Miracle-dz/UniFAR-FTUs huggingface dataset:
A Queueing Network Model for Performance Prediction of Apache Cassandra

NoSQL databases such as Apache Cassandra have attracted large interest in recent years thanks to their high availability, scalability, flexibility and low latency. Still, there is limited research work on performance engineering methods for NoSQL databases, which yet are needed since these systems are highly distributed and thus can incur significant cost/performance trade-offs. To address this need, we propose a novel queueing network model for the Cassandra NoSQL database aimed at supporting resource provisioning. The model defines explicitly key configuration parameters of Cassandra such as consistency levels and replication factor, allowing engineers to compare alternative system setups. Experimental results based on the YCSB benchmark indicate that, with a small amount of training for the estimation of its input parameters, the proposed model achieves good predictive accuracy across different loads and consistency levels. The average performance errors of the model compared to the real results are between 6% and 10%. We also demonstrate the applicability of our model to other NoSQL databases and we show other possible utilization of it.
MiR‐214 is an important regulator of the musculoskeletal metabolism and disease

MiR‐214 belongs to a family of microRNA (small, highly conserved noncoding RNA molecules) precursors that play a pivotal role in biological functions, such as cellular function, tissue development, tissue homeostasis, and pathogenesis of diseases. Recently, miR‐214 emerged as a critical regulator of musculoskeletal metabolism. Specifically, miR‐214 can mediate skeletal muscle myogenesis and vascular smooth muscle cell proliferation, migration, and differentiation. MiR‐214 also modulates osteoblast function by targeting specific molecular pathways and the expression of various osteoblast‐related genes; promotes osteoclast activity by targeting phosphatase and tensin homolog (Pten); and mediates osteoclast‐osteoblast intercellular crosstalk via an exosomal miRNA paracrine mechanism. Importantly, dysregulation in miR‐214 expression is associated with pathological bone conditions such as osteoporosis, osteosarcoma, multiple myeloma, and osteolytic bone metastasis of breast cancer. This review discusses the cellular targets of miR‐214 in bone, the molecular mechanisms governing the activities of miR‐214 in the musculoskeletal system, and the putative role of miR‐214 in skeletal diseases. Understanding the biology of miR‐214 could potentially lead to the development of miR‐214 as a possible biomarker and a therapeutic target for musculoskeletal diseases.
Allergy to Peanuts in Atopic Dermatitis Patients 14 Year or Older and the Association with Food Hypersensitivity, Inhalant Allergens, Asthma Bronchiale and Rhinitis

Background: In adult patients suffering from atopic dermatitis (AD), studies investigating the co-prevalence of AD and food allergy are still scarce, and exact data are not available. Aims and Objectives: To evaluate the occurrence of food allergy to peanuts in significant relation to food hypersensitivity, inhalant allergy and to asthma bronchial and rhinitis. Materials and Methods: Altogether 332 patients of AD 14 year or older were included in the study. The complete dermatological and allergological examinations were performed in all included patients (including examination of specific immunoglobulin E, skin prick test to different food and inhalant allergens, anamnestic data about food reactions, evaluation of allergic rhinitis, and allergic asthma bronchiale). We evaluated whether there was some relation between the food allergy to peanuts and followed parameters. Pairs of these categories were entered in the contingency tables, and the Chi-square test for the relationship of these variables was performed with the level of significance set to 5%. Results: Altogether 332 persons suffering from AD were included in the study of which 120 were male and 212 were female; the average age was 27.2 year. The significant relation between the allergy to peanuts and the occurrence of food hypersensitivity (FH) reactions to tomatoes, kiwi, apples, oranges, carrot and to the sensitization to grass, trees, mites, and the occurrence of rhinitis was found. Conclusion: The significant relation between the allergy to peanuts and the occurrence of FH reactions and the sensitization to inhalant allergens and rhinitis was found. The future studies may show if the decrease in food allergy to peanuts can lead to the decrease of the occurrence of other FH reactions and sensitization to inhalant allergens and rhinitis in AD patients.
Ferritinophagy/ferroptosis: Iron‐related newcomers in human diseases

Nuclear receptor coactivator 4 mediated ferritinophagy is an autophagic phenomenon that specifically involves ferritin to release intracellular free iron. Ferritinophagy is implicated in maintaining efficient erythropoiesis. Notably, ferritinophagy also plays a central role in driving some pathological processes, including Parkinson’s disease (PD) and urinary tract infections. Some evidence has demonstrated that ferritinophagy is critical to induce ferroptosis. Ferroptosis is a newly nonapoptotic form of cell death, characterized by the accumulation of iron‐based lipid reactive oxygen species. Ferroptosis plays an important role in inhibiting some types of cancers, such as hepatocellular carcinoma, pancreatic carcinoma, prostate cancer, and breast cancer. Conversely, the activation of ferroptosis accelerates neurodegeneration diseases, including PD and Alzheimer’s disease. Therefore, in this review, we summarize the regulatory mechanisms related to ferritinophagy and ferroptosis. Moreover, the distinctive effects of ferritinophagy in human erythropoiesis and some pathologies, coupled with the promotive or inhibitory role of tumorous and neurodegenerative diseases mediated by ferroptosis, are elucidated. Obviously, activating or inhibiting ferroptosis could be exploited to achieve desirable therapeutic effects on diverse cancers and neurodegeneration diseases. Interrupting ferritinophagy to control iron level might provide a potentially therapeutic avenue to suppress urinary tract infections.
Pericytes Elicit Resistance to Vemurafenib and Sorafenib Therapy in Thyroid Carcinoma via the TSP-1/TGFβ1 Axis

Purpose: The BRAFV600E oncogene modulates the papillary thyroid carcinoma (PTC) microenvironment, in which pericytes are critical regulators of tyrosine-kinase (TK)-dependent signaling pathways. Although BRAFV600E and TK inhibitors are available, their efficacy as bimodal therapeutic agents in BRAFV600E-PTC is still unknown. Experimental Design: We assessed the effects of vemurafenib (BRAFV600E inhibitor) and sorafenib (TKI) as single agents or in combination in BRAFWT/V600E-PTC and BRAFWT/WT cells using cell-autonomous, pericyte coculture, and an orthotopic mouse model. We also used BRAFWT/V600E-PTC and BRAFWT/WT-PTC clinical samples to identify differentially expressed genes fundamental to tumor microenvironment. Results: Combined therapy blocks tumor cell proliferation, increases cell death, and decreases motility via BRAFV600E inhibition in thyroid tumor cells in vitro. Vemurafenib produces cytostatic effects in orthotopic tumors, whereas combined therapy (likely reflecting sorafenib activity) generates biological fluctuations with tumor inhibition alternating with tumor growth. We demonstrate that pericytes secrete TSP-1 and TGFβ1, and induce the rebound of pERK1/2, pAKT and pSMAD3 levels to overcome the inhibitory effects of the targeted therapy in PTC cells. This leads to increased BRAFV600E-PTC cell survival and cell death refractoriness. We find that BRAFWT/V600E-PTC clinical samples are enriched in pericytes, and TSP1 and TGFβ1 expression evoke gene-regulatory networks and pathways (TGFβ signaling, metastasis, tumor growth, tumor microenvironment/ECM remodeling functions, inflammation, VEGF ligand–VEGF receptor interactions, immune modulation, etc.) in the microenvironment essential for BRAFWT/V600E-PTC cell survival. Critically, antagonism of the TSP-1/TGFβ1 axis reduces tumor cell growth and overcomes drug resistance. Conclusions: Pericytes shield BRAFV600E-PTC cells from targeted therapy via TSP-1 and TGFβ1, suggesting this axis as a new therapeutic target for overcoming resistance to BRAFV600E and TK inhibitors.
Therapeutic effects of different Atorvastatin doses on vulnerable plaques in coronary arteries assessed by intracoronary optical coherence tomography

Abstract The aim of this study was to evaluate optical coherence tomography (OCT) as an assessment of the efficacy of atorvastatin treatment. Twenty-four acute coronary syndrome (ACS) patients were allocated to conventional-dose (20 mg atorvastatin, n = 12) and intensive-dose (40–80 mg atorvastatin, n = 12) groups and correlations between changes in the OCT measurements and blood routine indexes were analyzed 9 months post-percutaneous coronary intervention (PCI). Treatment with atorvastatin resulted in a significant increase in the target thin cap fibroatheroma (TCFA) fibrous cap thicknesses in both groups. The increase was bigger in the intensive-dose group than in the conventional-dose group (184.1 ± 57.4 &mgr;m vs. 125.1 ± 28.6, P = .005). The TCFA lipid core arc in both groups was significantly decreased compared with baseline (72.9 ± 29.3 vs. 127.6 ± 50.8, P < .01 and 74.6 ± 32.9 vs. 132.6 ± 51.3, P < .01, respectively). Correlation analyses showed an inverse relationship between low-density lipoprotein cholesterol (LDL-c) levels and the TCFA cap thickness, and a direct relationship between C-reactive protein (CRP) level and lipid core arc. Statins significantly increased the TCFA fibrous cap thickness and reduced the lipid core arc, and OCT measurements accurately reflected the levels of blood LDL-c and CRP. Trial registration: (Chinese Clinical Trial Registry) ChiCTR-IPR-17010874
Optimising seed processing techniques to improve germination and sowability of native grasses for ecological restoration.

Grasslands across the globe are undergoing expansive degradation due to human impacts and climate change. If restoration of degraded native grassland is to be achieved at the scale now required, cost-effective means for seed-based establishment of grass species is crucial. However, grass seeds present numerous challenges associated with handling and germination performance that must be overcome to improve the efficiency of seeding. Previous research has demonstrated that complete removal of the palea and lemma (husk) maximises germination performance, hence we investigated the effects of complete husk removal on seed handling and germination of four temperate Australian grass species. Three techniques were tested to remove the husk - manual cleaning, flaming or acid digestion (the latter two followed by a manual cleaning step); these techniques were refined and adapted to the selected species, and germination responses were compared. The complete removal of the husk improved seed handling and sowability for all species. Germination was improved in Microlaena stipoides by 19% and in Rytidosperma geniculatum by 11%. Of the husk removal methods tested, flaming was detrimental to seed germination and fatal for one species (R. geniculatum). Compared to manual cleaning, sulphuric acid improved the overall efficacy of the cleaning procedure and increased germination speed (T50) in Austrostipa scabra, Chloris truncata and M. stipoides, and improved final germination in R. geniculatum by 13%. The seed processing methods developed and tested in the present study can be applied to grass species that present similar handling and germination performance impediments. These and other technological developments (seed coating and precision sowing) will facilitate more efficient grassland restoration at large scale.
Occurrence and characterization of hyperviscous K1 and K2 serotype in Klebsiella pneumoniae

BACKGROUND: Klebsiella pneumoniae causes both nosocomial and community-associated infections. Hypervirulent K. pneumoniae (hvKP), new variant of K. pneumoniae, can cause invasive infections in young healthy individuals as well as in the immunocompromised population. Hypervirulent strains frequently belong to capsular serotypes K1 or K2. Emergence of antimicrobial resistance in hvKP is a cause for concern. AIM AND OBJECTIVE: The present study was done to detect the K1 and K2 serotypes among clinical isolates of K. pneumoniae, spectrum of infections caused by them and presence of common beta-lactamases encoding genes in them. MATERIALS AND METHODS: A total of 370 isolates of K. pneumoniae, isolated from various clinical samples over a period of 1 year was included in this study. Antibiotic susceptibility testing to various classes of antimicrobials was done as per Clinical and Laboratory Standard Institute guidelines. The presence of K2A (specific to serotype K2), magA (specific to serotype K1), and rmpA genes was detected by multiplex polymerase chain reaction (PCR). Extended-spectrum beta-lactamases (TEM, SHV, and CTX-M), plasmid-mediated AmpCs (MOX, CIT, DHA, ACC, EBC, and FOX), and carbapenemase genes (IMP, VIM, NDM, KPC, and OXA-48) were also determined by PCR. RESULTS: Among the 370 isolates, 8 harbored K2A gene and one harbored magA. rmpA gene was detected in three isolates along with K1 or K2 serotypes. Seven K2A- positive isolates were resistant to one or more classes of antimicrobials. The studied ESBL genes were present in four isolates. Two isolates harbored carbapenemase genes (NDM-1, OXA-48) along with ESBLs. CONCLUSION: K2 serotype is more prevalent among hvKP isolates. They can harbor ESBLs and Carbapenemase genes. K1 serotype is rather uncommon in K. pneumoniae. Acquisition of multidrug-resistant genes by these strains adds to their virulence and limits the treatment options.
Laparoscopic sleeve gastrectomy combined with single-anastomosis duodenal-jejunal bypass in the treatment of type 2 diabetes mellitus of patients with body mass index higher than 27.5 kg/m2 but lower than 32.5 kg/m2

Abstract This study aimed to introduce this surgical technique laparoscopic sleeve gastrectomy combined with single-anastomosis duodenal-jejunal bypass (LDJB-LSG), and to confirm this new surgical technique was safe in the treatment of type 2 diabetes mellitus (T2DM) of patients with body mass index (BMI) higher than 27.5 kg/m2 but lower than 32.5 kg/m2. A total of 34 T2DM patients with (BMI) higher than 27.5 kg/m2 but lower than 32.5 kg/m2 were admitted to our department between January 2014 and October 2016, of whom 25 received laparoscopic gastric bypass surgery (LRYGB) and 9 received LDJB-LSG. The efficacy and safety were compared between the 2 groups. None in both groups died and had severe postoperative complications. All the surgeries were performed by laparoscopy, and none received switching to open surgery. Patients received regular follow-up after surgery and none were lost to follow-up. Our study indicates LDJB-LSG is similar to LRYGB in the improvements of the body weight, blood glucose, insulin resistance, islet &bgr; cell function, blood lipid profile and serum uric acid, and thus LDJB-LSG is applicable in T2DM patients with 27.5 kg/m2 ⩽ BMI ⩽ 32.5 kg/m2 and risk for gastric cancer. However, long-term therapeutic effects need to be evaluated by studies with multicenter, large sample size, and long-term follow-ups.
Non-Small Cell Lung Cancer in Countries of Central and Southeastern Europe: Diagnostic Procedures and Treatment Reimbursement Surveyed by the Central European Cooperative Oncology Group.

This article analyzes the availability of different diagnostic procedures of non-small cell lung cancer (NSCLC) and the reimbursement landscape of drugs for NSCLC in countries of central and southeastern Europe (CEE). A survey was conducted by the Central European Cooperative Oncology Group. Results of the survey show that both availability and reimbursement of diagnoses of molecular alterations in NSCLC, the detection of which is essential for therapeutic decisions, varies widely between countries of CEE. Not only is "reflex" testing often substituted by analyses performed only "on demand," but reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. It was concluded that a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. IMPLICATIONS FOR PRACTICE: This article provides an overview of the limitations in lung cancer treatment in countries of central and southeastern Europe, as well as the reimbursement status of various lung cancer treatment regimens in these countries, which directly impacts treatment options.
Structural network topology correlates of microstructural brain dysmaturation in term infants with congenital heart disease

Neonates with complex congenital heart disease (CHD) demonstrate microstructural brain dysmaturation, but the relationship with structural network topology is unknown. We performed diffusion tensor imaging (DTI) in term neonates with CHD preoperatively (N = 61) and postoperatively (N = 50) compared with healthy term controls (N = 91). We used network topology (graph) analyses incorporating different weighted and unweighted approaches and subject‐specific white matter segmentation to investigate structural topology differences, as well as a voxel‐based analysis (VBA) to confirm the presence of microstructural dysmaturation. We demonstrate cost‐dependent network inefficiencies in neonatal CHD in the pre‐ and postoperative period compared with controls, related to microstructural differences. Controlling for cost, we show the presence of increased small‐worldness (hierarchical fiber organization) in CHD infants preoperatively, that persists in the postoperative period compared with controls, suggesting the early presence of brain reorganization. Taken together, topological microstructural dysmaturation in CHD infants is accompanied by hierarchical fiber organization during a protracted critical period of early brain development. Our methodology also provides a pipeline for quantitation of network topology changes in neonates and infants with microstructural brain dysmaturation at risk for perinatal brain injury.
Novel approaches for the treatment of ventricular tachycardia

Ventricular tachycardia (VT) is a crucial cause of sudden cardiac death (SCD) and a primary cause of mortality and morbidity in patients with structural cardiac disease. VT includes clinical disorders varying from benign to life-threatening. Most life-threatening episodes are correlated with coronary artery disease, but the risk of SCD varies in certain populations, with various underlying heart conditions, specific family history, and genetic variants. The targets of VT management are symptom alleviation, improved quality of life, reduced implantable cardioverter defibrillator shocks, prevention of reduction of left ventricular function, reduced risk of SCD, and improved overall survival. Antiarrhythmic drug therapy and endocardial catheter ablation remains the cornerstone of guideline-endorsed VT treatment strategies in patients with structural cardiac abnormalities. Novel strategies such as epicardial ablation, surgical cryoablation, transcoronary alcohol ablation, pre-procedural imaging, and stereotactic ablative radiotherapy are an appealing area of research. In this review, we gathered all recent advances in innovative therapies as well as experimental evidence focusing on different aspects of VT treatment that could be significant for future favorable clinical applications.
Spatial Vulnerabilities of the Escherichia coli Genome to Spontaneous Mutations Revealed with Improved Duplex Sequencing

Investigation of spontaneous mutations by next-generation sequencing technology has attracted extensive attention lately due to the fundamental roles of spontaneous mutations in evolution and pathological processes. However, these studies only focused on the mutations accumulated through many generations during long-term (possibly be years of) culturing, but not the freshly generated mutations that occur at very low frequencies. In this study, we established a molecularly barcoded deep sequencing strategy to detect low abundant spontaneous mutations in genomes of bacteria cell cultures. Genome-wide spontaneous mutations in 15 Escherichia coli cell culture samples were defined with a high confidence (P < 0.01). We also developed a hotspot-calling approach based on the run-length encoding algorithm to find the genomic regions that are vulnerable to the spontaneous mutations. The hotspots for the mutations appeared to be highly conserved across the bacteria samples. Further biological annotation of these regions indicated that most of the spontaneous mutations were located at the repeat domains or nonfunctional domains of the genomes, suggesting the existence of mechanisms that could somehow prevent the occurrence of mutations in crucial genic areas. This study provides a more faithful picture of mutation occurrence and spectra in a single expansion process without long-term culturing.
Excision repair cross-complementing group 1 (ERCC1) overexpression inhibits cell apoptosis and is associated with unfavorable prognosis of esophageal squamous cell carcinoma

Abstract Excision repair cross-complementing group 1 (ERCC1) functions as a nucleotide excision repair (NER) enzyme. Altered ERCC1 expression or function is closely associated with cancer development and progression. This study determined the association of ERCC1 expression with survivin expression, clinicopathological characteristics, and survival of esophageal squamous cell carcinoma (ESCC) patients after postoperative concurrent chemoradiotherapy. Tissue specimens from 102 resected ESCC patients were acquired for immunohistochemical analysis of ERCC1 and survivin protein expression. ERCC1 expression was detected in 62.7% of ESCC tissues and in 9.8% of normal squamous epithelium tissues (P < .01), while survivin expression was detected in 60.8% of ESCC tissues and in 19.6% of normal squamous epithelia (P < .01). ERCC1 overexpression associated with advanced tumor clinical stage and lymph node metastasis (P < .05), but not with tumor size, depth of invasion, or differentiation (P > .05). ERCC1 overexpression was also associated with survivin levels (r = 0.42, P < .01) and worse progression-free survival of ESCC patients after concurrent chemoradiotherapy. Multivariate analysis data revealed that ERCC1 and survivin protein expression were independent predictors of overall survival of ESCC patients after chemotherapy and/or radiotherapy (P < .05). ERCC1 overexpression is an important phenotype that is associated with ESCC lymph node metastasis and advanced tumor clinical stages. ERCC1 expression may also inhibit ESCC cell apoptosis via regulating survivin expression, and ERCC1 and survivin overexpression are independent predictors of prognosis for ESCC patients who receive chemotherapy and/or radiotherapy.