Flexible transit routing model considering passengers’ willingness to pay

This paper proposes an alternative flexible transit model with two levels of bus stops, A level and B level. A-level bus stops are fixed, while B-level bus stops are flexible and provide service only when passengers indicate a strong willingness to pay (WTP). This fare structure encourages passengers to choose bus stops with their mobile phones or computers. An optimization model of 0-1 integer-programming is formulated based on whether certain B-level stops can be serviced. With a numerical example, we compare the performance of the proposed traversing method and a tabu search algorithm, both of which are adapted to solve the model. Finally, a real case is provided to evaluate the proposed transit system against comparable systems (e.g., a fixed-route transit system and a taxi service), and the result shows that the flexible transit routing model will help both passengers and bus companies, thus creating a win-win situation

A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency

BackgroundOncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance.ResultsIn reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5-100x more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels.ConclusionThese new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.Peer reviewe

Genome-Wide Meta-Analysis of Five Asian Cohorts Identifies PDGFRA as a Susceptibility Locus for Corneal Astigmatism

Corneal astigmatism refers to refractive abnormalities and irregularities in the curvature of the cornea, and this interferes with light being accurately focused at a single point in the eye. This ametropic condition is highly prevalent, influences visual acuity, and is a highly heritable trait. There is currently a paucity of research in the genetic etiology of corneal astigmatism. Here we report the results from five genome-wide association studies of corneal astigmatism across three Asian populations, with an initial discovery set of 4,254 Chinese and Malay individuals consisting of 2,249 cases and 2,005 controls. Replication was obtained from three surveys comprising of 2,139 Indians, an additional 929 Chinese children, and an independent 397 Chinese family trios. Variants in PDGFRA on chromosome 4q12 (lead SNP: rs7677751, allelic odds ratio = 1.26 (95% CI: 1.16–1.36), Pmeta = 7.87×10−9) were identified to be significantly associated with corneal astigmatism, exhibiting consistent effect sizes across all five cohorts. This highlights the potential role of variants in PDGFRA in the genetic etiology of corneal astigmatism across diverse Asian populations

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Systemic immune-inflammation index predicting chemoradiation resistance and poor outcome in patients with stage III non-small cell lung cancer

Abstract Background There is increasing evidence that the existence of systemic inflammation response is correlated with poor prognosis in several solid tumors. The aim of this retrospective study was to investigate the association between systemic immune-inflammation index (SII) and therapy response and overall survival in patients with stage III non-small cell lung cancer (NSCLC). The prognostic values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were also evaluated. Methods In total, 332 patients with new diagnosis of stage III NSCLC were included in this retrospective analysis. SII was defined as platelet counts × neutrophil counts/lymphocyte counts. Receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off value for SII, NLR, PLR and PNI. Univariate and multivariate survival analysis were performed to identify the factors correlated with overall survival. Results Applying cut-offs of ≥ 660 (SII), ≥ 3.57 (NLR), ≥ 147 (PLR), ≤ 52.95 (PNI), SII ≥ 660 was significantly correlated with worse ECOG PS (< 0.001), higher T stage (< 0.001), advanced clinical stage (p = 0.019), and lower response rate (p = 0.018). In univariate analysis, SII ≥ 660, NLR ≥ 3.57, PLR ≥ 147, and PNI ≤ 52.95 were significantly associated with worse overall survival (p all < 0.001). Patients with SII ≥ 660 had a median overall survival of 10 months, and patients with SII < 660 showed a median overall survival of 30 months. In multivariate analysis only ECOG PS (HR, 1.744; 95% CI 1.158–2.626; p = 0.008), T stage (HR, 1.332; 95% CI 1.032–1.718; p = 0.028), N stage (HR, 1.848; 95% CI 1.113–3.068; p = 0.018), SII (HR, 2.105; 95% CI 1.481–2.741; p < 0.001) and NLR ≥ 3.57 (HR, 1.934; 95% CI 1.448–2.585; p < 0.001) were independently correlated with overall survival. Conclusions This study demonstrates that the SII is an independent prognostic indicator of poor outcomes for patients with stage III NSCLC and is superior to other inflammation-based factors in terms of prognostic ability

GeSn/GaAs hetero-structure by magnetron sputtering

We report high quality GeSn/GaAs heterostructure photodetectors grown by a modified magnetron sputtering system. A metal-semiconductor-metal photoconductor is fabricated to examine the ability of photodetection for GeSn alloy. Then the GeSn/GaAs heterostructure photodetector is first demonstrated with a detectivity of.8\times 10^{9}$ Jones achieved at 1450 nm under an applied reverse voltage bias of -0.1 V, which is comparable to or even better than the GeSn-based photodetectors grown by chemical vapor deposition. The work provides an alternative technique for low cost and large-area fabrication of GeSn based devices.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)This work was supported in part by the A∗Star under Grant SERC 1720700038 and Grant SERC A1883c0002, in part by the Ministry of Education, Singapore, under Grant 2017-T1-002-117(RG 177/17), and in part by the Asian Office of Aerospace Research and Development under Grant FA2386-17-1-0039. (Li Qian and Jinchao Tong contributed equally to this work.) (Corresponding author: Li Qian.

Fufang Xueshuantong for Diabetic Kidney Disease: A Systematic Review and Meta-Analysis

Objective. The objective of this meta-analysis was to systematically assess the efficacy and safety of patented Chinese medicine Fufang Xueshuantong (FFXST) for the treatment of diabetic kidney disease (DKD). Methods. Randomized controlled trials (RCTs) of FFXST for DKD treatment were searched until May 31, 2020, in seven electronic databases: PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, and Chinese Biomedical Literature. The Cochrane risk test from the Cochrane Handbook was used as a bias tool to assess the methodological quality, and Review Manager (RevMan) 5.3 was used to analyze the results. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were used to classify the quality of evidence. Results. Thirteen RCTs involving 1,186 patients were included. The meta-analysis revealed that the efficacy of FFXST in treatment of DKD was significantly superior to that of the control treatment (P=0.0006). The urinary albumin excretion rate (P<0.01), urinary albumin creatinine ratio (P<0.0001), and microalbumin (P<0.0001) were lower in the treatment groups than in the control group. There was also a decrease in low-density lipoprotein cholesterol (P<0.0001), serum triglyceride (P=0.001), and C-reactive protein (P<0.0001) in the treatment groups compared with those in the control group. No significant difference in hemoglobin A1c level (P=0.76) and systolic blood pressure (P=0.34) was noted between the treatment and control groups. Three studies reported adverse events, including dizziness and intolerance. In the other 10 trials, adverse events were not mentioned. Conclusion. FFXST appears to be effective in the treatment of DKD. However, the low methodological quality of the RCTs suggests that larger, better-designed RCTs are required to verify the clinical effectiveness and safety of FFXST

Research on 2041 Cases of High Inpatient Expenditure and Influence Factors during 3 Years in a Single Center

Background: The study was to explore the causes of high inpatient expenditure through analyzing the distribution characteristics as well as the influence factors of high inpatient expenditure cases during 3 years within a Grade-A tertiary hospital through various aspects and multiple angles, thus identifying the major influence factors for high medical expenditure to develop further research. Methods: We retrospectively studied 2041 inpatient cases which cost more than RMB 100,000 Yuan per case in a Grade-A tertiary hospital from 2013 to 2015. We analyzed the compositions of the medical cost to evaluate the major factors that cause the high inpatient expenditure. All the data and materials were collected from medical record system, and the statistical methods included t-test, variance of analysis, and multivariate linear regression. Results: The average cost of the 2,041 cases was RMB 152,173 Yuan for medicines and materials of medical costs, which respectively accounted for 33.03% and 32.32% of the total cost; and the average length of hospital stay was 28.39 days/person. Diseases of skeletal and muscular system, circulatory system, and tumor were the top three disease categories of high inpatient expenditure, which accounted for 39.00%, 33.46%, and 18.03%, respectively. Complications, criticality of the disease, gender of the patients, the occurrence of death, and the excessive length of hospital stay all had great impacts on average medical expenditure, while age, hospital infection, and surgery showed no significant impact on average medical cost. Conclusions: The main factors for high inpatient expenditure included the inadequate use of high-value medicines and materials, lacking cost control measures within the hospital, the excessive length of hospital stay for inpatients, and the unnecessary treatment for the patients