bluuebunny/crossref_metadata_2025 huggingface dataset:
Vestibular Anatomic Localization of Pain Sensitivity in Women with Insertional Dyspareunia: A Different Approach to Address the Variability of Painful Intercourse
Authors: Lev-Sagie Ahinoam , Wertman Osnat , Lavee Yoav , Granot Michal
Published: June 2020

The pathophysiology underlying painful intercourse is challenging due to variability in manifestations of vulvar pain hypersensitivity. This study aimed to address whether the anatomic location of vestibular-provoked pain is associated with specific, possible causes for insertional dyspareunia. Women (n = 113) were assessed for “anterior” and “posterior” provoked vestibular pain based on vestibular tenderness location evoked by a Q-tip test. Pain evoked during vaginal intercourse, pain evoked by deep muscle palpation, and the severity of pelvic floor muscles hypertonicity were assessed. The role of potential confounders (vestibular atrophy, umbilical pain hypersensitivity, hyper-tonus of pelvic floor muscles and presence of a constricting hymenal-ring) was analyzed to define whether distinctive subgroups exist. Q-tip stimulation provoked posterior vestibular tenderness in all participants (6.20 ± 1.9). However, 41 patients also demonstrated anterior vestibular pain hypersensitivity (5.24 ± 1.5). This group (circumferential vestibular tenderness), presented with either vestibular atrophy associated with hormonal contraception use (n = 21), or augmented tactile umbilical-hypersensitivity (n = 20). The posterior-only vestibular tenderness group included either women with a constricting hymenal-ring (n = 37) or with pelvic floor hypertonicity (n = 35). Interestingly, pain evoked during intercourse did not differ between groups. Linear regression analyses revealed augmented coital pain experience, umbilical-hypersensitivity and vestibular atrophy predicted enhanced pain hypersensitivity evoked at the anterior, but not at the posterior vestibule (R = 0.497, p < 0.001). Distinguishing tactile hypersensitivity in anterior and posterior vestibule and recognition of additional nociceptive markers can lead to clinical subgrouping.
Somatotype Components as Useful Predictors of Disordered Eating Attitudes in Young Female Ballet Dance Students
Authors: Alvero-Cruz José Ramón , Parent Mathias Verónica , García-Romero Jerónimo C.
Published: June 2020

The current study used receiver operating characteristic (ROC) curve analysis to examine the accuracy of somatotype components in correctly classifying disordered eating attitudes (DEA) in female dance students. Participants were a sample of 81 female dancers distributed in two groups: beginner training (BT; age (mean ± SD) = 10.09 ± 1.2 years, n = 32) and advanced training (AT; age = 15.37 ± 2.1 years, n = 49). For evaluation of DEA, the Eating Attitudes Test- 26 (EAT-26) questionnaire was used. We defined an EAT-26 score ≥20 as positive for DEA. Somatotype components were calculated using the Heath-Carter anthropometric method. The risk of presenting DEA was 28.1% (n = 9) in the BT group and 6.1% (n = 3) in the AT group. In the BT group, mesomorphy demonstrated moderate–high accuracy in predicting DEA (area under the curve (AUC) = 0.82, 95% confidence interval (CI): 0.64–0.93). The optimal cut-off of 6.34 yielded a sensitivity of 0.77 and a specificity of 0.95. Ectomorphy showed moderate accuracy in predicting DEA (AUC = 0.768, 95% CI: 0.58–0.89). The optimal cut-off of 2.41 yielded a sensitivity of 0.78 and a specificity of 0.78. In the AT group, none of the components demonstrated accuracy in predicting DEA. Somatotype components were good predictors of disordered eating attitudes in the younger dance student group (beginner training). Further research is needed to identify the determinants of these differences between the two groups.
Immunoadsorption and Plasma Exchange in Seropositive and Seronegative Immune-Mediated Neuropathies
Authors: Davies Alexander J. , Fehmi Janev , Senel Makbule , Tumani Hayrettin , Dorst Johannes , Rinaldi Simon
Published: June 2020

The inflammatory neuropathies are disabling conditions with diverse immunological mechanisms. In some, a pathogenic role for immunoglobulin G (IgG)-class autoantibodies is increasingly appreciated, and immunoadsorption (IA) may therefore be a useful therapeutic option. We reviewed the use of and response to IA or plasma exchange (PLEx) in a cohort of 41 patients with nodal/paranodal antibodies identified from a total of 573 individuals with suspected inflammatory neuropathies during the course of routine diagnostic testing (PNAb cohort). 20 patients had been treated with PLEx and 4 with IA. Following a global but subjective evaluation by their treating clinicians, none of these patients were judged to have had a good response to either of these treatment modalities. Sequential serology of one PNAb+ case suggests prolonged suppression of antibody levels with frequent apheresis cycles or adjuvant therapies, may be required for effective treatment. We further retrospectively evaluated the serological status of 40 patients with either Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP), and a control group of 20 patients with clinically-isolated syndrome/multiple sclerosis (CIS/MS), who had all been treated with IgG-depleting IA (IA cohort). 32 of these patients (8/20 with CIDP, 13/20 with GBS, 11/20 with MS) were judged responsive to apheresis despite none of the serum samples from this cohort testing positive for IgG antibodies against glycolipids or nodal/paranodal cell-adhesion molecules. Although negative on antigen specific assays, three patients’ pre-treatment sera and eluates were reactive against different components of myelinating co-cultures. In summary, preliminary evidence suggests that GBS/CIDP patients without detectable IgG antibodies on routine diagnostic tests may nevertheless benefit from IA, and that an unbiased screening approach using myelinating co-cultures may assist in the detection of further autoantibodies which remain to be identified in such patients.
Exploring Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors for Organ Protection in COVID-19
Authors: Fernandez-Fernandez Beatriz , D’Marco Luis , Górriz Jose Luis , Jacobs-Cachá Conxita , Kanbay Mehmet , Luis-Lima Sergio , Porrini Esteban , Sarafidis Pantelis , Soler María José , Ortiz Alberto
Published: June 2020

Hospital admissions and mortality from the Coronavirus disease 2019 (COVID-19) pandemic are spreading throughout the world, and second and third waves are thought to be likely. Risk factors for severe COVID-19 include diabetes, chronic kidney disease and cardiovascular disease. Currently, there is no vaccine and no approved therapy. Therapeutic approaches are aimed at preventing viral replication and spread, limiting the impact of the inflammatory overdrive (cytokine storm), preventing thromboembolic complications and replacing or supporting organ function. However, despite organ support, mortality is currently 65% for those receiving advanced respiratory support and 78% for those requiring renal replacement therapies. Thus, efforts should be made to provide adjuvant organ protection therapy. This may imply novel therapies in clinical development (e.g., the Fas ligand trap asunercept), but uptake of repurposed drugs already in clinical use may be faster. In this regard, sodium glucose co-transporter-2 (SGLT2) inhibitors were recently shown to protect the heart and kidney both within and outside of a diabetic milieu context. Further, preclinical data support a beneficial effect for the lung. We now discuss the potential benefits and risks of SGLT2 inhibitors in COVID-19 and an ongoing clinical trial testing the impact of dapagliflozin on outcomes in COVID-19 patients with respiratory failure.
Role of Extracellular Vesicles in the Pathophysiology, Diagnosis and Tracking of Non-Alcoholic Fatty Liver Disease
Authors: Newman Lauren A. , Sorich Michael J. , Rowland Andrew
Published: June 2020

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting approximately one-third of the global population. Most affected individuals experience only simple steatosis—an accumulation of fat in the liver—but a proportion of these patients will progress to the more severe form of the disease, non-alcoholic steatohepatitis (NASH), which enhances the risk of cirrhosis and hepatocellular carcinoma. Diagnostic approaches to NAFLD are currently limited in accuracy and efficiency; and liver biopsy remains the only reliable way to confirm NASH. This technique, however, is highly invasive and poses risks to patients. Hence, there is an increasing demand for improved minimally invasive diagnostic tools for screening at-risk individuals and identifying patients with more severe disease as well as those likely to progress to such stages. Recently, extracellular vesicles (EVs)—small membrane-bound particles released by virtually all cell types into circulation—have emerged as a rich potential source of biomarkers that can reflect liver function and pathological processes in NAFLD. Of particular interest to the diagnosis and tracking of NAFLD is the potential to extract microRNAs miR-122 and miR-192 from EVs circulating in blood, particularly when using an isolation technique that selectively captures hepatocyte-derived EVs.
Endocrinopathies Associated with Immune Checkpoint Inhibitor Cancer Treatment: A Review
Authors: Okura Naoko , Asano Mai , Uchino Junji , Morimoto Yoshie , Iwasaku Masahiro , Kaneko Yoshiko , Yamada Tadaaki , Fukui Michiaki , Takayama Koichi
Published: June 2020

Treatment with immune checkpoint inhibitors has shown efficacy against a variety of cancer types. The effects of nivolumab and pembrolizumab on lung cancer have been reported, and further therapeutic advances are ongoing. The side effects of immune checkpoint inhibitors are very different from those of conventional cytocidal anticancer drugs and molecular targeted drugs, and they involve various organs such as the digestive and respiratory organs, thyroid and pituitary glands, and skin. The generic term for such adverse events is immune-related adverse events (irAEs). They are relatively infrequent, and, if mild, treatment with immune checkpoint inhibitors can be continued with careful control. However, early detection and appropriate treatment are critical, as moderate-to-severe irAEs are associated with markedly reduced organ function and quality of life, with fatal consequences in some cases. Of these, endocrinopathies caused by immune checkpoint inhibitors are sometimes difficult to distinguish from nonspecific symptoms in patients with advanced cancer and may have serious outcomes when the diagnosis is delayed. Therefore, it is necessary to anticipate and appropriately address the onset of endocrinopathies during treatment with immune checkpoint inhibitors. Here, we present a review of endocrine disorders caused by immune checkpoint inhibitor treatment.
Does SARS-CoV-2 Trigger Stress-Induced Autoimmunity by Molecular Mimicry? A Hypothesis
Authors: Cappello Francesco , Marino Gammazza Antonella , Dieli Francesco , Conway de Macario Everly , Macario Alberto JL
Published: June 2020

Viruses can generate molecular mimicry phenomena within their hosts. Why should severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not be considered one of these? Information in this short review suggests that it might be so and, thus, encourages research aiming at testing this possibility. We propose, as a working hypothesis, that the virus induces antibodies and that some of them crossreact with host’s antigens, thus eliciting autoimmune phenomena with devasting consequences in various tissues and organs. If confirmed, by in vitro and in vivo tests, this could drive researchers to find effective treatments against the virus.
Do Infants at Risk of Developing Cerebral Palsy or Other Neurodevelopmental Disorders Learn What They Practice?
Authors: Löwing Kristina , Holmström Linda , Almeida Rita , Eliasson Ann-Christin
Published: June 2020

Through secondary analyses of the Small Step. Randomized Control Trial, we tested the hypothesis that children at risk of developing cerebral palsy (CP) or other neurodevelopmental disorders would learn what they practice, i.e., that they would have a more rapid development within the specifically trained foci (hand use or mobility) of each time period compared to the development rate within the foci not trained at that time. Nineteen infants (6.3 (1.62) months corrected age) included in the Small Step program were assessed at six time points during the intervention. For statistical analysis, general and mixed linear models were used, and the independent variables were the Peabody Developmental Motor scale (stationary, locomotion, grasping and visuomotor sub scales), the Gross Motor Function Measure-66 and the Hand Assessment for Infants. Outcomes related to gross motor function improved significantly more after mobility training than after hand use training, while fine motor function was improved to the same extent following both training types. Significantly higher improvements after the first training period were seen in one out of three outcome measures in both gross and fine motor assessments. The improvements observed were all independent of diagnosis at two years. The concept “you learn what you practice” was most clearly confirmed in the case of gross motor development.
Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis
Authors: Kolarz Bogdan , Ciesla Marek , Dryglewska Magdalena , Majdan Maria
Published: June 2020

Protein citrullination is carried out by peptidylarginine deiminase type 4 (PAD4) enzyme. As a consequence of this process, post-translationally modified proteins are formed that become antigens for anti-citrullinated protein antibodies (ACPA). The study aimed at identifying whether the PADI4 gene is subject to epigenetic regulation through methylation of its promoter region, whether the degree of methylation differs in healthy individuals vs. rheumatoid arthritis (RA) patients and changes in correlation with ACPA, anti-PAD4 and disease activity. A total of 125 RA patients and 30 healthy controls were enrolled. Quantitative real-time methylation-specific PCR was used to analyze the methylation status. ACPA and anti-PAD4 antibodies were determined in serum by enzyme-linked immunosorbent immunoassay. The differences were observed in the degree of PADI4 gene promoter methylation between RA patients and HC, along with an upward trend for the methylation in RA, which was inversely proportional to the disease activity. A weak or modest negative correlation between the degree of PADI4 gene methylation and anti-PAD4, disease activity score (DAS28) and ACPA level has been found. The elevated methylation is associated with lower disease activity, lower levels of ACPA and aPAD4. The methylation degree in this area is growing up during effective treatment and might play a role in the RA pathophysiology and therefore could be a future therapeutic target.
Remission of Proteinuria May Protect against Progression to Chronic Kidney Disease in Pediatric-Onset IgA Nephropathy
Authors: Suh Jin-Soon , Jang Kyung Mi , Hyun Hyesun , Cho Myung Hyun , Lee Joo Hoon , Park Young Seo , Oh Jae Hyuk , Kim Ji Hong , Yoo Kee Hwan , Chung Woo Yeong , Kim Seong Heon , Kim Keehyuck , Lee Dae Yeol , Lee Jung Won , Cho Min Hyun , Park Hyewon , Koo Ja Wook , Han Kyoung Hee , Yang Eun Mi , Lee Keum Hwa , Shin Jae Il , Cho Heeyeon , Kim Kyo Soon , Ha Il-Soo , Park Yong Hoon , Kang Hee Gyung
Published: June 2020

Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulopathies diagnosed in children and adolescents. This study aimed to evaluate the clinical features in and outcomes of pediatric IgAN over the last 30 years. Patients who were diagnosed before age of 18 at 20 centers in Korea were evaluated retrospectively. Of the 1154 patients (768 males, 386 females) with a median follow-up of 5 years, 5.6% (n = 65) progressed to stage 3–5 chronic kidney disease (CKD). The 10- and 20-year CKD-free survival rates were 91.2% and 75.6%, respectively. Outcomes did not differ when comparing those in Korea who were diagnosed prior to versus after the year 2000. On multivariate analysis, combined asymptomatic hematuria and proteinuria as presenting symptoms and decreased renal function at the time of biopsy were associated with progression to CKD, while remission of proteinuria was negatively associated with this outcome. Patients who presented with gross hematuria or nephrotic syndrome tended toward positive outcomes, especially if they ultimately achieved remission. While remission of proteinuria might imply that the disease is inherently less aggressive, it also can be achieved by management. Therefore, more aggressive management might be required for pediatric-onset IgAN.
New Antithrombotic Drugs in Acute Coronary Syndrome
Authors: Zwart Bastiaan , Parker William A. E. , Storey Robert F.
Published: June 2020

In recent years, much progress has been made in the field of antithrombotic drugs in acute coronary syndrome (ACS) treatment, as reflected by the introduction of the more potent P2Y12-inhibitors prasugrel and ticagrelor, and novel forms of concomitant anticoagulation, such as fondaparinux and bivalirudin. However, despite substantial improvements in contemporary ACS treatment, there remains residual ischemic risk in this group and hence the need for even more effective antithrombotic drugs, while balancing antithrombotic efficacy against bleeding risk. This review discusses recently introduced and currently developed antiplatelet and anticoagulant drugs in ACS treatment.
ECG Changes in Melanoma Patients Undergoing Cancer Therapy—Data from the ECoR Registry
Authors: Pohl Julia , Mincu Raluca-Ileana , Mrotzek Simone Maria , Hinrichs Lena , Michel Lars , Livingstone Elisabeth , Zimmer Lisa , Wakili Reza , Schadendorf Dirk , Rassaf Tienush , Totzeck Matthias
Published: June 2020

We aimed to evaluate whether therapy with immune checkpoint inhibitors (ICI) leads to changes in electrocardiogram (ECG) parameters in melanoma patients. We retrospectively examined 41 patients (46% women, age 61 ± 12years) with advanced melanoma (stage III/IV) before and during ICI treatment from our “Essen Cardio-oncology Registry” (ECoR). ECGs were analyzed before and 4–12 weeks after therapy started (follow-up, 90 ± 51 days). Heart rate, PR time, QRS duration and duration of the corrected QT (QTc) interval were recorded. QT dispersion (QTd) was calculated. Heart rate, PR time, QRS and QTc did not differ when comparing values before and after therapy started. QTd was prolonged after therapy started (32 ± 16 ms vs. 47 ± 19 ms, n = 41, p < 0.0001). Subgroup analyses revealed prolonged QTd in patients that received a combination immunotherapy with ipilimumab and nivolumab (31 ± 14 ms vs. 50 ± 14 ms, n = 21, p < 0.0001), while QTd in patients with anti–programmed death 1 (PD-1) inhibitor monotherapy did not change after therapy started. QTd is prolonged in patients under ICI combination therapy, potentially signaling an increased susceptibility to ventricular arrhythmias.
Slug Is A Surrogate Marker of Epithelial to Mesenchymal Transition (EMT) in Head and Neck Cancer
Authors: Steinbichler T. B. , Dudas J. , Ingruber J. , Glueckert R. , Sprung S. , Fleischer F. , Cidlinsky N. , Dejaco D. , Kofler B. , Giotakis A. I. , Skvortsova I. I. , Riechelmann H.
Published: June 2020

Background: Epithelial to mesenchymal transition (EMT) promotes therapy resistance in head and neck cancer (HNC) cells. In this study, EMT was quantified in HNC tumor samples by the cellular co-localization of cytokeratin/vimentin, E-cadherin/β-catenin and by Slug expression. Methods: Tissue samples from HNC patients were stained with antibody pairs against cytokeratin/vimentin and E-cadherin/β-catenin. Epithelial–mesenchymal co-localization was quantified using immunofluorescence multichannel image cytometry. Double positivity was confirmed using confocal microscopy. Slug was semi-quantified by 2 specialists and quantified by bright field image cytometry. Results: Tumor samples of 102 patients were investigated. A loss of E-cadherin positive cells (56.9 ± 2.6% vs. 97.9 ± 1.0%; p < 0.0001) and E-cadherin/β-catenin double positive cells (15.4 ± 5.7% vs. 85.4 ± 1.2%; p < 0.0001) was observed in tumor samples. The percentage of Slug positive cells was increased in tumor samples (12.1 ± 3.6% vs. 3.2 ± 2.6%; p = 0.001). Ordinal Slug scores judged by two specialists closely correlated with percentage of Slug-positive cells (Spearman’s rho = 0.81; p < 0.001). Slug score correlated negatively with the percentage of E-cadherin positive cells (r = 0.4; p = 0.006), the percentage of E-cadherin/β-catenin positive cells (r = 0.5; p = 0.001) and positively with cytokeratin/vimentin positive cells (r = 0.4, p = 0.003). Conclusion: EMT can be assessed in HNC tumor probes by cytokeratin/vimentin co-expression and loss of E-cadherin/β-catenin co-expression. Slug score provides a convenient surrogate marker for EMT.
Validity of the STOP-Bang Questionnaire in Identifying OSA in a Dental Patient Cohort
Authors: Lonia Letizia , Scalese Marco , Rossato Gianluca , Bruno Giovanni , Zalunardo Francesca , De Stefani Alberto , Gracco Antonio
Published: June 2020

Background and objectives: Obstructive Sleep Apnea represents a widespread problem in the population, but it is often not diagnosed and not considered a true pathology. Different diagnostic tools are available for the diagnosis of sleep apnea. This study aims to demonstrate the ability of the STOP-Bang (Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender) questionnaire in identifying subjects with Obstructive Sleep Apnea (OSA) Syndrome, highlighting the role of dentists as epidemiological sentinels. Materials and methods: the STOP-Bang questionnaire was administered to a cohort of 1000 patients, assessing three private dental clinics in Italy. Excessive daytime sleepiness was measured using Epworth Sleepiness Scale (ESS) and defined as ≥ 10. Subjects were considered at risk of OSA if they had three or more positive items at STOP-Bang and were invited to undergo further examination with a type 3 polygraph. Presence of OSA was measured with the apnea-hypopnea index (AHI) and defined as AHI ≥ 5. Results: 482/1000 subjects (48.2%) had three or more positive items in the STOP-Bang questionnaire and were considered at risk for Obstructive Sleep Apnea Syndrome (OSAS). Excessive daytime sleepiness (EDS ≥ 10) was more frequent among subjects at risk for OSAS (73/482, 15.1%) vs. those not at risk for OSAS (30/518, 5.8%) (p < 0.0001). Moreover, 153/482 subjects at risk for OSAS (31.7%) accepted further examination with a type 3 polygraph. Presence of OSAS (AHI ≥ 5) was suggested in 121/153 subjects (79.1%, 95% CI 71.6% to 85.1%), with 76/121 subjects (62.8%) needing treatment (AHI ≥ 15). Conclusion: the high prevalence of OSAS highlights the role of dentists as “epidemiological sentinels”. The STOP-Bang questionnaire is a simple and efficacious instrument for screening sleep apnea patients.
Experimental and Theoretical Analysis of Lead Pb2+ and Cd2+ Retention from a Single Salt Using a Hollow Fiber PES Membrane
Authors: Hadi Salwa , Mohammed Ahmed A. , Al-Jubouri Sama M. , Abd Mahmood F. , Majdi Hasan Shaker , Alsalhy Qusay F. , Rashid Khalid T. , Ibrahim Salah S. , Salih Issam K. , Figoli Alberto
Published: June 2020

The present work reports the performance of three types of polyethersulfone (PES) membrane in the removal of highly polluting and toxic lead Pb2+ and cadmium Cd2+ ions from a single salt. This study investigated the effect of operating variables, including pH, types of PES membrane, and feed concentration, on the separation process. The transport parameters and mass transfer coefficient (k) of the membranes were estimated using the combined film theory-solution-diffusion (CFSD), combined film theory-Spiegler-Kedem (CFSK), and combined film theory-finely-porous (CFFP) membrane transport models. Various parameters were used to estimate the enrichment factors, concentration polarization modulus, and Péclet number. The pH values significantly affected the permeation flux of the Pb2+ solution but only had a slight effect on the Cd2+ solution. However, Cd2+ rejection was highly improved by increasing the pH value. The rejection of the PES membranes increased greatly as the heavy metal concentration rose, while the heavy metal concentration moderately affected the permeation flux. The maximum rejection of Pb2+ in a single-salt solution was 99%, 97.5%, and 98% for a feed solution containing 10 mg Pb/L at pH 6, 6.2, and 5.7, for PES1, PES2, and PES3, respectively. The maximum rejection of Cd2+ in single-salt solutions was 78%, 50.2%, and 44% for a feed solution containing 10 mg Cd/L at pH 6.5, 6.2, and 6.5, for PES1, PES2, and PES3, respectively. The analysis of the experimental data using the CFSD, CFSK, and CFFP models showed a good agreement between the theoretical and experimental results. The effective membrane thickness and active skin layer thickness were evaluated using the CFFP model, indicating that the Péclet number is important for determining the mechanism of separation by diffusion.
Integrated Physical-Constitutive Computational Framework for Plastic Deformation Modeling
Authors: Viernstein Bernhard , Kozeschnik Ernst
Published: June 2020

An integrated framework for deformation modeling has been developed, which combines a physical state parameter-based formulation for microstructure evolution during plastic deformation processes with constitutive creep models of polycrystalline materials. The implementations of power law, Coble, Nabarro–Herring and Harper–Dorn creep and grain boundary sliding are described and their contributions to the entire stress response at a virtual applied strain rate are discussed. The present framework simultaneously allows calculating the plastic deformation under prescribed strain rate or constant stress, as well as stress relaxation after preceding stress or strain loading. The framework is successfully applied for the construction of deformation mechanism maps.
Multi Draw Radius Die Design for Increases in Limiting Drawing Ratio
Authors: Phanitwong Wiriyakorn , Thipprakmas Sutasn
Published: June 2020

As a major sheet metal process for fabricating cup or box shapes, the deep drawing process is commonly applied in various industrial fields, such as those involving the manufacture of household utensils, medical equipment, electronics, and automobile parts. The limiting drawing ratio (LDR) is the main barrier to increasing the formability and production rate as well as to decrease production cost and time. In the present research, the multi draw radius (MDR) die was proposed to increase LDR. The finite element method (FEM) was used as a tool to illustrate the principle of MDR based on material flow. The results revealed that MDR die could reduce the non-axisymmetric material flow on flange and the asymmetry of the flange during the deep drawing process. Based on this material flow characteristic, the cup wall stretching and fracture could be delayed. Furthermore, the cup wall thicknesses of the deep drawn parts obtained by MDR die application were more uniform in each direction along the plane, at 45°, and at 90° to the rolling direction than those obtained by conventional die application. In the present research, a proper design for the MDR was suggested to achieve functionality of the MDR die as related to each direction along the plane, at 45°, and at 90° to the rolling direction. The larger draw radius positioned for at 45° to the rolling direction and the smaller draw radius positioned for along the plane and at 90° to the rolling direction were recommended. Therefore, by using proper MDR die application, the drawing ratio could be increased to be 2.75, an increase in LDR of approximately 22.22%.
A Preliminary Prototype High-Speed Feedback Control of an Artificial Cochlear Sensory Epithelium Mimicking Function of Outer Hair Cells
Authors: Yamazaki Hiroki , Yamanaka Dan , Kawano Satoyuki
Published: June 2020

A novel feedback control technique for the local oscillation amplitude in an artificial cochlear sensory epithelium that mimics the functions of the outer hair cells in the cochlea is successfully developed and can be implemented with a control time on the order of hundreds of milliseconds. The prototype artificial cochlear sensory epithelium was improved from that developed in our previous study to enable the instantaneous determination of the local resonance position based on the electrical output from a bimorph piezoelectric membrane. The device contains local patterned electrodes deposited with micro electro mechanical system (MEMS) technology that is used to detect the electrical output and oscillate the device by applying local electrical stimuli. The main feature of the present feedback control system is the principle that the resonance position is recognized by simultaneously measuring the local electrical outputs of all of the electrodes and comparing their magnitudes, which drastically reduces the feedback control time. In this way, it takes 0.8 s to control the local oscillation of the device, representing the speed of control with the order of one hundred times relative to that in the previous study using the mechanical automatic stage to scan the oscillation amplitude at each electrode. Furthermore, the intrinsic difficulties in the experiment such as the electrical measurement against the electromagnetic noise, adhesion of materials, and fatigue failure mechanism of the oscillation system are also shown and discussed in detail based on the many scientific aspects. The basic knowledge of the MEMS fabrication and the experimental measurement would provide useful suggestions for future research. The proposed preliminary prototype high-speed feedback control can aid in the future development of fully implantable cochlear implants with a wider dynamic range.
Simple Device to Measure Pressure Using the Stress Impedance Effect of Amorphous Soft Magnetic Thin Film
Authors: Froemel Joerg , Akita Satoru , Tanaka Shuji
Published: June 2020

A simple micro-machined pressure sensor, based on the stress-impedance (SI) effect, was fabricated herein using typical micro-fabrication technologies. To sense pressure, a 1-µm thin, soft magnetic metallic film of FeSiB was sputtered and used as a diaphragm. Its electrical response (impedance change) was measured under pressure in a frequency band from 5 to 500 MHz. A lumped-element equivalent electric circuit was used to separate the impedance of the soft magnetic metal from other parasitic elements. The impedance change clearly depended on the applied pressure. It was also shown that the impedance change could be explained by a change in relative permeability, according to the theory of the SI effect. The radial stress in the diaphragm and the relative permeability exhibited a linear relationship. At a measurement frequency of 200 MHz, the largest sensor response, with a gauge factor of 385.7, was found. It was in the same order as the conventional sensors. As the proposed device is very simple, it has the potential for application as a cheap pressure sensor.
Multi-Technique Characterization of a Fine Fraction of CDW and Assessment of Reactivity in a CDW/Lime System
Authors: Frías Moisés , Vigil de la Villa Raquel , Martínez-Ramírez Sagrario , Fernández-Carrasco Lucía , Villar-Cociña Ernesto , García-Giménez Rosario
Published: June 2020

This study analysed the fine particle (<5 mm) waste generated during siliceous or calcareous (depending on the composition of the original aggregate) concrete waste crushing. In the absence of industrial applications, such waste is amassed in open-air stockpiles on construction and demolition wastes (CDW) management plant grounds. The aim pursued was to find an outlet for that material in the cement industry. The starting waste, sourced from six Spanish management facilities, was characterised for its chemical and mineralogical composition, physical properties and pozzolanicity. The mineralogical phases in the CDW/lime system and their variations during the pozzolanic reaction were likewise identified. The findings showed that the fine waste consisted primarily in quartz, calcite, micas and feldspars, with smaller fractions of kaolinite and cement anhydrous phases. No portland cement hydration phases were identified. All six types analysed exhibited medium to low pozzolanicity, with the highest values recorded for the siliceous waste. Ettringite, C–S–H gels and calcium aluminate hydrates (C4AH13, C4AcH12) were identified during the pozzolanic reaction in CDW/lime system. Therefore, this type of waste can be reused as supplementary cementitious material with low-medium pozzolanic activity.
Tannin-Rich Plants as Natural Manipulators of Rumen Fermentation in the Livestock Industry
Authors: Fagundes G. M. , Benetel G. , Santos K. C. , Welter K. C. , Melo F. A. , Muir J. P. , Bueno I. C. S.
Published: June 2020

Condensed tannins (CTs) are plant anti-herbivore compounds with antimicrobial activity that can be used in ruminant diets as ruminal microbiome manipulators. However, not all CTs from fodder legumes are bioactive due to their wide structural diversity. The aim of our study was to investigate the effect of 10 CT-containing plants (Flemingia macrophylla, Leucaena leucocephala, Stylosanthes guianensis, Gliricidia sepium, Cratylia argentea, Cajanus cajan, Desmodium ovalifolium, Macrotiloma axilare, D. paniculatum, and Lespedeza procumbens) on in vitro fermentation kinetics of Nelore beef cattle. Polyethylene glycol (PEG), a specific CT-binding agent, was added to neutralize condensed tannin. Tifton and alfalfa hay were used as controls lacking CT. The experimental layout included a randomized complete block with factorial design and four blocks. The data were subjected to analysis of variance followed by Duncan’s test to determine differences (p < 0.05) among treatment means. The addition of PEG in browse incubations resulted in increased gas production, fermentation rate, short-chain fatty acid (SCFA) and N-NH3 release. Within our study, Lespedeza procumbens, Desmodium paniculatum, Leucaena leucocephala, Desmodium ovalifolium, and Flemingia macrophylla showed superior bioactivity compared to other species evaluated, suggesting a natural alternative for replacing ionophores to modify ruminal fermentation. Condensed tannins from L. pocumbens, D. paniculatum, L. leucocephala, D. ovalifolium, and F. macrophylla have the potential to modify rumen fermentation in beef cattle.
Evolution of the Multielemental Content along the Red Wine Production Process from Tempranillo and Grenache Grape Varieties
Authors: Bica Alexandra , Sánchez Raquel , Todolí José-Luis
Published: June 2020

In the present work, 38 elements were quantified in the different fractions generated by applying amateur winemaking methods. Inductively Coupled Plasma Mass Spectrometry was used as detection technique. Grapes were analyzed and separate metal profiles were also obtained for the skin and seeds. Additional vinification fractions included musts before and after the fermentation process. Meanwhile, solid fractions corresponded to the so-called hat, pressed pomace and the lees obtained after gravitational settling at the tank bottom. Wine was further analyzed. The obtained results revealed a different repartition depending on the particular element and winemaking solid and liquid fraction evaluated. The studies included vinification in presence and in absence of added yeast and grape geographical origin. Principal component analysis helped to discriminate among fractions and to determine the critical elements behaving differently. Finally, a mass balance allowed to unequivocally detect the migration of a given element to the winemaking fractions.
Vine-Canes as a Source of Value-Added Compounds for Cosmetic Formulations
Authors: Moreira Manuela M. , Rodrigues Francisca , Dorosh Olena , Pinto Diana , Costa Paulo C. , Švarc-Gajić Jaroslava , Delerue-Matos Cristina
Published: June 2020

The majority of works about vine-canes are focused on the evaluation of their chemical composition and antioxidant potential. To the best of our knowledge, the possible applications of produced extracts in cosmetic formulations have never been explored. The aim of the present study was to evaluate the antioxidant properties of vine-canes subcritical water extracts for use as active ingredients in the cosmetic industry. For that, the phenolic content and antioxidant activity of six vine-cane varieties, namely Alvarinho and Loureiro from the Minho region and Touriga Nacional and Tinta Roriz (TR) from both the Douro and Dão regions, were evaluated through spectrophotometric and chromatographic methods. All extracts presented similar antioxidant activity and the highest phenolic content was reported for TR variety from the Douro region (33.7 ± 1.9 mg GAE/g dw). The capacity of vine-cane extracts to capture reactive oxygen species superoxide (O2∙−) was also studied, with the highest IC50 value being obtained for Loureiro variety (56.68 ± 2.60 µg/mL). Furthermore, no adverse effects on HaCaT and HFF-1 dermal cell lines in concentrations below 100 and 1000 μg/mL, respectively, were determined. Finally, Loureiro vine-cane extract was incorporated into a topical formulation, and physical and microbiological properties were within expected values, demonstrating that vine-canes extracts can be successfully incorporated in cosmetic products.
Recent Advances in Microfluidic Paper-Based Analytical Devices toward High-Throughput Screening
Authors: Boobphahom Siraprapa , Nguyet Ly Mai , Soum Veasna , Pyun Nayoon , Kwon Oh-Sun , Rodthongkum Nadnudda , Shin Kwanwoo
Published: June 2020

Microfluidic paper-based analytical devices (µPADs) have become promising tools offering various analytical applications for chemical and biological assays at the point-of-care (POC). Compared to traditional microfluidic devices, µPADs offer notable advantages; they are cost-effective, easily fabricated, disposable, and portable. Because of our better understanding and advanced engineering of µPADs, multistep assays, high detection sensitivity, and rapid result readout have become possible, and recently developed µPADs have gained extensive interest in parallel analyses to detect biomarkers of interest. In this review, we focus on recent developments in order to achieve µPADs with high-throughput capability. We discuss existing fabrication techniques and designs, and we introduce and discuss current detection methods and their applications to multiplexed detection assays in relation to clinical diagnosis, drug analysis and screening, environmental monitoring, and food and beverage quality control. A summary with future perspectives for µPADs is also presented.
Verification of Chromatographic Profile of Primary Essential Oil of Pinus sylvestris L. Combined with Chemometric Analysis
Authors: Allenspach Martina , Valder Claudia , Flamm Daniela , Grisoni Francesca , Steuer Christian
Published: June 2020

Chromatographic profiles of primary essential oils (EO) deliver valuable authentic information about composition and compound pattern. Primary EOs obtained from Pinus sylvestris L. (PS) from different global origins were analyzed using gas chromatography coupled to a flame ionization detector (GC-FID) and identified by GC hyphenated to mass spectrometer (GC-MS). A primary EO of PS was characterized by a distinct sesquiterpene pattern followed by a diterpene profile containing diterpenoids of the labdane, pimarane or abietane type. Based on their sesquiterpene compound patterns, primary EOs of PS were separated into their geographical origin using component analysis. Furthermore, differentiation of closely related pine EOs by partial least square discriminant analysis proved the existence of a primary EO of PS. The developed and validated PLS-DA model is suitable as a screening tool to assess the correct chemotaxonomic identification of a primary pine EOs as it classified all pine EOs correctly.
Hybrid Nanocellulose-Copper (II) Oxide as Engine Oil Additives for Tribological Behavior Improvement
Authors: Hisham Sakinah , Kadirgama Kumaran , Mohammed Hussein A. , Kumar Amit , Ramasamy Devarajan , Samykano Mahendran , Rahman Saidur
Published: June 2020

Friction and wear are the main factors in the failure of the piston in automobile engines. The objective of this work was to improve the tribological behaviour and lubricant properties using hybrid Cellulose Nanocrystal (CNC) and Copper (II) oxide nanoparticles blended with SAE 40 as a base fluid. The two-step method was used in the hybrid nanofluid preparation. Three different concentrations were prepared in a range of 0.1% to 0.5%. Kinematic viscosity and viscosity index were also identified. The friction and wear behavior were evaluated using a tribometer based on ASTM G181. The CNC-CuO nano lubricant shows a significant improvement in term of viscosity index by 44.3–47.12% while for friction, the coefficient of friction (COF) decreases by 1.5%, respectively, during high and low-speed loads (boundary regime), and 30.95% during a high-speed, and low load (mixed regime). The wear morphologies results also show that a smoother surface was obtained after using CNC-CuO nano lubricant compared to SAE 40.
Critical Factors Involved in Primordia Building in Agaricus bisporus: A Review
Authors: Baars Johan J. P. , Scholtmeijer Karin , Sonnenberg Anton S. M. , van Peer Arend
Published: June 2020

The button mushroom Agaricus bisporus is an economically important crop worldwide. Many aspects of its cultivation are well known, except for the precise biological triggers for its fructification. By and large, for most basidiomycete species, nutrient availability, light and a drop in temperature are critical factors for fructification. A. bisporus deviates from this pattern in the sense that it does not require light for fructification. Furthermore its fructification seems to be inhibited by a self-generated factor which needs to be removed by microorganisms in order to initiate fruiting. This review explores what is known about the morphogenesis of fruiting initiation in A. bisporus, the microflora, the self-inhibitors for fruiting initiation and transcription factors involved. This information is subsequently contrasted with an overall model of the regulatory system involved in the initiation of the formation of primordia in basidiomycetes. The comparison reveals a number of the blank spots in our understanding of the fruiting process in A. bisporus.
Artificial Metalloenzymes: From Selective Chemical Transformations to Biochemical Applications
Authors: Himiyama Tomoki , Okamoto Yasunori
Published: June 2020

Artificial metalloenzymes (ArMs) comprise a synthetic metal complex in a protein scaffold. ArMs display performances combining those of both homogeneous catalysts and biocatalysts. Specifically, ArMs selectively catalyze non-natural reactions and reactions inspired by nature in water under mild conditions. In the past few years, the construction of ArMs that possess a genetically incorporated unnatural amino acid and the directed evolution of ArMs have become of great interest in the field. Additionally, biochemical applications of ArMs have steadily increased, owing to the fact that compartmentalization within a protein scaffold allows the synthetic metal complex to remain functional in a sea of inactivating biomolecules. In this review, we present updates on: (1) the newly reported ArMs, according to their type of reaction, and (2) the unique biochemical applications of ArMs, including chemoenzymatic cascades and intracellular/in vivo catalysis. We believe that ArMs have great potential as catalysts for organic synthesis and as chemical biology tools for pharmaceutical applications.
Characterization of Odor-Active Compounds, Polyphenols, and Fatty Acids in Coffee Silverskin
Authors: Angeloni Simone , Scortichini Serena , Fiorini Dennis , Sagratini Gianni , Vittori Sauro , Neiens Silva D. , Steinhaus Martin , Zheljazkov Valtcho D. , Maggi Filippo , Caprioli Giovanni
Published: June 2020

For the first time the volatile fraction of coffee silverskin has been studied focusing on odor-active compounds detected by gas chromatography-olfactometry/flame ionization detector (GC-O/FID) system. Two approaches, namely headspace (HS) analysis by solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) and odor-active compounds analysis by gas chromatography-olfactometry/flame ionization detector (GC-O/FID), have been employed to fully characterize the aroma profile of this by-product. This work also provided an entire characterization of the bioactive compounds present in coffee silverskin, including alkaloids, chlorogenic acids, phenolic acids, flavonoids, and secoiridoids, by using different extraction procedures and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) system. Coffee silverskin was shown to be a good source of caffeine and chlorogenic acids but also of phenolic acids and flavonoids. In addition, the fatty acid composition of the coffee silverskin was established by GC-FID system. The results from this research could contribute to the development of innovative applications and reuses of coffee silverskin, an interesting resource with a high potential to be tapped by the food and nutraceutical sector, and possibly also in the cosmetics and perfumery.
Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation
Authors: El-Sayed Ashraf S.A. , El-Sayed Manal T. , Rady Amgad M. , Zein Nabila , Enan Gamal , Shindia Ahmed , El-Hefnawy Sara , Sitohy Mahmoud , Sitohy Basel
Published: June 2020

Endophytic fungi have been considered as a repertoire for bioactive secondary metabolites with potential application in medicine, agriculture and food industry. The biosynthetic pathways by fungal endophytes raise the argument of acquisition of these machineries of such complex metabolites from the plant host. Diterpenoids “Taxol” is the most effective anticancer drug with highest annual sale, since its discovery in 1970 from the Pacific yew tree, Taxus brevifolia. However, the lower yield of Taxol from this natural source (bark of T. brevifolia), availability and vulnerability of this plant to unpredicted fluctuation with the ecological and environmental conditions are the challenges. Endophytic fungi from Taxus spp. opened a new avenue for industrial Taxol production due to their fast growth, cost effectiveness, independence on climatic changes, feasibility of genetic manipulation. However, the anticipation of endophytic fungi for industrial Taxol production has been challenged by the loss of its productivity, due to the metabolic reprograming of cells, downregulating the expression of its encoding genes with subculturing and storage. Thus, the objectives of this review were to (1) Nominate the endophytic fungal isolates with the Taxol producing potency from Taxaceae and Podocarpaceae; (2) Emphasize the different approaches such as molecular manipulation, cultural optimization, co-cultivation for enhancing the Taxol productivities; (3) Accentuate the genome mining of the rate-limiting enzymes for rapid screening the Taxol biosynthetic machinery; (4) Triggering the silenced rate-limiting genes and transcriptional factors to activates the biosynthetic gene cluster of Taxol.