Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the Interobserver Agreement in Computer-Aided Radiologic Tumor Measurement and Evaluation of Tumor Response

The accurate, objective, and reproducible evaluation of tumor response to therapy is indispensable in clinical trials. This study aimed at investigating the reliability and reproducibility of a computer-aided contouring (CAC) tool in tumor measurements and its impact on evaluation of tumor response in terms of RECIST 1.1 criteria. A total of 200 cancer patients were retrospectively collected in this study, which were randomly divided into two sets of 100 patients for experiential learning and testing. A total of 744 target lesions were identified by a senior radiologist in distinctive body parts, of which 278 lesions were in data set 1 (learning set) and 466 lesions were in data set 2 (testing set). Five image analysts were respectively instructed to measure lesion diameter using manual and CAC tools in data set 1 and subsequently tested in data set 2. The interobserver variability of tumor measurements was validated by using the coefficient of variance (CV), the Pearson correlation coefficient (PCC), and the interobserver correlation coefficient (ICC). We verified that the mean CV of manual measurement remained constant between the learning and testing data sets (0.33 vs. 0.32, p = 0.490), whereas it decreased for the CAC measurements after learning (0.24 vs. 0.19, p < 0.001). The interobserver measurements with good agreement (CV < 0.20) were 29.9% (manual) vs. 49.0% (CAC) in the learning set (p < 0.001) and 30.9% (manual) vs. 64.4% (CAC) in the testing set (p < 0.001). The mean PCCs were 0.56 ± 0.11 mm (manual) vs. 0.69 ± 0.10 mm (CAC) in the learning set (p = 0.013) and 0.73 ± 0.07 mm (manual) vs. 0.84 ± 0.03 mm (CAC) in the testing set (p < 0.001). ICCs were 0.633 (manual) vs. 0.698 (CAC) in the learning set (p < 0.001) and 0.716 (manual) vs. 0.824 (CAC) in the testing set (p < 0.001). The Fleiss’ kappa analysis revealed that the overall agreement was 58.7% (manual) vs. 58.9% (CAC) in the learning set and 62.9% (manual) vs. 74.5% (CAC) in the testing set. The 80% agreement of tumor response evaluation was 55.0% (manual) vs. 66.0% in the learning set and 60.6% (manual) vs. 79.7% (CAC) in the testing set. In conclusion, CAC can reduce the interobserver variability of radiological tumor measurements and thus improve the agreement of imaging evaluation of tumor response.
Distribution, Diversity and Roles of CRISPR-Cas Systems in Human and Animal Pathogenic Streptococci

Streptococci form a wide group of bacteria and are involved in both human and animal pathologies. Among pathogenic isolates, differences have been highlighted especially concerning their adaptation and virulence profiles. CRISPR-Cas systems have been identified in bacteria and many streptococci harbor one or more systems, particularly subtypes I-C, II-A, and III-A. Since the demonstration that CRISPR-Cas act as an adaptive immune system in Streptococcus thermophilus, a lactic bacteria, the diversity and role of CRISPR-Cas were extended to many germs and functions were enlarged. Among those, the genome editing tool based on the properties of Cas endonucleases is used worldwide, and the recent attribution of the Nobel Prize illustrates the importance of this tool in the scientific world. Another application is CRISPR loci analysis, which allows to easily characterize isolates in order to understand the interactions of bacteria with their environment and visualize species evolution. In this review, we focused on the distribution, diversity and roles of CRISPR-Cas systems in the main pathogenic streptococci.
Development and Prospect of Compressive Sensing

Compressive Sensing(CS) is a new developed theoretical framework for information acquisition and processing,which is based on matrix analysis,statistical probability theory,topological geometry,optimization and opsearch,functional analysis and so on.The high-dimensional signals can be recovered from the low-dimensional and sub-Nyquist sampling data based on the compressibility of signals.It not only inspires us to survey the linear problem again,but also enriches the optimization approaches for signal recovery to promote the combination of mathematics with engineering application.Nowadays the researches on compressive sensing have developed from the earlier concept understanding,numerical simulation,principle verification,and primary system designation,to the deeper researches on theory,development and application of practical system.In this paper,we introduce the basic idea of compressive sensing,and the development history,current and future challenges.
Case Report: A 91-Year-Old Patient With Non-Small Cell Lung Cancer Harboring MET Y1003S Point Mutation

Background The Y1003S point mutation in exon 14 of mesenchymal-epithelial transition (MET) is a rare mutation that can lead to oncogenic transformation. Few data are available on the characteristics of this mutation. This report presents an elderly patient with non-small cell lung cancer (NSCLC) and a Y1003S mutation in MET detected by next-generation sequencing (NGS). Case Report In October 2020, a 91-year-old male was admitted to the Department of Respiratory and Critical Care Medicine, Ruijin Hospital because of an increased carcinoembryonic antigen. Imaging revealed highly suspicious lesions in the right upper lobe of the lung, right apex, and left upper lobe with traction of the adjacent pleura. The patient was histologically confirmed as having adenocarcinoma and the MET Y1003S mutation was detected by the NGS subsequently. After evaluation, the patient started crizotinib treatment in December 2020. In the first assessment of tumor response, a chest CT scan in January 2021 showed a partial response. The patient experienced a pulmonary embolism and an abnormal liver function during the treatment and recovered after symptomatic treatment. He maintained a partial response in the last available assessment in July 2021, with the right upper lung lesion being 26 × 9 mm. Conclusion The MET Y1003S mutation was detected in this case, and the patient achieved a partial response using crizotinib. This case highlighted the role of NGS in detecting a rare mutation. Successful remission of complications in such an elderly patient necessitates careful and timely management.
Sleep Patterns, Genetic Susceptibility, and Incident Chronic Kidney Disease: A Prospective Study of 370 671 Participants

Objectives Unhealthy sleep behaviors may be potential risk factors for chronic kidney disease (CKD). We aimed to examine the associations of combined sleep patterns and genetic susceptibility with incident CKD. Methods This large-scale prospective cohort study included 370,671 participants without CKD at baseline (2006–2010) in UK Biobank data. Five sleep behaviors were made up of sleep duration, insomnia, snoring, chronotype, and daytime sleepiness according to questionnaire. Overall sleep patterns by summing the five scores were created. Weighted genetic risk score of kidney function was calculated. Incident CKD was recorded from death register, primary care, and hospital inpatient records. A subset of 41,130 individuals who participated both the initial assessment visit and follow-up visit (2012+) was also used. Results During a median follow-up of 10.6 years (about 3.9 million person-years), we documented 6,365 patients with incident CKD. In five sleep behaviors, sleep 7–8 h/day, free of insomnia and no frequent daytime sleepiness were independently associated with incident CKD, with a 12% (95%CI 7–16), 9% (3–14), 13% (9–18) lower risk, respectively. Compared to those with a sleep score of 0–1, participants with a score of 5 had a 21% (10–31%) lower risk of CKD. 17.1% of CKD in this cohort could be attributed to total poor sleep pattern. Participants with high genetic risk and intermediate or poor sleep pattern showed the highest risk of CKD (OR = 2.58, 95%CI 2.24–2.96; OR = 2.59, 95%CI 2.02–3.32, respectively), although there was no significant interaction between sleep patterns and genetic risk categories. Among individuals who participated both the initial assessment visit and follow-up visit, we found that the association between amelioration of sleep pattern and risk of CKD was significant after fully adjustment (OR = 0.60, 95%CI 0.36–0.99), compared with group of stable sleep pattern. Conclusion In this large prospective study, participants with a healthy sleep pattern was associated with a significant reduction of incident CKD risk no matter they had a high, intermediate, or low genetic risk.
RNA-Sequencing Analysis of the Spleen and Gill of Takifugu rubripes in Response to Vibrio harveyi Infection

Takifugu rubripes is commonly subjected to the disease-causing bacterium, Vibrio harveyi. However, the mechanism involved in the immune response of T. rubripes to V. harveyi infection is unclear. We conducted a transcriptomic analysis of the spleen and gill from T. rubripes infected with V. harveyi. We obtained 60,981,357 and 60,760,550 clean reads from the control and infected spleens, and 57,407,586 and 57,536,651 clean reads from the control and infected gills, respectively. We also identified 1,560 and 1,213 differentially expressed genes in the spleen and gill, respectively. Gene ontology analysis revealed that the most enriched biological process in both the spleen and gill was “immune response”. The most enriched Kyoto Encyclopedia of Genes and Genomes immune response–related pathways were the NOD-like receptor signaling pathway in the spleen and cytokine–cytokine receptor interaction in the gill. We found 10 candidate immune-related genes in the spleen and gill. These putative immune pathways and candidate genes will provide insight into the immune response mechanisms of T. rubripes against V. harveyi.
Peptide-Based Vaccines for Tuberculosis

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. As a result of the coronavirus disease 2019 (COVID-19) pandemic, the global TB mortality rate in 2020 is rising, making TB prevention and control more challenging. Vaccination has been considered the best approach to reduce the TB burden. Unfortunately, BCG, the only TB vaccine currently approved for use, offers some protection against childhood TB but is less effective in adults. Therefore, it is urgent to develop new TB vaccines that are more effective than BCG. Accumulating data indicated that peptides or epitopes play essential roles in bridging innate and adaptive immunity and triggering adaptive immunity. Furthermore, innovations in bioinformatics, immunoinformatics, synthetic technologies, new materials, and transgenic animal models have put wings on the research of peptide-based vaccines for TB. Hence, this review seeks to give an overview of current tools that can be used to design a peptide-based vaccine, the research status of peptide-based vaccines for TB, protein-based bacterial vaccine delivery systems, and animal models for the peptide-based vaccines. These explorations will provide approaches and strategies for developing safer and more effective peptide-based vaccines and contribute to achieving the WHO’s End TB Strategy.
The Effect of Mentoring on Undergraduate Mentors: A Systematic Review of the Literature

Multiple meta-analyses and systematic reviews have been conducted to evaluate methodological rigor in research on the effect that mentoring has on the mentee. However, little reliable information exists regarding the effect of mentoring on the mentor. As such, we conducted a systematic review of the literature focused on such an effect (if any) within the fields of science, technology, engineering, and mathematics (STEM), aiming to better understand the quality of the research that has been conducted. We focused on undergraduate or post-secondary students as mentors for near-peers and/or youth. This review functions to identify commonalities and disparities of the mentoring program and research components and further promote methodological rigor on the subject by providing a more consistent description of the metrics utilized across studies. We analyzed articles from 2013 to 2020 to determine the features of undergraduate mentor programs and research, the methodological rigor of research applied, and compared them to prior research of this nature. In total, 80 eligible articles were identified through Cronbach’s UTOS framework and evaluated. Our key findings were that nearly all studies employed non-experimental designs, most with solely qualitative measurements and all lacked a full description of program components and/or experimental design, including theoretical framework. Overall, we identified the following best practice suggestions for future research on the effect of mentoring on mentors, specifically: the employment of longitudinal and exploratory mixed methods designs, utilizing sequential collection, and experimental descriptions nested within a theoretical framework.
White Dwarfs as Physics Laboratories: Lights and Shadows

The evolution of white dwarfs is essentially a gravothermal process of cooling in which the basic ingredients for predicting their evolution are well identified, although not always well understood. There are two independent ways to test the cooling rate. One is the luminosity function of the white dwarf population, and another is the secular drift of the period of pulsation of those individuals that experience variations. Both scenarios are sensitive to the cooling or heating time scales, for which reason, the inclusion of any additional source or sink of energy will modify these properties and will allow to set bounds to these perturbations. These studies also require complete and statistical significant samples for which current large data surveys are providing an unprecedented wealth of information. In this paper we review how these techniques are applied to several cases like the secular drift of the Newton gravitational constant, neutrino magnetic moments, axions and weakly interacting massive particles (WIMPS).
Noninvasive Aortic Ultrafast Pulse Wave Velocity Associated With Framingham Risk Model: in vivo Feasibility Study

Background Aortic pulse wave velocity (PWV) enables the direct assessment of aortic stiffness, which is an independent risk factor of cardiovascular (CV) events. The aim of this study is to evaluate the association between aortic PWV and CV risk model classified into three groups based on the Framingham risk score (FRS), i.e., low-risk (<10%), intermediate-risk (10~20%) and high-risk (>20%). Methods To noninvasively estimate local PWV in an abdominal aorta, a high-spatiotemporal resolution PWV measurement method (>1 kHz) based on wide field-of-view ultrafast curved array imaging (ufcPWV) is proposed. In the ufcPWV measurement, a new aortic wall motion tracking algorithm based on adaptive reference frame update is performed to compensate errors from temporally accumulated out-of-plane motion. In addition, an aortic pressure waveform is simultaneously measured by applanation tonometry, and a theoretical PWV based on the Bramwell-Hill model (bhPWV) is derived. A total of 69 subjects (aged 23–86 years) according to the CV risk model were enrolled and examined with abdominal ultrasound scan. Results The ufcPWV was significantly correlated with bhPWV (r = 0.847, p < 0.01), and it showed a statistically significant difference between low- and intermediate-risk groups (5.3 ± 1.1 vs. 8.3 ± 3.1 m/s, p < 0.01), and low- and high-risk groups (5.3 ± 1.1 vs. 10.8 ± 2.5 m/s, p < 0.01) while there is no significant difference between intermediate- and high-risk groups (8.3 ± 3.1 vs. 10.8 ± 2.5 m/s, p = 0.121). Moreover, it showed a significant difference between two evaluation groups [low- (<10%) vs. higher-risk group (≥10%)] (5.3 ± 1.1 vs. 9.4 ± 3.1 m/s, p < 0.01) when the intermediate- and high-risk groups were merged into a higher-risk group. Conclusion This feasibility study based on CV risk model demonstrated that the aortic ufcPWV measurement has the potential to be a new approach to overcome the limitations of conventional systemic measurement methods in the assessment of aortic stiffness.
Safety of Neoadjuvant Immunotherapy in Resectable Cancers: A Meta-Analysis

Background Neoadjuvant immunotherapy has preliminarily been effective in multiple resectable cancers. However, its safety is still largely unknown. Methods A systematic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library up to February 28th, 2021. Pooled incidence and risk ratio (RR) of adverse events were calculated using the R software. Results Twenty-eight studies involving 2863 patients were included. First, the incidence for all-grade treatment-related adverse events (trAEs) was 94% (95% CI, 81%-98%), with 43% (95% CI, 24%-64%) for high-grade trAEs. For different treatment groups, neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy was associated with a higher incidence of all-grade [99% (95% CI, 98%-99%) vs. 76% (95% CI 47%-92%); P < 0.001] and high-grade [80% (58%-92%) vs. 15% (9%-24%); P < 0.001] trAEs compared with neoadjuvant ICIs alone. The most common high-grade trAEs were lipase increased (5%; 95% CI, 2%-10%), colitis (3%; 95% CI, 0-7%) and transaminitis (3%; 95% CI, 0-7%) for neoadjuvant ICIs, and neutropenia (53%; 95% CI, 31%-74%), anemia (8%; 95% CI, 3%-15%) and AST increased (4%; 95% CI, 2%-7%) for neoadjuvant ICIs plus chemotherapy. Furthermore, the incidence rates of progressive disease while on treatment, treatment-related surgical delays and deaths were 6% (95% CI, 4%-10%), 3.2% (12 of 377 patients) and 0.47% (5 of 1075 patients), respectively. Conclusion Compared with neoadjuvant ICIs alone, neoadjuvant ICIs plus chemotherapy had a higher incidence of trAEs. In addition, neoadjuvant immunotherapy had a low rate of progressive diseases, surgical delays and deaths.
Genetic Determinants of Visit-to-Visit Lipid Variability: Genome-Wide Association Study in Statin-Naïve Korean Population

Background and Aim There is a growing evidence that fluctuation in lipid profiles is important in cardiovascular outcomes. We aimed to identify single nucleotide polymorphism (SNP) variants associated with low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) variability in statin-naïve Korean subjects and evaluate their associations with coronary atherosclerosis. Methods In statin-naïve subjects from Gene-Environment of Interaction and phenotype cohort, we performed genome-wide association studies of lipid variability; the discovery (first) and replication (second) sets included 4,287 and 1,086 subjects, respectively. Coronary artery calcium (CAC) score and degree of coronary artery stenosis were used as outcome measures. Cholesterol variability was determined by standard deviation and average successive variability, and significant coronary atherosclerosis was defined as CAC score ≥400 or coronary stenosis ≥70%. Results Mean HDL-C and LDL-C level were 54 ± 12 and 123 ± 30 mg/dL in the first set and 53 ± 12 and 126 ± 29 mg/dL in the second set. APOA5 rs662799 and APOA5 rs2266788 were associated with LDL-C variability and PXDNL rs80056520, ALDH2 rs671, HECTD4 rs2074356, and CETP rs2303790 were SNPs associated for HDL-C variability. APOA5 rs662799 passed Bonferroni correction with p-value of 1.789 × 10−9. Among the SNPs associated with cholesterol variability, rs80056520 and rs2266788 variants were associated with CACS ≥400 and coronary stenosis ≥70% and rs662799 variant was associated with coronary stenosis ≥70%. Conclusion Two SNPs associated with LDL-C variability (APOA5 rs662799 and rs2266788) and one SNP associated with HDL-C variability (PXDNL rs80056520) were significantly associated with advanced coronary artery stenosis. Combining GWAS results with imaging parameters, our study may provide a deeper understanding of underlying pathogenic basis of the link between lipid variability and coronary atherosclerosis.
Has the Resignation of Independent Directors Holding Government Positions Improved Firm Performance?—A Quasi-Natural Experiment From China

The Organization Department of the Communist Party of China (CPC) announced the Opinions on Further Regulation on Party and Political Leaders and Cadres Working Part-Time (Holding Offices) in Enterprises to force the resignation of government officials holding the position of independent director in listed companies (GID). This paper empirically examines the impact of the GID resignation on firm performance using a difference-in-differences (DID) model, which is an exogenous event with a “natural experiment. ” The study finds that after the promulgation of the Opinions, firms that lose some of their political resources and their corporate performance decreases significantly compared to firms that do not experience GID resignations. A good external governance environment, while somewhat weakening, is not sufficient to offset the negative impact of the loss of political resources on firm performance. This paper further explores the mechanism by which the GID resignation affects firm performance: one important way in which the resignation of GIDs cause the loss of political resources on which the firm's development depends is that the loss of the firm's tax benefits after GID resignation directly leads to a decline in performance; it also leads to a reduction in the firm's financial subsidy income and a reduction in the amount of bank loans, but both of these do not have a significant effect on the decline in firm performance. The study suggests that GIDs play more of a resource-providing “official” role than an “independent director's” supervisory and advisory role in Chinese listed companies. The findings of this paper reveal the phenomenon of “Political-Business Spin” in China, which has some implications for developing countries, represented by China, to improve the independence of the board of directors and the corporate governance.
Profiling and Integrated Analysis of Differentially Expressed MicroRNAs as Novel Biomarkers of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a heterogeneous disease that has multiple etiologies. It is the most common primary liver cancer, the sixth highest cause of cancer incidences, and the fourth highest cause of cancer-related deaths. The discovery of new biomarkers for the early detection, treatment, and prognosis of HCC would therefore be extremely useful. This study investigated differentially expressed ribonucleic acid (RNA) profiles by constructing a genome-wide profile of clinical samples. Differential expression analysis identified 1,280 differentially expressed messenger RNAs (dif-mRNAs), 99 differentially expressed microRNAs (dif-miRNAs), 181 differentially expressed long non-coding RNAs (dif-lncRNAs), and 31 differentially expressed circular RNAs (dif-circRNAs). Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) path analysis were then conducted on these differentially expressed RNAs, revealing that they were clearly related to cell division, foreign body metabolism, and ribosome assembly. A competing endogenous RNA (ceRNA) network was then constructed based on the regulatory dif-miRNA-dif-mRNA and dif-miRNA-dif-lncRNA relationships. These results were also verified using HCC data from the Cancer Genome Atlas (TCGA); seven dif-miRNAs were verified in clinical samples by real-time quantitative polymerase chain reaction (RT-qPCR). Kaplan-Meier survival analysis revealed that the expression levels of Hsa-miR-1269a, Hsa-miR-421, and Hsa-miR-190b were correlated with overall survival. (P <0.05). Survival analysis of clinical samples showed that hsa-mir-1269a, hsa-mir-421 were associated with prognosis (p<0.05). This study revealed the general expression characteristics of specific differentially expressed miRNAs using a ceRNA network constructed from HCC samples. Hsa-mir-1269a, hsa-mir-421 may be promising candidates.