for Ag–Pb–Zn. Stable isotope data (O–H–S) from skarn amphiboles and associated sulfides are consistent with magmatic (or metamorphic) water and sulfur input during the retrograde skarn phase, while hydrosilicates and sulfides from the wall rocks display comparatively elevated δD and mixed δ34S consistent with progressive mixing or dilution of original magmatic (or metamorphic) waters within the Hera deposit by unexchanged waters typical of low latitude (tropical) meteoritic waters. High precision titanite (U–Pb) and biotite (Ar–Ar) geochronology reveals a manifold orebody commencing with high-T skarn and retrograde Pb–Zn-rich skarn formation at ≥403 Ma, Au–low-Fe sphalerite mineralization at 403.4 ± 1.1 Ma, foliation development remobilization or new mineralization at 390 ± 0.2 Ma followed by thrusting, orebody dismemberment at 384.8 ± 1.1 Ma and remobilization or new mineralization at 381.0 ± 2.2 Ma. The polymetallic nature of the Hera orebody is a result of multiple mineralization events during extension and compression and involving both magmatic and likely formational metal sources

Role of lncRNAs in acute pancreatitis: pathogenesis, diagnosis, and therapy

Acute pancreatitis (AP) is one of the most common acute abdominal diseases characterized by an injury and inflammatory disorder of the pancreas with complicated pathological mechanisms. Long non-coding RNAs (lncRNAs) have been shown to play an important role in various physiological and pathological processes in humans, and they have emerged as potential biomarkers of diagnosis and therapeutic targets in various diseases. Recently, accumulating evidence has shown significant alterations in the expression of lncRNAs, which are involved in the pathogenesis of AP, such as premature trypsinogen activation, impaired autophagy, inflammatory response, and acinar cell death. Moreover, lncRNAs can be the direct target of AP treatment and show potential as biomarkers for the diagnosis. Thus, in this review, we focus on the role of lncRNAs in the pathogenesis, diagnosis, and therapy of AP and emphasize the future directions to study lncRNAs in AP, providing new insight into understanding the cellular and molecular mechanisms of AP and seeking novel biomarkers for the diagnosis and therapeutic targets to improve clinical management in the future

JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China

ScopeThis study aimed to evaluate the effects of JK5G postbiotics to regulate imbalanced gut microbiota and its impacts on the efficacy and incidence rate of immune-related adverse events (irAEs) in non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs).MethodsThis randomized, double-blind, placebo-controlled trial was conducted in China and included non-squamous or squamous NSCLC patients without EGFR, ROS1, and ALK alteration, treatment-naive, and stage IIIb-IV. Patients were randomly (1:1) divided into two groups to receive four cycles (three weeks for each cycle) of programmed cell death-1 (PD-1) plus chemotherapy plus placebo (control group, n = 30) or to receive PD-1 plus chemotherapy plus JK5G postbiotics (JK5G group, n = 30). The primary endpoint was objective response rate. The secondary endpoints were quality of life (QoL), adverse effects, and the 16S DNA sequencing of gut microbiota, blood inflammatory cytokines, and lymphocyte subsets. This study was registered at www.chictr.org.cn (ChiCTR2200064690).ResultsSixty patients were enrolled. The objective response rate was 36.67% (11/30) in the control group and 50.00% (15/30) in the JK5G group (p = 0.297). The JK5G group had better QoL and nutritional levels, as well as lower depression symptoms than the control group (all p < 0.05). Moreover, the JK5G group had a lower incidence of anemia (63.33% vs. 13.33%, p < 0.001), decreased lymphocyte count (20.00% vs. 0%, p = 0.010), decreased appetite (53.33% vs. 16.67%, p = 0.003), nausea (33.33% vs. 6.67%, p = 0.010), and asthenia (30.00% vs. 6.67%, p = 0.017) than the control group. Moreover, JK5G attenuated gut microbiota imbalance, accompanied by increased Faecalibacterium, Ruminococcaceae, and fecal butyrate concentration, and diminished Escherichia-Shigella. Furthermore, JK5G administration significantly decreased the levels of pro-inflammatory markers, including TNF-α, IL-2, and C-reactive protein (CRP) (all p < 0.05). Significant increases in CD3+CD4+ T cells and CD4/CD8 ratio were observed in the peripheral blood of JK5G group patients (all p < 0.05). The enterotype data showed that patients were clustered into Blautia (E1) and Escherichia-Shigella (E2) enterotypes, and JK5G postbiotics intervention might be related to enterotype modulations.ConclusionOur current findings indicated that JK5G postbiotics might attenuate irAEs, and enhance the QoL and nutrition levels of advanced NSCLC patients who received ICIs. JK5G postbiotics could also improve the gut microbiota structures and ameliorate the tumor microenvironment and inflammation.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR2200064690

Giant electric energy density in epitaxial lead-free thin films with coexistence of ferroelectrics and antiferroelectrics

Ferroelectrics/antiferroelectrics with high dielectric breakdown strength have the potential to store a great amount of electrical energy, attractive for many modern applications in electronic devices and systems. Here we demonstrate that a giant electric energy density (154 J×cm-3, 3 times the highest value of lead-based systems and 5 times the value of the best dielectric/ferroelectric polymer), together with the excellent fatigue-free property, good thermal stability and high efficiency, is realized in pulsed laser deposited (Bi1/2Na1/2)0.9118La0.02Ba0.0582(Ti0.97Zr0.03)O3 (BNLBTZ) epitaxial lead-free relaxor thin films with the coexistence of ferroelectric (FE) and antiferroelectric (AFE) phases. This is endowed by high epitaxial quality, great relaxor dispersion and the coexistence of the FE/AFE phases near the morphotropic phase boundary (MPB). The giant energy storage effect of the BNLBTZ lead-free relaxor thin films may make a great impact on the modern energy storage technology

Analysis of Key Aroma Components of Three Representative Oolong Tea Varieties by Stir Bar Sorptive Extraction Combined with Gas Chromatography-Olfactory-Mass Spectrometry

Stir bar sorptive extraction (SBSE) combined with gas chromatography-olfactory-mass spectrometry (GC-O-MS) was used to identify and describe the key aroma components of three representative oolong tea varieties, Huangdan, Tieguanyin and Jinguanyin. Comparative analysis was conducted in terms of odor activity value (OAV), aroma character impact (ACI) value and sensory evaluation. The sensory evaluation showed that each variety showed obvious aroma characteristics. Huangdan oolong tea had an obvious floral aroma as well as a slight milky aroma. Tieguanyin oolong tea had a strong floral aroma. Jinguanyin oolong tea had a sweet fruity aroma as well as a slight woody aroma. According to the results of OAV and GC-O-MS analysis, geraniol, phytol, methyl jasmonate, trans-nerol tertiary alcohol, 2-nonone, and phenyl ethanol were identified as key aroma components in Huangdan oolong tea, which provided it with clean and high floral aroma and obvious milky aroma characteristics. In Tieguanyin oolong tea, linalool, 3,5-octylodiene-2-one, linalool oxide, cis-jasmonone, dehydrolinalool, and α-terpineol showed diverse floral aromas, which were closely related to the characteristic aroma of Tieguanyin oolong tea. The key aroma components identified in Jinguanyin oolong tea included linalool, canalaldehyde, geranyl acetone, cis-jasmonone and isoeugenol, which were responsible for the characteristic sweet floral and woody aromas of Jinguanyin oolong tea