bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Dyspepsia and Gastroparesis in Patients with Diabetes. A Clinical Point of View in the Year 2021
Authors: Bonetto Silvia , Gruden Gabriella , Beccuti Guglielmo , Ferro Arianna , Saracco Giorgio Maria , Pellicano Rinaldo
Published: March 2021

Diabetes mellitus is a widespread disease, and represents an important public health burden worldwide. Together with cardiovascular, renal and neurological complications, many patients with diabetes present with gastrointestinal symptoms, which configure the so-called diabetic enteropathy. In this review, we will focus on upper gastrointestinal symptoms in patients with diabetes, with particular attention to dyspepsia and diabetic gastroparesis (DG). These two clinical entities share similar pathogenetic mechanisms, which include autonomic neuropathy, alterations in enteric nervous system and histological abnormalities, such as interstitial cells of Cajal depletion. Moreover, the differential diagnosis may be challenging because of overlapping clinical features. Delayed gastric emptying should be documented to differentiate between DG and dyspepsia and it can be assessed through radioactive or non-radioactive methods. The clinical management of dyspepsia includes a wide range of different approaches, above all Helicobacter pylori test and treat. As regards DG treatment, a central role is played by dietary modification and glucose control and the first-line pharmacological therapy is represented by the use of prokinetics. A minority of patients with DG refractory to medical treatment may require more invasive therapeutic approaches, including supplemental nutrition, gastric electric stimulation, pyloromyotomy and gastrectomy.
Premature STEMI in Men and Women: Current Clinical Features and Improvements in Management and Prognosis
Authors: Lorca Rebeca , Pascual Isaac , Aparicio Andrea , Junco-Vicente Alejandro , Alvarez-Velasco Rut , Barja Noemi , Roces Luis , Suárez-Cuervo Alfonso , Diaz Rocio , Moris Cesar , Hernandez-Vaquero Daniel , Avanzas Pablo
Published: March 2021

Background: Coronary artery disease (CAD) is the most frequent cause of ST-segment elevation myocardial infarction (STEMI). Etiopathogenic and prognostic characteristics in young patients may differ from older patients and young women may present worse outcomes than men. We aimed to evaluate the clinical characteristics and prognosis of men and women with premature STEMI. Methods: A total 1404 consecutive patients were referred to our institution for emergency cardiac catheterization due to STEMI suspicion (1 January 2014–31 December 2018). Patients with confirmed premature (<55 years old in men and <60 in women) STEMI (366 patients, 83% men and 17% women) were included (359 atherothrombotic and 7 spontaneous coronary artery dissection (SCAD)). Results: Premature STEMI patients had a high prevalence of classical cardiovascular risk factors. Mean follow-up was 4.1 years (±1.75 SD). Mortality rates, re-hospitalization, and hospital stay showed no significant differences between sexes. More than 10% of women with premature STEMI suffered SCAD. There were no significant differences between sexes, neither among cholesterol levels nor in hypolipemiant therapy. The global survival rates were similar to that expected in the general population of the same sex and age in our region with a significantly higher excess of mortality at 6 years among men compared with the general population. Conclusion: Our results showed a high incidence of cardiovascular risk factors, a high prevalence of SCAD among young women, and a generally good prognosis after standardized treatment. During follow-up, 23% suffered a major cardiovascular event (MACE), without significant differences between sexes and observed survival at 1, 3, and 6 years of follow-up was 96.57% (95% CI 94.04–98.04), 95.64% (95% CI 92.87–97.35), and 94.5% (95% CI 91.12–97.66). An extra effort to prevent/delay STEMI should be invested focusing on smoking avoidance and optimal hypolipemiant treatment both in primary and secondary prevention.
Apheresis Efficacy and Tolerance in the Setting of HLA-Incompatible Kidney Transplantation
Authors: Noble Johan , Metzger Antoine , Naciri Bennani Hamza , Daligault Melanie , Masson Dominique , Terrec Florian , Imerzoukene Farida , Bardy Beatrice , Fiard Gaelle , Marlu Raphael , Chevallier Eloi , Janbon Benedicte , Malvezzi Paolo , Rostaing Lionel , Jouve Thomas
Published: March 2021

Nearly 18% of patients on a waiting list for kidney transplantation (KT) are highly sensitized, which make access to KT more difficult. We assessed the efficacy and tolerance of different techniques (plasma exchanges [PE], double-filtration plasmapheresis [DFPP], and immunoadsorption [IA]) to remove donor specific antibodies (DSA) in the setting of HLA-incompatible (HLAi) KT. All patients that underwent apheresis for HLAi KT within a single center were included. Intra-session and inter-session Mean Fluorescence Intensity (MFI) decrease in DSA, clinical and biological tolerances were assessed. A total of 881 sessions were performed for 45 patients: 107 DFPP, 54 PE, 720 IA. The procedures led to HLAi KT in 39 patients (87%) after 29 (15–51) days. A higher volume of treated plasma was associated with a greater decrease of inter-session class I and II DSA (p = 0.04, p = 0.02). IA, PE, and a lower maximal DSA MFI were associated with a greater decrease in intra-session class II DSA (p < 0.01). Safety was good: severe adverse events occurred in 17 sessions (1.9%), more frequently with DFPP (6.5%) p < 0.01. Hypotension occurred in 154 sessions (17.5%), more frequently with DFPP (p < 0.01). Apheresis is well tolerated (IA and PE > DFPP) and effective at removing HLA antibodies and allows HLAi KT for sensitized patients.
Inappropriate Heart Rate Response to Hypotension in Critically Ill COVID-19-Associated Acute Kidney Injury
Authors: Verney Charles , Legouis David , Voiriot Guillaume , Fartoukh Muriel , Labbé Vincent
Published: March 2021

Angiotensin-converting enzyme 2 (ACE2) receptor of severe acute respiratory syndrome coronavirus 2 is involved in baroreflex control mechanisms. We hypothesize that severe coronavirus infectious disease 2019 (COVID-19) patients may show an alteration in baroreflex-mediated heart rate changes in response to arterial hypotension. A pilot study was conducted to assess the response to hypotension in relation to continuous venovenous hemodiafiltration (CVVHDF) in critically ill patients with PCR-confirmed COVID-19 (from February to April 2020) and in critically ill non-COVID-19 patients with sepsis (from February 2018 to February 2020). The endpoint was a change in the heart rate in response to CVVHDF-induced hypotension. The association between COVID-19 status and heart rate change was estimated using linear regression. The study population included 6 COVID-19 patients (67% men; age 58 (53–64) years) and 12 critically ill non-COVID-19 patients (58% men; age 67 (51–71) years). Baseline characteristics, laboratory findings, hemodynamic parameters, and management before CVVHDF-induced hypotension were similar between the two groups, with the exception of a higher positive end-expiratory pressure and doses of propofol and midazolam administered in COVID-19 patients. Changes in the heart rate were significantly lower in COVID-19 patients as compared to critically ill non-COVID-19 patients (−7 (−9; −2) vs. 2 (2;5) bpm, p = 0.003), while the decrease in mean arterial blood pressure was similar between groups. The COVID-19 status was independently associated with a lower change in the heart rate (−11 (−20; −2) bpm; p = 0.03). Our findings suggest an inappropriate heart rate response to hypotension in severe COVID-19 patients compared to critically ill non-COVID-19 patients.
Factors Associated with Increased Risk of Early Severe Neonatal Morbidity in Late Preterm and Early Term Infants
Authors: Mengistu Tesfaye S. , Schreiber Veronika , Flatley Christopher , Fox Jane , Kumar Sailesh
Published: March 2021

Although the risk of neonatal mortality is generally low for late preterm and early term infants, they are still significantly predisposed to severe neonatal morbidity (SNM) despite being born at relatively advanced gestations. In this study, we investigated maternal and intrapartum risk factors for early SNM in late preterm and early term infants. This was a retrospective cohort study of non-anomalous, singleton infants (34+0–38+6 gestational weeks) born at the Mater Mother’s Hospital in Brisbane, Australia from January 2015 to May 2020. Early SNM was defined as a composite of any of the following severe neonatal outcome indicators: admission to neonatal intensive care unit (NICU) in conjunction with an Apgar score <4 at 5 min, severe respiratory distress, severe neonatal acidosis (cord pH < 7.0 or base excess <−12 mmol/L). Multivariable binomial logistic regression analyses using generalized estimating equations (GEE) were used to identify risk factors. Of the total infants born at 34+0–38+6 gestational weeks, 5.7% had at least one component of the composite outcome. For late preterm infants, pre-existing diabetes mellitus, instrumental birth and emergency caesarean birth for non-reassuring fetal status were associated with increased odds for early SNM, whilst for early term infants, pre-existing and gestational diabetes mellitus, antepartum hemorrhage, instrumental, emergency caesarean and elective caesarean birth were significant risk factors. In conclusion, we identified several risk factors contributing to early SNM in late preterm and early term cohort. Our results suggest that predicted probability of early SNM decreased as gestation increased.
Pain Sensitivity, Negative Affect, and Alcohol Use Disorder Status: A Moderated Mediation Study of Emotion Dysregulation
Authors: Kopera Maciej , Trucco Elisa M. , Suszek Hubert , Kobyliński Paweł , Wiśniewski Paweł , Wojnar Marcin , Jakubczyk Andrzej
Published: March 2021

Previous work suggests that the association between pain and emotional processes among individuals with alcohol use disorder (AUD) may differ from healthy controls. This study investigates whether pain sensitivity mediates the association between negative affect and emotional dysregulation and whether this association differs across AUD status using moderated mediation. The sample included 165 individuals diagnosed with AUD and 110 healthy controls. Of interest was pain sensitivity, as assessed with the Pain Sensitivity Questionnaire, negative affect, as assessed with the Beck Depression Inventory, and emotional dysregulation, as assessed with the Difficulties in Emotional regulation Scale. Age, biological sex, and current pain severity were included as covariates. The results support a moderated partial mediation model that explained 44% of the variance in emotional dysregulation. The findings indicate that negative affect is related to higher pain sensitivity across groups. Moreover, pain sensitivity partially mediated the association between negative affect and emotional dysregulation, but in opposite directions depending on AUD status. Among healthy controls, greater pain sensitivity was related to better emotional regulation, while greater pain sensitivity led to greater emotional dysregulation among individuals with AUD. The potential parallels in the underlying neurobiological mechanisms of emotionality, pain, and AUD suggest that interventions targeting pain may improve adaptive affect regulation skills, which in turn could reduce negative affect and its effect on pain sensitivity among individuals with AUD.
Preclinical Characterization of the Distribution, Catabolism, and Elimination of a Polatuzumab Vedotin-Piiq (POLIVY®) Antibody–Drug Conjugate in Sprague Dawley Rats
Authors: Yip Victor , Lee M. Violet , Saad Ola M. , Ma Shuguang , Khojasteh S. Cyrus , Shen Ben-Quan
Published: March 2021

Polatuzumab vedotin (or POLIVY®), an antibody–drug conjugate (ADC) composed of a polatuzumab monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a cleavable dipeptide linker, has been approved by the United States Food and Drug Administration (FDA) for the treatment of diffuse large B-cell lymphoma (DLBCL). To support the clinical development of polatuzumab vedotin, we characterized the distribution, catabolism/metabolism, and elimination properties of polatuzumab vedotin and its unconjugated MMAE payload in Sprague Dawley rats. Several radiolabeled probes were developed to track the fate of different components of the ADC, with 125I and 111In used to label the antibody component and 3H to label the MMAE payload of the ADC. Following a single intravenous administration of the radiolabeled probes into normal or bile-duct cannulated rats, blood, various tissues, and excreta samples were collected over 7–14 days post-dose and analyzed for radioactivity and to characterize the metabolites/catabolites. The plasma radioactivity of polatuzumab vedotin showed a biphasic elimination profile similar to that of unconjugated polatuzumab but different from unconjugated radiolabeled MMAE, which had a fast clearance. The vast majority of the radiolabeled MMAE in plasma remained associated with antibodies, with a minor fraction as free MMAE and MMAE-containing catabolites. Similar to unconjugated mAb, polatuzumab vedotin showed a nonspecific distribution to multiple highly perfused organs, including the lungs, heart, liver, spleen, and kidneys, where the ADC underwent catabolism to release MMAE and other MMAE-containing catabolites. Both polatuzumab vedotin and unconjugated MMAE were mainly eliminated through the biliary fecal route (>90%) and a small fraction (<10%) was eliminated through renal excretion in the form of catabolites/metabolites, among which, MMAE was identified as the major species, along with several other minor species. These studies provided significant insight into ADC’s absorption, distribution, metabolism, and elimination (ADME) properties, which supports the clinical development of POLIVY.
Special Issue: Emerging Technologies for Medical Imaging Diagnostics, Monitoring and Therapy of Cancers
Authors: Beheshti Mohsen , Mottaghy Felix M.
Published: March 2021

Molecular imaging and therapy play an increasingly important role in the field of “precision medicine” as an emergent prospect for management of the cancerous disease [...]
Whole-Body Pharmacokinetics and Physiologically Based Pharmacokinetic Model for Monomethyl Auristatin E (MMAE)
Authors: Chang Hsuan Ping , Cheung Yuen Kiu , Shah Dhaval K.
Published: March 2021

Monomethyl auristatin E (MMAE) is one of the most commonly used payloads for developing antibody–drug conjugates (ADC). However, limited studies have comprehensively evaluated the whole-body disposition of MMAE. Consequently, here, we have investigated the whole-body pharmacokinetics (PK) of MMAE in tumor-bearing mice. We show that while MMAE is rapidly eliminated from the plasma, it shows prolonged and extensive distribution in tissues, blood cells, and tumor. Highly perfused tissues (e.g., lung, kidney, heart, liver, and spleen) demonstrated tissue-to-plasma area under the concentration curve (AUC) ratios > 20, and poorly perfused tissues (e.g., fat, pancreas, skin, bone, and muscle) had ratios from 1.3 to 2.4. MMAE distribution was limited in the brain, and tumor had 8-fold higher exposure than plasma. A physiological-based pharmacokinetic (PBPK) model was developed to characterize the whole-body PK of MMAE, which accounted for perfusion/permeability-limited transfer of drug in the tissue, blood cell distribution of the drug, tissue/tumor retention of the drug, and plasma protein binding. The model was able to characterize the PK of MMAE in plasma, tissues, and tumor simultaneously, and model parameters were estimated with good precision. The MMAE PBPK model presented here can facilitate the development of a platform PBPK model for MMAE containing ADCs and help with their preclinical-to-clinical translation and clinical dose optimization.
A Comparative in Silico Analysis of CD24’s Prognostic Value in Human and Canine Prostate Cancer
Authors: Leis-Filho Antonio Fernando , Lainetti Patrícia de Faria , Franzoni Mayara Simão , Palmieri Chiara , Kobayshi Priscila Emiko , Laufer-Amorim Renee , Fonseca-Alves Carlos Eduardo
Published: March 2021

CD24 is a cell surface molecule anchored by glycosyl-phosphatidyl-inositol and expressed by different human cancers, including prostate cancer (PC). Some studies have demonstrated that CD24 expression is associated with poor patient outcome; however, few studies have investigated CD24 expression in spontaneous animal models of human PC, such as canine PC. This study aimed to evaluate the expression of CD24 in human PC using the in silico analysis of the data obtained from The Cancer Genome Atlas (TCGA) and comparing it with the previously published prostatic canine transcriptome data. In addition, CD24 expression was confirmed by immunohistochemistry in an independent cohort of canine prostatic samples and its prognostic significance assessed. The systematic review identified 10 publications fitting with the inclusion criteria of this study. Of the 10 manuscripts, 5 demonstrated a direct correlation between CD24 overexpression and patient prognoses. CD24 expression was also associated with PSA relapse (2/5) and tumor progression (1/5). However, the in silico analysis did not validate CD24 as a prognostic factor of human PC. Regarding canine PC, 10 out of 30 normal prostates and 27 out of 40 PC samples were positive for CD24. As in humans, there was no association with overall survival. Overall, our results demonstrated a significant CD24 overexpression in human and canine prostate cancer, although its prognostic value may be questionable. However, tumors overexpressing CD24 may be a reliable model for new target therapies and dogs could be used of a unique preclinical model for these studies.
‘Statistical Irreproducibility’ Does Not Improve with Larger Sample Size: How to Quantify and Address Disease Data Multimodality in Human and Animal Research
Authors: Basson Abigail R. , Cominelli Fabio , Rodriguez-Palacios Alexander
Published: March 2021

Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause of study irreproducibility. To emulate the repetition of studies and random sampling of study subjects, we first used various simulation methods of random number generation based on preclinical published disease outcome data from human gut microbiota-transplantation rodent studies (e.g., intestinal inflammation and univariate/continuous). We first used unimodal distributions (one-mode, Gaussian, and binomial) to generate random numbers. We showed that increasing N does not reproducibly identify statistical differences when group comparisons are repeatedly simulated. We then used multimodal distributions (>1-modes and Markov chain Monte Carlo methods of random sampling) to simulate similar multimodal datasets A and B (t-test-p = 0.95; N = 100,000), and confirmed that increasing N does not improve the ‘reproducibility of statistical results or direction of the effects’. Data visualization with violin plots of categorical random data simulations with five-integer categories/five-groups illustrated how multimodality leads to irreproducibility. Re-analysis of data from a human clinical trial that used maltodextrin as dietary placebo illustrated multimodal responses between human groups, and after placebo consumption. In conclusion, increasing N does not necessarily ensure reproducible statistical findings across repeated simulations due to randomness and multimodality. Herein, we clarify how to quantify, visualize and address disease data multimodality in research. Data visualization could facilitate study designs focused on disease subtypes/modes to help understand person–person differences and personalized medicine.
Liquid Biopsy Biomarkers in Urine: A Route towards Molecular Diagnosis and Personalized Medicine of Bladder Cancer
Authors: Ferro Matteo , La Civita Evelina , Liotti Antonietta , Cennamo Michele , Tortora Fabiana , Buonerba Carlo , Crocetto Felice , Lucarelli Giuseppe , Busetto Gian Maria , Del Giudice Francesco , de Cobelli Ottavio , Carrieri Giuseppe , Porreca Angelo , Cimmino Amelia , Terracciano Daniela
Published: March 2021

Bladder cancer (BC) is characterized by high incidence and recurrence rates together with genomic instability and elevated mutation degree. Currently, cystoscopy combined with cytology is routinely used for diagnosis, prognosis and disease surveillance. Such an approach is often associated with several side effects, discomfort for the patient and high economic burden. Thus, there is an essential demand of non-invasive, sensitive, fast and inexpensive biomarkers for clinical management of BC patients. In this context, liquid biopsy represents a very promising tool that has been widely investigated over the last decade. Liquid biopsy will likely be at the basis of patient selection for precision medicine, both in terms of treatment choice and real-time monitoring of therapeutic effects. Several different urinary biomarkers have been proposed for liquid biopsy in BC, including DNA methylation and mutations, protein-based assays, non-coding RNAs and mRNA signatures. In this review, we summarized the state of the art on different available tests concerning their potential clinical applications for BC detection, prognosis, surveillance and response to therapy.
Gut Microbiota and Non-Alcoholic Fatty Liver Disease Severity in Type 2 Diabetes Patients
Authors: Tsai Hui-Ju , Tsai Yi-Chun , Hung Wei-Wen , Hung Wei-Chun , Chang Chen-Chia , Dai Chia-Yen
Published: March 2021

Introduction: Non-alcoholic fatty liver disease (NAFLD) remains an important health issue worldwide. The increasing prevalence of NAFLD is linked to type 2 diabetes (T2D). The gut microbiota is associated with the development of NAFLD and T2D. However, the relationship between gut microbiota and NAFLD severity has remained unclear in T2D patients. The aim of this study was to evaluate the relationship of gut microbiota with the severity of NAFLD in T2D patients. Methods: This cross-sectional study used transient elastography (FibroScan) to evaluate the severity of hepatic steatosis. We utilized qPCR to measure the abundance of Bacteroidetes, Firmicutes, Faecalibacterium prausnitzii, Clostridium leptum group, Bacteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli. Results: Of 163 T2D patients, 83 with moderate to severe NAFLD had higher abundance of bacteria of the phylum Firmicutes with respect to 80 patients without NAFLD or with mild NAFLD. High abundance of the phylum Firmicutes increased the severity of NAFLD in T2D patients. A positive correlation between NAFLD severity and the phylum Firmicutes was found in T2D male patients with body mass index ≥24 kg/m2 and glycated hemoglobin <7.5%. Conclusion: Enrichment of the fecal microbiota with the phylum Firmicutes is significantly and positively associated with NAFLD severity in T2D patients. The gut microbiota is a potential predictor of NAFLD severity in T2D patients.
On the Moderating Effects of Country Governance on the Relationships between Corporate Governance and Firm Performance
Authors: Wu Chiu-Hui
Published: March 2021

This study further empirically examines the influence of board independence on financial performance by using the world’s top 1000 firms. CEO duality and the percentage of independent directors are used as the indicators of board independence. Moreover, this study re-addresses the findings in the literature by giving supplement in theory and conducting tests for the influence of board independence on firm performance as well as the moderating effects of country governance, focusing on regulatory quality and rule of law, with multi-level modeling, a more sophisticated statistical approach. Four hypotheses, based on agency theory and compensation theory, were developed. The results indicated that CEO duality and the percentage of independent directors exerted, respectively, negative and positive influence on Return on Assets (ROA), a firm performance indicator. Furthermore, regulatory quality and the rule of law positively moderated the negative effects of the former and negatively moderated the positive effects of the latter. Some practical implications were discussed based on the results obtained.
Decision Factors behind Cisco Networking Hardware Acceptance in Business Environments
Authors: Ostrowski Piotr , Wrycza Stanislaw , Gajda Damian , Marcinkowski Bartosz
Published: March 2021

Networking hardware might be considered a relatively unexposed enabler of the enormous success of the modern digital economy, and information technology of a global reach. The COVID-19 traffic spike across e-commerce portals puts further pressure on computer network component vendors and raises the bar regarding both performance and reliability. Therefore, the authors undertake a challenge of identifying factors influencing the level of Cisco switches acceptance among network administrators in business environments. To achieve that, Structural Equation Modelling is introduced. The feedback gathered from 205 study contributors enabled the authors to evaluate the significance of two domain-specific factors—Technological Innovation (TI) and Availability of Professional Training (APT). The APT was confirmed to have a significant impact on networking hardware acceptance. The study contributes to extending the decision-making rationale regarding the procurement of networking switches and shows the added value of technology-oriented professional training for job satisfaction and working efficiency.
Rural Roads Are Paving the Way for Land-Use Intensification in the Uplands of Laos
Authors: Castella Jean-Christophe , Phaipasith Sonnasack
Published: March 2021

Road expansion has played a prominent role in the agrarian transition that marked the integration of swidden-based farming systems into the market economy in Southeast Asia. Rural roads deeply altered the landscape and livelihood structures by allowing the penetration of boom crops such as hybrid maize in remote territories. In this article, we investigate the impact of rural road developments on livelihoods in northern Laos through a longitudinal study conducted over a period of 15 years in a forest frontier. We studied adaptive management strategies of local stakeholders through the combination of individual surveys, focus group discussions, participatory mapping and remote-sensing approaches. The study revealed the short-term benefits of the maize feeder roads on poverty alleviation and rural development, but also the negative long-term effects on agroecosystem health and agricultural productivity related to unsustainable land use. Lessons learnt about the mechanisms of agricultural intensification helped understanding the constraints faced by external interventions promoting sustainable land management practices. When negotiated by local communities for their own interest, roads may provide livelihood-enhancing opportunities through access to external resources, rather than undermining them.
Sustainable Tourism and Natural Protected Areas: Exploring Local Population Perceptions in a Post-Conflict Scenario
Authors: Andries Delia M. , Arnaiz-Schmitz Cecilia , Díaz-Rodríguez Pablo , Herrero-Jáuregui Cristina , Schmitz María F.
Published: March 2021

The expansion of urban areas around the world and the application of the sustainability paradigm to tourism discourses has favored an increase in the number of people visiting natural protected areas (NPAs) in their leisure time. While tourism is desired to boost the economy of destinations, mismanagement can bring negative consequences for social–ecological systems, particularly in post-conflict rural scenarios. In the context of a broader ethnographic research, we analyzed the perceptions of the local population about tourism development in the NPA Jaltepeque Estuary (El Salvador, Central America) and the establishment of a Biosphere Reserve in the area, using structured questionnaires and Multiple Correspondence Analysis for the typification of social actors. We found that overall, the population regards positively the development of tourism in the area. Fishermen are the only ones who highlight the negative economic consequences of tourism development, claiming disparity in the distribution of benefits and an increase in the cost of living. We conclude that although tourism development is an activity desired by local people, there is a need in the community to discuss how this process of socio-economic transformation should be approached and an evident conflict between two different models: the one desired and offered by the population and the one that is currently being developed in the nearby Costa del Sol corridor.
Tenofovir Alafenamide Rescues Renal Tubules in Patients with Chronic Hepatitis B
Authors: Sano Tomoya , Kawaguchi Takumi , Ide Tatsuya , Amano Keisuke , Kuwahara Reiichiro , Arinaga-Hino Teruko , Torimura Takuji
Published: March 2021

Nucles(t)ide analogs (NAs) are effective for chronic hepatitis B (CHB). NAs suppress hepatic decompensation and hepatocarcinogenesis, leading to a dramatic improvement of the natural course of patients with CHB. However, renal dysfunction is becoming an important issue for the management of CHB. Renal dysfunction develops in patients with the long-term treatment of NAs including adefovir dipivoxil and tenofovir disoproxil fumarate. Recently, several studies have reported that the newly approved tenofovir alafenamide (TAF) has a safe profile for the kidney due to greater plasma stability. In this mini-review, we discuss the effectiveness of switching to TAF for NAs-related renal tubular dysfunction in patients with CHB.
Primary Gastro-Intestinal Lymphoma and Gastro-Intestinal Adenocarcinoma: An Initial Study of CT Texture Analysis as Quantitative Biomarkers for Differentiation
Authors: Ding Lin , Wu Sisi , Shen Yaqi , Hu Xuemei , Hu Daoyu , Kamel Ihab , Li Zhen
Published: March 2021

Background: To explore the potential role of computed tomography (CT) texture analysis and an imaging biomarker in differentiating primary gastro-intestinal lymphoma (PGIL) from gastro-intestinal adenocarcinoma (GIAC). Methods: A total of 131 patients with surgical pathologically PGIL and GIAC were enrolled in this study. Histogram parameters of arterial and venous phases extracted from contrast enhanced modified discrete cosine transform (MDCT) images were compared between PGIL and GIAC by Mann–Whitney U tests. The optimal parameters for differentiating these two groups were obtained through receiver operating characteristic (ROC) curves and the area under the curve (AUC) was calculated. Results: Compared with GIAC, in arterial phase, PGIL had statistically higher 5th, 10th percentiles (p = 0.003 and 0.011) and statistically lower entropy (p = 0.001). In the venous phase, PGIL had statistically lower mean, median, 75th, 90th, 95th percentiles, and entropy (p = 0.036, 0.029, 0.007, 0.001 and 0.001, respectively). For differentiating PGIL from GIAC, V-median + A-5th percentile was an optimal parameter for combined diagnosis (AUC = 0.746, p < 0.0001), and the corresponding sensitivity and specificity were 81.7 and 64.8%, respectively. Conclusion: CT texture analysis could be useful for differential diagnosis of PGIL and GIAC.
Beneficial Influence of Water-Soluble PEG-Functionalized C60 Fullerene on Human Osteoblast Growth In Vitro
Authors: Piotrowski Piotr , Klimek Katarzyna , Ginalska Grazyna , Kaim Andrzej
Published: March 2021

The purpose of this study was to make an initial assessment of new PEG (polyethylene glycol)-functionalized C60 fullerene derivative for potential bone tissue engineering applications. Thus, Fourier Transform Infrared spectroscopy analysis, thermogravimetric analysis, and cyclic voltammetry measurement were performed. Moreover, cell culture experiments in vitro were carried out using normal human osteoblasts. Cell viability and proliferation were evaluated using colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test as well as by fluorescent staining. It was demonstrated that resultant derivative possessed good solubility in water, high temperature stability, and retained favorable electron accepting properties of C60 fullerene core. Most important, new fullerene derivatives at low concentrations did not exhibit cytotoxic effect and supported osteoblast proliferation compared to control. Thanks to all mentioned properties of new PEG-functionalized C60 fullerene derivative, it seems that it could be used as a component of polymer-based bone scaffolds in order to enhance their biological properties.
The Relation between Concrete, Mortar and Paste Scale Early Age Properties
Authors: Klun Martin , Bosiljkov Vlatko , Bokan-Bosiljkov Violeta
Published: March 2021

Microstructure development of concrete, mortar, and paste scale of cement-based material (CBM) during the early hydration stage has a significant impact on CBM’s physical, mechanical, and durability characteristics at the high maturity state. The research was carried out using compositions with increased autogenous shrinkage and extended early age period, proposed within the RRT+ programme of the COST Action TU1404. The electrical conductivity method, used to follow the solidification process of CBM, is capable of determining the initial and final setting time, and the end of the solidification process acceleration stage for the paste and mortar scale. Simultaneous ultrasonic P- and S-wave transmission measurements revealed that the ratio of velocities VP/VS is highly dependent on the presence of aggregates—it is considerably higher for the paste scale compared to the mortar and concrete scale. The deviation from the otherwise roughly constant ratio VP/VS for each scale may indicate cracks in the material. The non-linear correlation between the dynamic and static elastic moduli valid over the three scales was confirmed. Additionally, it was found that the static E-modulus correlates very well with the square of the VS and that the VS is highly correlated to the cube compressive strength—but a separate trendline exists for each CBM scale.
Enhanced Mathematical Model for Producing Highly Dense Metallic Components through Selective Laser Melting
Authors: Estrada-Díaz Jorge A. , Elías-Zúñiga Alex , Martínez-Romero Oscar , Olvera-Trejo Daniel
Published: March 2021

In this work, a previously developed mathematical model to predict bulk density of SLMed (produced via Selective Laser Melting) component is enhanced by taking laser power, scanning speed, hatch spacing, powder’s thermal conductivity and specific heat capacity as independent variables. Experimental data and manufacturing conditions for the selective laser melting (SLM) of metallic materials (which include aluminum, steel, titanium, copper, tungsten and nickel alloys) are adapted from the literature and used to evaluate the validity of the proposed enhanced model. A strong relation between dependent and independent dimensionless products is observed throughout the studied materials. The proposed enhanced mathematical model shows to be highly accurate since the computed root-mean-square-error values (RMSE) does not exceed 5 × 10−7. Furthermore, an analytical expression for the prediction of bulk density of SLMed components was developed. From this, an expression for determining the needed scanning speed, with respect to laser power, to achieve highly dense components produced via SLM, is derived.
Estimation of the Electricity Storage Volume Density of Compact SMESs of a New Concept Based on Si Microfabrication Technologies
Authors: Motohiro Tomoyoshi , Sasaki Minoru , Noh Joo-hyong , Takai Osamu
Published: March 2021

A compact superconducting magnetic energy storage system (SMES) produced by Si micro fabrication technologies has been proposed to improve electricity storage volume density, w, in the sub-Wh/L range of conventional SMESs and to produce them at a low cost by mass production. In parallel with the experimental development reported previously, a series of trials was performed to estimate a feasible value of w based on the calculation of the magnetic field generated by the compact SMES by improving the calculation models step by step. In this work, the experimentally obtained magnetic flux density dependence of superconductive critical current density was taken into consideration for the first time in this series of trials, together with the additional improvement of the calculation models. The results of the estimation indicated that a compact SMES produced by the proposed concept can attain a w in the Wh/L range or more, ranking with or surpassing that of presently used capacitors.
Solving Regression Problems with Intelligent Machine Learner for Engineering Informatics
Authors: Chou Jui-Sheng , Truong Dinh-Nhat , Tsai Chih-Fong
Published: March 2021

Machine learning techniques have been used to develop many regression models to make predictions based on experience and historical data. They might be used singly or in ensembles. Single models are either classification or regression models that use one technique, while ensemble models combine various single models. To construct or find the best model is very complex and time-consuming, so this study develops a new platform, called intelligent Machine Learner (iML), to automatically build popular models and identify the best one. The iML platform is benchmarked with WEKA by analyzing publicly available datasets. After that, four industrial experiments are conducted to evaluate the performance of iML. In all cases, the best models determined by iML are superior to prior studies in terms of accuracy and computation time. Thus, the iML is a powerful and efficient tool for solving regression problems in engineering informatics.
Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines
Authors: Muñoz-Garcia Javier , Mazza Mattia , Alliot Cyrille , Sinquin Corinne , Colliec-Jouault Sylvia , Heymann Dominique , Huclier-Markai Sandrine
Published: March 2021

Antimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by Alteromonas infernus bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apoptotic effect on osteosarcoma cells. Based on this observation, these EPSs could be employed as new drug delivery systems for therapeutic uses. A theranostic approach, i.e., combination of a predictive biomarker with a therapeutic agent, has been developed notably by combining with true pair of theranostic radionuclides, such as scandium 47Sc/44Sc. However, it is crucial to ensure that, once complexation is done, the biological properties of the vector remain intact, allowing the molecular tropism of the ligand to recognize its molecular target. It is important to assess if the biological properties of EPS evidenced on osteosarcoma cell lines remain when scandium is complexed to the polymers and can be extended to other cancer cell types. Scandium-EPS complexes were thus tested in vitro on human cell lines: MNNG/HOS osteosarcoma, A375 melanoma, A549 lung adenocarcinoma, U251 glioma, MDA231 breast cancer, and Caco2 colon cancer cells. An xCELLigence Real Cell Time Analysis (RTCA) technology assay was used to monitor for 160 h, the proliferation kinetics of the different cell lines. The tested complexes exhibited an anti-proliferative effect, this effect was more effective compared to EPS alone. This increase of the antiproliferative properties was explained by a change in conformation of EPS complexes due to their polyelectrolyte nature that was induced by complexation. Alterations of both growth factor-receptor signaling, and transmembrane protein interactions could be the principal cause of the antiproliferative effect. These results are very promising and reveal that EPS can be coupled to scandium for improving its biological effects and also suggesting that no major structural modification occurs on the ligand.
Affinity Purification of Angiotensin Converting Enzyme Inhibitory Peptides from Wakame (Undaria Pinnatifida) Using Immobilized ACE on Magnetic Metal Organic Frameworks
Authors: Feng Xuezhen , Liao Dankui , Sun Lixia , Wu Shanguang , Lan Ping , Wang Zefen , Li Chunzhi , Zhou Qian , Lu Yuan , Lan Xiongdiao
Published: March 2021

Angiotensin-I-converting enzyme (ACE) inhibitory peptides derived from marine organism have shown a blood pressure lowering effect with no side effects. A new affinity medium of Fe3O4@ZIF-90 immobilized ACE (Fe3O4@ZIF-90-ACE) was prepared and used in the purification of ACE inhibitory peptides from Wakame (Undaria pinnatifida) protein hydrolysate (<5 kDa). The Fe3O4@ZIF-90 nanoparticles were prepared by a one-pot synthesis and crude ACE extract from pig lung was immobilized onto it, which exhibited excellent stability and reusability. A novel ACE inhibitory peptide, KNFL (inhibitory concentration 50, IC50 = 225.87 μM) was identified by affinity purification using Fe3O4@ZIF-90-ACE combined with reverse phase-high performance liquid chromatography (RP-HPLC) and MALDI-TOF mass spectrometry. Lineweaver–Burk analysis confirmed the non-competitive inhibition pattern of KNFL, and molecular docking showed that it bound at a non-active site of ACE via hydrogen bonds. This demonstrates that affinity purification using Fe3O4@ZIF-90-ACE is a highly efficient method for separating ACE inhibitory peptides from complex protein mixtures and the purified peptide KNFL could be developed as a functional food ingredients against hypertension.
Self-Expandable Metal Stents for Left Sided Colon Obstruction from Diverticulitis. A Single Center Retrospective Series
Authors: Lamazza Antonietta , Carati Maria Vittoria , Guzzo Anna , Pronio Anna Maria , Nicolanti Virgilio , Antoniozzi Angelo , Sterpetti Antonio V. , Fiori Enrico
Published: March 2021

Background and Objectives: The incidence of diverticulitis is increasing in western countries. Complicated diverticulitis is defined as diverticulitis associated with localized or generalized perforation, localized or distant abscess, fistula, stricture or obstruction. Colonic symptomatic strictures are often treated with segmental colectomy. The aim of our study is to report our experience with Self Expandable Metal Stents (SEMS) placement to relieve sigmoid obstruction secondary to diverticulitis, either as a permanent solution or as a bridge to elective colectomy. Material and Methods: From January 2016 to December 2018, 21 patients underwent SEMS placement for sigmoid obstruction secondary to diverticulitis at our institution. In four patients with poor general conditions, SEMS was considered the definitive form of treatment. In 17 patients, the stent was placed as bridge to elective colectomy. Data were prospectively collected and retrospectively analyzed. Primary outcomes were postoperative mortality and morbidity after SEMS and subsequent elective colectomy. Results: There was no mortality or major morbidity after SEMS placement or subsequent elective colectomy. No stoma was performed. Conclusions: Placement of Colorectal Self Expandable Stent represents a useful tool to relieve obstruction in patients with left-sided colonic diverticulitis. SEMS placement makes it possible to transform an emergency clinical condition into an elective condition, giving time to resolve the inflammation and the infection inevitably associated with complicated diverticulitis.
A Goal Intervention Improves Language Fluency: Evidence from Parkinson’s Disease and Healthy Aging
Authors: Robinson Gail A. , Campbell Lara , Ceslis Amelia
Published: March 2021

Background: Parkinson’s disease [PD] is associated with reduced motor and cognitive initiation, and decreased goal-directed behavior including language generation. The current study investigated a novel goal intervention for language generation impairments in PD patients. Methods: Twenty-one PD patients and 22 healthy controls, matched for gender, age, and education, completed a cognitive baseline and language generation tasks (complex scene descriptions and phonemic/semantic word fluency) with standard and adapted instructions, which implements a target ‘goal’. In addition, participants completed self-report questionnaires for apathy and mood. Results: PD patients performed more poorly on two of three language generation tasks. The goal intervention was effective in increasing both the PD patient and healthy control groups’ language generation. However, there was no differential benefit of increased goal specificity and difficulty for PD patients. As a group, PD patients reported higher levels of apathy and depression than healthy controls. Specifically, PD patients with executive apathy were more likely to have language generation impairments than PD patients without executive apathy and controls. Apathy subscales and goal benefit were unrelated. Conclusions: The goal intervention was effective for PD patients and older adults, suggesting that enhanced goal specificity and difficulty may benefit individuals with PD or those aging naturally.
Carnauba Wax/Halloysite Nanotube with Improved Anti-Wetting and Permeability of Hydrophobic PVDF Membrane via DCMD
Authors: AbdulKadir Wan , Ahmad Abdul , Boon Seng Ooi
Published: March 2021

The hydrophobic membranes have been widely explored to meet the membrane characteristics for the membrane distillation (MD) process. Inorganic metal oxide nanoparticles have been used to improve the membrane hydrophobicity, but limited studies have used nano clay particles. This study introduces halloysite nanotube (HNT) as an alternative material to synthesis a hydrophobic poly(vinylidene fluoride) (PVDF)-HNT membrane. The PVDF membranes were fabricated using functionalized HNTs (e.g., carnauba wax and 1H,1H,2H,2H-perfluorooctyl-trichlorosilane (FOTS)). The results were determined by Fourier transform infrared-attenuated total reflection, scanning electron microscope, goniometer and porometer to determine the desired hydrophobic membrane for direct contact membrane distillation (DCMD). The addition of FOTS-HNT (fs-HNT) and carnauba wax-HNT (fw-HNT) in the PVDF membrane enhanced the water contact angle (CA) to 127° and 137°, respectively. The presence of fw-HNT in the PVDF membrane exhibited higher liquid entry pressure (LEP) (2.64 bar) compared to fs-HNT in the membrane matrix (1.44 bar). The PVDF/fw-HNT membrane (Pfw-HNT) obtained the highest flux of 7.24 L/m2h with 99.9% salt removal. A stable permeability in the Pfw-HNT membrane was obtained throughout 16 h of DCMD. The incorporation of fw-HNT in the PVDF membrane had improved the anti-wetting properties and the membrane performance with the anti-fouling effect.
Modification of Liquid Steel Viscosity and Surface Tension for Inert Gas Atomization of Metal Powder
Authors: Korobeinikov Iurii , Perminov Anton , Dubberstein Tobias , Volkova Olena
Published: March 2021

Inert gas atomization is one of the main sources for production of metal powder for powder metallurgy and additive manufacturing. The obtained final powder size distribution is controlled by various technological parameters: gas flow rate and pressure, liquid metal flow rate, gas type, temperature of spraying, configuration of nozzles, etc. This work explores another dimension of the atomization process control: modifications of the liquid metal properties and their effect on the obtained powder size. Series of double-alloyed Cr-Mn-Ni steels with sulfur and phosphorus were atomized with argon at 1600 °C. The results indicate that surface tension and viscosity modifications lead to yielding finer powder fractions. The obtained correlation is compared with the individual modification of surface tension with S and Se and modification of viscosity with phosphorus. Discrepancy of the results is discussed. Additives of surfactants and viscosity modifiers can be a useful measure for powder fractions control.