Miracle-dz/UniFAR-FTUs huggingface dataset:
Next Generation Cytogenetics in Myeloid Hematological Neoplasms: Detection of CNVs and Translocations

Simple Summary Conventional cytogenetic approaches are the gold standard for the identification of chromosomal alterations in myeloid neoplasms. Next-generation sequencing panels are a new approach for the detection of copy number variations (CNV) or translocations. Here we report on a commercial panel utility including frequent mutations, CNVs and translocations in myeloid neoplasms. A total of 135 patients with myeloid neoplasms and three with acute lymphoblastic leukemia were analyzed by NGS. When comparing with gold standard techniques, 48 frequent alterations were detected by both methodologies, ten of them observed only by conventional methods and another eight only by NGS. Additionally, 38 secondary CNVs were detected in any of the genes included in the panel for mutational analysis. With those results we determine that NGS represents a reliable complementary source of information for the analysis of CNVs and translocations. Abstract Conventional cytogenetics are the gold standard for the identification of chromosomal alterations recurrent in myeloid neoplasms. Some next-generation sequencing (NGS) panels are designed for the detection of copy number variations (CNV) or translocations; however, their use is far from being widespread. Here we report on the results of a commercial panel including frequent mutations, CNVs and translocations in myeloid neoplasms. Frequent chromosomal alterations were analyzed by NGS in 135 patients with myeloid neoplasms and three with acute lymphoblastic leukemia. NGS analysis was performed using the enrichment-capture Myeloid Neoplasm-GeneSGKit (Sistemas Genómicos, Spain) gene panel including 35 genes for mutational analysis and frequent CNVs and translocations. NGS results were validated with cytogenetics and/or MLPA when possible. A total of 66 frequent alterations included in NGS panel were detected, 48 of them detected by NGS and cytogenetics. Ten of them were observed only by cytogenetics (mainly trisomy 8), and another eight only by NGS (mainly deletion of 12p). Aside from this, 38 secondary CNVs were detected in any of the genes included mainly for mutational analysis. NGS represents a reliable complementary source of information for the analysis of CNVs and translocations. Moreover, NGS could be a useful tool for the detection of alterations not observed by conventional cytogenetics.
In Vitro Susceptibility to Miltefosine of Leishmania infantum (syn. L. chagasi) Isolates from Different Geographical Areas in Brazil

Treatment of visceral leishmaniasis in Brazil still relies on meglumine antimoniate, with less than ideal efficacy and safety, making new therapeutic tools an urgent need. The oral drug miltefosine was assayed in a phase II clinical trial in Brazil with cure rates lower than previously demonstrated in India. The present study investigated the susceptibility to miltefosine in 73 Brazilian strains of Leishmania infantum from different geographic regions, using intracellular amastigote and promastigote assays. The EC50 for miltefosine of 13 of these strains evaluated in intracellular amastigotes varied between 1.41 and 4.57 μM. The EC50 of the 73 strains determined in promastigotes varied between 5.89 and 23.7 μM. No correlation between in vitro miltefosine susceptibility and the presence of the miltefosine sensitive locus was detected among the tested strains. The relatively low heterogeneity in miltefosine susceptibility observed for the 73 strains tested in this study suggests the absence of decreased susceptibility to miltefosine in Brazilian L. infantum and does not exclude future clinical evaluation of miltefosine for VL treatment in Brazil.
Prenylated Flavonoid Glycosides with PCSK9 mRNA Expression Inhibitory Activity from the Aerial Parts of Epimedium koreanum

Phytochemical investigation on the n-BuOH-soluble fraction of the aerial parts of Epimedium koreanum using the PCSK9 mRNA monitoring assay led to the identification of four previously undescribed acylated flavonoid glycosides and 18 known compounds. The structures of new compounds were elucidated by NMR, MS, and other chemical methods. All isolated compounds were tested for their inhibitory activity against PCSK9 mRNA expression in HepG2 cells. Of the isolates, compounds 6, 7, 10, 15, and 17–22 were found to significantly inhibit PCSK9 mRNA expression. In particular, compound 7 was shown to increase LDLR mRNA expression. Thus, compound 7 may potentially increase LDL uptake and lower cholesterol levels in the blood.
Multidrug-Resistant Phenotypes of Escherichia coli Isolates in Wild Canarian Egyptian Vultures (Neophron percnopterus majorensis)

Simple Summary Increasing antimicrobial resistance is a global problem for both human and animal health. Escherichia coli is frequently used as a “sentinel” for antimicrobial resistance and as an indicator of faecal contamination of the environment. This study is a characterisation of the antimicrobial resistance phenotypes of E. coli isolates obtained from cloacal samples of Canarian Egyptian vultures. A total of 65 chickens and 38 adult and immature birds were studied. Antimicrobial susceptibility to 16 antibiotics of 12 different categories was determined in 103 E. coli isolates. We found a 39.8% prevalence of multidrug-resistant (MDR) E. coli. Almost all MDR phenotypes found included resistance to tetracycline, an antibiotic widely used in veterinary medicine. Resistance has also been found to chloramphenicol (13 MDR phenotypes), imipenem (5 MDR phenotypes) and others. Wild birds can act as reservoirs and disseminators of MDR E. coli, transferring them via faeces to the environment, feed or water. Our results highlight the need to minimise exposure of wild birds to antimicrobials from human activities to avoid the spread of antimicrobial resistance. Abstract The presence of multidrug-resistant (MDR) Escherichia coli in cloacal samples from Canarian Egyptian vultures was investigated. Samples were obtained from chicks (n = 65) and from adults and immature birds (n = 38). Antimicrobial susceptibility to 16 antibiotics included in 12 different categories was determined for 103 E. coli isolates. MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories. Forty-seven different resistance phenotypes were detected: 31 MDR (41 isolates) and 16 non-MDR (62 isolates). One isolate was resistant to all 12 antimicrobial categories and 2 phenotypes included resistance to 9 antimicrobial categories. Imipenem resistance was included in five MDR phenotypes, corresponding to five different isolates. Statistically significant differences in prevalence of MDR-phenotypes were found between chicks in nests and the rest of the animals, probably due to the shorter exposure time of chicks to antimicrobials. The main risk derived from MDR bacteria in scavengers is that it threatens the treatment of wild animals in rescue centres and could be transferred to other animals in the facilities. In addition to this, it could pose a health risk to veterinarians or other staff involved in wildlife protection programmes.
Robotic versus Laparoscopic Surgery for Spleen-Preserving Distal Pancreatectomies: Systematic Review and Meta-Analysis

Background: When oncologically feasible, avoiding unnecessary splenectomies prevents patients who are undergoing distal pancreatectomy (DP) from facing significant thromboembolic and infective risks. Methods: A systematic search of MEDLINE, Embase, and Web Of Science identified 11 studies reporting outcomes of 323 patients undergoing intended spleen-preserving minimally invasive robotic DP (SP-RADP) and 362 laparoscopic DP (SP-LADP) in order to compare the spleen preservation rates of the two techniques. The risk of bias was evaluated according to the Newcastle–Ottawa Scale. Results: SP-RADP showed superior results over the laparoscopic approach, with an inferior spleen preservation failure risk difference (RD) of 0.24 (95% CI 0.15, 0.33), reduced open conversion rate (RD of −0.05 (95% CI −0.09, −0.01)), reduced blood loss (mean difference of −138 mL (95% CI −205, −71)), and mean difference in hospital length of stay of −1.5 days (95% CI −2.8, −0.2), with similar operative time, clinically relevant postoperative pancreatic fistula (ISGPS grade B/C), and Clavien–Dindo grade ≥3 postoperative complications. Conclusion: Both SP-RADP and SP-LADP proved to be safe and effective procedures, with minimal perioperative mortality and low postoperative morbidity. The robotic approach proved to be superior to the laparoscopic approach in terms of spleen preservation rate, intraoperative blood loss, and hospital length of stay.
Nanoformulation Shows Cytotoxicity against Glioblastoma Cell Lines and Antiangiogenic Activity in Chicken Chorioallantoic Membrane

Glioblastoma (GB) is a histological and genetically heterogeneous brain tumor that is highly proliferative and vascularized. The prognosis is poor with currently available treatment. In this study, we evaluated the cytotoxicity and antiangiogenic activity of doxorubicin-loaded-chitosan-coated-arginylglycylaspartic acid-functionalized-poly(ε-caprolactone)-alpha bisabolol-LNC (AB-DOX-LNC-L-C-RGD). The nanoformulation was prepared by self-assembling followed by interfacial reactions, physicochemically characterized and evaluated in vitro against GB cell lines (U87MG and U138MG) and in vivo using the chicken chorioallantoic membrane assay (CAM). Spherical shape nanocapsules had a hydrodynamic mean diameter of 138 nm, zeta potential of +13.4 mV, doxorubicin encapsulation of 65%, and RGD conjugation of 92%. After 24 h of treatment (U87MG and U138MG), the median inhibition concentrations (IC50) were 520 and 490 nmol L−1 doxorubicin-equivalent concentrations, respectively. The treatment induced antiproliferative activity with S-phase cell-cycle arrest and apoptosis in the GB cells. Furthermore, after 48 h of exposure, evaluation of antiangiogenic activity (CAM) showed that the relative vessel growth following treatment with the nanocapsules was 5.4 times lower than that with the control treatment. The results support the therapeutic potential of the nanoformulation against GB and, thereby, pave the way for future preclinical studies.
Nucleoside Analogues Are Potent Inducers of Pol V-mediated Mutagenesis

Drugs targeting DNA and RNA in mammalian cells or viruses can also affect bacteria present in the host and thereby induce the bacterial SOS system. This has the potential to increase mutagenesis and the development of antimicrobial resistance (AMR). Here, we have examined nucleoside analogues (NAs) commonly used in anti-viral and anti-cancer therapies for potential effects on mutagenesis in Escherichia coli, using the rifampicin mutagenicity assay. To further explore the mode of action of the NAs, we applied E. coli deletion mutants, a peptide inhibiting Pol V (APIM-peptide) and metabolome and proteome analyses. Five out of the thirteen NAs examined, including three nucleoside reverse transcriptase inhibitors (NRTIs) and two anti-cancer drugs, increased the mutation frequency in E. coli by more than 25-fold at doses that were within reported plasma concentration range (Pl.CR), but that did not affect bacterial growth. We show that the SOS response is induced and that the increase in mutation frequency is mediated by the TLS polymerase Pol V. Quantitative mass spectrometry-based metabolite profiling did not reveal large changes in nucleoside phosphate or other central carbon metabolite pools, which suggests that the SOS induction is an effect of increased replicative stress. Our results suggest that NAs/NRTIs can contribute to the development of AMR and that drugs inhibiting Pol V can reverse this mutagenesis.
Assessment of Concentrated Liquid Coffee Acceptance during Storage: Sensory and Physicochemical Perspective

Concentrated liquid coffees (CLCs) refer to stored extracts stable at environmental temperature, used as ingredients in the retail market. Their low chemical stability affects the sensory profile. This study was performed in two CLCs, one without additives (BIB) and another with a mix of sodium benzoate and potassium sorbate additives (SD), stored at 25 °C for one year. Quantitative-Descriptive (QDA) and discriminant analyses permitted identifying the critical sensory attributes and their evolution over time. The concentrate without additives presented an acceptance limit of 196 days (evaluated at a 50% acceptance ratio), while the additives increased the shelf life up to 226 days (38.9% improvement). The rejection was related to a decreased aroma, increased acidity, and reduced bitterness. A bootstrapped feature selection version of Partial Least Square analysis further demonstrated that reactions of 5-caffeoylquinic acid (5CQA) and 3,5-dicaffeoylquinic acid (3,5diCQA) could cause changes in the aroma at the first degradation stage. In the following stages, changes in fructose and stearic acid contents, a key indicator of acceptance for both extracts possibly related to non-enzymatic reactions involving fructose and other compounds, might affect the bitterness and acidity. These results provided valuable information to understand flavor degradation in CLCs.
Highly Dissipative Materials for Damage Protection against Earthquake-Induced Structural Pounding

It is a common situation that seismic excitations may lead to collisions between adjacent civil engineering structures. This phenomenon, called earthquake-induced structural pounding, may result in serious damage or even the total collapse of the colliding structures. Filling the gap between two buildings erected close to one another by using visco-elastic materials can be considered to be one of the most effective methods to avoid seismic pounding. In this paper, a new polymer–metal composite material made of polyurethane and closed-cell aluminum foam is proposed as a pounding energy absorber for protection against earthquake hazards. The composite was created in two versions, with and without an adhesive interface. A series of experiments which reflect the conditions of seismic collision were performed: quasi-static compression, dynamic uniaxial compression and low-cycle dynamic compression with 10 loops of unloading at 10% strain. The composite material’s behavior was observed and compared with respect to uniform material specimens: polymer and metal foam. The experimental results showed that the maximum energy absorption efficiency in the case of the new material with the bonding layer was improved by 34% and 49% in quasi-static and dynamic conditions, respectively, in comparison to a sole polymer bumper. Furthermore, the newly proposed composites dissipated from 35% to 44% of the energy absorbed in the cyclic procedure, whereas the polymer specimen dissipated 25%. The capacity of the maintenance of the dissipative properties throughout the complete low-cycle loading was also satisfactory: it achieved an additional 100% to 300% of the energy dissipated in the first loading–unloading loop.
Cissus verticillata Extract Decreases Neuronal Damage Induced by Oxidative Stress in HT22 Cells and Ischemia in Gerbils by Reducing the Inflammation and Phosphorylation of MAPKs

In the present study, we examined the effects of Cissus verticillata leaf extracts (CVE) against hydrogen peroxide (H2O2)- and ischemia-induced neuronal damage in HT22 cells and gerbil hippocampus. Incubation with CVE produced concentration-dependent toxicity in HT22 cells. Significant cellular toxicity was observed with >75 μg/mL CVE. CVE treatment at 50 μg/mL ameliorated H2O2-induced reactive oxygen species formation, DNA fragmentation, and cell death in HT22 cells. In addition, incubation with CVE significantly mitigated the increase in Bax and decrease in Bcl-2 induced by H2O2 treatment in HT22 cells. In an in vivo study, the administration of CVE to gerbils significantly decreased ischemia-induced motor activity 1 d after ischemia, as well as neuronal death and microglial activation 4 d after ischemia, respectively. CVE treatment reduced the release of interleukin-1β, interleukin-6, and tumor necrosis factor-α 6 h after ischemia. Furthermore, CVE treatment significantly ameliorated ischemia-induced phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2, and p38. These results suggest that CVE has the potential to reduce the neuronal damage induced by oxidative and ischemic stress by reducing the inflammatory responses and phosphorylation of MAPKs, suggesting that CVE could be a functional food to prevent neuronal damage induced by ischemia.
Treatment of Urinary Tract Infections with Canephron® in Germany: A Retrospective Database Analysis

Objective: The goal of the present study was to evaluate treatment with Canephron® compared to standard antibiotic treatment after diagnosis of acute cystitis or urinary tract infection (UTI), with regard to the risk of sporadic recurrent UTIs, frequent recurrent UTIs, UTI-related sick leave, additional antibiotic prescriptions, and renal complications (pyelonephritis). Methods: This retrospective cohort study was based on data from the IMS® Disease Analyzer database (IQVIA), and included outpatients in Germany with at least one diagnosis of acute cystitis or UTI with a prescription of either Canephron® or standard antibiotics between January 2016 and June 2019 and treated in general practitioner (GP), gynecologist, or urologist practices, from which the data were obtained. Multivariable regression models were used to investigate the association between Canephron® prescription and the amount of sporadic or frequent recurrent UTIs, as well as the duration of UTI-related sick leave, the number of additional antibiotic prescriptions, and cases of pyelonephritis. The effects of Canephron® were adjusted for age, sex, insurance status, and Charlson comorbidity score (CCI). Results: 2320 Canephron® patients and 158,592 antibiotic patients were available for analysis. Compared to antibiotic prescription, Canephron® prescription was significantly associated with fewer sporadic recurrences of UTI infections 30–365 days after the index date (odds ratio (OR): 0.66; 95%, confidence interval (CI): 0.58–0.72), as well as less frequent recurrences of UTI infections (OR: 0.61; 95% CI: 0.49–0.88), and also with reduced additional antibiotic prescription within 31–365 days (OR: 0.57; 95% CI: 0.52–0.63). No significant differences were observed between the Canephron® and antibiotic cohorts with regard to the likelihood of sick leave (OR: 0.99; 95% CI: 0.86–1.14), new antibiotic prescription within 1–30 days (OR: 1.01; 95% CI: 0.87–1.16), or occurrence of pyelonephritis (Hazard Ratio (HR): 1.00; 95% CI: 0.67–1.48). Conclusion: These real-world data show that Canephron® is an effective, safe symptomatic treatment for acute cystitis or UTI. It should be considered as an alternative treatment, particularly to also strengthen antimicrobial stewardship strategies.
Toxicity and Antioxidant Activity of Fullerenol C60,70 with Low Number of Oxygen Substituents

Fullerene is a nanosized carbon structure with potential drug delivery applications. We studied the bioeffects of a water-soluble fullerene derivative, fullerenol, with 10-12 oxygen groups (F10-12); its structure was characterized by IR and XPS spectroscopy. A bioluminescent enzyme system was used to study toxic and antioxidant effects of F10-12 at the enzymatic level. Antioxidant characteristics of F10-12 were revealed in model solutions of organic and inorganic oxidizers. Low-concentration activation of bioluminescence was validated statistically in oxidizer solutions. Toxic and antioxidant characteristics of F10-12 were compared to those of homologous fullerenols with a higher number of oxygen groups:F24-28 and F40-42. No simple dependency was found between the toxic/antioxidant characteristics and the number of oxygen groups on the fullerene’s carbon cage. Lower toxicity and higher antioxidant activity of F24-28 were identified and presumptively attributed to its higher solubility. An active role of reactive oxygen species (ROS) in the bioeffects of F10-12 was demonstrated. Correlations between toxic/antioxidant characteristics of F10-12 and ROS content were evaluated. Toxic and antioxidant effects were related to the decrease in ROS content in the enzyme solutions. Our results reveal a complexity of ROS effects in the enzymatic assay system.
Dopant-Dependent Electrical and Biological Functionality of PEDOT in Bioelectronics

The aspiration to interact living cells with electronics challenges researchers to develop materials working at the interface of these two distinct environments. A successful interfacing coating should exhibit both biocompatibility and desired functionality of a bio-integrated device. Taking into account biodiversity, the tissue interface should be fine-tuned to the specific requirements of the bioelectronic systems. In this study, we pointed to electrochemical doping of conducting polymers as a strategy enabling the efficient manufacturing of interfacing platforms, in which features could be easily adjusted. Consequently, we fabricated conducting films based on a poly(3,4-ethylenedioxythiophene) (PEDOT) matrix, with properties modulated through doping with selected ions: PSS− (poly(styrene sulfonate)), ClO4− (perchlorate), and PF6− (hexafluorophosphate). Striving to extend the knowledge on the relationships governing the dopant effect on PEDOT films, the samples were characterized in terms of their chemical, morphological, and electrochemical properties. To investigate the impact of the materials on attachment and growth of cells, rat neuroblastoma B35 cells were cultured on their surface and analyzed using scanning electron microscopy and biological assays. Eventually, it was shown that through the choice of a dopant and doping conditions, PEDOT-based materials can be efficiently tuned with diversified physicochemical properties. Therefore, our results proved electrochemical doping of PEDOT as a valuable strategy facilitating the development of promising tissue interfacing materials with characteristics tailored as required.
Genetic Variation and Cardiovascular Risk Factors: A Cohort Study on Migrants from the Former Soviet Union and a Native German Population

Resettlers are a large migrant group of more than 2 million people in Germany who migrated mainly from the former Soviet Union to Germany after 1989. We sought to compare the distribution of the major risk factors for cardiovascular disease (CVD) and to investigate the overall genetic differences in a study population which consisted of resettlers and native (autochthone) Germans. This was a joint analysis of two cohort studies which were performed in the region of Augsburg, Bavaria, Germany, with 3363 native Germans and 363 resettlers. Data from questionnaires and physical examinations were used to compare the risk factors for cardiovascular diseases between the resettlers and native Germans. A population-based genome-wide association analysis was performed in order to identify the genetic differences between the two groups. The distribution of the major risk factors for CVD differed between the two groups. The resettlers lead a less active lifestyle. While female resettlers smoked less than their German counterparts, the men showed similar smoking behavior. SNPs from three genes (BTNL2, DGKB, TGFBR3) indicated a difference in the two populations. In other studies, these genes have been shown to be associated with CVD, rheumatoid arthritis and osteoporosis, respectively.