Quantile regression in partially linear varying coefficient models

Semiparametric models are often considered for analyzing longitudinal data for a good balance between flexibility and parsimony. In this paper, we study a class of marginal partially linear quantile models with possibly varying coefficients. The functional coefficients are estimated by basis function approximations. The estimation procedure is easy to implement, and it requires no specification of the error distributions. The asymptotic properties of the proposed estimators are established for the varying coefficients as well as for the constant coefficients. We develop rank score tests for hypotheses on the coefficients, including the hypotheses on the constancy of a subset of the varying coefficients. Hypothesis testing of this type is theoretically challenging, as the dimensions of the parameter spaces under both the null and the alternative hypotheses are growing with the sample size. We assess the finite sample performance of the proposed method by Monte Carlo simulation studies, and demonstrate its value by the analysis of an AIDS data set, where the modeling of quantiles provides more comprehensive information than the usual least squares approach.Comment: Published in at http://dx.doi.org/10.1214/09-AOS695 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Interpreting County Level COVID-19 Infection and Feature Sensitivity using Deep Learning Time Series Models

Interpretable machine learning plays a key role in healthcare because it is challenging in understanding feature importance in deep learning model predictions. We propose a novel framework that uses deep learning to study feature sensitivity for model predictions. This work combines sensitivity analysis with heterogeneous time-series deep learning model prediction, which corresponds to the interpretations of spatio-temporal features. We forecast county-level COVID-19 infection using the Temporal Fusion Transformer. We then use the sensitivity analysis extending Morris Method to see how sensitive the outputs are with respect to perturbation to our static and dynamic input features. The significance of the work is grounded in a real-world COVID-19 infection prediction with highly non-stationary, finely granular, and heterogeneous data. 1) Our model can capture the detailed daily changes of temporal and spatial model behaviors and achieves high prediction performance compared to a PyTorch baseline. 2) By analyzing the Morris sensitivity indices and attention patterns, we decipher the meaning of feature importance with observational population and dynamic model changes. 3) We have collected 2.5 years of socioeconomic and health features over 3142 US counties, such as observed cases and deaths, and a number of static (age distribution, health disparity, and industry) and dynamic features (vaccination, disease spread, transmissible cases, and social distancing). Using the proposed framework, we conduct extensive experiments and show our model can learn complex interactions and perform predictions for daily infection at the county level. Being able to model the disease infection with a hybrid prediction and description accuracy measurement with Morris index at the county level is a central idea that sheds light on individual feature interpretation via sensitivity analysis

Autotransplantation of Inferior Parathyroid glands during central neck dissection for papillary thyroid carcinoma: A retrospective cohort study

AbstractIntroduction: The management of inferior parathyroid glands during central neck dissection (CND) for papillary thyroid carcinoma (PTC) remains controversial. Most surgeons preserve inferior parathyroid glands in situ. Autotransplantation is not routinely performed unless devascularization or inadvertent parathyroidectomy occurs. This retrospective study aimed to compare the incidence of postoperative hypoparathyroidism and central neck lymph node (CNLN) recurrence in patients with PTC who underwent inferior parathyroid glands autotransplantation vs preservation in situ. Methods: This is a retrospective study which was conducted in a tertiary referral hospital. A total of 477 patients with PTC (pN1) who underwent total thyroidectomy (TT) and bilateral CND with/without lateral neck dissection were included. Patients' demographical characteristics, tumor stage, incidence of hypoparathyroidism, CNLN recurrence and the number of resected CNLN were analyzed. Results: Three hundred and twenty-one patients underwent inferior parathyroid glands autotransplantation (autotransplantation group). Inferior parathyroid glands were preserved in situ among 156 patients (preservation group). Permanent hypoparathyroidism rate was 0.9% (3/321) versus 3.8% (6/156) respectively (p = 0.028). Mean numbers of resected CNLN were 15 ± 3 (6–23) (autotransplantation group) versus 11 ± 3 (7–21) (preservation group) (p < 0.001). CNLN recurrence rate was 0.3% (1/321) versus 3.8% (6/156) respectively (p = 0.003). Conclusion: Inferior parathyroid glands autotransplantation during CND of PTC (pN1) might reduce permanent hypoparathyroidism and CNLN recurrence. Further study enrolling more patients with long-term follow-up is needed to support this conclusion

Granzyme A, which causes single‐stranded DNA damage, targets the double‐strand break repair protein Ku70

Granzyme A (GzmA) induces caspase-independent cell death with morphological features of apoptosis. Here, we show that GzmA at nanomolar concentrations cleaves Ku70, a key double-strand break repair (DSBR) protein, in target cells. Ku70 is cut after Arg(301), disrupting Ku complex binding to DNA. Cleaving Ku70 facilitates GzmA-mediated cell death, as silencing Ku70 by RNA interference increases DNA damage and cell death by GzmB cluster-deficient cytotoxic T lymphocytes or by GzmA and perforin, whereas Ku70 overexpression has the opposite effect. Ku70 has two known antiapoptotic effects—facilitating DSBR and sequestering bax to prevent its translocation to mitochondria. However, GzmA triggers single-stranded, not double-stranded, DNA damage, and GzmA-induced cell death does not involve bax. Therefore, Ku70 has other antiapoptotic functions in GzmA-induced cell death, which are blocked when GzmA proteolyses Ku70

Planar Möbius aromatic pentalenes incorporating 16 and 18 valence electron osmiums

夏海平课题组长期致力于芳香体系的拓展研究。作为金属杂戊搭炔化学又一重要进展，在此研究中，他们发现金属杂戊搭炔的卡拜碳原子宛如“变色龙”，既具有亲核性，又具有亲电性。通过金属杂戊搭炔与亲电试剂反应揭示了其三键迁移的神秘面纱，并成功地捕捉了三键迁移的中间体——金属中心为16电子的金属杂戊搭烯；通过金属杂戊搭炔与亲核试剂反应，得到金属中心为18电子的金属杂戊搭烯。 　　朱军课题组通过理论计算，对金属杂戊搭烯进行深入理论研究。发现金属中心16电子、18电子金属杂戊搭烯均具有芳香性。深入的CMO-NICS计算表明，本质上，金属杂戊搭炔中Mobius芳香性来源于金属杂戊搭烯，正如苯炔的芳香性来源于苯。Mobius芳香性自1958年提出以来，实际合成的例子稀少，且前人已分离并报道的Möbius芳香体系均具有扭曲的拓扑结构。金属杂戊搭烯/炔代表着一类平面型的Möbius芳香性体系。从而颠覆了传统的芳香化学，为构筑其他平面型Möbius芳香体系奠定了基础。 　　该工作的合成和结构表征是在夏海平教授指导下由博士生朱从青（第一作者）、罗明和硕士生朱琴完成，我校温庭斌教授参与了产物结构表征的讨论。理论计算由朱军副教授完成，我校吕鑫教授、美国佐治亚大学P.v.R.Schleyer教授和J.I-C.Wu博士也参与了芳香性的讨论。Aromaticity, a highly stabilizing feature of molecules with delocalized electrons in closed circuits, is generally restricted to ‘Hückel’ systems with 4n+2 mobile electrons. Although the Möbius concept extends the principle of aromaticity to 4n mobile electron species, the rare known examples have complex, twisted topologies whose extension is unlikely. Here we report the realization of osmapentalenes, the first planar Möbius aromatic complexes with 16 and 18 valence electron transition metals. The Möbius aromaticity of these osmapentalenes, documented by X-ray structural, magnetic and theoretical analyses, demonstrates the basis of the aromaticity of the parent osmapentalynes. All these osmapentalenes are formed by both electrophilic and nucleophilic reactions of the in-plane π component of the same carbyne carbon, illustrating ambiphilic carbyne reactivity, which is seldom observed in transition metal chemistry. Our results widen the scope of Möbius aromaticity dramatically and open prospects for the generalization of planar Möbius aromatic chemistry.国家自然科学基金委、科技部和美国科学基金会的资

Danggui Buxue Tang – A Chinese herbal decoction activates the phosphorylations of extracellular signal-regulated kinase and estrogen receptor α in cultured MCF-7 cells

AbstractDanggui Buxue Tang (DBT), a Chinese herbal decoction used to treat ailments in women, contains Radix Astragali (Huangqi; RA) and Radix Angelicae Sinensis (Danggui; RAS). The weight ratio of RA to RAS used in DBT must be 5:1 as stipulated as early as AD 1247; however, DBT’s mechanism of action has never been described. Here, the estrogenic effects of DBT were investigated by determining the phosphorylations of estrogen receptor α (ERα) and extracellular signal-regulated kinase 1/2 (Erk1/2) in cultured MCF-7 cells. The application of DBT triggered the phosphorylation of ERα and Erk1/2 in a time-dependent manner. In contrast to the effect of estrogen, DBT triggered ERα phosphorylation at both S118 and S167. This DBT-specific phosphorylation was not triggered by an extract of one of the individual herbs, or by mixing the extracts of RA and RAS. DBT-induced downstream signals are described here. These signals suggest the uniqueness of this Chinese herbal decoction that requires a well-defined formulation

A Chinese Herbal Decoction, Danggui Buxue Tang, Stimulates Proliferation, Differentiation and Gene Expression of Cultured Osteosarcoma Cells: Genomic Approach to Reveal Specific Gene Activation

Danggui Buxue Tang (DBT), a Chinese herbal decoction used to treat ailments in women, contains Radix Astragali (Huangqi; RA) and Radix Angelicae Sinensis (Danggui; RAS). When DBT was applied onto cultured MG-63 cells, an increase of cell proliferation and differentiation of MG-63 cell were revealed: both of these effects were significantly higher in DBT than RA or RAS extract. To search for the biological markers that are specifically regulated by DBT, DNA microarray was used to reveal the gene expression profiling of DBT in MG-63 cells as compared to that of RA- or RAS-treated cells. Amongst 883 DBT-regulated genes, 403 of them are specifically regulated by DBT treatment, including CCL-2, CCL-7, CCL-8, and galectin-9. The signaling cascade of this DBT-regulated gene expression was also elucidated in cultured MG-63 cells. The current results reveal the potential usage of this herbal decoction in treating osteoporosis and suggest the uniqueness of Chinese herbal decoction that requires a well-defined formulation. The DBT-regulated genes in the culture could serve as biological responsive markers for quality assurance of the herbal preparation