bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome Missegregation in Single Human Oocytes Is Related to the Age and Gene Expression Profile
Authors: Barone Stefano , Sarogni Patrizia , Valli Roberto , Pallotta Maria Michela , Silvia Gazzi , Frattini Annalisa , Khan Abdul Waheed , Rapalini Erika , Parri Cristiana , Musio Antonio
Published: March 2020

The growing trend for women to postpone childbearing has resulted in a dramatic increase in the incidence of aneuploid pregnancies. Despite the importance to human reproductive health, the events precipitating female age-related meiotic errors are poorly understood. To gain new insight into the molecular basis of age-related chromosome missegregation in human oocytes, we combined the transcriptome profiles of twenty single oocytes (derived from females divided into two groups according to age <35 and ≥35 years) with their chromosome status obtained by array comparative genomic hybridization (aCGH). Furthermore, we compared the transcription profile of the single oocyte with the surrounding cumulus cells (CCs). RNA-seq data showed differences in gene expression between young and old oocytes. Dysregulated genes play a role in important biological processes such as gene transcription regulation, cytoskeleton organization, pathways related to RNA maturation and translation. The comparison of the transcription profile of the oocyte and the corresponding CCs highlighted the differential expression of genes belonging to the G protein-coupled receptor superfamily. Finally, we detected the loss of a X chromosome in two oocytes derived from women belonging to the ≥35 years age group. These aneuploidies may be caused by the detriment of REEP4, an endoplasmic reticulum protein, in women aged ≥35 years. Here we gained new insight into the complex regulatory circuit between the oocyte and the surrounding CCs and uncovered a new putative molecular basis of age-related chromosome missegregation in human oocytes.
Epigenetic Modification of CFTR in Head and Neck Cancer
Authors: Shin Yonghwan , Kim Minkyoung , Won Jonghwa , Kim Junchul , Oh Seog Bae , Lee Jong-Ho , Park Kyungpyo
Published: March 2020

Cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, is critical for secretion and absorption across diverse epithelia. Mutations or absence of CFTR result in pathogeneses, including cancer. While CFTR has been proposed as a tumor suppressing gene in tumors of the intestine, lung, and breast cancers, its effects in head and neck cancer (HNC) have yet to be investigated. This study aimed to define expression patterns and epigenetic modifications of CFTR in HNC. CFTR was expressed in normal but not in HNC cells and tissues. Treatment with 5-aza-2′-deoxycytidine (5-Aza-CdR) was associated with rescued expression of CFTR, whose function was confirmed by patch clamp technique. Further experiments demonstrated that CFTR CpG islands were hypermethylated in cancer cells and tissues and hypomethylated in normal cells and tissue. Our results suggest that CFTR epigenetic modifications are critical in both down-regulation and up-regulation of CFTR expression in HNC and normal cells respectively. We then investigated the impact of CFTR on expressions and functions of cancer-related genes. CFTR silencing was closely associated with changes to other cancer-related genes, suppressing apoptosis while enhancing proliferation, cell motility, and invasion in HNC. Our findings demonstrate that hypermethylation of CFTR CpG islands and CFTR deficiency is closely related to HNC.
Glucocerebrosidase: Functions in and Beyond the Lysosome
Authors: Boer Daphne E.C. , van Smeden Jeroen , Bouwstra Joke A. , Aerts Johannes M.F.G
Published: March 2020

Glucocerebrosidase (GCase) is a retaining β-glucosidase with acid pH optimum metabolizing the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose. Inherited deficiency of GCase causes the lysosomal storage disorder named Gaucher disease (GD). In GCase-deficient GD patients the accumulation of GlcCer in lysosomes of tissue macrophages is prominent. Based on the above, the key function of GCase as lysosomal hydrolase is well recognized, however it has become apparent that GCase fulfills in the human body at least one other key function beyond lysosomes. Crucially, GCase generates ceramides from GlcCer molecules in the outer part of the skin, a process essential for optimal skin barrier property and survival. This review covers the functions of GCase in and beyond lysosomes and also pays attention to the increasing insight in hitherto unexpected catalytic versatility of the enzyme.
Prevalence of the Genus Propionibacterium in Primary and Persistent Endodontic Lesions: A Systematic Review
Authors: Dioguardi Mario , Alovisi Mario , Crincoli Vito , Aiuto Riccardo , Malagnino Giancarlo , Quarta Cristian , Laneve Enrica , Sovereto Diego , Lo Russo Lucio , Troiano Giuseppe , Lo Muzio Lorenzo
Published: March 2020

Propionibacterium are anaerobic/aero-tolerant rod Gram-positive bacteria, and numerous studies are associated with primary and secondary endodontic infections. The data in the literature on the prevalence of Propionibacterium are conflicting, and there are studies that report conflicting data on the prevalence in primary and secondary endodontic infections. This review aims to clarify the prevalence of bacteria of the genus Propionibacterium in endodontic lesions. The present systematic review work was performed on the basis of the Prisma protocol. A search was carried out on the PubMed and Scopus databases with the use of keywords. The research produced 410 records, which, after the elimination of the overlaps and the application of the inclusion and exclusion criteria, led to a number of 36 included articles divided by the three outcomes. The first outcome concerns prevalence of bacteria of the genus Propionibacterium in primary and secondary endodontic lesions. The secondary outcome, differences in the prevalence of bacteria of the genus Propionibacterium between primary endodontic infections and secondary endodontic infections. The tertiary outcome, differences in the prevalence of Propionibacterium Acnes compared to Propionibacterium propionicum in endodontic infections. The results of the meta-analysis show that the genus Propionibacterium bacteria are more prevalent in secondary endodontic infections and that P. acnes has a higher prevalence than P. propionicum.
Is There a Role for Levo-Thyroxine for the Treatment of Arterial Erectile Dysfunction? The Clinical Relevance of the Mean Platelet Volume
Authors: Cannarella Rossella , Calogero Aldo E. , Aversa Antonio , Condorelli Rosita A. , La Vignera Sandro
Published: March 2020

Background: Arterial erectile dysfunction (ED) is an early sign of vascular damage. Rare evidence has been published so far as to whether subclinical hypothyroidism (SCH) affects arterial erectile function. Therefore, the objective of this study was to fill this gap. Methods: Patients with arterial ED and SCH were consecutive enrolled and randomly divided into Group A (n = 20) and Group B (n = 20). Group A was treated with levo-thyroxine (LT4) at the dose of 1 µg/kg/day for six months, whereas patients of the group B did not receive any treatment. Thyroid stimulating hormone (TSH), free-thyroxine (FT4), peak systolic velocity (PSV), International Index of Erectile Function 5-item version (IIEF-5) score, mean platelet volume (MPV), and total cholesterol were evaluated at enrollment (T0) and after six months (T1). Patients without hypertension, diabetes mellitus, dyslipidemia, not on drugs, and with normal total testosterone (TT) values were included in this study. Results: Group A and B did not differ for age (61.2 ± 4.8 vs. 60.3 ± 5.6 years), body-mass index (28.7 ± 2.5 vs. 28.3 ± 2.6 Kg/m2), and serum TT levels (481.2 ± 54.0 vs. 492.1 ± 59.7 ng/dL). At T0, serum TSH levels (6.5 ± 1.2 vs. 6.0 ± 1.0 µIU/mL), FT4 (8.8 ± 0.6 vs. 8.8 ± 0.6 pmol/L), PSV (26.5 ± 1.4 vs. 25.8 ± 2.1 cm/s), IIEF-5 score (8.2 ± 1.7 vs. 9.0 ± 1.7), and total cholesterol (167.8 ± 21.7 vs. 171.6 ± 21.3 mg/dL) did not significantly differ in patients of Group A vs. those of Group B. MPV was significantly higher in Group A than in Group B (12.3 ± 0.3 vs. 11.8 ± 0.7 fL). At T1, Group A showed significantly lower TSH (2.26 ± 0.5 µIU/mL), MPV (9.5 ± 0.3 fL), and total cholesterol (137.8 ± 29.2 mg/dL) and significantly higher FT4 (9.3 ± 0.4 pmol/L), PSV (40.0 ± 2.6 cm/s), and IIEF-5 score (20.2 ± 3.6) compared to pre-treatment values. None of these endpoints showed significant change at T1 compared to T0 in patients of group B. Conclusions: Lt4 therapy is associated with an improvement of the erectile function at the vascular level, a decrease in MPV and total cholesterol. LT4 therapy should be considered in patients with arterial ED and SCH.
Breast-Specific Gamma Imaging with [99mTc]Tc-Sestamibi: An In Vivo Analysis for Early Identification of Breast Cancer Lesions Expressing Bone Biomarkers
Authors: Urbano Nicoletta , Scimeca Manuel , Di Russo Carmela , Bonanno Elena , Schillaci Orazio
Published: March 2020

The main purpose of this pilot investigation was to evaluate the possible relationship among [99mTc]Tc-Sestamibi uptake, the presence of breast osteoblast-like cells, and the expression of molecules involved in bone metabolism, such as estrogen receptor, bone morphogenetic proteins-2, and PTX3. To this end, forty consecutive breast cancer patients who underwent both breast-specific gamma imaging with [99mTc]Tc-Sestamibi and breast bioptic procedure were retrospectively enrolled. From each diagnostic paraffin block collected in the study, histological diagnosis, immunohistochemical investigations, and energy dispersive X-ray microanalysis were performed. Our data highlight the possible use of breast-specific gamma imaging with [99mTc]Tc-Sestamibi for the early detection of breast cancer lesions expressing bone biomarkers in the presence of breast osteoblast-like cells. Specifically, we show a linear association among sestamibi uptake, the presence of breast osteoblast-like cells, and the expression of estrogen receptor, bone morphogenetics proteins-2, and PTX3. Notably, we also observed an increase of [99mTc]Tc-Sestamibi in breast cancer lesions with magnesium-substituted hydroxyapatite. In conclusion, in this pilot study we evaluated data from the nuclear medicine unit and anatomic pathology department on breast cancer osteotropism, identifying a new possible interpretation of Breast Specific Gamma Imaging with [99mTc]Tc-Sestamibi analysis.
Impact of Neoadjuvant Chemotherapy on the Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Multi-Institutional Retrospective Review
Authors: Beal Eliza W. , Suarez-Kelly Lorena P. , Kimbrough Charles W. , Johnston Fabian M. , Greer Jonathan , Abbott Daniel E. , Pokrzywa Courtney , Raoof Mustafa , Lee Byrne , Grotz Travis E. , Leiting Jennifer L. , Fournier Keith , Lee Andrew J. , Dineen Sean P. , Powers Benjamin , Veerapong Jula , Baumgartner Joel M. , Clarke Callisia , Mogal Harveshp , Russell Marti C. , Zaidi Mohammed Y. , Patel Sameer H. , Dhar Vikrom , Lambert Laura , Hendrix Ryan J. , Hays John , Abdel-Misih Sherif , Cloyd Jordan M.
Published: March 2020

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000–2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.
Prospective Evaluation of Intensity of Symptoms, Therapeutic Procedures and Treatment in Palliative Care Patients in Nursing Homes
Authors: Puente-Fernández Daniel , Roldán-López Concepción B. , Campos-Calderón Concepción P. , Hueso-Montoro Cesar , García-Caro María P. , Montoya-Juarez Rafael
Published: March 2020

The aim of the study is to evaluate the intensity of symptoms, and any treatment and therapeutic procedures received by advanced chronic patients in nursing homes. A multi-centre prospective study was conducted in six nursing homes for five months. A nurse trainer selected palliative care patients from whom the sample was randomly selected for inclusion. The Edmonton Symptoms Assessment Scale, therapeutic procedures, and treatment were evaluated. Parametric and non-parametric tests were used to evaluate month-to-month differences and differences between those who died and those who did not. A total of 107 residents were evaluated. At the end of the follow-up, 39 had (34.6%) died. All symptoms (p < 0.050) increased in intensity in the last week of life. Symptoms were more intense in those who had died at follow-up (p < 0.05). The use of aerosol sprays (p = 0.008), oxygen therapy (p < 0.001), opioids (p < 0.001), antibiotics (p = 0.004), and bronchodilators (p = 0.003) increased in the last week of life. Peripheral venous catheters (p = 0.022), corticoids (p = 0.007), antiemetics (p < 0.001), and antidepressants (p < 0.05) were used more in the patients who died. In conclusion, the use of therapeutic procedures (such as urinary catheters, peripheral venous catheter placement, and enteral feeding) and drugs (such as antibiotics, anxiolytics, and new antidepressant prescriptions) should be carefully considered in this clinical setting.
Targeted Exome Sequencing Provided Comprehensive Genetic Diagnosis of Congenital Anomalies of the Kidney and Urinary Tract
Authors: Ahn Yo Han , Lee Chung , Kim Nayoung K. D. , Park Eujin , Kang Hee Gyung , Ha Il-Soo , Park Woong-Yang , Cheong Hae Il
Published: March 2020

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in children. The search for genetic causes of CAKUT has led to genetic diagnosis in approximately 5–20 % of CAKUT patients from Western countries. In this study, genetic causes of CAKUT in Korean children were sought using targeted exome sequencing (TES) of 60 genes reported to cause CAKUT in human or murine models. We identified genetic causes in 13.8% of the 94 recruited patients. Pathogenic single nucleotide variants of five known disease-causing genes, HNF1B, PAX2, EYA1, UPK3A, and FRAS1 were found in 7 cases. Pathogenic copy number variations of 6 patients were found in HNF1B, EYA1, and CHD1L. Genetic abnormality types did not significantly differ according to CAKUT phenotypes. Patients with pathogenic variants of targeted genes had syndromic features more frequently than those without (p < 0.001). This is the first genetic analysis study of Korean patients with CAKUT. Only one-seventh of patients were found to have pathogenic mutations in known CAKUT-related genes, indicating that there are more CAKUT-causing genes or environmental factors to discover.
Antibodies against Malondialdehyde in Haemodialysis Patients and Its Association with Clinical Outcomes: Differences between Subclasses and Isotypes
Authors: Samal Shailesh Kumar , Qureshi Abdul Rashid , Rahman Mizanur , Stenvinkel Peter , Frostegård Johan
Published: March 2020

Patients on haemodialysis (HD-patients) have an increased risk of premature death. Low levels of IgM antibodies against malondialdehyde (anti-MDA) are associated with increased risk of cardiovascular disease (CVD) with underlying potential mechanisms described. Here, we studied subclasses and isotypes of anti-MDA in 210 HD-patients with mortality as outcome (56% men, median age 66, Interquartile range (IQR) 51–74 years, vintage time 29 (15–58) months, mean follow up period of 41 (20–60)months). Patients were also divided into inflamed c-reactive protein (CRP >5.6 mg/mL) and non-inflamed. Antibody levels were measured by ELISA. In multivariate risk analysis, patients in low tertile of IgM anti-MDA sub-distribution hazard ratio (sHR 0.54); 95% confidence interval (CI: 0.34–0.89) inversely and significantly associated with all-cause mortality after five years, after adjusting for confounders. Low tertile of IgG (sHR 0.48, 95%CI: 0.25–0.90, p = 0.02) and IgG1 (sHR 0.50, CI: 0.24–1.04, p = 0.06) was associated low mortality among non-inflamed patients. In contrast, anti-MDA IgG2 among inflamed patients was significantly associated with increased mortality, IgG2(sHR 2.33, CI: 1.16–4.68, p = 0.01). IgM anti-MDA was a novel biomarker among HD-patients with low levels being associated with mortality, while low levels of IgG and IgG1 but not IgA anti-MDA were associated with mortality only among non-inflamed patients. IgG2 anti-MDA was a significant risk marker among inflamed patients, which could be related to infection.
Degenerative Cervical Myelopathy: How to Identify the Best Responders to Surgery?
Authors: Severino Rocco , Nouri Aria , Tessitore Enrico
Published: March 2020

Surgery is the only definitive treatment for degenerative cervical myelopathy (DCM), however, the degree of neurological recovery is often unpredictable. Here, we assess the utility of a multidimensional diagnostic approach, consisting of clinical, neurophysiological, and radiological parameters, to identify patients likely to benefit most from surgery. Thirty-six consecutive patients were prospectively analyzed using the modified Japanese Orthopedic Association (mJOA) score, MEPs/SSEPs and advance and conventional MRI parameters, at baseline, and 3- and 12-month postoperatively. Patients were subdivided into “normal” and “best” responders (<50%, ≥50% improvement in mJOA), and correlation between Diffusion Tensor Imaging (DTI) parameters, mJOA, and MEP/SSEP latencies were examined. Twenty patients were “best” responders and 16 were “normal responders”, but there were no statistical differences in age, T2 hyperintensity, and midsagittal diameter between them. There was a significant inverse correlation between the MEPs central conduction time and mJOA in the preoperative period (p = 0.0004), and a positive correlation between fractional anisotropy (FA) and mJOA during all the phases of the study, and statistically significant at 1-year (r = 0.66, p = 0.0005). FA was significantly higher amongst “best responders” compared to “normal responders” preoperatively and at 1-year (p = 0.02 and p = 0.009). A preoperative FA > 0.55 was predictor of a better postoperative outcome. Overall, these results support the concept of a multidisciplinary approach in the assessment and management of DCM.
Risk, Diagnostic and Predictor Factors for Classical Hodgkin Lymphoma in HIV-1-Infected Individuals: Role of Plasma Exosome-Derived miR-20a and miR-21
Authors: Hernández-Walias Francisco J. , Vázquez Esther , Pacheco Yolanda , Rodríguez-Fernández José M. , Pérez-Elías María J. , Dronda Fernando , Casado José L. , Moreno Ana , Hermida José M. , Quereda Carmen , Hernando Asunción , Tejerina-Picado Francisco , Asensi Víctor , Galindo María J. , Leal Manuel , Moreno Santiago , Vallejo Alejandro
Published: March 2020

The incidence of classical Hodgkin lymphoma (cHL) in the HIV-1 setting has increased 5–25-fold compared to that observed in the general population. This study aimed to determine whether selected micro RNAs (miRs) and other soluble biomarkers and cellular subsets are dysregulated in cHL and could be used as biomarkers. This was a retrospective and longitudinal matched case-control study of 111 Caucasian, HIV-1-infected adult individuals, including 37 individuals with cHL and 74 with no type of cancer. Immunovirological data, plasma exosome-derived miR-16, miR-20a, miR-21, miR-221, miR-223, miR-106a, miR-185, miR-23, miR-30d, miR-222, miR-146a and miR-324, plasma IL-6, sCD14, sCD27, sCD30, sIL-2R, TNFR1, and cell phenotyping of T and B lymphocytes and natural killer (NK) cells were analyzed. Before cHL diagnosis, miR-20a, miR-21, and sCD30 were higher in cHL (p = 0.008, p = 0.009 and p = 0.042, respectively), while miR-16 was down-regulated (p = 0.040). miR-20a and miR-21 were independently associated with cHL (p = 0.049 and p = 0.035, respectively). The combination of miR-20a and miR-21 showed a good AUC value of 0.832 with a moderate likelihood ratio positive (LR+) value of 5.6 and a slight likelihood ratio negative (LR−) value of 0.23. At cHL diagnosis, miR-20a, miR-21 and miR-324 were overexpressed in cHL (p = 0.005, p = 0.024, and p = 0.001, respectively), while miR-223, miR-16, miR-185 and miR-106a were down regulated (p = 0.042, p = 0.007, p = 0.006, and p = 0.002, respectively). In addition, sCD14, sCD27, sCD30 and IL2R levels were higher in these individuals (p = 0.038, p = 0.010, p = 0.030, p = 0.006, respectively). miR-20a was independently associated with cHL (p = 0.011). The diagnostic value of miR-20a showed good AUC value of 0.754 (p = 0.074) with a slight LR+ value of 2 and a slight LR− of 0.25. After chemotherapy, miR-20a was higher in those individuals who had an adverse outcome (p < 0.001), while sCD14 and sCD30 were higher (p < 0.001). A specific signature of miRs and cytokines associated with a subsequent cHL diagnosis was found in this study, especially miR-20a and miR-21. Also, another biomarker signature was found at cHL diagnosis, with a relevant discriminant disease value for miR-20a. Of note, miR-20a expression was higher in those individuals who had an adverse clinical outcome after chemotherapy.
Transradial and Transfemoral Approach in Patients with Prior Coronary Artery Bypass Grafting
Authors: Januszek Rafał , Siudak Zbigniew , Malinowski Krzysztof Piotr , Wańha Wojciech , Wojakowski Wojciech , Gąsior Mariusz , Bartuś Stanisław , Dudek Dariusz
Published: March 2020

The relationship between periprocedural complications and the type of vascular access in patients with prior history of coronary artery bypass grafting (CABG) and treated with percutaneous coronary interventions (PCIs) is less investigated than in the overall group of patients treated with PCI. The aim of the current study was to assess the relationship between the type of vascular access and selected periprocedural complications in a group of patients with prior history of CABG and treated with PCIs. Based on a Polish nationwide registry of interventional cardiology procedures called ORPKI, the authors analyzed 536,826 patients treated with PCI between 2014 and 2018. The authors extracted 32,225 cases with prior history of CABG. Then, patients with femoral and radial access as well as right and left radial access were compared. This comparison was proceeded by propensity score matching (PSM). After PSM, a multifactorial analysis revealed that patients treated with PCI from femoral access were significantly more often related to periprocedural deaths (odds ratio [OR]: 1.79; 95%, confidence interval [CI]: 1.1–3.0, p = 0.02) and cardiac arrests (OR: 1.98; 95%, CI: 1.38–2.87, p < 0.001). After inclusion of the Killip class grade and the occurrence of cardiac arrests before PCI into the PSM, the significance remained for procedural related cardiac arrests (OR: 1.55; 95%, CI: 1.07–2.28, p = 0.022]). However, a comparison of right and left radial access showed no significant differences between procedure-related complications. It has been confirmed that there is a statistical association between femoral access (compared to radial access) and a higher rate of periprocedural cardiac arrests in patients with prior history of CABG treated with PCI.
To Treat or Not to Treat: Importance of Functional Dependence in Deciding Intravenous Thrombolysis of “Mild Stroke” Patients
Authors: Merlino Giovanni , Smeralda Carmelo , Lorenzut Simone , Gigli Gian Luigi , Surcinelli Andrea , Valente Mariarosaria
Published: March 2020

Intravenous thrombolysis (IVT) in patients with a low National Institutes of Health Stroke Scale (NIHSS) score of 0–5 remains controversial. IVT should be used in patients with mild but nevertheless disabling symptoms. We hypothesize that response to IVT of patients with “mild stroke” may depend on their level of functional dependence (FD) at hospital admission. The aims of our study were to investigate the effect of IVT and to explore the role of FD in influencing the response to IVT. This study was a retrospective analysis of a prospectively collected database, including 389 patients stratified into patients receiving IVT (IVT+) and not receiving IVT (IVT −) just because of mild symptoms. Barthel index (BI) at admission was used to assess FD, dividing subjects with BI score < 80 (FD+) and with BI score ≥ 80 (FD−). The efficacy endpoints were the rate of positive disability outcome (DO+) (3-month mRS score of 0 or 1), and the rate of positive functional outcome (FO+) (mRS score of zero or one, plus BI score of 95 or 100 at 3 months). At the multivariate analysis, IVT treatment was an independent predictor of DO+ (OR 3.12, 95% CI 1.34−7.27, p = 0.008) and FO+ (OR: 4.70, 95% CI 2.38−9.26, p = 0.001). However, FD+ IVT+ patients had a significantly higher prevalence of DO+ and FO+ than those FD+ IVT–. Differently, IVT treatment did not influence DO+ and FO+ in FD– patients. In FD+ patients, IVT treatment represented the strongest independent predictor of DO+ (OR 6.01, 95% CI 2.59–13.92, p = 0.001) and FO+ (OR 4.73, 95% CI 2.29–9.76, p = 0.001). In conclusion, alteplase seems to improve functional outcome in patients with “mild stroke”. However, in our experience, this beneficial effect is strongly influenced by FD at admission.
High-Sensitivity Troponin T Testing: Consequences on Daily Clinical Practice and Effects on Diagnosis of Myocardial Infarction
Authors: Zachoval Christian Frédéric , Dolscheid-Pommerich Ramona , Graeff Ingo , Goldschmidt Bernd , Grigull Andreas , Stoffel-Wagner Birgit , Nickenig Georg , Zimmer Sebastian
Published: March 2020

It remains unclear how introduction of high-sensitivity troponin T testing, as opposed to conventional troponin testing, has affected the diagnosis of acute myocardial infarction (AMI) and resource utilization in unselected hospitalized patients. In this retrospective analysis, we include all consecutive cases from our center during two corresponding time frames (10/2016–04/2017 and 10/2017–04/2018) for which different troponin tests were performed: conventional troponin I (cTnI) and high-sensitivity troponin T (hs-TnT) assays. Testing was performed in 18,025 cases. The incidence of troponin levels above the 99th percentile was significantly higher in cases tested using hs-TnT. This was not associated with increased utilization of echocardiography, coronary angiography, or percutaneous coronary intervention. Although there were no changes in local standard operating procedures, study site personnel, or national coding guidelines, the number of coded AMI significantly decreased after introduction of hs-TnT. In this single-center retrospective study comprising 18,025 mixed medical and surgical cases with troponin testing, the introduction of hs-TnT was not associated with changes in resource utilization among the general cohort, but instead, led to a decrease in the international classification of diseases (ICD)-10 coded diagnosis of AMI.
Analysis of Faecal Zonulin and Calprotectin Concentrations in Healthy Children During the First Two Years of Life. An Observational Prospective Cohort Study
Authors: Łoniewska Beata , Adamek Karolina , Węgrzyn Dagmara , Kaczmarczyk Mariusz , Skonieczna-Żydecka Karolina , Clark Jeremy , Adler Grażyna , Tousty Joanna , Uzar Izabela , Tousty Piotr , Łoniewski Igor
Published: March 2020

Factors affecting the intestinal-barrier permeability of newborns, such as body mass index (BMI), nutrition and antibiotics, are assumed to affect intestinal-barrier permeability in the first two years of life. This study assessed 100 healthy, full-term newborns to 24 months old. Faecal zonulin/calprotectin concentrations were measured at 1, 6, 12, 24 months as gut-permeability markers. Zonulin concentrations increased between 1 and 12 months (medians: 114.41, 223.7 ng/mL; respectively), whereas calprotectin concentrations decreased between one and six months (medians: 149. 29, 109.28 µg/mL); both then stabilized (24 months: 256.9 ng/mL zonulin; 59.5 µg/mL calprotectin). In individual children, high levels at one month gave high levels at older ages (correlations: calprotectin: between 1 and 6 or 12 months: correlation coefficient (R) = 0.33, statistical significance (p) = 0.0095; R = 0.28, p = 0.032; zonulin: between 1 and 24 months: R = 0.32; p = 0.022, respectively). Parameters which gave marker increases: antibiotics during pregnancy (calprotectin; six months: by 80%, p = 0.038; 12 months: by 48%, p = 0.028); vaginal birth (calprotectin: 6 months: by 140%, p = 0.005); and > 5.7 pregnancy-BMI increase (zonulin: 12 months: by 74%, p = 0.049). Conclusions: “Closure of the intestines” is spread over time and begins between the sixth and twelfth month of life. Antibiotic therapy, BMI increase > 5.7 during pregnancy and vaginal birth are associated with increased intestinal permeability during the first two years of life. Stool zonulin and calprotectin concentrations were much higher compared with previous measurements at older ages; clinical interpretation and validation are needed (no health associations found).
A Novel Fault Location Approach for Scientific Cabled Seafloor Observatories
Authors: Yang Fan , Lyu Feng
Published: March 2020

The maintenance of scientific cabled seafloor observatories (CSOs) is not only extremely difficult but also of high cost for their subsea location. Therefore, the cable fault detection and location are essential and must be carried out accurately. For this purpose, a novel on-line fault location approach based on robust state estimation is proposed, considering state data gross errors in sensor measurements and the influence of temperature on system parameter variation. The circuit theory is used to build state estimation equations and identify the power system topology of faulty CSOs. This method can increase the accuracy of fault location, and reduce the lose form shutting down a faulty CSO in traditional fault location methods. It is verified by computer simulation and the laboratory prototype of a planned CSO in the East China Sea, and the fault location error is proved to be less than 1 km.
VIScous Vorticity Equation (VISVE) for Turbulent 2-D Flows with Variable Density and Viscosity
Authors: Kinnas Spyros A.
Published: March 2020

The general vorticity equation for turbulent compressible 2-D flows with variable viscosity is derived, based on the Reynolds-Averaged Navier-Stokes (RANS) equations, and simplified versions of it are presented in the case of turbulent or cavitating flows around 2-D hydrofoils.
Rural-Urban Migration and its Effect on Land Transfer in Rural China
Authors: Xu Dingde , Yong Zhuolin , Deng Xin , Zhuang Linmei , Qing Chen
Published: March 2020

Labor force rural-urban migration will lead to changes to the land use patterns of farmers. Using the survey data on dynamic migration of the Chinese labor force in 2014, iv-probit and iv-tobit models were used to analyze the impact of labor migration on the land transfer of farmers. The results show that: (1) Off-farm employment would significantly impact land transfer of farmers and the results are robust. With every 10% increase in the proportion of off-farm employment of farmers, the average probability of rent-in land of farmers decreases by 1.55%, and the average transfer in land area of farmers decreased by 1.04%. Similarly, with every 10% increase in the proportion of off-farm employment of farmers, the average probability of rent-out land of farmers increases by 4.77%, and the average transfer out land area of farmers increases by 3.98%. (2) Part-time employment also has a significant impact on land transfer of farmers, but the impact of part-time employment on land transfer in is not robust. Specifically, with every 10% increase in part-farm employment, the average probability of rent-out land of farmers increases by 7.64%, and the average transfer out land area of farmers increases by 6.85%.
Is the Application of Plant Probiotic Bacterial Consortia Always Beneficial for Plants? Exploring Synergies between Rhizobial and Non-Rhizobial Bacteria and Their Effects on Agro-Economically Valuable Crops
Authors: Menéndez Esther , Paço Ana
Published: March 2020

The overgrowth of human population and the demand for high-quality foods necessitate the search for sustainable alternatives to increase crop production. The use of biofertilizers, mostly based on plant probiotic bacteria (PPB), represents a reliable and eco-friendly solution. This heterogeneous group of bacteria possesses many features with positive effects on plants; however, how these bacteria with each other and with the environment when released into a field has still barely been studied. In this review, we focused on the diversity of root endophytic rhizobial and non-rhizobial bacteria existing within plant root tissues, and also on their potential applications as consortia exerting benefits for plants and the environment. We demonstrated the benefits of using bacterial inoculant consortia instead of single-strain inoculants. We then critically discussed several considerations that farmers, companies, governments, and the scientific community should take into account when a biofertilizer based on those PPBs is proposed, including (i) a proper taxonomic identification, (ii) the characterization of the beneficial features of PPB strains, and (iii) the ecological impacts on plants, environment, and plant/soil microbiomes. Overall, the success of a PPB consortium depends on many factors that must be considered and analyzed before its application as a biofertilizer in an agricultural system.
Preparation, Microstructure, Mechanical Properties and Biocompatibility of Ta-Coated 3Y-TZP Ceramic Deposited by a Plasma Surface Alloying Technique
Authors: Zheng Ke , Li Liangliang , Dong Yaqian , Gao Jie , Hei Hongjun , Ma Yong , Zhou Bin , He Zhiyong , Wang Yongsheng , Yu Shengwang , Tang Bin , Wu Yucheng
Published: March 2020

A Ta coating has been successfully fabricated on the surface of zirconia polycrystals ceramic (3 mol% yttria, 3Y-TZP) by a plasma surface alloying technique. The X-ray diffraction (XRD) and scanning electron microscopy (SEM) results showed that a α-Ta coating with a continuous and compact surface morphology which consisted of a deposited layer with a thickness of 390 nm and a diffusion layer with a thickness of 200 nm covered the 3Y-TZP. Due to the effect of inhabitation the t→m transformation by the deposited Ta coating, the biaxial flexural strength caused by the phase transformation during hydrothermal aging is reduced e.g., p < 0.05 after 20 h and/or 100 h. In addition, the Ta coating shows non-cytotoxicity and improved proliferation ability of osteoblasts.
Microstructure Characterization and Interfacial Reactions between Au-Sn Solder and Different Back Metallization Systems of GaAs MMICs
Authors: Wu Na , Hu Yongfang , Sun Shufeng
Published: March 2020

GaAs monolithic microwave integrated circuits (MMICs) with different back metallization systems (TiW/Au and Au/Ti/Au) exhibit different problems in the automatic Au-Sn eutectic bonding process, such as edge breakage or excessive voids. In this study, the formation mechanism of the edge breakage and excessive voids were investigated to prevent the damage of the MMICs in mass production scenarios. The microstructure and elemental distribution were studied using a scanning electron microscope and energy-dispersive spectroscopy. The void contents of the brazed region were measured with three-dimensional computed tomography. The top Au layer of the TiW/Au metallization partially dissolved in the melting An-Sn solder. Consequently, liquidus temperature of the solder increased, leading to isothermal solidification with the formation of ζ-Au5Sn in the scrubbing process, which was the reason for the edge breakage. The terminal Au film of the Au/Ti/Au metallization completely dissolved in the melting An-Sn solder. The metallurgical combination was achieved by the formation of the TiAu4 intermetallic compound between the Au-Sn solder and the Ti layer. The wettability of Au-Sn solder on Ti layer should be improved to prevent the formation of the excessive voids.
Persistence for a Two-Stage Reaction-Diffusion System
Authors: Cantrell Robert Stephen , Cosner Chris , Martínez Salomé
Published: March 2020

In this article, we study how the rates of diffusion in a reaction-diffusion model for a stage structured population in a heterogeneous environment affect the model’s predictions of persistence or extinction for the population. In the case of a population without stage structure, faster diffusion is typically detrimental. In contrast to that, we find that, in a stage structured population, it can be either detrimental or helpful. If the regions where adults can reproduce are the same as those where juveniles can mature, typically slower diffusion will be favored, but if those regions are separated, then faster diffusion may be favored. Our analysis consists primarily of estimates of principal eigenvalues of the linearized system around ( 0 , 0 ) and results on their asymptotic behavior for large or small diffusion rates. The model we study is not in general a cooperative system, but if adults only compete with other adults and juveniles with other juveniles, then it is. In that case, the general theory of cooperative systems implies that, when the model predicts persistence, it has a unique positive equilibrium. We derive some results on the asymptotic behavior of the positive equilibrium for small diffusion and for large adult reproductive rates in that case.
Least-Squares Solutions of Eighth-Order Boundary Value Problems Using the Theory of Functional Connections
Authors: Johnston Hunter , Leake Carl , Mortari Daniele
Published: March 2020

This paper shows how to obtain highly accurate solutions of eighth-order boundary-value problems of linear and nonlinear ordinary differential equations. The presented method is based on the Theory of Functional Connections, and is solved in two steps. First, the Theory of Functional Connections analytically embeds the differential equation constraints into a candidate function (called a constrained expression) containing a function that the user is free to choose. This expression always satisfies the constraints, no matter what the free function is. Second, the free-function is expanded as a linear combination of orthogonal basis functions with unknown coefficients. The constrained expression (and its derivatives) are then substituted into the eighth-order differential equation, transforming the problem into an unconstrained optimization problem where the coefficients in the linear combination of orthogonal basis functions are the optimization parameters. These parameters are then found by linear/nonlinear least-squares. The solution obtained from this method is a highly accurate analytical approximation of the true solution. Comparisons with alternative methods appearing in literature validate the proposed approach.
Designing Developable C-Bézier Surface with Shape Parameters
Authors: Li Caiyun , Zhu Chungang
Published: March 2020

Developable surface plays an important role in geometric design, architectural design, and manufacturing of material. Bézier curve and surface are the main tools in the modeling of curve and surface. Since polynomial representations can not express conics exactly and have few shape handles, one may want to use rational Bézier curves and surfaces whose weights control the shape. If we vary a weight of rational Bézier curve or surface, then all of the rational basis functions will be changed. The derivation and integration of the rational curve will yield a high degree curve, which means that the shape of rational Bézier curve and surface is not easy to control. To solve this problem of shape controlling for a developable surface, we construct C-Bézier developable surfaces with some parameters using a dual geometric method. This yields properties similar to Bézier surfaces so that it is easy to design. Since C-Bézier basis functions have only two parameters in every basis, we can control the shape of the surface locally. Moreover, we derive the conditions for C-Bézier developable surface interpolating a geodesic.
Analysis and Characterization of the Weld Pool and Bead Geometry of Inconel 625 Super-TIG Welds
Authors: Park Jung Hyun , Cheepu Muralimohan , Cho Sang Myung
Published: March 2020

The welding market is changing globally, becoming eco-friendly, robotized and automated. The tungsten inert gas welding (TIG) process is indispensable in industries that require high-quality welds with the absence of spatter and fumes. However, the production rate of TIG welding is very low, which limits its many applications. The present study introduces a novel TIG welding method called super-TIG welding. Super-TIG welding is able to produce a high production rate of welds compared to other fusion welding methods. In super-TIG welding, the novel C-type filler is used, which is different from the conventional TIG welding of circular wire. The relations of the heat input ratio in super-TIG welding to weld pool length and weld bead geometry were measured using the Inconel 625 C-filler. Two types of deposition techniques were used for a bead-on-plate welds, such as stringer beads and oscillation beads. The weld pool and bead geometry measurements are found to be different between stringer beads and oscillation bead techniques. The length of the molten pool and bead size were higher for oscillation beads over the stringer beads. These changes were associated with the difference in heat transfer contact area and bead height.
Magnetic Properties of Fe(II) Complexes of Cyclam Derivative with One p-Aminobenzyl Pendant Arm
Authors: Drahoš Bohuslav , Antal Peter , Šalitroš Ivan , Herchel Radovan
Published: March 2020

In order to prepare an Fe(II) spin crossover (SCO) complex that could be consequently modified to a bimetallic coordination compound that possesses another magnetic property of interest, a specially designed ligand L-NH2 (1-(4-aminobenzyl)-4,11-bis(pyridine-2-ylmethyl)- 1,4,8,11-tetraazacyclotetradecane) was prepared. This ligand consists of a macrocyclic cyclam part containing two 2-pyridylmethyl pendant arms (expecting SCO upon Fe(II) complexation) and one p-aminobenzyl pendant arm with an NH2 group. The presence of this group enables the consequent transformation to various functional groups for the selective complexation of other transition metals or lanthanides (providing the second property of interest). Furthermore, the performed theoretical calculations (TPSSh/def2-TZVP) predicted SCO behavior for the Fe(II) complex of L-NH2. Thus, Fe(II) complexes [Fe(L-NH2)](ClO4)2 (1) and [Fe(L-NH2)]Cl2·6H2O (2) were synthesized and thoroughly characterized. Based on the crystal structure of an isostructural analogous Ni(II) complex [Ni(L-NH2)]Cl2·6H2O (3), the coordination number six was confirmed with an octahedral coordination sphere and a cis-arrangement of the pyridine pendant arms. The measured magnetic data confirmed the high-spin behavior of both compounds with large magnetic anisotropy (D = 17.8 for 1 and 20.9 cm−1 for 2 complemented in both cases also with large rhombicity), though unfortunately without any indication of the SCO behavior with decreasing temperature. The lack of SCO can be ascribed to the crystal packing and/or the non-covalent intermolecular interactions stabilizing the high-spin state in the solid state.
A Metabolomics Analysis of Adiposity and Advanced Prostate Cancer Risk in the Health Professionals Follow-Up Study
Authors: Dickerman Barbra A. , Ebot Ericka M. , Healy Brian C. , Wilson Kathryn M. , Eliassen A. Heather , Ascherio Alberto , Pernar Claire H. , Zeleznik Oana A. , Vander Heiden Matthew G. , Clish Clary B. , Giovannucci Edward , Mucci Lorelei A.
Published: March 2020

Obesity is associated with a higher risk of advanced prostate cancer, but men with the same body mass index (BMI) may differ in their underlying metabolic health. Using metabolomics data from nested case-control studies in the Health Professionals Follow-Up Study, we calculated Pearson correlations between 165 circulating metabolites and three adiposity measures (BMI, waist circumference, and derived fat mass from a validated prediction equation) to identify adiposity-associated metabolites. We used Lasso to further select metabolites for prediction models of adiposity measures, which we used to calculate metabolic scores representing metabolic obesity. In an independent set of 212 advanced prostate cancer cases (T3b/T4/N1/M1 or lethal during follow-up) and 212 controls, we used logistic regression to evaluate the associations between adiposity measures and metabolic scores with risk of advanced disease. All adiposity measures were associated with higher blood levels of carnitines (Pearson r range, 0.16 to 0.18) and lower levels of glutamine (r = −0.19) and glycine (r, −0.29 to −0.20), in addition to alterations in various lipids. No adiposity measure or metabolic score was associated with risk of advanced prostate cancer (e.g., odds ratio for a 5 kg/m2 increase in BMI 0.96 (95% CI: 0.73, 1.27) and BMI metabolic score 1.18 (95% CI: 0.57, 2.48)). BMI, waist circumference, and derived fat mass were associated with a broad range of metabolic alterations. Neither adiposity nor metabolic scores were associated with risk of advanced prostate cancer.
An Untargeted Metabolomics Approach to Investigate the Metabolic Effect of Beetroot Juice Supplementation in Fencers—A Preliminary Study
Authors: Kozlowska Lucyna , Mizera Olga , Mroz Anna
Published: March 2020

This study aimed at assessment of the long-term (4 weeks) metabolic effect of a diet with and without beetroot juice supplementation in fencers using the untargeted metabolomics method with the UPLC Q-TOF/MS system to carry out an analysis of urine samples. Ten women and 10 men underwent the cardiovascular fitness VO2max test at baseline—(B) and after two stages of implementation of the dietary recommendations—the first 4 weeks without beetroot juice (D) and the second with 26 g/d of freeze-dried beetroot juice supplementation (D&J). The urine samples were collected one hour after the VO2max test at B and after D and D&J. The meal before the VO2max test after D&J contained beetroot juice, whereas to the meal at B and after D maltodextrin was added. Changes in metabolites and VO2max were significant only for comparison of D versus D&J. During D and D&J, there were no significant changes in the physical activity level, body mass, and body composition. We observed significant changes in tyrosine and tryptophan metabolism, mainly associated with such neurotransmitter’s metabolism as: Serotonin, noradrenaline, and adrenaline. Changes in signal intensity of bile acid, AICAR, and 4-Hydroxynonenal (peroxidation of polyunsaturated fatty acids product) were also observed. The obtained results indicate that long-term beetroot juice supplementation induces considerable changes in metabolism.