bluuebunny/crossref_metadata_2025 huggingface dataset:
Correction: Sato, K., et al. Identification of a Novel Oligosaccharide in Maple Syrup as a Potential Alternative Saccharide for Diabetes Mellitus Patients. Int. J. Mol. Sci. 2019, 20, 5041
Authors: Sato Kanta , Nagai Noriaki , Yamamoto Tetsushi , Mitamura Kuniko , Taga Atsushi
Published: July 2020

The authors wish to make the following corrections to this paper [...]
Simple and Divided Leaves in Ferns: Exploring the Genetic Basis for Leaf Morphology Differences in the Genus Elaphoglossum (Dryopteridaceae)
Authors: Vasco Alejandra , Ambrose Barbara A.
Published: July 2020

Despite the implications leaves have for life, their origin and development remain debated. Analyses across ferns and seed plants are fundamental to address the conservation or independent origins of megaphyllous leaf developmental mechanisms. Class I KNOX expression studies have been used to understand leaf development and, in ferns, have only been conducted in species with divided leaves. We performed expression analyses of the Class I KNOX and Histone H4 genes throughout the development of leaf primordia in two simple-leaved and one divided-leaved fern taxa. We found Class I KNOX are expressed (1) throughout young and early developing leaves of simple and divided-leaved ferns, (2) later into leaf development of divided-leaved species compared to simple-leaved species, and (3) at the leaf primordium apex and margins. H4 expression is similar in young leaf primordia of simple and divided leaves. Persistent Class I KNOX expression at the margins of divided leaf primordia compared with simple leaf primordia indicates that temporal and spatial patterns of Class I KNOX expression correlate with different fern leaf morphologies. However, our results also indicate that Class I KNOX expression alone is not sufficient to promote divided leaf development in ferns. Class I KNOX patterns of expression in fern leaves support the conservation of an independently recruited developmental mechanism for leaf dissection in megaphylls, the shoot-like nature of fern leaves compared with seed plant leaves, and the critical role marginal meristems play in fern leaf development.
SVD++ Recommendation Algorithm Based on Backtracking
Authors: Wang Shijie , Sun Guiling , Li Yangyang
Published: July 2020

Collaborative filtering (CF) has successfully achieved application in personalized recommendation systems. The singular value decomposition (SVD)++ algorithm is employed as an optimized SVD algorithm to enhance the accuracy of prediction by generating implicit feedback. However, the SVD++ algorithm is limited primarily by its low efficiency of calculation in the recommendation. To address this limitation of the algorithm, this study proposes a novel method to accelerate the computation of the SVD++ algorithm, which can help achieve more accurate recommendation results. The core of the proposed method is to conduct a backtracking line search in the SVD++ algorithm, optimize the recommendation algorithm, and find the optimal solution via the backtracking line search on the local gradient of the objective function. The algorithm is compared with the conventional CF algorithm in the FilmTrust, MovieLens 1 M and 10 M public datasets. The effectiveness of the proposed method is demonstrated by comparing the root mean square error, absolute mean error and recall rate simulation results.
Studying the Influences of Bus Stop Type and Specifications on Bicycle Flow and Capacity for Better Bicycle Efficiency
Authors: Yan Xingchen , Chen Jun , Ye Xiaofei , Wang Tao , Yang Zhen , Bai Hua
Published: July 2020

This study aimed to explore the effects of type and specifications of bus stop on bicycle speed and cycle track capacity. This paper investigates the traffic flow operations of tracks at basic sections, curbside stops, and bus bays by video recording. T-test and comparative study were used to analyze the influences of stop types on bicycle speed and capacity of track. The relationships between stop specifications and speed and capacity of track are analyzed with correlation analysis. The main results are as follows: (1) Without passengers crossing, bus bays have significant impact on bicycle speed, while it is not for curbside stops; (2) except platform length, there are strong negative relationships between bicycle speed and density of platform access, total width of platform accesses (TWPA), total width of platform accesses-to-platform length ratio (TWPA-to-PL ratio), total width of platform accesses-to-track width ratio (TWPA-to-TW ratio); (3) curbside stop and bus bay reduce track capacities by 32% and 13.5% on average, respectively; and (4) in contrast to bus bays, curbside stops have more significant impact on capacity of track, which also presents in the influence of the setting parameters of stops. Based the results above, some suggestions on stop specifications are finally proposed.
Process of Attack on Cashew Tree Branches by Diastocera trifasciata (Coleoptera: Cerambycidae) and the Relationship between These Attacks and the Phenological Stages in the Gbêkê Region (Central Côte d’Ivoire)
Authors: Ouali-N’Goran San-Whouly M. , Akessé Ettien Narcice , Ouattara Gniré Mariam , Koné Daouda
Published: July 2020

Cerambycidae Diastocera trifasciata attacks were studied from October 2015 to September 2017 in three cashew tree orchards in the locality of Brobo in central Côte d’Ivoire. One hundred fifty-three (153) cashew trees, arranged on a diagonal from each orchard, were selected for sampling. The attacked plants and the branches cut per tree were counted every 15 days. Biotic parameters, namely phenological stages of trees, and abiotic factors, which are rainfall, relative humidity and average temperature, were recorded throughout the study. Attacks were observed from mid-September to January from the pre-flowering vegetative stage to the flowering stage. Attack period duration was therefore four and a half months per year. The peak of attacks was recorded in November with an attack rate of 88.02% in 2015 and 75.49% in 2016. No attack was recorded from February to mid-September, corresponding to the flowering, fruiting and post-harvest vegetative growth stages. This description of the attack process and the determination of D. trifasciata attack periods provides essential data for the implementation of an effective and sustainable control method of this species.
EPNs Exhibit Repulsion to Prenol in Pluronic Gel Assays
Authors: Baiocchi Tiffany , Li Chunjie , Dillman Adler R.
Published: July 2020

Entomopathogenic nematodes (EPNs) are lethal parasites of insects that have become valuable in biological control and as a model system for studying host–parasite interactions, behavioral ecology, neurobiology, and genomics, among other fields. Their ability to locate hosts is paramount to successful infection and host seeking has been extensively studied in many species in the lab. Here, we explored the usefulness of pluronic gel as a medium to assess EPN host seeking in the lab by characterizing the response of Steinernema carpocapsae, S. feltiae, S. glaseri, S. riobrave, Heterorhabditis bacteriophora, and H. indica to the odor prenol. We found that the infective juveniles (IJs) of these species were repelled by prenol in pluronic gel. We then evaluated how storing the IJs of S. carpocapsae, S. feltiae, and S. glaseri for different amounts of time affected their behavioral responses to prenol. The response of S. carpocapsae was significantly affected by the storage time, while the responses of S. feltiae and S. glaseri were unaffected. Our data support the notion that pluronic gel is a useful medium for studying EPN behavior and that the response of S. carpocapsae to informative odors is significantly affected by long-term storage.
Delirium Post-Stroke: Short- and Long-Term Effect on Depression, Anxiety, Apathy and Aggression (Research Study—Part of PROPOLIS Study)
Authors: Kowalska Katarzyna , Droś Jakub , Mazurek Małgorzata , Pasińska Paulina , Gorzkowska Agnieszka , Klimkowicz-Mrowiec Aleksandra
Published: July 2020

Background: Stroke patients are particularly vulnerable to delirium episodes, but very little is known about its subsequent adverse mental health outcomes. The author’s objective was to explore the association between in-hospital delirium and depression, anxiety, anger and apathy after stroke. Methods: A total of 750 consecutive patients with acute stroke or transient ischemic attack, were screened for delirium during hospitalization. Patients underwent mental health evaluation in hospital, 3 and 12 months post-stroke; depression, apathy, anxiety and anger were the outcomes measured at all evaluation check points. Results: Delirium was an independent risk factor for depression (OR = 2.28, 95%CI 1.15–4.51, p = 0.017) and aggression (OR = 3.39, 95%CI 1.48–7.73, p = 0.004) at the hospital, for anxiety 3 months post-stroke (OR = 2.83, 95%CI 1.25–6.39, p = 0.012), and for apathy at the hospital (OR = 4.82, 95%CI 2.25–10.47, p < 0.001), after 3 (OR = 3.84, 95%CI 1.31–11.21, p = 0.014) and 12 months (OR = 4.95, 95%CI 1.68–14.54, p = 0.004) post stroke. Conclusions: The results of this study confirm, that mental health problems are very frequent complications of stroke. Delirium in the acute phase of stroke influences mental health of patients. This effect is especially significant in the first months post-stroke and vanishes with time, which suggests that in-hospital delirium might not be a damaging occurrence in most measures of mental health problems from a long-term perspective.
Multimodality Imaging in the Diagnostic Work-Up of Endocarditis and Cardiac Implantable Electronic Device (CIED) Infection
Authors: Galea Nicola , Bandera Francesco , Lauri Chiara , Autore Camillo , Laghi Andrea , Erba Paola Anna
Published: July 2020

Infective endocarditis (IE) is a serious cardiac condition, which includes a wide range of clinical presentations, with varying degrees of severity. The diagnosis is multifactorial and a proper characterization of disease requires the identification of the primary site of infection (usually the cardiac valve) and the search of secondary systemic complications. Early depiction of local complications or distant embolization has a great impact on patient management and prognosis, as it may induce to aggressive antibiotic treatment or, in more advanced cases, cardiac surgery. In this setting, the multimodality imaging has assumed a pivotal role in the clinical decision making and it requires the physician to be aware of the advantages and disadvantages of each imaging technique. Echocardiography is the first imaging test, but it has several limitations. Therefore, the integration with other imaging modalities (computed tomography, magnetic resonance imaging, nuclear imaging) becomes often necessary. Different strategies should be applied depending on whether the infection is suspected or already ascertained, whether located in native or prosthetic valves, in the left or right chambers, or if it involves an implanted cardiac device. In addition, detection of extracardiac IE-related lesions is crucial for a correct management and treatment. The aim of this review is to illustrate strengths and weaknesses of the various methods in the most common clinical scenarios.
3D Printing Approach in Dentistry: The Future for Personalized Oral Soft Tissue Regeneration
Authors: Nesic Dobrila , Schaefer Birgit M. , Sun Yue , Saulacic Nikola , Sailer Irena
Published: July 2020

Three-dimensional (3D) printing technology allows the production of an individualized 3D object based on a material of choice, a specific computer-aided design and precise manufacturing. Developments in digital technology, smart biomaterials and advanced cell culturing, combined with 3D printing, provide promising grounds for patient-tailored treatments. In dentistry, the “digital workflow” comprising intraoral scanning for data acquisition, object design and 3D printing, is already in use for manufacturing of surgical guides, dental models and reconstructions. 3D printing, however, remains un-investigated for oral mucosa/gingiva. This scoping literature review provides an overview of the 3D printing technology and its applications in regenerative medicine to then describe 3D printing in dentistry for the production of surgical guides, educational models and the biological reconstructions of periodontal tissues from laboratory to a clinical case. The biomaterials suitable for oral soft tissues printing are outlined. The current treatments and their limitations for oral soft tissue regeneration are presented, including “off the shelf” products and the blood concentrate (PRF). Finally, tissue engineered gingival equivalents are described as the basis for future 3D-printed oral soft tissue constructs. The existing knowledge exploring different approaches could be applied to produce patient-tailored 3D-printed oral soft tissue graft with an appropriate inner architecture and outer shape, leading to a functional as well as aesthetically satisfying outcome.
The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer
Authors: Dion Ludivine , Carton Isis , Jaillard Sylvie , Nyangoh Timoh Krystel , Henno Sébastien , Sardain Hugo , Foucher Fabrice , Levêque Jean , de la Motte Rouge Thibault , Brousse Susie , Lavoué Vincent
Published: July 2020

Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications on molecular and genetic alterations in EOC. Approximately 15% of all EOCs are due to BRCA1 or BRCA2 mutations. Four histologic subtypes characterized by different mutations have been described: serous, endometrioid, mucinous, and clear-cell. Between 20–30% of high-grade serous EOCs have a BRCA mutation. Tumors with BRCA mutations are unable to repair double-strand DNA breaks, making them more sensitive to platinum-based chemotherapy and to PolyAdenosine Diphosphate-Ribose Polymerase (PARP) inhibitors. Olaparib is a PARP inhibitor with proven efficacy in BRCA-mutated ovarian cancer, but its effectiveness remains to be demonstrated in tumors with a BRCAness (breast cancer) profile (i.e., also including sporadic tumors in patients with deficient DNA repair genes). A universally accepted molecular definition of BRCAness is required to identify optimal theranostic strategies involving PARP inhibitors. Gene expression analyses have led to the identification of four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated, and immunoreactive. These subtypes are not mutually exclusive but are correlated with prognosis. They are not yet used in routine clinical practice. A greater understanding of EOC subtypes could improve patient management.
Nephroprotection by SGLT2 Inhibition: Back to the Future?
Authors: De Nicola Luca , Gabbai Francis B. , Garofalo Carlo , Conte Giuseppe , Minutolo Roberto
Published: July 2020

The introduction of sodium/glucose cotransporter 2 inhibitors (SGLT2i) has opened new perspectives for the management of diabetic population at risk of or with chronic kidney disease (CKD). More important, recent, large real-world studies have repositioned the nephroprotective efficacy of SGLT2i emerged from randomized trials within the frame of effectiveness. Furthermore, the salutary effects of these agents may extend to the nondiabetic population according to the positive results of current studies. Nevertheless, the clear benefits of these agents on the prevention of organ damage contrast with their unexpected, limited use in clinical practice. One potential barrier is the acute decline in glomerular filtration rate (GFR) commonly observed at the beginning of treatment. This phenomenon is reminiscent of the early response to the traditional nephroprotective interventions, namely blood pressure lowering, dietary protein and salt restriction and the inhibition of the renin–angiotensin system. Under this perspective, the “check-mark” sign observed in the GFR trajectory over the first weeks of SGT2i therapy should renew interest on the very basic goal of CKD treatment, i.e., alleviate hyperfiltration in viable nephrons in order to prolong their function.
Hemostatic Changes in Patients with COVID-19: A Meta-Analysis with Meta-Regressions
Authors: Di Minno Matteo Nicola Dario , Calcaterra Ilenia , Lupoli Roberta , Storino Antonio , Spedicato Giorgio Alfredo , Maniscalco Mauro , Di Minno Alessandro , Ambrosino Pasquale
Published: July 2020

Background: Complications of coronavirus disease 2019 (COVID-19) include coagulopathy. We performed a meta-analysis on the association of COVID-19 severity with changes in hemostatic parameters. Methods: Data on prothrombin time (PT), activated partial thromboplastin time (aPTT), D-Dimer, platelets (PLT), or fibrinogen in severe versus mild COVID-19 patients, and/or in non-survivors to COVID-19 versus survivors were systematically searched. The standardized mean difference (SMD) was calculated. Results: Sixty studies comparing 5487 subjects with severe and 9670 subjects with mild COVID-19 documented higher PT (SMD: 0.41; 95%CI: 0.21, 0.60), D-Dimer (SMD: 0.67; 95%CI: 0.52, 0.82), and fibrinogen values (SMD: 1.84; 95%CI: 1.21, 2.47), with lower PLT count (SMD: −0.74; 95%CI: −1.01, −0.47) among severe patients. Twenty-five studies on 1511 COVID-19 non-survivors and 6287 survivors showed higher PT (SMD: 0.67; 95%CI: 0.39, 0.96) and D-Dimer values (SMD: 3.88; 95%CI: 2.70, 5.07), with lower PLT count (SMD: −0.60, 95%CI: −0.82, −0.38) among non-survivors. Regression models showed that C-reactive protein values were directly correlated with the difference in PT and fibrinogen. Conclusions: Significant hemostatic changes are associated with COVID-19 severity. Considering the risk of fatal complications with residual chronic disability and poor long-term outcomes, further studies should investigate the prognostic role of hemostatic parameters in COVID-19 patients.
Usefulness of 18F-FDG PET/CT in Patients with Cardiac Implantable Electronic Device Suspected of Late Infection
Authors: Rubini Giuseppe , Ferrari Cristina , Carretta Domenico , Santacroce Luigi , Ruta Rossella , Iuele Francesca , Lavelli Valentina , Merenda Nunzio , D’Agostino Carlo , Sardaro Angela , Niccoli Asabella Artor
Published: July 2020

The presence of a cardiovascular implantable electronic device (CIED) can be burdened by complications such as late infections that are associated with significant morbidity and mortality and require immediate and effective treatment. The aim of this study was to evaluate the role of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) in patients with suspected CIED infection. Fifteen patients who performed a 18F-FDG PET/CT for suspicion of CIED infection were retrospectively analyzed; 15 patients, with CIED, that underwent 18F-FDG PET/CT for oncological reasons, were also evaluated. Visual qualitative analysis and semi-quantitative analysis were performed. All patients underwent standard clinical management regardless 18F-FDG PET/CT results. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) resulted as 90.91%, 75%, 86.67%, 90.91% and 75% respectively. Maximum standardized uptake values (SUVmax) and semi-quantitative ratio (SQR) were collected and showed differences statistically significant between CIED infected patients and those who were not. Exploratory cut-off values were derived from receiver operating characteristic (ROC) curves for SUVmax (2.56) and SQR (4.15). This study suggests the clinical usefulness of 18F-FDG PET/CT in patients with CIED infection due to its high sensitivity, repeatability and non-invasiveness. It can help the clinicians in decision making, especially in patients with doubtful clinical presentation. Future large-scale and multicentric studies should be conducted to establish precise protocols about 18F-FDG PET/CT performance.
Cluster Analysis: A New Approach for Identification of Underlying Risk Factors and Demographic Features of First Trimester Pregnancy Women
Authors: Gárate-Escamilla Anna Karen , Garza-Padilla Edelmiro , Carvajal Rivera Agustín , Salas-Castro Celina , Andrès Emmanuel , Hajjam El Hassani Amir
Published: July 2020

Thyroid pathology is reported internationally in 5–10% of all pregnancies. The overall aim of this research was to determine the prevalence of hypothyroidism and risk factors during the first trimester screening in a Mexican patients sample. We included the records of 306 patients who attended a prenatal control consultation between January 2016 and December 2017 at the Women’s Institute in Monterrey, Mexico. The studied sample had homogeneous demographic characteristics in terms of age, weight, height, BMI (body mass index) and number of pregnancies. The presence of at least one of the risk factors for thyroid disease was observed in 39.2% of the sample. Two and three clusters were identified, in which patients varied considerably among risk factors, symptoms and pregnancy complications. Compared to Cluster 0, one or more symptoms or signs of hypothyroidism occurred, while Cluster 1 was characterized by healthier patients. When three clusters were used, Cluster 2 had a higher TSH (thyroid stimulating hormone) value and pregnancy complications. There were no significant differences in perinatal variables. In addition, high TSH levels in first trimester pregnancy are characterized by pregnancy complications and decreased newborn weight. Our findings underline the high degree of disease heterogeneity with existing pregnant hypothyroid patients and the need to improve the phenotyping of the syndrome in the Mexican population.
Endothelial Progenitor Cells as a Marker of Vascular Damage But not a Predictor in Acute Microangiopathy-Associated Stroke
Authors: Wiśniewski Adam , Boinska Joanna , Ziołkowska Katarzyna , Lemanowicz Adam , Filipska Karolina , Serafin Zbigniew , Ślusarz Robert , Rość Danuta , Kozera Grzegorz
Published: July 2020

Background: The aim of the study was to assess the number of endothelial progenitor cells (EPCs) in patients with acute stroke due to cerebral microangiopathy and evaluate whether there is a relationship between their number and clinical status, radiological findings, risk factors, selected biochemical parameters, and prognosis, both in ischemic and hemorrhagic stroke. Methods: In total, 66 patients with lacunar ischemic stroke, 38 patients with typical location hemorrhagic stroke, and 22 subjects from the control group without acute cerebrovascular incidents were included in the prospective observational study. The number of EPCs was determined in serum on the first and eighth day after stroke onset using flow cytometry and identified with the immune-phenotype classification determinant (CD)45−, CD34+, CD133+. Results: We demonstrated a significantly higher number of EPCs on the first day of stroke compared to the control group (med. 17.75 cells/µL (0–488 cells/µL) vs. 5.24 cells/µL (0–95 cells/µL); p = 0.0006). We did not find a relationship between the number of EPCs in the acute phase of stroke and the biochemical parameters, vascular risk factors, or clinical condition. In females, the higher number of EPCs on the first day of stroke is related to a favorable functional outcome on the eighth day after the stroke onset compared to males (p = 0.0355). We found that a higher volume of the hemorrhagic focus on the first day was correlated with a lower number of EPCs on the first day (correlation coefficient (R) = −0.3378, p = 0.0471), and a higher number of EPCs on the first day of the hemorrhagic stroke was correlated with a lower degree of regression of the hemorrhagic focus (R = −0.3896, p = 0.0367). Conclusion: The study showed that endothelial progenitor cells are an early marker in acute microangiopathy-associated stroke regardless of etiology and may affect the radiological findings in hemorrhagic stroke. Nevertheless, their prognostic value remains doubtful in stroke patients.
The Effect of a Pulmonary Rehabilitation on Lung Function and Exercise Capacity in Patients with Burn: A Prospective Randomized Single-Blind Study
Authors: Won Yu Hui , Cho Yoon Soo , Joo So Young , Seo Cheong Hoon
Published: July 2020

We performed pulmonary function (PF) tests and factors affecting PF evaluation in 120 patients with inhalation injury to evaluate the effects of pulmonary rehabilitation (PR) in burn patients with inhalation injury. Patients were randomized into pulmonary rehabilitation (PR) group and conventional rehabilitation (CON) group. PF tests, including forced vital capacity (FVC), 1-s forced expiratory volume FEV1), maximum voluntary ventilation (MVV), and respiratory muscles strength (maximal expiratory pressure (MEP) and maximal inspiratory pressure (MIP)), were measured by mouth pressure meter in the sitting position. Diffusing capacity for carbon monoxide (DLco) was determined by the single-breath carbon monoxide technique. Peak cough flow (PCF) was measured by a peak flow meter. Diaphragmatic mobility (DM) was evaluated on anteroposterior fluoroscopy. All evaluations were performed in all groups at baseline and after 12 weeks. There were no differences in evaluations between the PR group and CON group before the intervention. There were significant improvements in the PCF and MIP (%) changes, taken before and after rehabilitation in the PR group, compared with the changes in the CON group (p = 0.01, and p = 0.04). There were no significant changes in the other parameters in the PR group compared with the changes in the CON group (p > 0.05). There were significant differences in DLco (%), MIP, MIP (%), and DM between the PR group and the CON group (p = 0.02, p = 0.005, and p = 0.001) after 12 weeks of rehabilitation. There were no differences between the PR group and CON group after 12 weeks rehabilitation in the other parameters (p > 0.05). PR for patients with major burns and smoke inhalation induced improved PCF, MIP, MIP (%), DLco (%), and DM. These results show that PR should be a fundamental component of the treatment program for patients with burns.
A Systematic Review and Meta-Analysis of Interventions for Actinic Keratosis from Post-Marketing Surveillance Trials
Authors: Steeb Theresa , Wessely Anja , Harlaß Matthias , Heppt Franz , Koch Elias A. T. , Leiter Ulrike , Garbe Claus , Schöffski Oliver , Berking Carola , Heppt Markus V.
Published: July 2020

Multiple interventions are available for the treatment of actinic keratosis (AK) showing high efficacy in pivotal trials. However, data from post-marketing surveillance studies have received little attention until now. Here, we systematically investigate interventions for AK from post-marketing surveillance trials as a proxy for real-world efficacy and tolerability. A systematic literature search was conducted in Medline, Embase, and CENTRAL. Pertinent trial registers were hand-searched until 25 March 2020. Results were pooled using a random-effects model to calculate pooled proportions and relative risks (RR) or were described qualitatively. Eleven records with a total sample size of n = 4109 were included. Three of the studies had an active-controlled design, while seven were single-armed. Participant complete clearance ranged from 23.1% for diclofenac sodium 3% gel to 88.9% for ingenol mebutate 0.05% gel. The lesion-specific clearance rate for photodynamic therapy (PDT) was 74% (95% confidence interval (CI) 56–87%). The recurrence rate was significantly higher for diclofenac sodium 3% in comparison to imiquimod 5% cream (RR 1.10, 95% CI 1.02–1.1.8) and ranged from 10.6% for ingenol mebutate 0.015% gel to 23.5% for PDT. Few patients discontinued the trials due to adverse events. The results from the majority of the post-marketing surveillance studies deviated from those of pivotal trials.
ErBb Family Proteins in Cholangiocarcinoma and Clinical Implications
Authors: Jin Wook
Published: July 2020

The erythroblastic leukemia viral oncogene homolog (ErBb) family consists of the receptor tyrosine kinases (RTK) epidermal growth factor receptor (EGFR; also called ERBB1), ERBB2, ERBB3, and ERBB4. This family is closely associated with the progression of cholangiocarcinoma (CC) through the regulation of cellular networks, which are enhanced during tumorigenesis, metastasis, and chemoresistance. Additionally, the constitutive activation of cellular signaling by the overexpression and somatic mutation-mediated alterations conferred by the ErBb family on cholangiocarcinoma and other cancers enhances tumor aggressiveness and chemoresistance by contributing to the tumor microenvironment. This review summarizes the recent findings on the molecular functions of the ErBb family and their mutations during the progression of cholangiocarcinoma. It also discusses the developments and applications of various devising strategies for targeting the ErBb family through different inhibitors in various stages of clinical trials, which are essential for improving targeted clinical therapies.
Altered Metabolome of Lipids and Amino Acids Species: A Source of Early Signature Biomarkers of T2DM
Authors: Hameed Ahsan , Mojsak Patrycja , Buczynska Angelika , Suleria Hafiz Ansar Rasul , Kretowski Adam , Ciborowski Michal
Published: July 2020

Diabetes mellitus, a disease of modern civilization, is considered the major mainstay of mortalities around the globe. A great number of biochemical changes have been proposed to occur at metabolic levels between perturbed glucose, amino acid, and lipid metabolism to finally diagnoe diabetes mellitus. This window period, which varies from person to person, provides us with a unique opportunity for early detection, delaying, deferral and even prevention of diabetes. The early detection of hyperglycemia and dyslipidemia is based upon the detection and identification of biomarkers originating from perturbed glucose, amino acid, and lipid metabolism. The emerging “OMICS” technologies, such as metabolomics coupled with statistical and bioinformatics tools, proved to be quite useful to study changes in physiological and biochemical processes at the metabolic level prior to an eventual diagnosis of DM. Approximately 300–400 such metabolites have been reported in the literature and are considered as predicting or risk factor-reporting metabolic biomarkers for this metabolic disorder. Most of these metabolites belong to major classes of lipids, amino acids and glucose. Therefore, this review represents a snapshot of these perturbed plasma/serum/urinary metabolic biomarkers showing a significant correlation with the future onset of diabetes and providing a foundation for novel early diagnosis and monitoring the progress of metabolic syndrome at early symptomatic stages. As most metabolites also find their origin from gut microflora, metabolism and composition of gut microflora also vary between healthy and diabetic persons, so we also summarize the early changes in the gut microbiome which can be used for the early diagnosis of diabetes.
Virtual Reality Aggression Prevention Therapy (VRAPT) versus Waiting List Control for Forensic Psychiatric Inpatients: A Multicenter Randomized Controlled Trial
Authors: Klein Tuente Stéphanie , Bogaerts Stefan , Bulten Erik , Keulen-de Vos Marije , Vos Maarten , Bokern Hein , IJzendoorn Sarah van , Geraets Chris N. W. , Veling Wim
Published: July 2020

Many forensic psychiatric inpatients have difficulties regulating aggressive behavior. Evidence of effective aggression treatments is limited. We designed and investigated the effectiveness of a transdiagnostic application of a virtual reality aggression prevention training (VRAPT). In this randomized controlled trial at four Dutch forensic psychiatric centers, 128 inpatients with aggressive behavior were randomly assigned to VRAPT (N = 64) or waiting list control group (N = 64). VRAPT consisted of 16 one-hour individual treatment sessions twice a week. Assessments were done at baseline, post-treatment and at 3-month follow-up. Primary outcome measures were aggressive behavior observed by staff and self-reported aggressive behavior. Analysis was by intention to treat. This trial was registered in the Dutch Trial Register (NTR, TC = 6340). Participants were included between 1 March 2017, and 31 December 2018. Compared to waiting list, VRAPT did not significantly decrease in self-reported or observed aggressive behavior (primary outcomes). Hostility, anger control, and non-planning impulsiveness improved significantly in the VRAPT group compared to the control group at post-treatment. Improvements were not maintained at 3-month follow-up. Results suggest that VRAPT does not decrease aggressive behavior in forensic inpatients. However, there are indications that VRAPT temporarily influences anger control skills, impulsivity and hostility.
A Look into Liver Mitochondrial Dysfunction as a Hallmark in Progression of Brain Energy Crisis and Development of Neurologic Symptoms in Hepatic Encephalopathy
Authors: Kosenko Elena , Tikhonova Lyudmila , Alilova Gubidat , Montoliu Carmina
Published: July 2020

Background: The relationship between liver disease and neuropathology in hepatic encephalopathy is well known, but the genesis of encephalopathy in liver failure is yet to be elucidated. Conceptually, the main cause of hepatic encephalopathy is the accumulation of brain ammonia due to impaired liver detoxification function or occurrence of portosystemic shunt. Yet, as well as taking up toxic ammonia, the liver also produces vital metabolites that ensure normal cerebral function. Given this, for insight into how perturbations in the metabolic capacity of the liver may be related to brain pathology, it is crucial to understand the extent of ammonia-related changes in the hepatic metabolism that provides respiratory fuel for the brain, a deficiency of which can give rise to encephalopathy. Methods: Hepatic encephalopathy was induced in starved rats by injection of ammonium acetate. Ammonia-induced toxicity was evaluated by plasma and freeze-clamped liver and brain energy metabolites, and mitochondrial, cytoplasmic, and microsomal gluconeogenic enzymes, including mitochondrial ketogenic enzymes. Parameters of oxidative phosphorylation were recorded polarographically with a Clark-type electrode, while other measures were determined with standard fluorometric enzymatic methods. Results: Progressive impairment of liver mitochondrial respiration in the initial stage of ammonia-induced hepatotoxicity and the subsequent energy crisis due to decreased ATP synthesis lead to cessation of gluconeogenesis and ketogenesis. Reduction in glucose and ketone body supply to the brain is a terminal event in liver toxicity, preceding the development of coma. Conclusions: Our study provides a framework to further explore the relationship between hepatic dysfunction and progression of brain energy crisis in hepatic encephalopathy.
Choroidal Rift: A New OCT Finding in Eyes with Central Serous Chorioretinopathy
Authors: Battista Marco , Borrelli Enrico , Veronese Chiara , Gelormini Francesco , Sacconi Riccardo , Querques Lea , Prascina Francesco , Vella Giovanna , Ciardella Antonio P , Bandello Francesco , Querques Giuseppe
Published: July 2020

Central serous chorioretinopathy (CSC) is a complex and not entirely understood retinal disease. The aim of our research was to describe a novel optical coherence tomography (OCT) finding named “choroidal rift”, which may be identified in the choroid of eyes with CSC. We collected data from 357 patients (488 eyes) with CSC who had structural OCT and OCT angiography (OCTA) scans obtained. Choroidal rifts were identified as polygonal (and not round-shaped) hyporeflective lesions without hyperreflective margins. Choroidal rifts had to be characterized by a size superior to that of the largest choroidal vessel. Finally, hyporeflective lesions were graded as choroidal rifts only if these lesions had a main development perpendicular to the retinal pigment epithelium. OCT analysis allowed the identification of choroidal rifts in ten eyes from nine patients, all with chronic CSC, with an estimated prevalence rate of 2.1%. In three out of ten cases with choroidal rifts, these lesions spanned all the choroidal layers. In the remaining cases, choroidal rifts only partially spanned the choroidal thickness. In OCTA, choroidal rifts were characterized by the absence of flow. Combining structural OCT and OCTA information, we hypothesized that choroidal rifts may represent interruptions of the choroidal stroma in correspondence of fragile regions (in between expanded larger-sized choroidal vessels). Choroidal rift represents a novel OCT feature, which may characterize eyes with chronic CSC and may have a role in the development of irreversible chorio-retinal changes.
Assessment of the Most Impactful Combination of Factors Associated with Nocturia and to Define Nocturnal Polyuria by Multivariate Modelling
Authors: Olesen Tine , Paul Jerome , Gramme Pierre , Drake Marcus J. , Vandewalle Johan , Everaert Karel
Published: July 2020

Background: Nocturia is common and associated with multiple disease states. Many potential mechanisms have been proposed for nocturia, which also remains challenging to manage. Purpose: To use multivariate analysis to determine which combinations of factors can accurately discriminate clinically significant nocturia in patients to facilitate clinical management and treatment decisions. Patients and methods: Data analysis was based on frequency volume charts from three randomized controlled trials. There were 1479 patients included, of which 215 patients had no/mild nocturia and 1264 had clinically significant nocturia with at least two voids per night. Factors studied that may influence nocturia were demographics, sleep duration, functional bladder capacity, 24 h urine volume and literature-suggested definitions of nocturnal polyuria. We used univariate analysis and cross-validated multivariate modelling to assess association between factors and nocturia status, redundancy between factors and whether the combined use of factors could explain patients′ nocturia status. Results: The multivariate analyses showed that the most useful definitions of nocturia are ’Nocturia Index’ (NI) and ‘Nocturnal Urine Production per hour’ (NUPh) in combination with functional bladder capacity and sleep duration. Published definitions providing binary nocturnal polyuria outcomes had lower performance than continuous indices. These analyses also showed that NI was not specific to nocturnal polyuria as it also captured nocturia due to low functional bladder capacity. By contrast, NUPh was demonstrated to be specific to nocturnal polyuria. Conclusion: NUPh has previously been shown among elderly males to be essential in nocturia and a very valid measure of nocturnal polyuria. However, the current, large and independent dataset now confirms that it can be applied in an adult population with a complaint of nocturia covering both males and females.
Chronoradiation Therapy for Prostate Cancer: Morning Proton Beam Therapy Ameliorates Worsening Lower Urinary Tract Symptoms
Authors: Negoro Hiromitsu , Iizumi Takashi , Mori Yutaro , Matsumoto Yoshitaka , Chihara Ichiro , Hoshi Akio , Sakurai Hideyuki , Nishiyama Hiroyuki , Ishikawa Hitoshi
Published: July 2020

Background and Purpose: Worsening lower urinary tract symptoms (LUTS) are a frequent adverse event following proton beam therapy (PBT) for localized prostate cancer. We investigated the differences in worsening LUTS among patients who received PBT at different times of day. Participants and Methods: Among 173 patients who underwent PBT for prostate cancer, 168 patients (median age 68.5 years) completed international prostate symptom score (IPSS) questionnaires and were included. Changes in the IPSS from baseline to the end of PBT were assessed by multiple linear regression analysis for age, National Comprehensive Cancer Network risk classification, androgen deprivation therapy, fractional PBT dose, clinical target volume, severity of IPSS, diabetes, LUTS medication use before PBT, anti-coagulant therapy and radiation time of day (morning (08:30–10:30), around noon (10:31–14:30), and late afternoon (14:31–16:30)). Results: IPSS total score and IPSS-Quality of Life (QoL) score (12 patients were excluded due to missing IPSS-QoL score) increased from eight to 14.9 (p < 0.0001) and from two to four (p < 0.0001), respectively. Time of day (morning) was the only determinant for worsening LUTS (β = −0.24, p < 0.01), voiding subscore (β = −0.22, p < 0.05) and IPSS-QoL (β = −0.27, p < 0.005), and was a determinant in item four (urgency) (β = −0.28, p < 0.005) with age (β = 0.19, p < 0.05). Conclusions: Morning PBT for localized prostate cancer significantly ameliorated worsening LUTS and improved QoL compared with treatment around noon or late afternoon. Chronoradiation therapy for localized prostate cancer may be effective and further research to elucidate the underlying mechanism is warranted.
Natriuretic Peptides, Cognitive Impairment and Dementia: An Intriguing Pathogenic Link with Implications in Hypertension
Authors: Gallo Giovanna , Bianchi Franca , Cotugno Maria , Volpe Massimo , Rubattu Speranza
Published: July 2020

The natriuretic peptides (NPs) belong to a family of cardiac hormones that exert relevant protective functions within the cardiovascular system. An increase of both brain and atrial natriuretic peptide levels, particularly of the amino-terminal peptides (NT-proBNP and NT-proANP), represents a marker of cardiovascular damage. A link between increased NP levels and cognitive decline and dementia has been reported in several human studies performed both in general populations and in cohorts of patients affected by cardiovascular diseases (CVDs). In particular, it was reported that the elevation of NP levels in dementia can be both dependent and independent from CVD risk factors. In the first case, it may be expected that, by counteracting early on the cardiovascular risk factor load and the pathological processes leading to increased aminoterminal natriuretic peptide (NT-proNP) level, the risk of dementia could be significantly reduced. In case of a link independent from CVD risk factors, an increased NP level should be considered as a direct marker of neuronal damage. In the context of hypertension, elevated NT-proBNP and mid-regional (MR)-proANP levels behave as markers of brain microcirculatory damage and dysfunction. The available evidence suggests that they could help in identifying those subjects who would benefit most from a timely antihypertensive therapy.
Impact of Incomplete Coronary Revascularization on Late Ischemic and Bleeding Events after Transcatheter Aortic Valve Replacement
Authors: Carmona Adrien , Marchandot Benjamin , Severac François , Kibler Marion , Trimaille Antonin , Heger Joe , Peillex Marilou , Matsushita Kensuke , Ristorto Jessica , Hoang Viet Anh , Hess Sébastien , Jesel Laurence , Ohlmann Patrick , Morel Olivier
Published: July 2020

Background: The impact of coronary artery disease (CAD) and revascularization by percutaneous coronary intervention (PCI) on prognosis in patients undergoing transcatheter aortic valve replacement (TAVR) remain debated. A dismal prognosis in patients undergoing PCI has been associated with elevated baseline SYNTAX score (bSS) and residual SYNTAX score (rSS). The objective was to investigate whether the degree of bSS and rSS impacted ischemic and bleeding events after TAVR. Methods: bSS and rSS were calculated in 311 patients admitted for TAVR. The primary outcome was the occurrence of major adverse cardiac events (MACE), a composite endpoint of myocardial infarction, stroke, cardiovascular death, or rehospitalization for heart failure. The occurrence of late major/life-threatening bleeding complications (MLBCs) and each primary endpoint individually were the secondary endpoints. Results: bSS > 22 was associated with higher occurrence of MACE (p = 0.013). rSS > 8 and bSS > 22 had no impact on overall cardiovascular mortality. rSS > 8 and bSS > 22 were associated with higher rates of myocardial infarction (p = 0.001 and p = 0.004) and late occurrence of MLBCs. Multivariate analysis showed that bSS > 22 (sHR 2.48) and rSS > 8 (sHR 2.35) remained predictors of MLBCs but not of myocardial infarction. Conclusions: Incomplete coronary revascularization and CAD burden did not impact overall and cardiac mortality but constitute predictors of late MLBCs in TAVR patients.
Neutralizing Antibody Production in Asymptomatic and Mild COVID-19 Patients, in Comparison with Pneumonic COVID-19 Patients
Authors: Ko Jae-Hoon , Joo Eun-Jeong , Park Su-Jin , Baek Jin Yang , Kim Won Duk , Jee Jaehwan , Kim Chul Joong , Jeong Chul , Kim Yae-Jean , Shon Hye Jin , Kang Eun-Suk , Choi Young Ki , Peck Kyong Ran
Published: July 2020

Objectives: To investigate antibody production in asymptomatic and mild COVID-19 patients. Methods: Sera from asymptomatic to severe COVID-19 patients were collected. Microneutralization (MN), fluorescence immunoassay (FIA), and enzyme-linked immunosorbent assay (ELISA) were performed. Results: A total of 70 laboratory-confirmed COVID-19 patients were evaluated, including 15 asymptomatic/anosmia, 49 mild symptomatic, and 6 pneumonia patients. The production of the neutralizing antibody was observed in 100% of pneumonia, 93.9% of mild symptomatic, and 80.0% of asymptomatic/anosmia groups. All the patients in the pneumonia group showed high MN titer (≥1:80), while 36.7% of mild symptomatic and 20.0% of asymptomatic/anosmia groups showed high titer (p < 0.001). Anti-SARS-CoV-2 antibodies could be more sensitively detected by FIA IgG (98.8%) and ELISA (97.6%) in overall. For the FIA IgG test, all patients in the pneumonia group exhibited a high COI value (≥15.0), while 89.8% of mild symptomatic and 73.3% of asymptomatic/anosmia groups showed a high value (p = 0.049). For the ELISA test, all patients in the pneumonia group showed a high optical density (OD) ratio (≥3.0), while 65.3% of mild symptomatic and 53.3% of asymptomatic/anosmia groups showed a high ratio (p = 0.006). Conclusions: Most asymptomatic and mild COVID-19 patients produced the neutralizing antibody, although the titers were lower than pneumonia patients. ELISA and FIA sensitively detected anti-SARS-CoV-2 antibodies.
Quickcard-Based Approach to Guiding Specific Nonpharmacological Treatments in a German Parkinson’s Network
Authors: Kerkemeyer Linda , Achtert Katharina , Claus Inga , Happe Svenja , Overbeck Jeannette , Kleen Nadine , Palesch Anja , Schmuck Clara , Krouß Sabrina , Perick Jürgen , Depenbrock Luisa , Nagel Michael , Siebecker Frank , Rose Olaf , Warnecke Tobias
Published: July 2020

Interdisciplinary care has been shown to be effective at optimizing the treatment of patients with Parkinson’s disease. An optimized collaboration between the various healthcare providers involved in the treatment process facilitates successful care. One of the main shortcomings in the German healthcare system is the limited and unstandardized communication between practitioners. The Parkinson’s network Münsterland+ (PNM+) is an interdisciplinary network of medical and non-medical experts involved in the treatment of Parkinson’s patients: neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, Parkinson’s nurses, pharmacists, patients, and relatives. The PNM+ elaborates guideline-based therapy recommendations, provided as so-called “Quickcards”. Thereby, the communication of the treating neurologist and therapists is based on a coordinated feedback system and suggestions to adequately select and, if necessary, adjust the therapy. In the German healthcare system, with its fragmented structures, the PNM+ and its activities have been shown to enhance integration of the healthcare providers and thereby optimize the care of Parkinson’s disease patients. Future research should evaluate the effects and cost-effectiveness.