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Most hospitals have financial assistance programs for low-income patients. We use administrative data from Kaiser Permanente to study the effects of financial assistance on health care utilization. Using a regression discontinuity design based on an income threshold for program eligibility, we find that financial assistance increases the likelihood of inpatient, ambulatory, and emergency department encounters by 3.6 pp (59 percent), 13.4 pp (20 percent), and 6.7 pp (53 percent), respectively, though effects dissipate three quarters after program receipt. Financial assistance also increases the detection and management of treatment-sensitive conditions (e.g., drugs treating diabetes), suggesting that financial assistance may increase receipt of high-value care. (JEL G51, I11, I12, I13, I32)

Resveratrol (RES) is a non-flavonoid polyphenol compound that can be involved in follicular development and ovulation. However, the mechanism by which resveratrol regulates the apoptosis of porcine ovarian granulosa cells (POGCs) through long non-coding RNA (lncRNA) is poorly understood. We generated POGCs models of different doses of RES (0, 25, 50, 75, and 100 μM). It was observed that the cell viability was the highest in the 50 μM group, and the highest apoptosis rates were recorded in the 100 μM group. Therefore, a control group (n = 3, 0 μM RES group), a low RES group (n = 3, 50 μM RES group), and a high RES group (n = 3, 100 μM RES group) of POGCs were created for next RNA sequencing. Gene Ontology (GO) indicated that differentially expressed lncRNAs associated with apoptotic process were highly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of lncRNA target genes found that the Wnt signaling pathway and PI3K-Akt signaling pathway were both enriched. Furthermore, we constructed lncRNA-mRNA networks related to Metabolic and Cell Apoptosis, respectively. In the networks, five key-lncRNAs were screened, which may play a significant role in the process of POGCs metabolism and apoptosis. Furthermore, we focused on the function of a lnc-GAM (lncRNA associated with Granulosa cells Apoptosis and Metabolism) and verified that lnc-GAM could influence cell apoptosis in POGCs development by affecting the mRNA expression of apoptosis-related markers, and also affects the secretion of steroid hormones and related genes expression in POGCs cultured in vitro. Our study provides seminal data and important new insights into the regulation of reproductive mechanisms in porcine and other female mammals.

IntroductionTherapeutic drug monitoring (TDM) has been shown to be clinically beneficial for critically ill patients. However, this is a burden for neonates or children with small circulating blood volumes. Here, we aimed to develop and validate a microsampling TDM platform (including dried blood spots (DBS) and capillary microsamples (CMS)) for the simultaneous quantification of vancomycin, meropenem, and linezolid.MethodsPaired DBS and CMS samples were obtained from an intensive care unit (ICU) to evaluate its clinical application. Estimated plasma concentrations (EPC) were calculated from DBS concentrations. Agreement between methods was evaluated using Deming regression and Bland-Altman difference plots.ResultsThe microsampling methods validation showed excellent reliability and compatibility with the analysis of the sample matrix and hematocrit range of the studied population. The DBS and CMS accuracy and precision results were within accepted ranges and samples were stable at room temperature for at least 2 days and 8 h, respectively. Hematocrit had no impact on CMS, but sightly impacted DBS measurements. The CMS and DBS antibiotic concentrations correlated well (r > 0.98). The drug concentration ratio in DBS samples to that in CMS was 1.39 for vancomycin, 1.34 for meropenem, and 0.94 for linezolid. The EPC calculated from the DBS using individual hematocrit ranges presented comparable absolute values for vancomycin (slope: 1.06) and meropenem (slope: 1.04), with a mean of 98% and 99% of the measured CMS concentrations, respectively.DiscussionThis study provides a microsampling TDM platform validated for clinical use for a rapid quantification of three antibiotics and is suitable for real-time TDM-guided personalization of antimicrobial treatment in critically ill children.

Therapeutic drug monitoring (TDM) of antimicrobials is extremely useful in critically ill patients. However, it’s a burden for neonate or children with small circulating blood volume. In the present study, we aimed to develop and validate a microsampling TDM platform (including dried blood spots (DBS) and capillary microsamples (CMS)) for the simultaneous quantification of vancomycin, meropenem and linezolid. Paired DBS and CMS samples were obtained from ICU to evaluate its clinical application. Estimated plasma concentrations (EPC) were calculated from DBS concentrations. Agreement between methods was evaluated using Deming regression and Bland–Altman difference plots. Results for microsampling methods validation showed excellent reliability and compatible with the analysis of sample matrix and hematocrit range of the studied population. DBS and CMS results for accuracy and precision were within accepted ranges, samples were stable at room temperature for at least 2 days and 10h, respectively. Hematocrit has no impact on CMS, but sightly impact on DBS measurement. The CMS and DBS antibiotics concentrations correlated well (r > 0.98). The ratio of the drug concentration in DBS samples to that in CMS was 1.39 for vancomycin ,1.34 for meropenem and 0.94 for linezolid. EPC calculated from DBS using individual hematocrit presented comparable absolute values for vancomycin (slope:1.06) and meropenem(slope:1.04), being in mean 98%,99% of the measured CMS concentrations, respectively. Conclusion: This study provides a microsampling TDM platform validated for clinical use for a rapid quantification of three antibiotics in a small volume of blood and is suitable for real-time TDM-guided personalization of antimicrobial treatment in critically ill children.

Multimodal emotion recognition in conversations (mERC) is an active research topic in natural language processing (NLP), which aims to predict human's emotional states in communications of multiple modalities, e,g., natural language and facial gestures. Innumerable implicit prejudices and preconceptions fill human language and conversations, leading to the question of whether the current data-driven mERC approaches produce a biased error. For example, such approaches may offer higher emotional scores on the utterances by females than males. In addition, the existing debias models mainly focus on gender or race, where multibias mitigation is still an unexplored task in mERC. In this work, we take the first step to solve these issues by proposing a series of approaches to mitigate five typical kinds of bias in textual utterances (i.e., gender, age, race, religion and LGBTQ+) and visual representations (i.e, gender and age), followed by a Multibias-Mitigated and sentiment Knowledge Enriched bi-modal Transformer (MMKET). Comprehensive experimental results show the effectiveness of the proposed model and prove that the debias operation has a great impact on the classification performance for mERC. We hope our study will benefit the development of bias mitigation in mERC and related emotion studies., 10 pages, 5 figures, accepted to NLPCC 2022

The potentially pathogenic species of the genus Vibrio pose a threat to both humans and animals, creating medical burdens and economic losses to the mariculture industry. Improvements in surveillance and diagnosis are needed to successfully manage vibriosis outbreaks. Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) can provide rapid diagnosis and has been widely used in the identification of Vibrio spp. The main weakness of this technology is the limited number of strains and species of Vibrio in the existing commercial database. Here, we develop a new in-house database named PVBase containing 790 main spectra projections (MSP) of ten Vibrio species that come from various regions of China and include abundant clinical and environmental strains. PVBase was validated through a blind test of 65 Vibrio strains. The identification accuracy and scoring of Vibrio strains was greatly improved through the addition of PVBase. Identification accuracy increased from 73.4 to 100%. The number of strains with identification scores above 2.2 increased from 53.1% to 96.9% and 53.1% of strains had an identification score above 2.59. Moreover, perfect discrimination was obtained when using all of the MSPs created for the Vibrio species, even for very closely related species such as V. cholerae, V. albensis, and V. mimicus or V. alginolyticus, V. parahaemolyticus, and V. harveyi. In addition, we used phyloproteomic analysis to study whether there are differences in protein fingerprints of different regions or pathogenic strains. We found that MSP characteristics of Vibrio species were not related to their region or source. With the construction of PVBase, the identification efficiency of potentially pathogenic Vibrio species has been greatly improved, which is an important advance for epidemic prevention and control, and aquaculture disease detection.

With currently available molecular imaging techniques, hepatocellular carcinoma (HCC), a liver cancer with high mortality rates and poor treatment responses, is mostly diagnosed at its late stage. This is largely due to the lack of highly sensitive contrast agents with high liver specificity. Herein, we report a novel bimodal contrast agent molecule CNCI-1 for the effective detection of HCC at its early stage both in vitro and in vivo. The agent has high liver specificity with effective X-ray computed tomography (CT)/near-infrared (NIR) imaging functions. It has been successfully applied to in vivo NIR imaging with high sensitivity and high selectivity to the HCC region of the HepG2 tumor-xenografted mice model and LM3 orthotopic hepatoma mice model. Moreover, the agent was found to be noninvasive and hepatocarcinoma cells preferential. Furthermore, it also enhanced the tumor imaging by revealing the blood vessels nearby for the CT image acquisition in the VX2 orthotopic hepatoma rabbit model. Our design strategy provides a new avenue to develop the medical relevant bimodal contrast agents for diagnosis of HCC at its early stage.

Fang Cheng,1,2 Qiang Li,1,2 Jinglin Wang,1,2 Zhendi Wang,3 Fang Zeng,1,2 Yu Zhang1,2 1Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, People’s Republic of China; 3Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Fang Zeng; Yu ZhangDepartment of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaEmail fancyzeng@126.com; zhangwkp@163.comObjective: Oral sodium bicarbonate is often used to correct acid-base disturbance in patients with chronic kidney disease (CKD). However, there is little evidence on patient-level benign outcomes to support the practice.Methods: We conducted a systematic review and meta-analysis to examine the efficacy and safety of oral sodium bicarbonate in CKD patients. A total of 1853 patients with chronic metabolic acidosis or those with low-normal serum bicarbonate (22– 24 mEq/L) were performed to compare the efficacy and safety of oral sodium bicarbonate in patients with CKD.Results: There was a significant increase in serum bicarbonate level (MD 2.37 mEq/L; 95% CI, 1.03 to 3.72) and slowed the decline in estimated glomerular filtration rate (eGFR) (MD − 4.44 mL/min per 1.73 m2, 95% CI, − 4.92 to − 3.96) compared with the control groups. The sodium bicarbonate lowered T50-time, an indicator of vascular calcification (MD − 20.74 min; 95% CI, − 49.55 to 8.08); however, there was no significant difference between the two groups. In addition, oral sodium bicarbonate dramatically reduced systolic blood pressure (MD − 2.97 mmHg; 95% CI, − 5.04 to − 0.90) and diastolic blood pressure (MD − 1.26 mmHg; 95% CI, − 2.33 to − 0.19). There were no statistically significant body weight, urine pH and mean mid-arm muscle circumference.Conclusion: Treatment of metabolic acidosis with sodium bicarbonate may slow the decline rate of kidney function and potentially significantly improve vascular endothelial function in patients with CKD.Prospero Registration Number: CRD42020207185.Keywords: chronic kidney disease, metabolic acidosis, sodium bicarbonate, kidney function, cardiovascular risk

Job shop scheduling problem (JSP) is one of the most difficult optimization problems in manufacturing industry, and flexible job shop scheduling problem (FJSP) is an extension of the classical JSP, which further challenges the algorithm performance. In FJSP, a machine should be selected for each process from a given set, which introduces another decision element within the job path, making FJSP be more difficult than traditional JSP. In this paper, a variant of grasshopper optimization algorithm (GOA) named dynamic opposite learning assisted GOA (DOLGOA) is proposed to solve FJSP. The recently proposed dynamic opposite learning (DOL) strategy adopts the asymmetric search space to improve the exploitation ability of the algorithm and increase the possibility of finding the global optimum. Various popular benchmarks from CEC 2014 and FJSP are used to evaluate the performance of DOLGOA. Numerical results with comparisons of other classic algorithms show that DOLGOA gets obvious improvement for solving global optimization problems and is well-performed when solving FJSP.

Shujie Wang1,*, Erhei Dai2,*, Xiaoyuan Jiang3, Lijun Zeng3, Qiaoxiang Cheng2,3, Ying Jing3, Lingfei Hu3, Zhe Yin3, Bo Gao3, Jinglin Wang3, Guixin Duan4, Xuehui Cai1, Dongsheng Zhou3 1State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, People’s Republic of China; 2Department of Laboratory Medicine, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei 050021, People’s Republic of China; 3State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, People’s Republic of China; 4Animal Science and Technology College, Heilongjiang Bayi Agricultural University, Daqing 163000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongsheng ZhouState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, No. 20 Dongdajie Street, Fengtai District, Beijing 100071, People’s Republic of ChinaTel +86 106 694 8503Email dongshengzhou1977@gmail.comXuehui CaiState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 678 Haping Road, Xiangfang District, Harbin 150069, People’s Republic of ChinaTel +86 4 515 105 1766Email aci139@sina.comBackground: Multiple incompatibility (Inc) groups of plasmids have been identified in Enterobacteriaceae species, but there are still quite a few sequenced plasmids that could not be assigned to any known Inc groups.Methods: One IncFIIpKF727591β plasmid p205880-qnrS and two IncpKPHS1 plasmids p11219-CTXM and p205880-NR1 were fully sequenced in this work. Detailed genomic comparison was applied to all available sequenced plasmids of IncFIIpKF727591 or IncpKPHS1 group.Results: p205880-qnrS carried a novel transposon Tn6396, which was an ISKpn19-compsite transposon and represented a prototype transposable element carrying a minimum core qnrS1 module. p11219-CTXM harbored a novel transposon Tn6559, which was generated from integration of a truncated IS903D–blaCTX-M-14–ISEcp1 unit into the Tn3-family cryptic unit transposon Tn1722. Two Inc groups, IncFIIpKF727591 and IncpKPHS1, of plasmids from Enterobacteriaceae species were proposed, and IncFIIpKF727591 was further grouped into two subgroups IncFIIpKF727591α and IncFIIpKF727591β. Each of the 11 IncFIIpKF727591 plasmids carried multiple accessory modules including at least one resistance module, and the relatively small IncFIIpKF727591 backbones could acquire a wealth of foreign genetic contents. The modular structures of plasmid backbones were conserved within each of IncFIIpKF727591α and IncFIIpKF727591β subgroups but dramatically different, although with similar gene organizations, between these two subgroups. The IncpKPHS1 backbones were conserved with respect to modular structures, and only four of the 14 IncpKPHS1 plasmids carried accessory modules, two of which contained resistance genes.Conclusion: A genomic comparison of sequenced IncpKPHS1 or IncFIIpKF727591 plasmids provides insights into modular differences and genetic diversification of these plasmids, some of which carries antimicrobial resistance genes.Keywords: plasmids, IncFIIpKF727591, IncpKPHS1, Tn6396, Tn6559

Diffusion plays a critical role in establishing functional bio/solid soft interfaces for bioassays, biosensors, and biofuel cells. An understanding of micro-diffusion near the interface is significant for developing high-performance bioassays, biosensors, and biofuel cells. Herein, we explored micro-diffusion behavior at different temperature gaps in microfluidic chip and enzyme-linked immunosorbent assay (ELISA) microplates. It exhibited that temperature gap could distinctly promote directional diffusion of molecules in microfluidic chip from high concentration zone to low concentration zone. In addition, experimental results of specially designed ELISA also partly confirmed that the temperature gap could effectively improve the performance of ELISA by 54.5%. In compared with conventional ELISA, the as-prepared temperature-gap functional module in microfluidic chip has obvious advantages of miniaturization, integration, customization, and low cost. All in all, the current work indicates that temperature-gap function has great potential in biomedical detection, food safety, and so on. It can be utilized to develop novel biological detection approaches and related instruments or microfluidic chips.

Epsilon-toxin (ETX) is produced by types B and D strains of Clostridium perfringens, which cause fatal enterotoxaemia in sheep, goats and cattle. Previous studies showed that only a restricted number of cell lines are sensitive to ETX and ETX-induced hemolysis has not previously been reported. In this study, the hemolytic ability of ETX was examined using erythrocytes from 10 species including murine, rabbit, sheep, monkey and human. We found that ETX caused hemolysis in human erythrocytes (HC50 = 0.2 μM) but not erythrocytes from the other test species. Moreover, the mechanism of ETX-induced hemolysis was further explored. Recent studies showed that some bacterial toxins induce hemolysis through purinergic receptor (P2) activation. Hence, the function of purinergic receptors in ETX-induced hemolysis was tested, and we found that the non-selective P2 receptor antagonists PPADS inhibited ETX-induced lysis of human erythrocytes in a concentration-dependent manner, indicating that ETX-induced hemolysis requires activation of purinergic receptors. P2 receptors comprise seven P2X (P2X1–7) and eight P2Y (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11–P2Y14) receptor subtypes. The pattern of responsiveness to more selective P2-antagonists implies that both P2Y13 and P2X7 receptors are involved in ETX-induced hemolysis in human species. Furthermore, we demonstrated that extracellular ATP is likely not involved in ETX-induced hemolysis and the activation of P2 receptors. These findings clarified the mechanism of ETX-induced hemolysis and provided new insight into the activities and ETX mode of action.

Purpose. To investigate the efficacy of XingZhi-YiNao (XZYN) granules and hyperbaric oxygenation (HBO) for cognition and motor dysfunction in patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods. Eighty-nine patients with DEACMP were randomly divided into control group (n=19), HBO group (n=32), and XZYN group (n=38). All patients received conventional treatment. HBO group received HBO therapy once daily. XZYN group received extra XZYN granules plus HBO treatment. The related indexes including activity of daily living (ADL) scale, Montreal cognitive assessment (MoCA) scale, and mini mental state examination (MMSE) scale were measured. Cerebral white matter injury, age related white matter changes (ARWMC) scale, and the amplitude and latency of P300 were assessed. Results. Compared with control group, the neurological function scores of ADL, MoCA, and MMSE in HBO and XZYN groups were significantly improved, the impairment degree of brain white matter and cognition function were obviously alleviated, the latencies of P300 were significantly shortened, and the amplitudes of P300 were evidently increased (P<0.05). Treatment efficacy of XZYN group was superior to that of HBO group (P<0.05). Conclusion. Combined XZYN granules and HBO can significantly improve cognition and motor functions in patients with DEACMP.

A previous investigation showed that MX10 virus, recently isolated in China, belongs to the Oriental-Australian (O/A) genotype of Sindbis virus (SINV) (Wang Jinglin, 2011, ATMH). Similar to the MRE16 isolate, the prototype O/A genotype of SINV, two derivate viruses with obviously different plaque morphologies were derived from MX10 virus, which were accordingly denoted as MX10-LP and MX10-SP. MX10-LP virus exhibited higher neurovirulence in neonatal mice than MX10-SP virus. Analysis of the complete genome revealed seven nucleotide differences between MX10-LP and MX10-SP. Compared with MRE16 virus, MRE16SP virus has a deletion of 30 aa in the E2 gene (200-229), which has been shown to be the molecular basis for the different plaque morphology. However, the MX10-SP virus did not have the 30-amino-acid deletion in the E2 gene. These results demonstrate that the molecular basis for the different plaque morphology of MX10 virus, the first strain of the O/A genotype of SINV isolated from China, is different from that of the prototype MRE16 virus.

Nowadays, most of multimedia information processing application systems are still realized in the monolithic and stove-pipe manner. This design pattern makes building and maintaining such multimedia systems intractable, costly and time-consumed. As a new style software design model, Service Oriented Architecture promises a more agile solution for developing large-scale Internet-based applications and has been widely accepted by the academic community and industries. However, the current service invoking method: SOAP does not apply to the multimedia area directly. This paper intends to solve this problem. Aiming at it, this paper proposes a new remote object access protocol based on SOAP which defines the correlative message format and the interaction model between the service and its client. According to the proposed approach, a service-composition-based prototype multimedia information processing system is constructed. Through the experiment, we prove that the performance of our method is excellent compared with other methods.