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BackgroundOpioid overdose-related deaths have increased dramatically in recent years. Combating the opioid epidemic requires better understanding of the epidemiology of opioid poisoning (OP) and opioid use disorder (OUD). ObjectiveWe aimed to discover geospatial patterns in nonmedical opioid use and its correlations with demographic features related to despair and economic hardship, most notably the US presidential voting patterns in 2016 at census tract level in New York State. MethodsThis cross-sectional analysis used data from New York Statewide Planning and Research Cooperative System claims data and the presidential voting results of 2016 in New York State from the Harvard Election Data Archive. We included 63,958 patients who had at least one OUD diagnosis between 2010 and 2016 and 36,004 patients with at least one OP diagnosis between 2012 and 2016. Geospatial mappings were created to compare areas of New York in OUD rates and presidential voting patterns. A multiple regression model examines the extent that certain factors explain OUD rate variation. ResultsSeveral areas shared similar patterns of OUD rates and Republican vote: census tracts in western New York, central New York, and Suffolk County. The correlation between OUD rates and the Republican vote was .38 (P

ObjectiveTo explore the exposure-lag-response relationship between temperature and risk of varicella incidence,and to provide a scientific evidence for early warning and precise prevention and control of varicella epidemic.MethodsDaily varicella cases and daily meteorological data were collected in Minhang District, Shanghai from 2010 to 2022. A distributed lag nonlinear model was used to determine the exposure-lag-response relationship between temperature and risk of varicella incidence. Furthermore, effect of temperature on the incidence risk was determined across different age groups.ResultsIn 2010‒2022, the total number of notified varicella cases was 26 207 in Minhang District, with the highest incidence in the group aged 3‒14 years (50.35%). The seasonal pattern of daily varicella cases showed a double peak. The large peak was found in November and December, followed by a smaller peak in May and June. Moreover, the distributed lag nonlinear model showed a unimodal curve in the relationship between temperature and varicella incidence. The RR value reached its maximum peak of 1.90 (95%CI: 1.25‒2.87) at 7 ℃. A reverse U-shape was found in the lag-response curves between temperature and varicella incidence. Furthermore, the effect of temperature on the varicella incidence showed a unimodal pattern in the varicella cases aged 3‒14 years. The RR value reached its peak at 11 ℃ (RR=2.89, 95%CI: 1.33‒6.24). In contrast, the effect of temperature on the varicella incidence in the cases aged 15 years and above showed a unimodal pattern, with RR value reaching the peak at 5 ℃ (RR=2.14, 95%CI: 1.33‒3.44).ConclusionThe unimodal curve is found in the relationship between temperature and varicella incidence. Low temperature is associated with increased risk of varicella incidence. Children aged 3‒14 years are more susceptible to the effect of temperature on the varicella incidence.

In order to better understand the hydrolysis and pyrolysis process of polylactic acid (PLA), we carried out in-situ experiments by observing the decomposition process of PLA at high temperature (up to 285[degrees]C) in both aqueous and anhydrous environments through fused silica capillary reactor (FSCR) combined with Raman spectroscopy analysis. By analyzing the strength change of characteristic peaks of PLA with increasing temperature, it was found that the initial melting temperature of PLA, in both the hydrolysis and pyrolysis processes, is around 170[degrees]C. Based on infrared spectroscopy analysis, it was found that the products of PLA pyrolysis are C[O.sub.2], C[H.sub.3]CH=C=O, and C[H.sub.3]CHO, indicating that the pyrolysis process of PLA results from a free radical reaction. By comparing the Raman peak area ratios at different peak positions at different temperatures, it was found that the hydrolysis process of PLA mainly involves breaking the COC and CCO bonds of PLA, producing lactic acid, ethanol, C[O.sub.2], and [H.sub.2]O. The hydrolysis reaction rate of PLA increases with the increase of temperature and exhibits a slow-fast-slow S-shaped trend. The kinetic process of hydrolysis of PLA was well described using the Logistic model. The activation energy for the hydrolysis (Q) of PLA is 18.1 kcal*[mol.sup.-1] in the temperature range of 250-285[degrees]C. The results of this study provide important insights and crucial parameters for the production and application of PLA. KEYWORDS activation energy, fused silica capillary reactor, hydrolysis, polylactic acid, pyrolysis, Raman spectrum Highlights * Determined the melting temperature of PLA by in-situ experiments. * For the hydrolysis process of PLA, the reaction rate and activation energy were quantified by fitting experimental data. * Gained valuable insights into the hydrolysis and pyrolysis mechanisms of PLA., 1 | INTRODUCTION With growing concern for sustainable development, there has been an increased focus on biodegradable polymers as alternatives to synthetic plastics. Polylactic acid (PLA), typically derived from agricultural [...]

AIM: To address the challenges of data labeling difficulties, data privacy, and necessary large amount of labeled data for deep learning methods in diabetic retinopathy (DR) identification, the aim of this study is to develop a source-free domain adaptation (SFDA) method for efficient and effective DR identification from unlabeled data. METHODS: A multi-SFDA method was proposed for DR identification. This method integrates multiple source models, which are trained from the same source domain, to generate synthetic pseudo labels for the unlabeled target domain. Besides, a softmax-consistence minimization term is utilized to minimize the intra-class distances between the source and target domains and maximize the inter-class distances. Validation is performed using three color fundus photograph datasets (APTOS2019, DDR, and EyePACS). RESULTS: The proposed model was evaluated and provided promising results with respectively 0.8917 and 0.9795 F1-scores on referable and normal/abnormal DR identification tasks. It demonstrated effective DR identification through minimizing intra-class distances and maximizing inter-class distances between source and target domains. CONCLUSION: The multi-SFDA method provides an effective approach to overcome the challenges in DR identification. The method not only addresses difficulties in data labeling and privacy issues, but also reduces the need for large amounts of labeled data required by deep learning methods, making it a practical tool for early detection and preservation of vision in diabetic patients.

Abstract Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo.

Abstract The neutrinophilic two Higgs doublet model is one of the simplest models to explain the origin of tiny Dirac neutrino masses. This model introduces a new Higgs doublet with eV scale VEV to naturally generate the tiny neutrino masses. Depending on the same Yukawa coupling, the neutrino oscillation patterns can be probed with the dilepton signature from the decay of charged scalar $$H^\pm $$ H ± . For example, the normal hierarchy predicts BR $$(H^+\rightarrow e^+\nu )\ll $$ ( H + → e + ν ) ≪ BR $$(H^+\rightarrow \mu ^+\nu )\approx $$ ( H + → μ + ν ) ≈ BR $$(H^+\rightarrow \tau ^+\nu )\simeq 0.5$$ ( H + → τ + ν ) ≃ 0.5 when the lightest neutrino mass is below 0.01 eV, while the inverted hierarchy predicts BR $$(H^+\rightarrow e^+\nu )/2\simeq $$ ( H + → e + ν ) / 2 ≃ BR $$(H^+\rightarrow \mu ^+\nu )\simeq $$ ( H + → μ + ν ) ≃ BR $$(H^+\rightarrow \tau ^+\nu )\simeq 0.25$$ ( H + → τ + ν ) ≃ 0.25 . By precise measurement of BR $$(H^+\rightarrow \ell ^+\nu )$$ ( H + → ℓ + ν ) , we are hopefully to probe the lightest neutrino mass and the atmospheric mixing angle $$\theta _{23}$$ θ 23 . Through the detailed simulation of the dilepton signature and corresponding backgrounds, we find that the 3 TeV CLIC could discover $$M_{H^+}\lesssim 1220$$ M H + ≲ 1220 GeV for NH and $$M_{H^+}\lesssim 1280$$ M H + ≲ 1280 GeV for IH. Meanwhile, the future 100 TeV FCC-hh collider could probe $$M_{H^+}\lesssim 1810$$ M H + ≲ 1810 GeV for NH and $$M_{H^+}\lesssim 2060$$ M H + ≲ 2060 GeV for IH.

ABSTRACT Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = −0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = −0.4451) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = −0.3868) was negatively correlated (r = −0.4, 95% CI: −0.7 to −0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.

Abstract Background There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. Methods BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student’s t-test. Results The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. Conclusions Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells.

Abstract Background To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. Methods A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. Results The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson’s trichrome staining results (r = 0.687, P

Background Based on the particularity of children and the adjustment of birth policy in recent years, the development of pediatrician team is becoming more and more important. However, most of the current studies on the shortage of pediatricians are qualitative, lacking of quantitative researches. Objective To establish a multi-perspective demand forecasting model, comprehensively analyze the shortage of pediatricians in Jiangsu, and provide reference for promoting the development of children's health during the "14th Five-Year Plan" period in Jiangsu Province and accelerating the construction of pediatrician team in the new era. Methods According to the relevant indicators of pediatric medical services in Jiangsu Province in 2018 obtained from "2018 Jiangsu Provincial Health Service Survey and Analysis Report", and the basic data of pediatrics in each city of Jiangsu Province was obtained from "2019 Jiangsu Provincial Statistical Yearbook" and the database of the Jiangsu Provincial Health Statistics Information Center. Using SPSS 24.0 analysis software, a multi-perspective demand forecasting model was developed from the perspectives of supply and demand, and a comprehensive analysis of the number of pediatrician shortage in Jiangsu Province was performed. Results The proportion of female physicians in the pediatrician team in Jiangsu is relatively high. The young and middle pediatricians occupy a leading position. The academic backgrounds of the pediatricians are mainly undergraduate. The professional title structure is much reasonable. Most of pediatricians have been working for over 20 years. Combined with the basic situation of the pediatrician team in Jiangsu and the perspective of supply and demand, the shortage number of pediatricians in Jiangsu Province was 18 300 and the average shortage number of physicians in 13 cities was 1 500. Conclusion There is an overdemand of resources for pediatric care and a high workload for physicians with an imbalance in the gender and title structure of the workforce; the special practice environment leads to increased practice risk. It is necessary to strengthen the personnel training and introduction policies, consolidate the professional foundation of personnel, and explore a new management model of "Internet + medical consortium".