On estimating the change point in generalized linear models

Statistical models incorporating change points are common in practice, especially in the area of biomedicine. This approach is appealing in that a specific parameter is introduced to account for the abrupt change in the response variable relating to a particular independent variable of interest. The statistical challenge one encounters is that the likelihood function is not differentiable with respect to this change point parameter. Consequently, the conventional asymptotic properties for the maximum likelihood estimators fail to hold in this situation. In this paper, we propose an estimating procedure for estimating the change point along with other regression coefficients under the generalized linear model framework. We show that the proposed estimators enjoy the conventional asymptotic properties including consistency and normality. Simulation work we conducted suggests that it performs well for the situations considered. We applied the proposed method to a case-control study aimed to examine the relationship between the risk of myocardial infarction and alcohol intake.Comment: Published in at http://dx.doi.org/10.1214/193940307000000239 the IMS Collections (http://www.imstat.org/publications/imscollections.htm) by the Institute of Mathematical Statistics (http://www.imstat.org

Aberrant lysosomal carbohydrate storage accompanies endocytic defects and neurodegeneration in Drosophila benchwarmer

Lysosomal storage is the most common cause of neurodegenerative brain disease in preadulthood. However, the underlying cellular mechanisms that lead to neuronal dysfunction are unknown. Here, we report that loss of Drosophila benchwarmer (bnch), a predicted lysosomal sugar carrier, leads to carbohydrate storage in yolk spheres during oogenesis and results in widespread accumulation of enlarged lysosomal and late endosomal inclusions. At the bnch larval neuromuscular junction, we observe similar inclusions and find defects in synaptic vesicle recycling at the level of endocytosis. In addition, loss of bnch slows endosome-to-lysosome trafficking in larval garland cells. In adult bnch flies, we observe age-dependent synaptic dysfunction and neuronal degeneration. Finally, we find that loss of bnch strongly enhances tau neurotoxicity in a dose-dependent manner. We hypothesize that, in bnch, defective lysosomal carbohydrate efflux leads to endocytic defects with functional consequences in synaptic strength, neuronal viability, and tau neurotoxicity

The Impact of University-Specific WeChat Official Accounts on the Socialist Values of Art Students A Exploration Based on the “BIFT Art Sea Studio” WeChat Official Account

In contemporary higher education, the rise of social media has provided universities with new platforms for information dissemination, establishing connections, and shaping institutional culture. Universityspecific WeChat Official Accounts have emerged as crucial tools for interaction and information dissemination between universities and students. However, their influence on students' ideological perspectives, particularly in shaping socialist values, remains relatively underexplored. This research focuses on investigating the potential impact of the "BIFT ART SEA STUDIO" WeChat Official Account on the socialist values of art students. Socialist values, as an integral component of Chinese socialism, play a crucial role in guiding higher education. Art students, epitomizing creative thinking, contribute not only to the individual formation of values but also play a pivotal role in the inheritance and innovation of institutional culture. The "BIFT ART SEA STUDIO" WeChat Official Account, as a primary channel for information dissemination and interaction, is of particular interest in its potential influence on shaping the socialist values of art students. Through an in-depth exploration of the content, interactive strategies, and levels of student engagement on the "BIFT ART SEA STUDIO" WeChat Official Account, this research aims to unveil the mechanisms through which university-specific WeChat Official Accounts influence the socialist values of art students. The findings of this study contribute to a nuanced understanding of the role of social media in higher education and provide empirical insights for the development of informed educational management strategies. In essence, this research addresses existing gaps in the literature, delving into the substantive impact of university-specific WeChat Official Accounts on the socialist values of art students and offering practical recommendations and theoretical guidance for social media operations in higher education institutions

New tumor-targeted nanosized delivery carrier for oligonucleotides: characteristics in vitro and in vivo

Tianyang Zhou1,2, Xin Jia1, Huixiang Li3, Jin Wang3, Hongling Zhang1,2, Youmei A1,2, Zhenzhong Zhang1,21School of Pharmaceutical Sciences, 2Nanotechnology Research Center for Drugs, 3Department of Pathology, Medical School of Zhengzhou University, Zhengzhou, People’s Republic of ChinaBackground: The purpose of this study was to investigate the in vitro and in vivo characteristics of a new tumor-targeted nanosized delivery carrier for antisense oligonucleotide (ASON).Methods: Polyethylenimine (PEI) was used to condense ASON to form nanosized complexes (PEI/ASON), which were then modified using asparagine-glycine-arginine (NGR) peptide to obtain a tumor-targeted nanosized delivery carrier (NGR/PEI/ASON). The conditions required to form PEI/ASON were investigated.Results: A linear correlation between the natural logarithm of the N/P ratio (PEI to ASON) and the zeta potential of the PEI/ASON complexes was found, ranging from 1.5 to 5.0. The pH of the solution strongly influenced the zeta potential of the PEI/ASON complexes. PEI/ASON and NGR/PEI/ASON were stable in RPMI-1640 culture medium in the presence of Dextran 70. Incorporation of ASON into PEI/ASON and NGR/PEI/ASON complexes prevented degradation of ASON by DNase I.Conclusion: Both ASON/PEI and NGR/PEI/ASON complexes enhanced the uptake of ASON by EC9706 cells in vitro. In vivo, NGR/PEI/ASON complexes had the ability to target tumor tissues effectively.Keywords: nanosized delivery system, squamous cell carcinoma, antisense oligonucleotid

The efficacy of upfront craniocerebral radiotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors in patients with epidermal growth factor receptor-positive non-small cell lung cancer with brain metastases

The present study aims to investigate the therapeutic value of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) combined with cranial radiotherapy (RT) in patients with EGFR-positive non-small cell lung cancer (NSCLC) and brain metastases (BMs).MethodologyThis is a retrospective study that involved 213 patients with EGFR-NSCLC and BMs, with the patients divided into two groups: the upfront cranial RT (ucRT) group (n = 96) and the non-ucRT group (n = 117). All patients were administered with osimertinib, and those in the ucRT group also underwent RT. The overall survival (OS), progression-free survival (PFS) and intracranial PFS (IPFS) of the two groups were compared.ResultsThe ucRT group manifested a markedly higher IPFS than the non-ucRT group (29.65 months vs 21.8 months; P < 0.0001). The subgroup analysis revealed that patients with oligometastases (OLOGO-BMs; 1–3 BMs) demonstrated a notably longer OS (44.5 months vs 37.3 months; P < 0.0001), PFS (32.3 months vs 20.8 months; P = 0.6884) and IPFS (37.8 months vs 22.1 months; P < 0.0001) in the ucRT group than in the non-ucRT group. However, for patients with multiple BMs, there was no significant difference in OS (27.3 months vs 34.4 months; P = 0.0710) and PFS (13.7 months vs 13.2 months; P = 0.0516) between the ucRT group and the non-ucRT group; the ucRT group exhibited a higher IPFS (26.4 months vs 21.35 months; P = 0.0028). Cox’s multivariate analysis of patients with OLOGO-BM indicated that the use of ucRT was linked to a better OS (heart rate [HR] = 0.392; 95% confidence interval [CI]: 0.178–0.863; P = 0.020) and PFS (HR = 0.558; 95% CI: 0.316–0.986; P = 0.044).ConclusionUpfront cerebral cranial stereotactic radiosurgery can improve outcomes in EGFR-positive patients with NSCLC and OLOGO-BM. However, for patients with multiple BMs, the preferable strategy may be pre-treatment with EGFR-TKIs

THE EFFECT OF ASTRAGALUS EXTRACTIVE ON ALVEOLAR BONE REBUILDING PROGRESS OF TOOTH EXTRACTED SOCKET OF OVARIECTOMIED RATS

Background: Postmenopausal osteoporosis (PMO) is an estrogen deficiency condition that causes severe loss of bone mass in the vertebrae and long bones. We explored the effect and the possible underlying mechanism of the extracts of Astragalus (AE) on the tooth alveolar bone rebuilding progress of postmenopausal osteoporosis of PMO animal models. Material and methods: The PMO models were acquired by ovariectomy. After 8 weeks the first left maxillary molars of the rats were extracted and AE was administered orally for 8 weeks. Then the histological morphology and the transcription and expression of TGF-β1 and TNF-α in the tooth extracted socket were detected by HE dying, QRT-PCR and ELISA. Results: The results showed that the new bone volume and TGF-β1 was significantly lower in PMO group than the control group and AE group at the observing period. At the same time TNF-α in PMO group was significantly higher than the other two groups. Moreover AE group had no significant differences with the control group in all data at the observing period. Conclusion: AE has positive effect on alveolar bone rebuilding progress of tooth extracted socket of PMO rats. AE also has the potential to enhance the expression of TGF-β1and decrease the expression of TNF-α of the rebuilding tooth extracted socket

JNK Pathway-Associated Phosphatase/DUSP22 Suppresses CD4+ T-Cell Activation and Th1/Th17-Cell Differentiation and Negatively Correlates with Clinical Activity in Inflammatory Bowel Disease

This study aimed to investigate the role of JNK pathway-associated phosphatase (JKAP) in inflammatory bowel disease (IBD). JKAP expression was analyzed in the intestinal mucosa of 81 IBD patients and 25 healthy controls (HCs) by qPCR and immunoblotting. The correlations of JKAP with clinical activity and inflammatory cytokines were performed. JKAP expression before and after infliximab treatment was also measured. CD4+ T cells were isolated from peripheral blood in active IBD patient and HCs and transduced with lentivirus-encoding JKAP (LV-JKAP), anti-JKAP (LV-anti-JKAP), or empty vector (LV-scramble), and JKAP functions on IBD CD4+ T cells were subsequently investigated. JKAP expression was decreased in inflamed mucosa of active IBD patients and was negatively correlated with disease activity [Crohn’s disease activity index (CDAI), Mayo index, C-reactive protein, and erythrocyte sedimentation rate], interleukin-17, and tumor necrosis factor (TNF)-α levels. Anti-TNF-α treatment up-regulated JKAP expression in CD patients, and baseline JKAP expression was elevated in response patients than in failure patients. Transduction of LV-JKAP into CD4+ T cells inhibited the percentages of CD25+ and CD69+ cells and proliferation. Moreover, inhibition of JKAP promotes Th1/Th17 cell differentiation. Our data indicated that the decreased expression of JKAP in intestinal mucosa contributed to the pathogenesis of IBD, through facilitating CD4+ T-cell activation, proliferation, and Th1/Th17-cell differentiation

Properties of tungsten mine waste geopolymeric binder

Tungsten mine waste mud (TMWM) geopolymeric binder is a new cementitious material with a very high early age strength. It is obtained from dehydroxylated mine waste powder mix with minor quantities of calcium hydroxide and activated with NaOH and water-glass solutions. Tests on properties of TMWM binders such as workability, setting time, unrestrained shrinkage, water absorption and static modulus of elasticity were carried out and the results are reported in this paper. This is followed by comparisons with literature related data and a discussion about it. The results showed that current devices use to assess OPC fresh properties are not recommended to evaluate TMWM binders. It has also been found that traditional procedures used to evaluate unrestrained shrinkage may be responsible for misleading results when using those new binders. Water absorption data shows that TMWM has a very compacted structure. Results concerning the static modulus of elasticity are similar to the ones obtained by other authors. However the hypothesis related to modulus of elasticity decrease due to the use of high Al/Si alkali activated mixtures was not confirmed

Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development

Epidermal growth factor receptor pathway substrate clone 15 (Eps15) is a protein implicated in endocytosis, endosomal protein sorting, and cytoskeletal organization. Its role is, however, still unclear, because of reasons including limitations of dominant-negative experiments and apparent redundancy with other endocytic proteins. We generated Drosophila eps15-null mutants and show that Eps15 is required for proper synaptic bouton development and normal levels of synaptic vesicle (SV) endocytosis. Consistent with a role in SV endocytosis, Eps15 moves from the center of synaptic boutons to the periphery in response to synaptic activity. The endocytic protein, Dap160/intersectin, is a major binding partner of Eps15, and eps15 mutants phenotypically resemble dap160 mutants. Analyses of eps15 dap160 double mutants suggest that Eps15 functions in concert with Dap160 during SV endocytosis. Based on these data, we hypothesize that Eps15 and Dap160 promote the efficiency of endocytosis from the plasma membrane by maintaining high concentrations of multiple endocytic proteins, including dynamin, at synapses

Efficient photocatalytic production of hydrogen peroxide using dispersible and photoactive porous polymers

Developing efficient artificial photocatalysts for the biomimetic photocatalytic production of molecular materials, including medicines and clean energy carriers, remains a fundamentally and technologically essential challenge. Hydrogen peroxide is widely used in chemical synthesis, medical disinfection, and clean energy. However, the current industrial production, predominantly by anthraquinone oxidation, suffers from hefty energy penalties and toxic byproducts. Herein, we report the efficient photocatalytic production of hydrogen peroxide by protonation-induced dispersible porous polymers with good charge-carrier transport properties. Significant photocatalytic hydrogen peroxide generation occurs under ambient conditions at an unprecedented rate of 23.7 mmol g–1 h–1 and an apparent quantum efficiency of 11.3% at 450 nm. Combined simulations and spectroscopies indicate that sub-picosecond ultrafast electron “localization” from both free carriers and exciton states at the catalytic reaction centers underlie the remarkable photocatalytic performance of the dispersible porous polymers