Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation Profiling of Malignant Lymphoma by Next-Generation Sequencing of Circulating Cell-Free DNA

Background: Malignant lymphomas are a group of distinct lymphoid neoplasms, exhibiting marked diversity in biological behaviors and clinical outcomes. Liquid biopsy, such as circulating cell-free DNA (cfDNA), has recently been attempted to be used for mutation profiling of lymphomas using next-generation sequencing (NGS). However, only limited data about cfDNA are restricted in Hodgkin's lymphoma and B cell lymphoma, and there is no report in the T cell lymphoma so far. Patient and Methods: Medical records of a total of 50 lymphoma patients were retrospectively reviewed, and cfDNA samples were analyzed by capture-based NGS targeting 390 lymphoma- and cancer- relevant genes. We sought to explore the clinical utility of cfDNA in establishing the mutation profiles of different lymphoma subtypes and analyze the correlation between cfDNA concentration and other clinical indices such as serum LDH and IPI. Results: Somatic alterations were identified in cfDNA samples with a median of 64 variants per sample. The concentration of cfDNA in the plasma was found to be significantly correlated with the clinical indices in diffuse large B cell lymphoma (DLBCL). The genetic heterogeneity of different lymphoma subtypes was clearly observed in cfDNAs from germinal center B-cell (GCB) DLBCL, non-GCB DLBCL and natural killer/T-cell lymphoma (NKTCL), confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas. Conclusion: Our findings demonstrate that NGS-based cfDNA mutation profiling reveals genetic heterogeneity across lymphoma subtypes, with potential implications for the discovery of therapeutic targets, the exploration of genome evolution and the development of risk-adapted treatment.
The Effect of HER2 Single Nucleotide Polymorphisms on Cervical Cancer Susceptibility and Survival in a Chinese Population

Background: Cervical cancer (CCa) is a multifactorial gynecologic disease worldwide. Effects of HER2 polymorphisms, especially those in exonic region, have been investigated in many gynecologic diseases. In this study, we evaluated the influence of functional HER2 polymorphisms on susceptibility and survival of CCa in a Chinese population. Methods: We genotyped the HER2 exonic polymorphisms by TaqMan in both case-control study (413 CCa patients vs. 396 controls) and survival study (413 CCa patients). Logistic regression and Cox regression were adopted to evaluate the genetic association with the risk and outcomes of CCa, respectively. Results: In the case-control study, there was no significant difference between patients and controls in either HER2 rs1136201 or rs1058808. However, when combined, these two polymorphisms demonstrated a significant hazardous effect for CCa (P = 0.012). Besides, number of variants was also influential (P trend =0.002). In survival analysis, dominant model of rs1136201 and co-dominant modelof rs1058808 were significantly associated with the survival (P = 0.037 and P =0.028). The combination of rs1136201 and rs1058808 also negatively impacted CCa survival (P = 0.009). Cox regression further revealed the significance of the polymorphism combination (β = 0.38, P = 0.025, HR= 1.47, 95%CI = 1.05-2.05). Functional assay of these polymorphisms demonstrated that rs1058808 G allele was associated with stronger expression of HER2 gene. Conclusions: Our results suggested that the combination of HER2 rs1136201and rs1058808 was significantly associated with the susceptibility of CCa. Besides, this combination of polymorphism s also substantially impacted the survival of CCa patients.
Adjuvant Radiochemotherapy versus Chemotherapy Alone for Gastric Cancer: Implications for Target Definition

The INT0116 trial was a milestone study and laid the foundation for the adjuvant radiotherapy (RT) associated to concurrent chemotherapy (CT) for the treatment of gastric cancer (GC) after gastrectomy. However, it is still controversial whether adding RT to CT could further benefit D2-dissected GC patients. The ARTIST trial indicated that the addition of RT to CT did not have a positive impact on disease-free survival (DFS). Nevertheless, in a subgroup of 396 patients with positive pathological lymph nodes, combined treatment with RT was superior to CT alone. A similar randomized Chinese trial confirmed the superiority of adding RT to CT in terms of DFS for patients with D2 lymphadenectomy. However, several previous randomized studies provided inconsistent results with the benefits of combined treatment of RT and CT. The inconsistent results of several studies may be due to the differences between tumor epidemiology, treatment policies, and treatment outcomes. During the past decade, major progress in accurate target delineation utilizing RT technology has been observed. However, even though the use of adjuvant RT doubled after the INT-0116 trial results became public, the fraction of patients receiving adjuvant RT was still low according to the SEER database. The low rate of adjuvant RT can partially be explained by concern over toxicity while undergoing RT. Several studies have also defined the specific location of locoregional recurrence for postoperative RT in GC, but these studies are still limited. A number of retrospective studies demonstrated that the most prevalent nodal recurrence was outside the D2 dissection field. In order to overcome the restricted nature of a retrospective study and provide more individual radiation field determination, additional large-scale prospective multicenter studies are required to evaluate the optimal RT target.
Chemical Composition and Role of Opioidergic System in Antinociceptive Effect of Ziziphora Clinopodioides Essential Oil

Introduction: Ziziphora Clinopodioides has been used widely for various therapeutic purposes in Iranian folk medicine. The current study aimed to determine interaction of antinociceptive effect of the Essential Oil of Ziziphora Clinopodioides (EOZC) and opioidergic system in male rats using formalin test. Methods: Sixty-four male Wistar rats were divided into eight groups. The groups 1 to 7 were injected with normal saline, vehicle (Tween-80, 0.5%), 10, 20, 40 mg/kg of the EOZC, morphine (5 mg/kg) and naloxone (2 mg/kg), respectively. Thirty minutes later, the formalin test was performed by intraplantar injection of formalin (50 μL, 2%). In group 8, naloxone (2 mg/kg) was injected 15 min before injection of EOZC (20 mg/kg), followed by formalin at 15 min later. The formalin test was done as time spent for licking and biting of the injected paw. Formalin induced a biphasic pain reaction. The chemical composition of EOZC was identified using Gas Chromatography-Mass Spectrometry (GC-MS). Results: EOZC (10, 20, and 40 mg/kg) dose dependently and morphine (5 mg/kg) reduced pain responses in the both phases of pain (P<0.05). Naloxone (2 mg/kg) alone had no effect on the severity of pain (P>0.05) but pretreatment with naloxone inhibited EOZC-induced antinociception activity (P<0.05). Based on the GC-MS results, EOZC comprised 65.22% carvacrol, 19.51% thymol, 4.86% p-cymene and 4.63% γ-terpinene. Conclusion: These results demonstrate that EOZC has antinociceptive effect and this effect might mediate via opioidergic pathways.
First-line continual EGFR-TKI plus local ablative therapy demonstrated survival benefit in EGFR-mutant NSCLC patients with oligoprogressive disease

Introduction: The effect of local ablative therapy (LAT) for oligoprogressive epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer (NSCLC) remains undetermined. This study aimed to investigate the survival benefit of addition of LAT to EGFR-TKIs in EGFR-mutant NSCLC patients with oligoprogression during TKI therapy. Materials and Methods: Patients with stage IIIB/IV EGFR mutant NSCLC who had oligoprogressive disease during the first-line EGFR-TKI therapy from March 2011 to February 2016 were identified. The primary research point were progression-free survival1 (PFS1), defined as time of initiation of TKI therapy to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 defined progress disease (PD) or death and PFS2, defined as time of initiation of TKI therapy to off-TKI PD. The second research piont inclued overal survival (OS) and safety. Results: A total of 206 patients were included. The median follow-up time was 42 months (20.0-69.6 months). The median PFS1, median PFS2 and median OS for the related cohort were 10.7 months (95% CI, 10.1-13.3 months), 18.3 months (95% CI, 17.4-19.2 months) and 37.4 months (95% CI, 35.9-38.9 months) respectively. Survival rates of 1 year, 2 years and 3 years were 94.1%, 78.9%, and 54.7%, respectively. Multivariate analysis revealed that female, EGFR exon 19 mutation, one metastatic lesion, partial or complete response to prior EGFR TKIs therapy were the independent prognostic factors. No unexpected toxicities were observed. Conclusion: The current study suggested that the addition of LAT to EGFR-TKI could provide satisfactory survival benefit for EGFR-mutant NSCLC patients with oligoprogression during first-line EGFR-TKI treatment.
High Expression Levels of AGGF1 and MFAP4 Predict Primary Platinum-Based Chemoresistance and are Associated with Adverse Prognosis in Patients with Serous Ovarian Cancer

Primary platinum-based chemoresistance occurs in approximately one-third of patients with serous ovarian cancer (SOC); however, traditional clinical indicators are poor predictors of chemoresistance. So we aimed to identify novel genes as predictors of primary platinum-based chemoresistance. Gene expression microarray analyses were performed to identify the genes related to primary platinum resistance in SOC on two discovery datasets (GSE51373, GSE63885) and one validation dataset (TCGA). Univariate and multivariate analyses with logistic regression were performed to evaluate the predictive values of the genes for platinum resistance. Machine learning algorithms (linear kernel support vector machine and artificial neural network) were applied to build prediction models. Univariate and multivariate analyses with Cox proportional hazards regression and log-rank tests were used to assess the effects of these gene signatures for platinum resistance on prognosis in two independent datasets (GSE9891, GSE32062). AGGF1 and MFAP4 were found highly expressed in patients with platinum-resistant SOC and independently predicted platinum resistance. Platinum resistance prediction models based on these targets had robust predictive power (highest AUC: 0.8056, 95% CI: 0.6338-0.9773; lowest AUC: 0.7245, 95% CI: 0.6052-0.8438). An AGGF1- and MFAP4-centered protein interaction network was built, and hypothetical regulatory pathways were identified. Enrichment analysis indicated that aberrations of extracellular matrix may play important roles in platinum resistance in SOC. High AGGF1 and MFAP4 expression levels were also related to shorter recurrence-free and overall survival in patients with SOC after adjustment for other clinical variables. Therefore, AGGF1 and MFAP4 are potential predictive biomarkers for response to platinum-based chemotherapy and survival outcomes in SOC.
E-Skin: From Humanoids to Humans

With robots starting to enter our lives in a number of ways (e.g., social, assistive, and surgery), the electronic skin (e-skin) is becoming increasingly important. The capability of detecting subtle pressure or temperature changes makes the e-skin an essential component of a robot’s body or an artificial limb [1] , [2] . This is because the tactile feedback enabled by e-skin plays a fundamental role in providing action-related information such as slip during manipulation/control tasks such as grasping, and estimation of contact parameters (e.g., force, soft contact, hardness, texture, and temperature during exploration [3] ). It is critical for the safe robotic interaction—albeit as a coworker in the futuristic industry 4.0 setting or to assist the elderly at home.
An Empirical Study on Security Knowledge Sharing and Learning in Open Source Software Communities

Open source software (OSS) security has been the focus of the security community and practitioners over the past decades. However, the number of new vulnerabilities keeps increasing in today’s OSS systems. With today’s increasingly important and complex OSS, lacking software security knowledge to handle security vulnerabilities in OSS development will result in more breaches that are serious in the future. Learning software security is a difficult and challenging task since the domain is quite context specific and the real project situation is necessary to apply the security concepts within the specific system. Many OSS proponents believe that the OSS community offers significant learning opportunities from its best practices. However, studies that specifically explore security knowledge sharing and learning in OSS communities are scarce. This research is intended to fill this gap by empirically investigating factors that affect knowledge sharing and learning about software security and the relationship among them. A conceptual model is proposed that helps to conceptualize the linkage between socio-technical practices and software security learning processes in OSS communities. A questionnaire and statistical analytical techniques were employed to test hypothesized relationships in the model to gain a better understanding of this research topic.
Lost expression of cell adhesion molecule 1 is associated with bladder cancer progression and recurrence and its overexpression inhibited tumor cell malignant behaviors

Cell adhesion molecule 1 (CADM1) regulates cell-cell adhesion and an altered expression level is associated with tumorigenesis and progression. The present study assessed CADM1 expression level in 84 bladder tissues to investigate the association with clinicopathological parameters from bladder cancer patients and then investigated the effects of CADM1 overexpression on T24 bladder cancer cells in vitro. The results demonstrated that expression level of CADM1 protein was significantly reduced in bladder cancer tissues (0.26±0.14) compared with in normal bladder mucosa (0.69±0.092; P<0.01), and methylation of CADM1 promoter was responsible for silencing of CADM1 protein expression and significantly associated with tumor size, recurrence, pathology classification and clinical stage (P<0.05). Overexpression of CADM1 protein inhibited tumor cell proliferation, reduced tumor cell invasion capacity and induced tumor cell apoptosis in vitro. At the gene level, CADM1 expression level upregulated caspase-3 activity and expression of Bax and p27 protein and downregulated levels of B cell lymphoma-2, cyclinD1, cyclinE1 and cyclin dependent kinase 2 proteins. Furthermore, overexpression of CADM1 regulated the expression level of epithelial to mesenchymal transition markers, including increased expression level of E-cadherin and β-catenin, whereas it decreased the levels of Vimentin. The present study demonstrated that lost expression of CADM1 protein may exert an essential role in the development and progression of bladder cancer and suggested that CADM1 may be a novel molecular target for the control of this disease in clinical practice.
The application of omics techniques to understand the role of the gut microbiota in inflammatory bowel disease

The aetiopathogenesis of inflammatory bowel diseases (IBD) involves the complex interaction between a patient’s genetic predisposition, environment, gut microbiota and immune system. Currently, however, it is not known if the distinctive perturbations of the gut microbiota that appear to accompany both Crohn’s disease and ulcerative colitis are the cause of, or the result of, the intestinal inflammation that characterizes IBD. With the utilization of novel systems biology technologies, we can now begin to understand not only details about compositional changes in the gut microbiota in IBD, but increasingly also the alterations in microbiota function that accompany these. Technologies such as metagenomics, metataxomics, metatranscriptomics, metaproteomics and metabonomics are therefore allowing us a deeper understanding of the role of the microbiota in IBD. Furthermore, the integration of these systems biology technologies through advancing computational and statistical techniques are beginning to understand the microbiome interactions that both contribute to health and diseased states in IBD. This review aims to explore how such systems biology technologies are advancing our understanding of the gut microbiota, and their potential role in delineating the aetiology, development and clinical care of IBD.
Flow Cytometry of CD64, HLA-DR, CD25, and TLRs for Diagnosis and Prognosis of Sepsis in Critically Ill Patients Admitted to the Intensive Care Unit: A Review Article

Sepsis is an important health problem with a high burden on health systems. Finding new aspects of immune system function in sepsis showed a new role for flow cytometry in the diagnosis of sepsis. We made a review on the role of CD64, HLA-DR, CD25, and TLRs as more useful flow cytometric tools in diagnosing sepsis, both in adults, and neonates. According to our results, we concluded that for diagnosis and treatment of the septic, flow cytometry can play an important role so that it can be used as a novel method in individualized treatment of septic patients based on their immune system situation.
Effects of Polymer/Surfactant as Carriers on the Solubility and Dissolution of Fenofibrate Solid Dispersion

The purpose of this work is to investigate the effects of polymer/surfactant as carriers on the solubility and dissolution of fenofibrate solid dispersions (FF SDs) with the aid of systematic research on the physicochemical properties of the polymer/surfactant system and further highlight the importance of studying polymer/surfactant interaction in the preformulation. The critical micelle concentration (CMC) of sodium lauryl sulfate (SLS) and critical aggregation concentration (CAC) of polymer/SLS solutions were obtained through conductivity measurement. Meanwhile, surface tension, viscosity, morphology, and wettability of polymer/SLS with different weight ratios of SLS were analyzed to screen out the suitable content of SLS (weight%, 5% in carriers) incorporated in SDs. Polymer/SLS coprecipitate and FF SDs were prepared by the solvent evaporation method. The results from differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis showed that FF was molecularly dispersed in SDs. Compared to the solubility of FF in povidone/SLS (PVP/SLS) solutions, the increment of FF solubility in copovidone/SLS (VA64/SLS) solutions was due to the formation of free SLS micelles, which have been confirmed by transmission electron microscopy (TEM). Particularly, the wettability of FF SDs and physical mixtures (PMs) was also determined by the sessile drop technique. A linear relationship between the wettability of carriers and that of FF SDs was found, which revealed the significant role of carriers on the surface composition of FF SDs. As the molecular weight of PVP increased, the wettability of carriers decreased, thus leading to the reduction of the dissolution rate of SDs. Although the presence of SLS did not enhance the dissolution of FF SDs, it increased the amount of drug released at the initial stage. All these results indicated that the polymer/SLS interaction would affect the performance of SDs; hence, it was necessary to study their properties in the preformulation.
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Key message Degradation of nitrogen-rich purines is tightly and oppositely regulated under drought and low nitrogen supply in bread wheat. Allantoin is a key target metabolite for improving nitrogen homeostasis under stress. Abstract The metabolite allantoin is an intermediate of the catabolism of purines (components of nucleotides) and is known for its housekeeping role in nitrogen (N) recycling and also for its function in N transport and storage in nodulated legumes. Allantoin was also shown to differentially accumulate upon abiotic stress in a range of plant species but little is known about its role in cereals. To address this, purine catabolic pathway genes were identified in hexaploid bread wheat and their chromosomal location was experimentally validated. A comparative study of two Australian bread wheat genotypes revealed a highly significant increase of allantoin (up to 29-fold) under drought. In contrast, allantoin significantly decreased (up to 22-fold) in response to N deficiency. The observed changes were accompanied by transcriptional adjustment of key purine catabolic genes, suggesting that the recycling of purine-derived N is tightly regulated under stress. We propose opposite fates of allantoin in plants under stress: the accumulation of allantoin under drought circumvents its degradation to ammonium (NH 4+ ) thereby preventing N losses. On the other hand, under N deficiency, increasing the NH 4+ liberated via allantoin catabolism contributes towards the maintenance of N homeostasis.
Are Booster Seats More Effective than Child Safety Seats or Seat Belts at Reducing Traffic Fatalities among Children?

In an effort to increase booster seat use among children, the National Highway Traffic Safety Administration is encouraging state legislators to promote stricter booster seat laws, yet there is a paucity of information on booster seat efficacy relative to other forms of restraint. Using data from the Fatality Analysis Reporting System for the period 2008–16, the current study examines the effectiveness of booster seats relative to child safety seats and adult seat belts. For children two to five years of age, we find some evidence to suggest that booster seats are the least effective form of restraint. For children six to nine years of age, all three forms of restraint appear equally effective.
The Effects of Graduation Requirements on Risky Health Behaviors of High School Students

Previous studies have shown that years of formal schooling attained affects health behaviors, but little is known about how the stringency of academic programs affects such behaviors, especially among youth. Using national survey data from the Youth Risk Behavior Surveillance System, we study the effects of mathematics and science high school graduation requirements (HSGR) on high school students’ risky health behaviors—specifically on drinking, smoking, and marijuana use. We find that an increase in mathematics and science HSGR has significant negative impacts on alcohol consumption among high school students, especially males and nonwhite students. The effects of math and science HSGR on smoking and marijuana use are also negative but generally less precisely estimated. Our results suggest that curriculum design may have potential as a policy tool to curb youth drinking.
Equitable Learning Environments in K-12 Computing

The current efforts to expand computer science (CS) education in K-12 schools, such as the “CS for All” initiative, highlight the need for all students to get an opportunity to study computing. However, as recent research has shown, diversity in computing at the K-12 level remains problematic, and additional research is needed to look at how computer science learning environments can impact minority student interest and retention in CS. In this article, we report results from an in-depth qualitative study of high school computer science teachers’ perspective on barriers to increasing diversity in their classes. Based on teachers’ experiences, we provide practical recommendations on how to encourage equitable learning environments in K-12 computer science courses.