Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating cloud migration options for relational databases

Migrating the database layer remains a key challenge when moving a software system to a new cloud provider. The database is often very large, poorly documented, and used to store business-critical information. Most cloud providers offer a variety of services for hosting databases and the most suitable choice depends on the database size, workload, performance requirements, cost, and future business plans. Current approaches do not support this decision-making process, leading to errors and inaccurate comparisons between database migration options. The heterogeneity of databases and clouds means organisations often have to develop their own ad-hoc process to compare the suitability of cloud services for their system. This is time consuming, error prone, and costly. This thesis contributes to addressing these issues by introducing a three-phase methodology for evaluating cloud database migration options. The first phase defines the planning activities, such as, considering downtime tolerance, existing infrastructure, and information sources. The second phase is a novel method for modelling the structure and the workload of the database being migrated. This addresses database heterogeneity by using a multi-dialect SQL grammar and annotated text-to-model transformations. The final phase consumes the models from the second and uses discrete-event simulation to predict migration cost, data transfer duration, and cloud running costs. This involved the extension of the existing CloudSim framework to simulate the data transfer to a new cloud database. An extensive evaluation was performed to assess the effectiveness of each phase of the methodology and of the tools developed to automate their main steps. The modelling phase was applied to 15 real-world systems, and compared to the leading approach there was a substantial improvement in: performance, model completeness, extensibility, and SQL support. The complete methodology was applied to four migrations of two real-world systems. The results from this showed that the methodology provided significantly improved accuracy over existing approaches.
Therapeutic approaches to cholinergic deficiency in Lewy body diseases

ABSTRACT Introduction: Cortical cholinergic denervation resulting from degeneration of the nucleus basalis of Meynert (NBM) is a primary contributor to cognitive impairment and neuropsychiatric symptoms in the Lewy body diseases Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), and dementia with Lewy bodies (DLB). Considering the morbidity associated with cognitive impairment and neuropsychiatric symptoms in these diseases, it is important to investigate all potential therapies to improve these symptoms. Areas covered: The authors review the current landscape of pharmacological and surgical therapies for mitigating the cortical cholinergic deficiency in PD, PDD, and DLB. Expert opinion: The cholinesterase inhibitors rivastigmine, donepezil, and galantamine are currently the primary pharmacological treatments available to improve cognition and associated neuropsychiatric symptoms in Lewy body diseases. Other possible pharmacological strategies include increasing acetylcholine release with 5-HT4 agonists or directly stimulating cholinergic receptors with muscarinic and nicotinic agonists. The side effect profile of muscarinic agonists is a deterrent to their future study, but 5-HT4 and nicotinic agonists deserve further investigation. Targeting the basal forebrain with either deep brain stimulation (DBS)- or cell-based therapies is another strategy to mitigate cortical cholinergic deficiency. Before NBM DBS studies continue, it will be important to resolve issues related to targeting, stimulation pattern, and duration.
The role of preoperative albumin‐bilirubin grade for oncological risk stratification in liver transplant patients with hepatocellular carcinoma

Albumin‐bilirubin (ALBI) score was shown to correlate with liver function and tumor recurrence after hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to assess the prognostic value of ALBI grade in liver transplantation (LT) patients with HCC.
Vascularized composite allotransplantation versus solid organ transplantation: innate-adaptive immune interphase.

PURPOSE OF REVIEW Vascularized composite allotransplantation (VCA), a life-enhancing treatment for patients with complex tissue defects, trauma or illness, expounds upon the foundation of solid organ transplantation (SOT), the gold standard in end-stage organ failure. As innate and adaptive immunity remain the fundamental concern, this review highlights divergent immunobiology responses in VCA and SOT recipients. RECENT FINDINGS Host innate immune activation drives peritransplant tissue ischemia-reperfusion injury (IRI). Despite the direct relationship between ischemia-reperfusion (IR)-stress and cell-mediated acute rejection, the mechanism of how IRI may affect VCA loss needs investigation. With skin grafts being highly immunogenic, the incidence of cell-mediated rejection is higher in VCA than SOT; whereas ex-vivo perfusion may exert cytoprotection against IRI in VCA and SOT. New treatment concepts, such as topical immunosuppression or cell-based tolerogenic therapies, may avoid systemic immunosuppression in VCA. Although antibody-mediated rejection is relatively rare in VCA and its disease seems to be distinct from that in SOT, little is known as to whether and how IRI may influence humoral immune rejection cascade in VCA or SOT. SUMMARY Further understanding of the innate-adaptive immune crosstalk should contribute to much needed development of novel therapies to improve VCA outcomes, based on strategies established in SOT.
Peripheral neuropathies after bariatric surgery. Preliminary results from a single-centre prospective studyin Northern Italy

Introduction: Bariatric surgery (BS) has gained popularity in order to treat morbid obesity. However, post-operative (PO) neurologic complications have become increasingly recognized. Our aim was to examine incidence, clinical presentation, and outcomes of neurologic disorders secondary to BS. Methods: Patients who underwent BS between the years 2012 and 2015 at Parma University were included in this survey, and assessed before (T0) and 1 year after surgery (T1). Baseline characteristics and medical comorbidities, type of surgery, and PO complications were retrieved. Patients with a previous history of peripheral neuropathic disease were excluded from the analysis. If a patient presented with a new onset neurologic symptom including extremity numbness, paresthesia, muscle weakness, the status was considered “positive” for PO-neuropathy. Results: Overall, we retrieved data from 61 patients (n=30 Roux-en-Y Gastric bypasses, n=31 Gastric banding; 81.0% females). Of them, 7 (11.4%) developed some signs of PO-neuropathy, that eventually disappeared at T+24 months. The most common manifestations were paresthesia (n=6) and muscle weakness (n=4), similarly distributed in Gastric Bypass (n=4) and Gastric Banding (n=3) groups. Although patients affected by PO-neuropathy exhibited higher SF-36 score at T0 (p=0.018), no significant differences were found regarding BMI (T0, T1), percentual weight loss, serological data (i.e. vitamin B1, B2, B6, B12: in all cases p>0.05). Conclusion: PO-BS neuropathy is usually associated with lower levels of vitamin B1, B2, B12. However, no differences in PO-BMI, excess weight loss, and metabolic data levels were found. Larger data and more extended follow-up are required to validate our results. (www.actabiomedica.it)
Clinical Outcomes of an Asymmetric Model of Intrastromal Corneal Ring Segments for the Correction of Keratoconus.

PURPOSE To evaluate the clinical outcomes of a new model of intrastromal corneal ring segments (ICRSs) (Keraring AS) in patients with keratoconus and quantify subsequent changes in refraction and corneal topography. METHODS This nonrandomized, single-center, retrospective observational study explores the effect of progressive thickness ICRS implantation in patients with keratoconus with a 3-month follow-up. After creating an intrastromal tunnel using a femtosecond laser, 1 or 2 ICRSs of progressive thicknesses (150/250 μm or 200/300 μm) and 160-degree arc length were implanted. Changes in uncorrected distance visual acuity, best-corrected distance visual acuity, refractive outcomes, corneal astigmatism, and maximum keratometry readings were recorded before and after surgery. RESULTS The study cohort consisted of 82 patients (104 eyes) with a mean age of 31.2 ± 10 years. At 3 months, ICRS implantation significantly improved uncorrected and corrected visual acuities from 0.82 to 0.46 (logarithm of the minimum angle of resolution [LogMAR]) and from 0.31 to 0.21 (LogMAR), respectively (P < 0.001). The mean spherical error reduced from -1.74 diopters (D) to -0.90 D (P < 0.001), and the mean cylindrical error reduced from -4.22 D to -2.01 D (P < 0.001). The manifest refraction spherical equivalent reduced from -3.85 D to -1.91 D (P < 0.001). All topographic parameters were reduced, including maximum keratometry (53.6 D vs. 50.3 D) and keratometric astigmatism (-4.6 D vs. -2.2 D) (P < 0.001). CONCLUSIONS The Keraring AS provides a new, apparently safe, and effective means of improving visual acuity and reducing the refractive error and mean keratometry in eyes with asymmetric keratoconus.
The relationship between blood lead level and the severity of abdominal pain in opioid-addicted patients during a hospital outbreak

Abstract An increase in the incidence of abdominal pain in opioid abusers over a period of time increased the suspicion of lead poisoning. The severity of abdominal pain and its relationship with blood lead level (BLL) were investigated during a hospital outbreak. This was a descriptive, cross-sectional study on opioid-addicted patients presenting with abdominal pain. Pain severity was measured based on the numerical rating scale (NRS). Blood lead and serum uric acid levels were determined. The presence of basophilic stippling was sought in the peripheral blood smear. Also, the X-ray was performed to assess abdominal cavity. Of 239 patients, 160 opioid addicts presenting with abdominal pain participated in the study. There were significant associations between the severity of abdominal pain and the type of opioid, the route and, duration of opioid consumption, the presence of basophilic stippling in peripheral blood smear and radio-opaque opioids in abdominal X-ray, as well as BLL and serum uric acid level (P < 0.0001). Opium abuse is a common cause of lead poisoning in Iran. The patients with lead poisoning may present with abdominal pain. The severity of abdominal pain significantly correlated with BLL. Continuous screening of BLL is recommended in opioid abusers.
Prevalence of metabolic syndrome and its risk factors among 10,348 police officers in a large city of China

Abstract The aim of this study was to assess the prevalence of metabolic syndrome (MS) and its risk factors among the police officers in a large city of China. A cross-sectional study was conducted in 10,348 police officers in 2017 in Changsha, a provincial capital located in central-south China. All participants underwent a physical examination to measure the compotents of MS and completed a questionnaire to collect data on potential risk factors. According to the current guidelines of China, MS was defined as the presence of any 3 of the following five traits: abdominal obesity, defined as a waist circumference ≥90 cm in men and ≥85 cm in women; fasting serum triglycerides ≥1.70 mmol/L, or drug treatment for elevated triglycerides; fasting serum high-density lipoprotein cholesterol <1.03 mmol/L, or drug treatment for low high-density lipoprotein cholesterol; blood pressure ≥130/85 mmHg, or drug treatment for elevated blood pressure; fasting plasma glucose ≥6.1 mmol/L, or 2-hour plasma glucose ≥7.8 mmol/L after a 75-g oral glucose load, or drug treatment for elevated blood glucose. The prevalence of MS was 23.2% (95% confidence interval [CI]: 22.2%–24.2%). The main risk factors associated with MS were older age (odds ratio [OR] 1.546, 95% CI 1.431–1.670), being male (OR 11.256, 95%CI 7.147–17.726), alcohol consumption (OR 1.250, 95% CI 1.070–1.461), and tobacco use (OR 1.398, 95% CI 1.232–1.586). Exercise was associated with decreased risk of MS (OR 0.865, 95% CI 0.755–0.991). The prevalence of MS was low in the study population. Its risk factors were similar to those identified in the general population of China. Lifestyle intervention is warranted in policemen to reduce the risk of MS and prevent diabetes and cardiovascular disease.
Relationship of Biological Markers of Body Fat Distribution and Corticosteroidogenic Enzyme Activities in Women with Polycystic Ovary Syndrome

Abstract The aim of the study is to determine the impact of different anthropometric measurements of fat distribution on baseline sex-steroid concentrations and corticosteroidogenic enzyme activity in women with polycystic ovary syndrome compared to those with regular menstrual cycles. The current cross-sectional study included 106 normal cycling controls and 268 polycystic ovary syndrome patients. Patients with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided in normoandrogenemic (n=91) and hyperandrogenemic (n=177). Anthropometric, biochemical, and hormone parameters were assessed and correlated with corticosteroidogenic enzyme activities in all three groups. Corticosteroidogenic enzyme activities were calculated using product-to-precursor ratios. Regarding sex-steroids individually, anthropometric parameters correlated with the concentrations of several androgens in polycystic ovary syndrome patients, most of them in patients with biochemical hyperandrogenism. The androgen precursors androstenedione, 17-hydroxyprogesterone, and dehydroepiandrosterone were less correlated with anthropometric parameters. The 17,20 lyase activity, in both Δ4 and Δ5 pathways, correlated with several anthropometric measurements in normo- and hyperandrogenemic polycystic ovary syndrome patients. The 17,20 lyase enzyme activity (Δ4 pathway) also correlated with conicity index, visceral adiposity index, and lipid accumulation product in the control group. 17-Hydroxylase activity positively correlated with waist-height ratio in both polycystic ovary syndrome groups. In contrast, 17-hydroxilase negatively correlated with the conicity index. Anthropometric markers of adiposity are associated with androgen levels and their precursors in blood. Body fat distribution correlates with the activities of some steroidogenic enzyme in both normo-and hyperandrogenemic polycystic ovary syndrome phenotypes. The molecular mechanisms involved in these associations are largely unclear and more investigations are required.
Ligelizumab for Chronic Spontaneous Urticaria.

BACKGROUND In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose-response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists. METHODS In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose-response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial. RESULTS A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose-response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged. CONCLUSIONS A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.).
Allele-specific nonstationarity in evolution of influenza A virus surface proteins

Significance Control of rapidly evolving pathogens requires prediction of evolution. One obstacle to such predictions is the ever-changing environment, which determines strain fitness. Here, we show that fitness conferred by an amino acid variant at surface proteins of influenza A virus changes systematically with time since this variant appeared. The direction of this change depends on its functional role. At antigenic regions, variants become less fit with time. Conversely, variants at internal regions become more fit with time. This dynamic can be explained by a simple model: while the fitness of amino acids deeply embedded in the protein increases due to substitutions elsewhere, that of amino acids exposed to the immune system drops as herd immunity adapts to them. Influenza A virus (IAV) is a major public health problem and a pandemic threat. Its evolution is largely driven by diversifying positive selection so that relative fitness of different amino acid variants changes with time due to changes in herd immunity or genomic context, and novel amino acid variants attain fitness advantage. Here, we hypothesize that diversifying selection also has another manifestation: the fitness associated with a particular amino acid variant should decline with time since its origin, as the herd immunity adapts to it. By tracing the evolution of antigenic sites at IAV surface proteins, we show that an amino acid variant becomes progressively more likely to become replaced by another variant with time since its origin—a phenomenon we call “senescence. ” Senescence is particularly pronounced at experimentally validated antigenic sites, implying that it is largely driven by host immunity. By contrast, at internal sites, existing variants become more favorable with time, probably due to arising contingent mutations at other epistatically interacting sites. Our findings reveal a previously undescribed facet of adaptive evolution and suggest approaches for prediction of evolutionary dynamics of pathogens.
Peroxisome Proliferator–Activated Receptor-δ Acts within Peripheral Myeloid Cells to Limit Th Cell Priming during Experimental Autoimmune Encephalomyelitis

Key Points Deficiency of PPAR-δ in peripheral myeloid cells enhances EAE severity. Deficiency of PPAR-δ increases production of IL-12p40 homodimer by dendritic cells. Peroxisome proliferator-activated receptor (PPAR)-δ is a fatty acid–activated transcription factor that regulates metabolic homeostasis, cell growth, and differentiation. Previously, we reported that mice with a global deficiency of PPAR-δ develop an exacerbated course of experimental autoimmune encephalomyelitis (EAE), highlighting a role for this nuclear receptor in limiting the development of CNS inflammation. However, the cell-specific contribution of PPAR-δ to the more severe CNS inflammatory response remained unclear. In this study, we studied the specific involvement of PPAR-δ in myeloid cells during EAE using mice that had Cre-mediated excision of floxed Ppard driven by the lysozyme M (LysM) promoter (LysMCre:Ppardfl/fl). We observed that LysMCre:Ppardfl/fl mice were more susceptible to EAE and developed a more severe course of this disease compared with Ppardfl/fl controls. The more severe EAE in LysMCre:Ppardfl/fl mice was associated with an increased accumulation of pathogenic CD4+ T cells in the CNS and enhanced myelin-specific Th1 and Th17 responses in the periphery. Adoptive transfer EAE studies linked this EAE phenotype in LysMCre:Ppardfl/fl mice to heightened Th responses. Furthermore, studies using an in vitro CD11b+ cell:Th cell coculture system revealed that CD11b+CD11c+ dendritic cells (DC) from LysMCre:Ppardfl/fl mice had a heightened capacity to prime myelin oligodendrocyte glycoprotein (MOG)–specific Th cells compared with Ppardfl/fl counterparts; the effects of DC on Th1 cytokine production were mediated through production of the IL-12p40 homodimer. These studies revealed a role for PPAR-δ in DC in limiting Th cell priming during EAE.
Low serum level of sirtuin 1 predicts coronary atherosclerosis plaques during computed tomography angiography among an asymptomatic cohort.

OBJECTIVES Whether in asymptomatic populations levels of serum sirtuin 1 (Sirt1) are associated with coronary atherosclerosis plaque characteristics remains unclear. This article aims to evaluate the possibility of Sirt1 serum levels predicting high-risk coronary plaques revealed through computed tomography angiography (CTA). METHODS The current cross-sectional investigation was performed on patients from non high-risk plaque (HRP) group (control group) as well as HRP group. CTA was conducted and the Framingham Risk Score (FRS) was generated each patient. Serum Sirt1 level was determined through ELISA. Univariate analysis and receiver-operating characteristic curve were used to examine the role of Sirt1 to predict HRP. RESULTS Lower Sirt1 serum levels were observed in patients in the HRP group in comparison with those in the control group. Gender, hyperlipidemia, age, the total cholesterol to high-density lipoproteincholesterol (HDL-C) ratio, HDL-C, apolipoprotein B and Sirt1 displayed independent association with HRP as revealed by the univariate analysis. Area under curve of the univariate model for HRP was 0.848 (95% confidence interval: 0.798-0.899); 75.4% specificity, 75.2% sensitivity, the negative predictive value was 83.0%, and the positive predictive value was 66.2%. CONCLUSION Low serum level of Sirt1 predicted HRP in individuals with low-intermediate FRS, implying that Sirt1 may play a predictive role in the plaque screening before coronary CTA.