Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of peripheral nerve and autonomic nervous system function and the stage of microangiopathy in patients with secondary Raynaud's phenomenon in the course of connective tissue diseases.

BACKGROUND The pathogenesis of secondary Raynaud's phenomenon (SRP) associated with connective tissue diseases (CTD) is not entirely understood. Nervous system dysfunction and microangiopathy are considered to be causes of this pathology. OBJECTIVES Peripheral and autonomic nervous system function, the stage of microangiopathy, and the relationships between these in patients with SRP were analyzed. MATERIAL AND METHODS In the study, 20 patients with CTD-related SRP and 30 healthy controls were subject to capillaroscopy, standard conduction velocity tests and conduction velocity distribution (CVD) tests in ulnar and peroneal nerves, heart rate variability (HRV), and sympathetic skin response (SSR) tests. RESULTS There were no significant differences in the standard motor and sensory conduction velocity tests, or in CVD tests in the ulnar and peroneal nerves in SRP patients compared with the controls. The patients with SRP had a significantly lower SSR amplitude and longer latency in hands and feet. The patients with CTD-related SRP had a significantly lower mean HRV with higher low frequency (LF) values in the spectral analysis and expiration/inspiration ratio (E/I) during deep breathing. There was no correlation between the stage of microangiopathy and neurophysiological test results. CONCLUSIONS Correct standard conduction velocity and CVD testing in patients with SPR suggest that vasomotor disturbances may occur in CTD regardless of peripheral neuropathy. The lack of relationship between SSR and microangiopathy could confirm that these 2 processes occur independently in patients with CTD-related SRP. Autonomic nervous system impairment together with normal peripheral nerve function suggest the central origin of CTD-related SRP.
Bone-specific Alkaline Phosphatase – a Potential Biomarker for Skeletal Growth Assessment

Objective The present study was aimed to assess levels of serum Bone-specific alkaline phosphatase (BALP) and serum Insulin-like growth factor-1 (IGF-1) and comparing with cervical vertebral maturation index (CVMI) stages. Design Cross-sectional study. Setting Maulana Azad Institute of Dental Sciences, New Delhi, India. Participants 150 subjects (75 males and 75 females) in the age group of 8–20 years. Methods Subjects were divided into six CVMI stages. Enzyme-linked immunosorbant assay was performed for the estimation of serum BALP and serum IGF-1 levels. Mann–Whitney U test was performed to compare mean ranks of serum BALP and serum IGF-1 with different CVMI stages. Spearman correlation between serum BALP and serum IGF-1 was done across 6 CVMI stages. Results Peak serum IGF-1 levels were found at CVMI stages 4 and 3 for males and females respectively. Peak levels for serum BALP were found at stage 3 for both genders with significant differences from other stages. A statistically significant correlation was seen between serum IGF-1 and serum BALP from CVMI stages 1 to 3 and 4 to 6 (p < .01). Conclusions BALP showed promising results and can be employed as a potential biomarker for the estimation of growth status.
Antioxidant effect of thiazolidine molecules in cell culture media improves stability and performance

The ability of cell culture media components to generate reactive species as well as their sensitivity to oxidative degradation, affects the overall stability of media and the behavior of cells cultured in vitro. This study investigates the influence of thiazolidine molecules, formed from the condensation between cysteine and alpha‐ketoacids, on the stability of these complex mixtures and on the performance of cell culture processes aiming to produce therapeutically relevant monoclonal antibodies. Results presented in this study indicate that 2‐methyl‐1,3‐thiazolidine‐2,4‐dicarboxylic acid and 2‐(2‐carboxyethyl)−1,3‐thiazolidine‐2,4‐dicarboxylic acid, obtained by condensation of cysteine with pyruvate or alpha‐ketoglutarate, respectively, are able to stabilize cell culture media formulations, in particular redox sensitive molecules like folic acid, thiamine, l‐methionine (met) and l‐tryptophan (trp). The use of thiazolidine containing feeds in Chinese hamster ovary fed‐batch processes showed prolonged culture duration and increased productivity. This enhanced performance was correlated with lower reactive species generation, extracellularly and intracellularly. Moreover, an anti‐oxidative response was triggered via the induction of superoxide dismutase and an increase in the total glutathione pool, the major intracellular antioxidant. In total, the results confirm that cells in vitro are not cultured in an oxidant‐free environment, a concept that has to be considered when studying the influence of reactive species in human diseases. Furthermore, this study indicates that thiazolidines are an interesting class of antioxidant molecules, capable of increasing cell culture media stability and process performance. © 2017 American Institute of Chemical Engineers Biotechnol. Prog. , 33:759–770, 2017
Anxiety and depression in patients with end-stage renal disease: impact and management challenges – a narrative review

Psychiatric disorders commonly co-exist with the diagnosis of chronic kidney disease (CKD). Research on depression and CKD has increased to a great extent. Multiple studies have demonstrated that depression is more prevalent in CKD and that end-stage renal disease is a robust risk factor for adverse outcomes such as hospitalization and mortality, yet these are often underdiagnosed or untreated. This review provides a selective overview on the prevalence rates of depression and anxiety in patients with CKD and across renal replacement therapies, the factors most consistently associated with symptoms of distress and their clinical implications. Finally, treatment and management strategies from relevant literature are appraised and discussed.
SETDB1 Is Involved in Postembryonic DNA Methylation and Gene Silencing in Drosophila

DNA methylation is fundamental for the stability and activity of genomes. Drosophila melanogaster and vertebrates establish a global DNA methylation pattern of their genome during early embryogenesis. Large-scale analyses of DNA methylation patterns have uncovered revealed that DNA methylation patterns are dynamic rather than static and change in a gene-specific fashion during development and in diseased cells. However, the factors and mechanisms involved in dynamic, postembryonic DNA methylation remain unclear. Methylation of lysine 9 in histone H3 (H3-K9) by members of the Su(var)3–9 family of histone methyltransferases (HMTs) triggers embryonic DNA methylation in Arthropods and Chordates. Here, we demonstrate that Drosophila SETDB1 (dSETDB1) can mediate DNA methylation and silencing of genes and retrotransposons. We found that dSETDB1 tri-methylates H3-K9 and binds methylated CpA motifs. Tri-methylation of H3-K9 by dSETDB1 mediates recruitment of DNA methyltransferase 2 (Dnmt2) and Su(var)205, the Drosophila ortholog of mammalian “Heterochromatin Protein 1”, to target genes for dSETDB1. By enlisting Dnmt2 and Su(var)205, dSETDB1 triggers DNA methylation and silencing of genes and retrotransposons in Drosophila cells. DSETDB1 is involved in postembryonic DNA methylation and silencing of Rt1b{} retrotransposons and the tumor suppressor gene retinoblastoma family protein 1 (Rb) in imaginal discs. Collectively, our findings implicate dSETDB1 in postembryonic DNA methylation, provide a model for silencing of the tumor suppressor Rb, and uncover a role for cell type-specific DNA methylation in Drosophila development.
Associations of Forest Type, Parasitism and Body Condition of Two European Passerines, Fringilla coelebs and Sylvia atricapilla

Human-induced forest modification can alter parasite-host interactions and might change the persistence of host populations. We captured individuals of two widespread European passerines (Fringilla coelebs and Sylvia atricapilla) in southwestern Germany to disentangle the associations of forest types and parasitism by haemosporidian parasites on the body condition of birds. We compared parasite prevalence and parasite intensity, fluctuating asymmetries, leukocyte numbers, and the heterophil to lymphocyte ratio (H/L-ratio) among individuals from beech, mixed-deciduous and spruce forest stands. Based on the biology of bird species, we expected to find fewer infected individuals in beech or mixed-deciduous than in spruce forest stands. We found the highest parasite prevalence and intensity in beech forests for F. coelebs. Although, we found the highest prevalence in spruce forests for S. atricapilla, the highest intensity was detected in beech forests, partially supporting our hypothesis. Other body condition or health status metrics, such as the heterophil to lymphocyte ratio (H/L-ratio), revealed only slight differences between bird populations inhabiting the three different forest types, with the highest values in spruce for F. coelebs and in mixed-deciduous forests for S. atricapilla. A comparison of parasitized versus non-parasitized individuals suggests that parasite infection increased the immune response of a bird, which was detectable as high H/L-ratio. Higher infections with blood parasites for S. atricapilla in spruce forest indicate that this forest type might be a less suitable habitat than beech and mixed-deciduous forests, whereas beech forests seem to be a suboptimal habitat regarding parasitism for F. coelebs.
In Silico Estimation of Chemical Carcinogenicity with Binary and Ternary Classification Methods

Carcinogenicity is one of the most concerned properties of chemicals to human health, thus it is important to identify chemical carcinogenicity as early as possible. In this study, 829 diverse compounds with rat carcinogenicity were collected from Carcinogenic Potency Database (CPDB). Using six types of fingerprints to represent the molecules, 30 binary and ternary classification models were generated to predict chemical carcinogenicity by five machine learning methods. The models were evaluated by an external validation set containing 87 chemicals from ISSCAN database. The best binary model was developed by MACCS keys and kNN algorithm with predictive accuracy at 83.91 %, while the best ternary model was also generated by MACCS keys and kNN algorithm with overall accuracy at 80.46 %. Furthermore, the best binary and ternary classification models were used to estimate carcinogenicity of tobacco smoke components containing 2251 compounds. 981 ones were predicted as carcinogens by binary classification model, while 110 compounds were predicted as strong carcinogens and 807 ones as weak carcinogens by ternary classification model. The results indicated that our models would be helpful for prediction of chemical carcinogenicity.
Evolving treatment implementation among HIV–infected pregnant women and their partners: results from a national surveillance study in Italy, 2001–2015

Background The current global and national indications for antiretroviral treatment (ART, usually triple combination therapy) in adolescent and adults, including pregnant women, recommend early ART before immunologic decline, pre–exposure chemoprophylaxis (PrEP), and treatment of HIV–negative partners in serodiscordant couples. There is limited information on the implementation of these recommendations among pregnant women with HIV and their partners. Methods The present analysis was performed in 2016, using data from clinical records of pregnant women with HIV, followed between 2001 and 2015 at hospital or university clinics within a large, nationally representative Italian cohort study. The study period was divided in three intervals of five years each (2001–2005, 2006–2010, 2011–2015), and the analysis evaluated temporal trends in rates of HIV diagnosis in pregnancy, maternal antiretroviral treatment at conception, prevalence of HIV infection among partners of pregnant women with HIV, and proportion of seronegative and seropositive male partners receiving antiretroviral treatment. Results The analysis included 2755 pregnancies in women with HIV. During the three time intervals considered the rate of HIV diagnosis in pregnancy (overall 23.3%), and the distribution of HIV status among male partners (overall 48.7% HIV–negative, 28.6% HIV–positive and 22.8% unknown) remained substantially unchanged. Significant increases were observed in the proportion of women with HIV diagnosed before pregnancy who were on antiretroviral treatment at conception (from 62.0% in 2001–2005 to 81.3% in 2011–2015, P < 0.001), and in the proportion of HIV–positive partners on antiretroviral treatment (from 73.3% in 2001–2005 to 95.8% in 2011–2015, P = 0.002). Antiretroviral treatment was administered in 99.1% of the pregnancies that did not end early because of miscarriage, termination, or intrauterine death, and in 75.3% of those not ending in a live birth. No implementation of antiretroviral treatment was introduced among male HIV–negative partners. Conclusions The results suggest good implementation of antiretroviral treatment among HIV–positive women and their HIV–positive partners, but no implementation, even in recent years, of Pre–Exposure Prophylaxis (PrEP) among uninfected male partners. Further studies should assess the determinants of this occurrence and clarify the attitudes and the potential barriers to PrEP use.
New Antibacterial Phenone Derivatives Asperphenone A–C from Mangrove-Derived Fungus Aspergillus sp. YHZ-1

Marine fungi are a promising source of novel bioactive natural products with diverse structure. In our search for new bioactive natural products from marine fungi, three new phenone derivatives, asperphenone A–C (1–3), have been isolated from the ethyl acetate extract of the fermentation broth of the mangrove-derived fungus, Aspergillus sp. YHZ-1. The chemical structures of these natural products were elucidated on the basis of mass spectrometry, one- and two-dimensional NMR spectroscopic analysis and asperphenone A and B were confirmed by single-crystal X-ray crystallography. Compounds 1 and 2 exhibited weak antibacterial activity against four Gram-positive bacteria, Staphylococcus aureus CMCC(B) 26003, Streptococcus pyogenes ATCC19615, Bacillus subtilis CICC 10283 and Micrococcus luteus, with the MIC values higher than 32.0 µM.
CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest

Research into the biology of soft tissue sarcomas has uncovered very few effective treatment strategies that improve upon the current standard of care which usually involves surgery, radiation, and chemotherapy. Many patients with large (>5 cm), high-grade sarcomas develop recurrence, and at that point have limited treatment options available. One challenge is the heterogeneity of genetic drivers of sarcomas, and many of these are not validated targets. Even when such genes are tractable targets, the rarity of each subtype of sarcoma makes advances in research slow. Here we describe the development of a synergistic combination treatment strategy that may be applicable in both soft tissue sarcomas as well as sarcomas of bone that takes advantage of targeting the cell cycle. We show that Rb-positive cell lines treated with the CDK4/6 inhibitor palbociclib reversibly arrest in the G1 phase of the cell cycle, and upon drug removal cells progress through the cell cycle as expected within 6–24 hours. Using a long-term high-throughput assay that allows us to examine drugs in different sequences or concurrently, we found that palbociclib-induced cell-cycle arrest poises Rb-positive sarcoma cells (SK-LMS1 and HT-1080) to be more sensitive to agents that work preferentially in S–G2 phase such as doxorubicin and Wee1 kinase inhibitors (AZD1775). The synergy between palbociclib and AZD1775 was also validated in vivo using SK-LMS1 xenografts as well as Rb-positive patient-derived xenografts (PDX) developed from leiomyosarcoma patients. This work provides the necessary preclinical data in support of a clinical trial utilizing this treatment strategy. Mol Cancer Ther; 16(9); 1751–64. ©2017 AACR.
Priority Queue Based Reactive Buffer Management Policy for Delay Tolerant Network under City Based Environments

Delay Tolerant Network (DTN) multi-copy routing protocols are privileged to create and transmit multiple copies of each message that causes congestion and some messages are dropped. This process is known as reactive drop because messages were dropped re-actively to overcome buffer overflows. The existing reactive buffer management policies apply a single metric to drop source, relay and destine messages. Hereby, selection to drop a message is dubious because each message as source, relay or destine may have consumed dissimilar magnitude of network resources. Similarly, DTN has included time to live (ttl) parameter which defines lifetime of message. Hence, when ttl expires then message is automatically destroyed from relay nodes. However, time-to-live (ttl) is not applicable on messages reached at their destinations. Moreover, nodes keep replicating messages till ttl expires even-though large number of messages has already been dispersed. In this paper, we have proposed Priority Queue Based Reactive Buffer Management Policy (PQB-R) for DTN under City Based Environments. The PQB-R classifies buffered messages into source, relay and destine queues. Moreover, separate drop metric has been applied on individual queue. The experiment results prove that proposed PQB-R has reduced number of messages transmissions, message drop and increases delivery ratio.
Influence of vacancy defects on the damage mechanics of graphene nanoribbons

Using molecular dynamics simulations, graphene nanoribbons with armchair chirality were subjected to displacement-controlled uniaxial tension until complete fracture at 300 K in order to understand their damage mechanics. Graphene nanoribbons with and without a vacancy defect were simulated to compare the effect of the defect on the fracture behavior. Simulations were performed for graphene nanoribbons with lengths ranging from 2.5 to 15 nm. The stress–strain curve of each case is reported, and the influence of defect on the material properties is discussed. For each sample, damage mechanics types were observed and discussed. Results show a negligible effect of the single vacancy defect on the ultimate strength of the graphene nanoribbon. However, having a single vacancy defect does influence the failure strain, as well as the damage mechanics past the ultimate stress point.
Life-Span Exposure to Low Doses of Aspartame Beginning during Prenatal Life Increases Cancer Effects in Rats

Background In a previous study conducted at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the first time that aspartame (APM) is a multipotent carcinogenic agent when various doses are administered with feed to Sprague-Dawley rats from 8 weeks of age throughout the life span. Objective The aim of this second study is to better quantify the carcinogenic risk of APM, beginning treatment during fetal life. Methods We studied groups of 70–95 male and female Sprague-Dawley rats administered APM (2,000, 400, or 0 ppm) with feed from the 12th day of fetal life until natural death. Results Our results show a) a significant dose-related increase of malignant tumor–bearing animals in males (p < 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a significant increase in incidence of lymphomas/leukemias in males treated with 2,000 ppm (p < 0.05) and a significant dose-related increase in incidence of lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p < 0.01); and c) a significant dose-related increase in incidence of mammary cancer in females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05). Conclusions The results of this carcinogenicity bioassay confirm and reinforce the first experimental demonstration of APM’s multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans. Furthermore, the study demonstrates that when life-span exposure to APM begins during fetal life, its carcinogenic effects are increased.
Combining fragmentation and encryption to protect privacy in data storage

The impact of privacy requirements in the development of modern applications is increasing very quickly. Many commercial and legal regulations are driving the need to develop reliable solutions for protecting sensitive information whenever it is stored, processed, or communicated to external parties. To this purpose, encryption techniques are currently used in many scenarios where data protection is required since they provide a layer of protection against the disclosure of personal information, which safeguards companies from the costs that may arise from exposing their data to privacy breaches. However, dealing with encrypted data may make query processing more expensive. In this article, we address these issues by proposing a solution to enforce the privacy of data collections that combines data fragmentation with encryption. We model privacy requirements as confidentiality constraints expressing the sensitivity of attributes and their associations. We then use encryption as an underlying (conveniently available) measure for making data unintelligible while exploiting fragmentation as a way to break sensitive associations among attributes. We formalize the problem of minimizing the impact of fragmentation in terms of number of fragments and their affinity and present two heuristic algorithms for solving such problems. We also discuss experimental results, comparing the solutions returned by our heuristics with respect to optimal solutions, which show that the heuristics, while guaranteeing a polynomial-time computation cost are able to retrieve solutions close to optimum.
Folate and B12 serum levels in association with depression in the aged: a systematic review and meta-analysis

Objectives: To systematically review and meta-analyse existing evidence on the association between folate/B12, and depression among the aged people. Methods: Following PRISMA/STROBE guidelines, the Medline abstracts were retrieved using an algorithm comprising relevant MeSH terms. Publications on the association of folate/B12 serum measurements with depression were abstracted independently by two reviewers and included in both gender and gender-specific meta-analyses, following recarculations of published data as appropriate. The Newcastle-Ottawa scale was used to evaluate the quality of included studies. Results: Both gender data were contributed by 11 folate-related (7949 individuals) and 9 B12-related studies (6308 individuals), whereas gender-specific data by 4 folate-related (3409 individuals) and 3 B12-related studies (1934 individuals). A statistically significant overall association between both exposures of interest (low folate and B12 levels) and depression was observed (ORfolate:1.23, 95%CI:1.07–1.43, ORB12:1.20, 95%CI:1.02–1.42). Gender-specific estimates pointed to a statistically significant positive association between low B12 levels and depression only among women (OR:1.33, 95%CI:1.02–1.74); the gender specific associations of low folate levels with depression were, however, non-significant and of counter-direction (ORfemales:1.37, 95%CI:0.90–2.07; ORmales:0.84, 95%CI:0.57–1.25). Conclusion: Low folate and B12 serum levels seem to be associated with depression in the aged. The gender-specific analyses are confined to a positive association of low B12 with depression among older women and call for further research in this direction.