Guidance on Individualized Treatment Rule Estimation in High Dimensions

Individualized treatment rules, cornerstones of precision medicine, inform patient treatment decisions with the goal of optimizing patient outcomes. These rules are generally unknown functions of patients' pre-treatment covariates, meaning they must be estimated from clinical or observational study data. Myriad methods have been developed to learn these rules, and these procedures are demonstrably successful in traditional asymptotic settings with moderate number of covariates. The finite-sample performance of these methods in high-dimensional covariate settings, which are increasingly the norm in modern clinical trials, has not been well characterized, however. We perform a comprehensive comparison of state-of-the-art individualized treatment rule estimators, assessing performance on the basis of the estimators' accuracy, interpretability, and computational efficacy. Sixteen data-generating processes with continuous outcomes and binary treatment assignments are considered, reflecting a diversity of randomized and observational studies. We summarize our findings and provide succinct advice to practitioners needing to estimate individualized treatment rules in high dimensions. All code is made publicly available, facilitating modifications and extensions to our simulation study. A novel pre-treatment covariate filtering procedure is also proposed and is shown to improve estimators' accuracy and interpretability

Supply Chain Information Collaborative Simulation Model Integrating Multi-Agent and System Dynamics

Supply chain collaboration management is a systematic, integrated and agile advanced management mode, which helps to improve the competitiveness of enterprises and the entire supply chain. In order to realise the synergy of supply chain, the most important is to realise the dynamic synergy of information. Here we proposed a strategy to integrate system dynamics and multi-agent system modelling methods. Based on the strategy of supply chain information sharing and coordination, a two-level aggregation hybrid model was designed and established. Through the computer simulation analysis of the two modes before and after information collaboration, it is found that under the information collaboration mode, the change trend of order or inventory of suppliers and manufacturers always closely matches that of retailers. After the implementation of supply chain information coordination, ordering and inventory can be reasonably planned and matched, and problems such as over-stocking or short-term failure to meet order demands caused by poor information communication will no longer occur, which can greatly reduce the “bullwhip effect”

A nonparametric framework for treatment effect modifier discovery in high dimensions

Heterogeneous treatment effects are driven by treatment effect modifiers, pre-treatment covariates that modify the effect of a treatment on an outcome. Current approaches for uncovering these variables are limited to low-dimensional data, data with weakly correlated covariates, or data generated according to parametric processes. We resolve these issues by developing a framework for defining model-agnostic treatment effect modifier variable importance parameters applicable to high-dimensional data with arbitrary correlation structure, deriving one-step, estimating equation and targeted maximum likelihood estimators of these parameters, and establishing these estimators' asymptotic properties. This framework is showcased by defining variable importance parameters for data-generating processes with continuous, binary, and time-to-event outcomes with binary treatments, and deriving accompanying multiply-robust and asymptotically linear estimators. Simulation experiments demonstrate that these estimators' asymptotic guarantees are approximately achieved in realistic sample sizes for observational and randomized studies alike. This framework is applied to gene expression data collected for a clinical trial assessing the effect of a monoclonal antibody therapy on disease-free survival in breast cancer patients. Genes predicted to have the greatest potential for treatment effect modification have previously been linked to breast cancer. An open-source R package implementing this methodology, unihtee, is made available on GitHub at https://github.com/insightsengineering/unihtee

Design, Synthesis, and Structure-Activity Relationships of 3,4,5-Trisubstituted 4,5-Dihydro-1,2,4-oxadiazoles as TGR5 Agonists

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Single-cell RNA-seq reveals novel regulators of human embryonic stem cell differentiation to definitive endoderm

Background: Human pluripotent stem cells offer the best available model to study the underlying cellular and molecular mechanisms of human embryonic lineage specification. However, it is not fully understood how individual stem cells exit the pluripotent state and transition towards their respective progenitor states. Results: Here, we analyze the transcriptomes of human embryonic stem cell-derived lineage-specific progenitors by single-cell RNA-sequencing (scRNA-seq). We identify a definitive endoderm (DE) transcriptomic signature that leads us to pinpoint a critical time window when DE differentiation is enhanced by hypoxia. The molecular mechanisms governing the emergence of DE are further examined by time course scRNA-seq experiments, employing two new statistical tools to identify stage-specific genes over time (SCPattern) and to reconstruct the differentiation trajectory from the pluripotent state through mesendoderm to DE (Wave-Crest). Importantly, presumptive DE cells can be detected during the transitory phase from Brachyury (T)+ mesendoderm toward a CXCR4+ DE state. Novel regulators are identified within this time window and are functionally validated on a screening platform with a T-2A-EGFP knock-in reporter engineered by CRISPR/Cas9. Through loss-of-function and gain-of-function experiments, we demonstrate that KLF8 plays a pivotal role modulating mesendoderm to DE differentiation. Conclusions: We report the analysis of 1776 cells by scRNA-seq covering distinct human embryonic stem cell-derived progenitor states. By reconstructing a differentiation trajectory at single-cell resolution, novel regulators of the mesendoderm transition to DE are elucidated and validated. Our strategy of combining single-cell analysis and genetic approaches can be applied to uncover novel regulators governing cell fate decisions in a variety of systems. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1033-x) contains supplementary material, which is available to authorized users

Journey with Ting-Peng Liang in Pacific Asia Information Systems Field

Our respectful old friend Professor Ting-Peng Liang (in short, TP) whom we loved suddenly passed away on May 20, 2021. But we cannot forget his smile and passion, and his inerasable footprints in PACIS, PAJAIS, and AIS Community. He was the founder of PACIS, founding editor-in-chief of PAJAIS, and past president of AIS to list just a few. He was the pioneer who received the first AIS Fellow and the first LEO Award from Asia Pacific. That is why the leaders of the information systems field organized the first ever special tribute session in PACIS 2021 in memory of TP (https://aisel.aisnet.org/pacis2021/253/

Immune Protection Induced on Day 10 Following Administration of the 2009 A/H1N1 Pandemic Influenza Vaccine

BACKGROUND: The 2009 swine-origin influenza virus (S-OIV) H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation. METHODOLOGY/PRINCIPAL FINDINGS: 58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 µg, single-dose). The sera were collected before Day 0 (pre-vaccination) and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%). This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21). However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1∶40, Group 1) more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer <1∶40, Group 2). The titer of the specific antibody against the 2009 A/H1N1 influenza was much higher in Group 1 (geometric mean titer: 146 on Day 21) than that in Group 2 (geometric mean titer: 70 on Day 21). CONCLUSIONS/SIGNIFICANCE: Recipients could gain sufficient protection as early as 10 days after vaccine administration. The protection could last at least 60 days. Individuals with a stronger pre-existing seasonal influenza antibody response may have a relatively higher potential for developing a stronger humoral immune response after vaccination with the 2009 A/H1N1 pandemic influenza vaccine

Measurement of azimuthal asymmetries in inclusive charged dipion production in e+e−e^+e^- annihilations at s\sqrt{s} = 3.65 GeV

We present a measurement of the azimuthal asymmetries of two charged pions in the inclusive process $e^+e^-\rightarrow \pi\pi X$ based on a data set of 62 $\rm{pb}^{-1}$ at the center-of-mass energy $\sqrt{s}=3.65$ GeV collected with the BESIII detector. These asymmetries can be attributed to the Collins fragmentation function. We observe a nonzero asymmetry, which increases with increasing pion momentum. As our energy scale is close to that of the existing semi-inclusive deep inelastic scattering experimental data, the measured asymmetries are important inputs for the global analysis of extracting the quark transversity distribution inside the nucleon and are valuable to explore the energy evolution of the spin-dependent fragmentation function.Comment: 7 pages, 5 figure

Study of D+→K−π+e+νeD^{+} \to K^{-} \pi^+ e^+ \nu_e

We present an analysis of the decay $D^{+} \to K^{-} \pi^+ e^+ \nu_e$ based on data collected by the BESIII experiment at the $\psi(3770)$ resonance. Using a nearly background-free sample of 18262 events, we measure the branching fraction $\mathcal{B}(D^{+} \to K^{-} \pi^+ e^+ \nu_e) = (3.71 \pm 0.03 \pm 0.08)\%$. For $0.8<m_{K\pi}<1.0$ GeV/$c^{2}$ the partial branching fraction is $\mathcal{B}(D^{+} \to K^{-} \pi^+ e^+ \nu_e)_{[0.8,1]} = (3.33 \pm 0.03 \pm 0.07)\%$. A partial wave analysis shows that the dominant $\bar K^{*}(892)^{0}$ component is accompanied by an \emph{S}-wave contribution accounting for $(6.05\pm0.22\pm0.18)\%$ of the total rate and that other components are negligible. The parameters of the $\bar K^{*}(892)^{0}$ resonance and of the form factors based on the spectroscopic pole dominance predictions are also measured. We also present a measurement of the $\bar K^{*}(892)^{0}$ helicity basis form factors in a model-independent way.Comment: 17 pages, 6 figure

Study of J/ψJ/\psi and ψ(3686)→Σ(1385)0Σˉ(1385)0\psi(3686)\rightarrow\Sigma(1385)^{0}\bar\Sigma(1385)^{0} and Ξ0Ξˉ0\Xi^0\bar\Xi^{0}

We study the decays of $J/\psi$ and $\psi(3686)$ to the final states $\Sigma(1385)^{0}\bar\Sigma(1385)^{0}$ and $\Xi^0\bar\Xi^{0}$ based on a single baryon tag method using data samples of $(1310.6 \pm 7.0) \times 10^{6}$ $J/\psi$ and $(447.9 \pm 2.9) \times 10^{6}$ $\psi(3686)$ events collected with the BESIII detector at the BEPCII collider. The decays to $\Sigma(1385)^{0}\bar\Sigma(1385)^{0}$ are observed for the first time. The measured branching fractions of $J/\psi$ and $\psi(3686)\rightarrow\Xi^0\bar\Xi^{0}$ are in good agreement with, and much more precise, than the previously published results. The angular parameters for these decays are also measured for the first time. The measured angular decay parameter for $J/\psi\rightarrow\Sigma(1385)^{0}\bar\Sigma(1385)^{0}$, $\alpha =-0.64 \pm 0.03 \pm 0.10$, is found to be negative, different to the other decay processes in this measurement. In addition, the "12\% rule" and isospin symmetry in the $J/\psi$ and $\psi(3686)\rightarrow\Xi\bar\Xi$ and $\Sigma(1385)\bar{\Sigma}(1385)$ systems are tested.Comment: 11 pages, 7 figures. This version is consistent with paper published in Phys.Lett. B770 (2017) 217-22