Miracle-dz/UniFAR-FTUs huggingface dataset:
Mining Bug Databases for Unidentified Software Vulnerabilities

Identifying software vulnerabilities is becoming more important as critical and sensitive systems increasingly rely on complex software systems. It has been suggested in previous work that some bugs are only identified as vulnerabilities long after the bug has been made public. These vulnerabilities are known as hidden impact vulnerabilities. This paper discusses existing bug data mining classifiers and present an analysis of vulnerability databases showing the necessity to mine common publicly available bug databases for hidden impact vulnerabilities. We present a vulnerability analysis from January 2006 to April 2011 for two well known software packages: Linux kernel and MySQL. We show that 32% (Linux) and 62% (MySQL) of vulnerabilities discovered in this time period were hidden impact vulnerabilities. We also show that the percentage of hidden impact vulnerabilities has increased from 25% to 36% in Linux and from 59% to 65% in MySQL in the last two years. We then propose a hidden impact vulnerability identification methodology based on text mining classifier for bug databases. Finally, we discuss potential challenges faced by a development team when using such a classifier.
Establishing a Twin Register: An Invaluable Resource for (Behavior) Genetic, Epidemiological, Biomarker, and ‘Omics’ Studies

Twin registers are wonderful research resources for research applications in medical and behavioral genetics, epidemiology, psychology, molecular genetics, and other areas of research. New registers continue to be launched all over the world as researchers from different disciplines recognize the potential to boost and widen their research agenda. In this article, we discuss multiple aspects that need to be taken into account when initiating a register, from its preliminary sketch to its actual development. This encompasses aspects related to the strategic planning and key elements of research designs, promotion and management of a twin register, including recruitment and retaining of twins and family members of twins, phenotyping, database organization, and collaborations between registers. We also present information on questions unique to twin registers and twin-biobanks, such as the assessment of zygosity by SNP arrays, the design of (biomarker) studies involving related participants, and the analyses of clustered data. Altogether, we provide a number of basic guidelines and recommendations for reflection when planning a twin register.
Human anti‐saliva immune response following experimental exposure to the visceral leishmaniasis vector, Lutzomyia longipalpis

Experiments in animals verified that phlebotomine saliva enhances Leishmania infection, and vaccination with saliva prevents disease. We have shown that individuals from an endemic area of visceral leishmaniasis displayed robust antibody responses to saliva from the vector Lutzomyia longipalpis, which correlated with anti‐parasite cell‐mediated immunity. Here, we explored human anti‐saliva responses following exposure to sand flies, using an in vivo bite model in which normal volunteers were exposed four times to 30 laboratory‐reared Lu. longipalpis. Following the third exposure, normal volunteers developed diverse dermatological reactions at the site of insect bite. Serum from normal volunteers displayed high levels of anti‐salivary gland sonicate IgG1, IgG4 and IgE as well as several salivary gland proteins. Furthermore, following in vitro stimulation with salivary gland sonicate, there was an increased frequency of CD4+CD25+ and CD8+CD25+ T cells as well as IFN‐γ and IL‐10 synthesis. Strikingly, 1 year after the first exposure, PBMC from the volunteers displayed recall IFN‐γ responses that correlated with a significant reduction in infection rates using a macrophage‐lymphocyte autologous culture. Together, these data suggest that human immunization against sand fly saliva is feasible and recall responses are obtained even 1 year after exposure, opening perspectives for vaccination in man.
Microsatellite instability in colorectal cancer

Colorectal cancer (CRC) is a heterogeneous disease that is caused by the interaction of genetic and environmental factors. Although it is one of the most common cancers worldwide, CRC would be one of the most curable cancers if it is detected in the early stages. Molecular changes that occur in colorectal cancer may be categorized into three main groups: 1) Chromosomal Instability (CIN), 2) Microsatellite Instability (MSI), and 3) CpG Island Methylator phenotype (CIMP). Microsatellites, also known as Short Tandem Repeats (STRs) are small (1-6 base pairs) repeating stretches of DNA scattered throughout the entire genome and account for approximately 3 % of the human genome. Due to their repeated structure, microsatellites are prone to high mutation rate. Microsatellite instability (MSI) is a unique molecular alteration and hyper-mutable phenotype, which is the result of a defective DNA mismatch repair (MMR) system, and can be defined as the presence of alternate sized repetitive DNA sequences which are not present in the corresponding germ line DNA. The presence of MSI is found in sporadic colon, gastric, sporadic endometrial and the majority of other cancers. Approximately, 15-20 % of colorectal cancers display MSI. Determination of MSI status in CRC has prognostic and therapeutic implications. As well, detecting MSI is used diagnostically for tumor detection and classification. For these reasons, microsatellite instability analysis is becoming more and more important in colorectal cancer patients. The objective of this review is to provide the comprehensive summary of the update knowledge of colorectal cancer classification and diagnostic features of microsatellite instability.
The Continuing Mystery of Lipid Rafts † and

Since its initial formalization nearly 20 years ago, the concept of lipid rafts has generated a tremendous amount of attention and interest and nearly as much controversy. The controversy is perhaps surprising because the notion itself is intuitive: compartmentalization in time and space is a ubiquitous theme at all scales of biology, and therefore, the partitioning of cellular membranes into lateral subdivision should be expected. Nevertheless, the physicochemical principles responsible for compartmentalization and the molecular mechanisms by which they are functionalized remain nearly as mysterious today as they were two decades ago. Herein, we review recent literature on this topic with a specific focus on the major open questions in the field including: (1) what are the best tools to assay raft behavior in living membranes? (2) what is the function of the complex lipidome of mammalian cells with respect to membrane organization? (3) what are the mechanisms that drive raft formation and determine their properties? (4) how can rafts be modulated? (5) how is membrane compartmentalization integrated into cellular signaling? Despite decades of intensive research, this compelling field remains full of fundamental questions. © 2016 Elsevier Ltd. All rights reserved.
Differentiation of Mesenchymal Stem Cells Towards Nephrogenic Lineage and Their Enhanced Resistance to Oxygen Peroxide-induced Oxidative Stress.

INTRODUCTION Mesenchymal stem cells (MSCs) have been publicized to ameliorate kidney injury both in vitro and in vivo. However, very less is known if MSCs can be differentiated towards renal lineages and their further application potential in kidney injuries. MATERIALS AND METHODS The present study developed a conditioning system of growth factors fibroblast growth factor 2, transforming growth factor-β2, and leukemia inhibitory factor for in vitro differentiation of MSCs isolated from different sources towards nephrogenic lineage. Less invasively isolated adipose-derived MSCs were also compared to bone marrow-derived MSCs for their differentiation potential to induce renal cell. Differentiated MSCs were further evaluated for their resistance to oxidative stress induced by oxygen peroxide. RESULTS A combination of growth factors successfully induced differentiation of MSCs. Both types of differentiated cells showed significant expression of pronephrogenic markers (Wnt4, Wt1, and Pax2) and renal epithelial markers (Ecad and ZO1). In contrast, expression of mesenchymal stem cells marker Oct4 and Vim were downregulated. Furthermore, differentiated adipose-derived MSCs and bone marrow-derived MSCs showed enhanced and comparable resistance to oxygen peroxide-induced oxidative stress. CONCLUSIONS Adipose-derived MSC provides a promising alternative to bone marrow-derived MSC as a source of autologous stem cells in human kidney injuries. In addition, differentiated MSCs with further in vivo investigations may serve as a cell source for tissue engineering or cell therapy in different renal ailments.
Use of Laser Assisted Optical Rotational Cell Analyzer (LoRRca MaxSis) in the Diagnosis of RBC Membrane Disorders, Enzyme Defects, and Congenital Dyserythropoietic Anemias: A Monocentric Study on 202 Patients

Chronic hemolytic anemias are a group of heterogeneous diseases mainly due to abnormalities of red cell (RBC) membrane and metabolism. The more common RBC membrane disorders, classified on the basis of blood smear morphology, are hereditary spherocytosis (HS), elliptocytosis, and hereditary stomatocytoses (HSt). Among RBC enzymopathies, the most frequent is pyruvate kinase (PK) deficiency, followed by glucose-6-phosphate isomerase, pyrimidine 5′ nucleotidase P5′N, and other rare enzymes defects. Because of the rarity and heterogeneity of these diseases, diagnosis may be often challenging despite the availability of a variety of laboratory tests. The ektacytometer laser-assisted optical rotational cell analyser (LoRRca MaxSis), able to assess the RBC deformability in osmotic gradient conditions (Osmoscan analysis), is a useful diagnostic tool for RBC membrane disorders and in particular for the identification of hereditary stomatocytosis. Few data are so far available in other hemolytic anemias. We evaluated the diagnostic power of LoRRca MaxSis in a large series of 140 patients affected by RBC membrane disorders, 37 by enzymopathies, and 16 by congenital diserythropoietic anemia type II. Moreover, nine patients with paroxysmal nocturnal hemoglobinuria (PNH) were also investigated. All the hereditary spherocytoses, regardless the biochemical defect, showed altered Osmoscan curves, with a decreased Elongation Index (EI) max and right shifted Omin; hereditary elliptocytosis (HE) displayed a trapezoidal curve and decreased EImax. Dehydrated hereditary stomatocytosis (DHSt) caused by PIEZO1 mutations was characterized by left-shifted curve, whereas KCNN4 mutations were associated with a normal curve. Congenital diserythropoietic anemia type II and RBC enzymopathies had Osmoscan curve within the normal range except for glucosephosphate isomerase (GPI) deficient cases who displayed an enlarged curve associated with significantly increased Ohyper, offering a new diagnostic tool for this rare enzyme defect. The Osmoscan analysis performed by LoRRca MaxSis represents a useful and feasible first step screening test for specialized centers involved in the diagnosis of hemolytic anemias. However, the results should be interpreted by caution because different factors (i.e., splenectomy or coexistent diseases) may interfere with the analysis; additional tests or molecular investigations are therefore needed to confirm the diagnosis.
Immunotherapy for pulmonary squamous cell carcinoma and colon carcinoma with pembrolizumab

Rationale: Novel treatment strategies such as immunotherapy are being evaluated to further improve the outcomes of colorectal cancer patients. To our knowledge, this is the first report to show both the successful treatment of pulmonary squamous cell carcinoma (SCC) with pembrolizumab alongside histological and immunohistochemical findings of resected colon cancer under immunotherapy for lung cancer. Patient concerns: This patient was a 70-year-old man who presented with a right lung tumor and simultaneous adenocarcinoma of the sigmoid colon. Diagnoses: Biopsy examination revealed squamous cell carcinoma in the right lung and adenocarcinoma of the sigmoid colon. Interventions: The patient underwent successful pembrolizumab treatment as first-line immunotherapy for lung cancer, as demonstrated by computed tomography, and the sigmoid colon tumor was excised during an immunotherapy-free window. Outcomes: No unusual tumor growth in the right lung or abnormal abdominal signs was observed during the 9-month follow-up. Lessons: Microscopically, the resected colon cancer specimen was characterized by numerous lymphoid cells in the partial stroma, with a large number of infiltrating lymphocytes consisting of CD3+, CD8+ T cells. In summary, this case demonstrates how immunotherapy affects PD-L1-negative colon cancer and indicates future treatment prospects.
Telomere Length and Lung Cancer Mortality among Heavy Smokers

Background: Accumulating evidence suggests that short telomere length is associated with increased overall mortality, but the relationship with cancer mortality is less clear. We examined whether telomere length (global, and chromosome arm 5p- and 13q-specific) is associated with lung cancer mortality among cases from the β-Carotene and Retinol Efficacy Trial of heavy smokers. Methods: Telomere length was measured on average 6 years before diagnosis for 788 lung cancer cases. Adjusted Cox proportional hazards models of all-cause and lung cancer–specific mortality were assessed for lung cancer overall and by histotype. Results: Short telomere length was associated with increased mortality for small cell lung cancer (SCLC), particularly stage III/IV SCLC [HR and 95% confidence interval for shortest vs. longest telomere length tertile: 3.32 (1.78–6.21)]. Associations were strongest for those randomized to the active intervention and when telomere length was measured ≤5 years before diagnosis. All-cause mortality patterns were similar. Short chromosome 5p telomere length was suggestively associated with lung cancer mortality, but there was no association with chromosome 13q telomere length. Conclusions: Our large prospective study suggests that among heavy smokers who developed lung cancer, short prediagnosis telomere length is associated with increased risk of death from SCLC. Impact: This is the first study to examine telomere length and mortality in lung cancer cases by histotype. If the association between short telomere length and SCLC mortality is replicated, elucidation of mechanisms through which telomere length influences survival for this highly aggressive cancer may inform more effective use of telomere-targeted therapeutics. Cancer Epidemiol Biomarkers Prev; 27(7); 829–37. ©2018 AACR.
Inhibition of mTOR signaling Confers Protection against Cerebral Ischemic Injury in Acute Hyperglycemic Rats

Hyperglycemia is known to exacerbate neuronal death resulted from cerebral ischemia. The mechanisms are not fully understood. The mammalian target of rapamycin (mTOR) pathway regulates cell growth, division and apoptosis. Recent studies suggest that activation of mTOR may mediate ischemic brain damage. The objective of the present experiment is to explore whether mTOR mediates ischemic brain damage in acute hyperglycemic animals. Rats were subjected to 10 min of forebrain ischemia under euglycemic, hyperglycemic and rapamycin-treated hyperglycemic conditions. The rat brain samples were collected from the cortex and hippocampi after 3h and 16h of reperfusion. The results showed that hyperglycemia significantly increased neuronal death in the cortex and hippocampus and the exacerbation effect of hyperglycemia was associated with further activation of mTOR under control and/or ischemic conditions. Inhibition of mTOR with rapamycin ameliorated the damage and suppressed hyperglycemia-elevated p-MTOR, p-P70S6K and p-S6. In addition, hyperglycemia per se increased the levels of cytosolic cytochrome c and autophagy marker LC3-II, while rapamycin alleviated these alterations. It is concluded that activation of mTOR signaling may play a detrimental role in mediating the aggravating effect of hyperglycemia on cerebral ischemia.
Are engineered nano iron oxide particles safe? an environmental risk assessment by probabilistic exposure, effects and risk modeling

Abstract Nano iron oxide particles are beneficial to our daily lives through their use in paints, construction materials, biomedical imaging and other industrial fields. However, little is known about the possible risks associated with the current exposure level of engineered nano iron oxides (nano-FeOX) to organisms in the environment. The goal of this study was to predict the release of nano-FeOX to the environment and assess their risks for surface waters in the EU and Switzerland. The material flows of nano-FeOX to technical compartments (waste incineration and waste water treatment plants) and to the environment were calculated with a probabilistic modeling approach. The mean value of the predicted environmental concentrations (PECs) of nano-FeOX in surface waters in the EU for a worst-case scenario (no particle sedimentation) was estimated to be 28 ng/l. Using a probabilistic species sensitivity distribution, the predicted no-effect concentration (PNEC) was determined from ecotoxicological data. The risk characterization ratio, calculated by dividing the PEC by PNEC values, was used to characterize the risks. The mean risk characterization ratio was predicted to be several orders of magnitude smaller than 1 (1.4 × 10−4). Therefore, this modeling effort indicates that only a very limited risk is posed by the current release level of nano-FeOX to organisms in surface waters. However, a better understanding of the hazards of nano-FeOX to the organisms in other ecosystems (such as sediment) needs to be assessed to determine the overall risk of these particles to the environment.
Ameliorative effects of Spirulina platensis against lead-induced nephrotoxicity in newborn rats: Modulation of oxidative stress and histopathological changes

Our experimental work was aimed at evaluating the safety and protective effects of dietary spirulina supplementation on the kidney of newborn rats, the offspring of lead contaminated lactating mothers. Female rats were randomly divided into four groups: group I (control) was given a normal diet, group II (positive control, S) received a diet enriched with spirulina, group III received only lead through drinking water (Pb), and group IV received both a diet enriched with spirulina and lead contaminated water (S Pb). The treatment of pregnant rats with lead administrated in drinking water, from the 5th day of pregnancy until day 14 after delivery, induced an increased level of renal lipid peroxidation, protein carbonyl, hydrogen peroxide and advanced oxidation protein product, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in newborns. A statistically significant increase of renal DNA, mRNA, hematological parameters as well as in plasma urea and creatinine serum levels and lactate dehydrogenase was seen in pups, while those of uric acid declined. Interestingly, these biochemical modifications were accompanied by a significant decrease of lactate dehydrogenase in kidney, plasma alkaline phosphatase and gamma glutamyl-transpeptidase levels, urinary levels of creatinine and urea. Conversely, supplementation of lead-treated mother's with spirulina alleviated hematotoxicity induced by lead as evidenced, by restoring the biochemical markers cited above to near normal levels. Nevertheless, the distorted histoarchitecture in rat kidney attenuated following spirulina supplementation. It can be then concluded that spirulina is an important protective source against kidney impairments.
Non-invasive Investigation of Human Hippocampal Rhythms Using Magnetoencephalography: A Review

Hippocampal rhythms are believed to support crucial cognitive processes including memory, navigation, and language. Due to the location of the hippocampus deep in the brain, studying hippocampal rhythms using non-invasive magnetoencephalography (MEG) recordings has generally been assumed to be methodologically challenging. However, with the advent of whole-head MEG systems in the 1990s and development of advanced source localization techniques, simulation and empirical studies have provided evidence that human hippocampal signals can be sensed by MEG and reliably reconstructed by source localization algorithms. This paper systematically reviews simulation studies and empirical evidence of the current capacities and limitations of MEG “deep source imaging” of the human hippocampus. Overall, these studies confirm that MEG provides a unique avenue to investigate human hippocampal rhythms in cognition, and can bridge the gap between animal studies and human hippocampal research, as well as elucidate the functional role and the behavioral correlates of human hippocampal oscillations.
CsA inhibits IL-22 production by memory CD4+ T cells from patients with psoriasis

IL-22 is involved in psoriasis and exacerbates disease progression. Cyclosporine A (CsA) is an immunosuppressant drug that has been used in the treatment of psoriasis for more than 20 years. We determined IL-22 producing T cells and their phenotype, and demonstrated that IL-22 is mainly produced by CD4+ memory T cells not CD8+ T cells in peripheral blood from healthy adults. We compared Th17 and Th1 with the percentages of IL-22 producing CD4+ T cells, and demonstrated that Th1 is the majority Th subset in the blood, as the percentage of Th1 cells is significantly larger than the percentage of IL-22 producing CD4+ T cells or Th17 cells. We analyzed the correlation of IL-22, IL-17 and IFN-γ produced by CD4+ T cells from healthy adults, and confirmed that there is a subset of Th22 cells that does not produce IL-17 or IFN-γ. Furthermore, we observed that the percentage of IL-22 producing CD4+ T cells is elevated in psoriasis compared to healthy donors, and that the majority of these cells are memory CD4+ T cells. We also investigated the inhibitory effects of CsA on IL-22 production by CD4+ T cells from both healthy donors and patients with psoriasis. We observed that CsA inhibits the production of IL-22 by CD4+ T cells from healthy donors in a dose-dependent manner, and that it inhibits IL- 22, IFN-γ and IL-17 production by CD4+ T cells in psoriasis. The obtained results provide critical information regarding the clinical efficacies of CsA in the treatment of psoriasis.
Changes in blood flow at the mandibular angle and Horner syndrome in a rat model of superior cervical ganglion block

Background A stellate ganglion block (SGB) causes increased blood flow in the maxillofacial region, exhibiting the potential for regenerative effects in damaged tissue. The focus of this study was to understand the efficacy of SGB for regenerative effects against nerve damage. A rat model of the superior cervical ganglion block (SCGB) was created instead of SGB, and facial blood flow, as well as sympathetic nervous system function, were measured. Methods A vertical incision was made on the left side of the neck of a Wistar rat, and a 5-mm resection of the superior cervical ganglion was performed at the back of the bifurcation of the internal and external branches of the left common carotid artery. Blood flow in the skin at the mandibular angle and mean facial temperature were measured using a laser-Doppler blood flow meter and a thermographic camera, respectively, over a 5-week period after the block. In addition, the degree of ptosis and miosis were assessed over a period of 6 months. Results The SCGB rat showed significantly higher blood flow at the mandibular angle on the block side (P < 0.05) for 3 weeks, and significantly higher skin temperature (P < 0.05) for 1 week after the block. In the SCGB rat, ptosis and miosis occurred immediately after the block, and persisted even 6 months later. Conclusions SCGB in rats can cause an increase in the blood flow that persists over 3 weeks.