bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal Muscle Gene Expression in Long-Term Endurance and Resistance Trained Elderly
Authors: Bolotta Alessandra , Filardo Giuseppe , Abruzzo Provvidenza Maria , Astolfi Annalisa , De Sanctis Paola , Di Martino Alessandro , Hofer Christian , Indio Valentina , Kern Helmut , Löfler Stefan , Marcacci Maurilio , Zampieri Sandra , Marini Marina , Zucchini Cinzia
Published: June 2020

Physical exercise is deemed the most efficient way of counteracting the age-related decline of skeletal muscle. Here we report a transcriptional study by next-generation sequencing of vastus lateralis biopsies from elderly with a life-long high-level training practice (n = 9) and from age-matched sedentary subjects (n = 5). Unsupervised mixture distribution analysis was able to correctly categorize trained and untrained subjects, whereas it failed to discriminate between individuals who underwent a prevalent endurance (n = 5) or a prevalent resistance (n = 4) training, thus showing that the training mode was not relevant for sarcopenia prevention. KEGG analysis of transcripts showed that physical exercise affected a high number of metabolic and signaling pathways, in particular those related to energy handling and mitochondrial biogenesis, where AMPK and AKT-mTOR signaling pathways are both active and balance each other, concurring to the establishment of an insulin-sensitive phenotype and to the maintenance of a functional muscle mass. Other pathways affected by exercise training increased the efficiency of the proteostatic mechanisms, consolidated the cytoskeletal organization, lowered the inflammation level, and contrasted cellular senescence. This study on extraordinary individuals who trained at high level for at least thirty years suggests that aging processes and exercise training travel the same paths in the opposite direction.
Estimating the Risk of COVID-19 Death during the Course of the Outbreak in Korea, February–May 2020
Authors: Shim Eunha , Mizumoto Kenji , Choi Wongyeong , Chowell Gerardo
Published: June 2020

Background: In Korea, a total of 10,840 confirmed cases of COVID-19 including 256 deaths have been recorded as of May 9, 2020. The time-delay adjusted case fatality risk (CFR) of COVID-19 in Korea is yet to be estimated. Methods: We obtained the daily series of confirmed cases and deaths in Korea reported prior to May 9, 2020. Using statistical methods, we estimated the time-delay adjusted risk for death from COVID-19 in Daegu, Gyeongsangbuk-do, other regions in Korea, as well as the entire country. Results: Our model-based crude CFR fitted the observed data well throughout the course of the epidemic except for the very early stage in Gyeongsangbuk-do; this was partially due to the reporting delay. Our estimates of the risk of death in Gyeongsangbuk-do reached 25.9% (95% Credible Interval (CrI): 19.6%–33.6%), 20.8% (95% CrI: 18.1%–24.0%) in Daegu, and 1.7% (95% CrI: 1.1%–2.5%) in other regions, whereas the national estimate was 10.2% (95% CrI: 9.0%–11.5%). Conclusions: The latest estimates of CFR of COVID-19 in Korea are considerably high, even with the early implementation of public health interventions including widespread testing, social distancing, and delayed school openings. Geographic differences in the CFR are likely influenced by clusters tied to hospitals and nursing homes.
Comparison of White Blood Cell Scintigraphy, FDG PET/CT and MRI in Suspected Diabetic Foot Infection: Results of a Large Retrospective Multicenter Study
Authors: Lauri Chiara , Glaudemans Andor W.J.M. , Campagna Giuseppe , Keidar Zohar , Muchnik Kurash Marina , Georga Stamata , Arsos Georgios , Noriega-Álvarez Edel , Argento Giuseppe , Kwee Thomas C. , Slart Riemer H.J.A. , Signore Alberto
Published: June 2020

Diabetic foot infections (DFIs) represent one of the most frequent and disabling morbidities of longstanding diabetes; therefore, early diagnosis is mandatory. The aim of this multicenter retrospective study was to compare the diagnostic accuracy of white blood cell scintigraphy (WBC), 18F-fluorodeoxyglucose positron emission tomography/computed tomography ((18F) FDG PET/CT), and Magnetic Resonance Imaging (MRI) in patients with suspected DFI. Images and clinical data from 251 patients enrolled by five centers were collected in order to calculate the sensitivity, specificity, and accuracy of WBC, FDG, and MRI in diagnosing osteomyelitis (OM), soft-tissue infection (STI), and Charcot osteoarthropathy. In OM, WBC acquired following the European Society of Nuclear Medicine (EANM) guidelines was more specific and accurate than MRI (91.9% vs. 70.7%, p < 0.0001 and 86.2% vs. 67.1%, p = 0.003, respectively). In STI, both FDG and WBC achieved a significantly higher specificity than MRI (97.9% and 95.7% vs. 83.6%, p = 0.04 and p = 0.018, respectively). In Charcot, both MRI and WBC demonstrated a significantly higher specificity and accuracy than FDG (88.2% and 89.3% vs. 62.5%, p = 0.0009; 80.3% and 87.9% vs. 62.1%, p < 0.02, respectively). Moreover, in Charcot, WBC was more specific than MRI (89.3% vs. 88.2% p < 0.0001). Given the limitations of a retrospective study, WBC using EANM guidelines was shown to be the most reliable imaging modality to differentiate between OM, STI, and Charcot in patients with suspected DFI.
Soluble Urokinase Plasminogen Activator Receptor (suPAR) Concentrations Are Elevated in Patients with Neuroendocrine Malignancies
Authors: Özdirik Burcin , Stueven Anna , Knorr Jana , Geisler Lukas , Mohr Raphael , Demir Münevver , Hellberg Teresa , Loosen Sven H. , Benz Fabian , Wiedenmann Bertram , Tacke Frank , Wree Alexander , Jann Henning , Roderburg Christoph
Published: June 2020

Neuroendocrine neoplasia (NEN) comprises heterogeneous tumors that are challenging to diagnose and, especially in cases of poorly differentiated (G3) NEN, are associated with very limited survival. Novel biomarkers allowing an early diagnosis as well as an optimal selection of suitable treatment options are urgently needed to improve the outcome of these patients. Recently, alterations of soluble urokinase-type plasminogen activator receptor (suPAR) serum levels were described in various types of cancers. However, the role of circulating suPAR as a biomarker in patients with NEN is unknown. In this study, we measured suPAR serum levels in a large and well-characterized cohort of 187 patients with NEN (neuroendocrine carcinomas (NEC) n = 30; neuroendocrine tumors (NET), n = 157) as well as 44 healthy controls. suPAR concentrations were significantly elevated in patients compared to controls. However, suPAR concentrations were independent of tumor-related factors such as the proliferation activity according to Ki-67, tumor grading, TNM (TNM classification of malignant tumors) stage, somatostatin receptor expression or clinical features such as functional or nonfunctional disease and the presence of tumor relapse. Interestingly, suPAR concentrations in NET patients were similar when compared to those measured in NEC patients. In contrast to previous results from other malignancies, in our analysis suPAR levels were not a significant predictor of overall survival. In conclusion, our data suggests that suPAR serum concentrations are elevated in NEN patients but do not allow prediction of outcome.
Frontiers of Robotic Colonoscopy: A Comprehensive Review of Robotic Colonoscopes and Technologies
Authors: Ciuti Gastone , Skonieczna-Żydecka Karolina , Marlicz Wojciech , Iacovacci Veronica , Liu Hongbin , Stoyanov Danail , Arezzo Alberto , Chiurazzi Marcello , Toth Ervin , Thorlacius Henrik , Dario Paolo , Koulaouzidis Anastasios
Published: June 2020

Flexible colonoscopy remains the prime mean of screening for colorectal cancer (CRC) and the gold standard of all population-based screening pathways around the world. Almost 60% of CRC deaths could be prevented with screening. However, colonoscopy attendance rates are affected by discomfort, fear of pain and embarrassment or loss of control during the procedure. Moreover, the emergence and global thread of new communicable diseases might seriously affect the functioning of contemporary centres performing gastrointestinal endoscopy. Innovative solutions are needed: artificial intelligence (AI) and physical robotics will drastically contribute for the future of the healthcare services. The translation of robotic technologies from traditional surgery to minimally invasive endoscopic interventions is an emerging field, mainly challenged by the tough requirements for miniaturization. Pioneering approaches for robotic colonoscopy have been reported in the nineties, with the appearance of inchworm-like devices. Since then, robotic colonoscopes with assistive functionalities have become commercially available. Research prototypes promise enhanced accessibility and flexibility for future therapeutic interventions, even via autonomous or robotic-assisted agents, such as robotic capsules. Furthermore, the pairing of such endoscopic systems with AI-enabled image analysis and recognition methods promises enhanced diagnostic yield. By assembling a multidisciplinary team of engineers and endoscopists, the paper aims to provide a contemporary and highly-pictorial critical review for robotic colonoscopes, hence providing clinicians and researchers with a glimpse of the major changes and challenges that lie ahead.
COVID-19 Related Coagulopathy: A Distinct Entity?
Authors: Marchandot Benjamin , Sattler Laurent , Jesel Laurence , Matsushita Kensuke , Schini-Kerth Valerie , Grunebaum Lelia , Morel Olivier
Published: June 2020

The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare communities across the globe on an unprecedented scale. Patients have had diverse clinical outcomes, but those developing COVID-19-related coagulopathy have shown a disproportionately worse outcome. This narrative review summarizes current evidence regarding the epidemiology, clinical features, known and presumed pathophysiology-based models, and treatment guidance regarding COVID-19 coagulopathy.
Virtual Histology to Evaluate Mechanisms of Pulmonary Artery Lumen Enlargement in Response to Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension
Authors: Magoń Wojciech , Stępniewski Jakub , Waligóra Marcin , Jonas Kamil , Przybylski Roman , Sikorska Martyna , Podolec Piotr , Kopeć Grzegorz
Published: June 2020

Chronic thromboembolic pulmonary hypertension (CTEPH) results from an obstruction of pulmonary arteries (PAs) by organized thrombi. The stenosed PAs are targeted during balloon pulmonary angioplasty (BPA). We aimed to evaluate the mechanism of BPA in inoperable patients with CTEPH. We analyzed stenosed PAs with intravascular grey-scale ultrasound (IVUS) to determine the cross-sectional area (CSA) of arterial lumen and of organized thrombi. The composition of organized thrombi was assessed using virtual histology. We distinguished two mechanisms of BPA: Type A with dominant vessel stretching, and type B with dominant thrombus compression. PAs were assessed before (n = 159) and after (n = 98) BPA in 20 consecutive patients. Organized thrombi were composed of dark-green (57.1 (48.0–64.0)%), light-green (34.0 (21.4–46.4)%), red (6.4 (2.9–11.7)%;) and white (0.2 (0.0–0.9)%) components. The mechanism type depended on vessel diameter (OR = 1.09(1.01–1.17); p = 0.03). In type B mechanism, decrease in the amount of light-green component positively correlated with an increase in lumen area after BPA (r = 0.50; p = 0.001). The mechanism of BPA depends on the diameter of the vessel. Dilation of more proximal PAs depends mainly on stretching of the vessel wall while dilation of smaller PAs depends on compression of the organized thrombi. The composition of the organized thrombi contributes to the effect of BPA.
High Blood Pressure Is Associated with Tubulointerstitial Damage along with Glomerular Damage in Glomerulonephritis. A large Cohort Study
Authors: Bazzi Claudio , Seccia Teresa M , Napodano Pietro , Campi Cristina , Caroccia Brasilina , Cattarin Leda , Calò Lorenzo A
Published: June 2020

The key role of arterial hypertension in chonic kidney disease (CKD) progression is widely recognized, but its contribution to tubulointerstitial damage (TID) in glomerulonephritis (GN) remains uncertain. Hence, the objective of this study is to clarify whether TID is associated with glomerular damage, and whether the damage at the tubulointerstitial compartment is more severe in hypertensive patients. The study included retrospectively consecutive patients referred to the Nephrology Unit with diagnoses of primary glomerulonephritis, lupus nephritis (LN), and nephroangiosclerosis (NAS) at biopsy. At least six glomeruli per biopsy were analysed through light and immunofluorescence microscopy. Global glomerulosclerosis (GGS%), TID, and arteriolar hyalinosis (AH) were used as markers of CKD severity. Of the 448 patients of the cohort, 403 received a diagnosis of GN, with the remaining being diagnosed with NAS. Hypertension was found in 52% of the overall patients, with no significant differences among those with GN, and reaching 88.9% prevalence rate in NAS. The hypertensive patients with GN had more marked damage in glomerular and tubular compartments than normotensives independently of the amount of proteinuria. Moreover, hypertension and GGS% were found to be strongly associated with TID in GN. In GN patients, not only the severity of glomerular damage but also the extent of TID was associated with high blood pressure.
P2Y12 Inhibitor Monotherapy with Clopidogrel versus Ticagrelor in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Chen Po-Wei , Feng Wen-Han , Ho Ming-Yun , Su Chun-Hung , Huang Sheng-Wei , Cheng Chung-Wei , Yeh Hung-I , Chen Ching-Pei , Huang Wei-Chun , Fang Ching-Chang , Lin Hui-Wen , Lin Sheng-Hsiang , Hsieh I-Chang , Li Yi-Heng
Published: June 2020

Background: P2Y12 inhibitor monotherapy is an alternative antiplatelet strategy in patients undergoing percutaneous coronary intervention (PCI). However, the ideal P2Y12 inhibitor for monotherapy is unclear. Methods and Results: We performed a multicenter, retrospective, observational study to compare the efficacy and safety of monotherapy with clopidogrel versus ticagrelor in patients with acute coronary syndrome (ACS) undergoing PCI. From 1 January 2014 to 31 December 2018, 610 patients with ACS who received P2Y12 monotherapy with either clopidogrel (n = 369) or ticagrelor (n = 241) after aspirin was discontinued prematurely were included. Inverse probability of treatment weighting was used to balance covariates between the groups. The primary endpoint was the composite of all-cause mortality, recurrent ACS or unplanned revascularization, and stroke within 12 months after discharge. Overall, 84 patients reached the primary endpoint, with 57 (15.5%) in the clopidogrel group and 27 (11.2%) in the ticagrelor group. Multivariate adjustment in Cox proportional-hazards models revealed a lower risk of the primary endpoint with ticagrelor than with clopidogrel (adjusted hazard ratio (aHR): 0.67, 95% confidence interval (CI): 0.49–0.93). Ticagrelor significantly reduced the risk of recurrent ACS or unplanned revascularization (aHR: 0.46, 95% CI: 0.28–0.75). No significant difference in all-cause mortality and major bleeding events was observed between the 2 groups. Conclusions: Among patients with ACS undergoing PCI who cannot complete course of dual antiplatelet therapy, a significantly lower risk of cardiovascular events was associated with ticagrelor monotherapy than with clopidogrel monotherapy. The major bleeding risk was similar in both the groups.
The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia
Authors: Muñoz Miguel , Coveñas Rafael
Published: June 2020

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy. To treat the disease successfully, new therapeutic strategies are urgently needed. One of these strategies can be the use of neurokinin-1 receptor (NK-1R) antagonists (e.g., aprepitant), because the substance P (SP)/NK-1R system is involved in cancer progression, including AML. AML patients show an up-regulation of the NK-1R mRNA expression; human AML cell lines show immunoreactivity for both SP and the NK-1R (it is overexpressed: the truncated isoform is more expressed than the full-length form) and, via this receptor, SP and NK-1R antagonists (aprepitant, in a concentration-dependent manner) respectively exert a proliferative action or an antileukemic effect (apoptotic mechanisms are triggered by promoting oxidative stress via mitochondrial Ca++ overload). Aprepitant inhibits the formation of AML cell colonies and, in combination with chemotherapeutic drugs, is more effective in inducing cytotoxic effects and AML cell growth blockade. NK-1R antagonists also exert an antinociceptive effect in myeloid leukemia-induced bone pain. The antitumor effect of aprepitant is diminished when the NF-κB pathway is overactivated and the damage induced by aprepitant in cancer cells is higher than that exerted in non-cancer cells. Thus, the SP/NK-1R system is involved in AML, and aprepitant is a promising antitumor strategy against this hematological malignancy. In this review, the involvement of this system in solid and non-solid tumors (in particular in AML) is updated and the use of aprepitant as an anti-leukemic strategy for the treatment of AML is also mentioned (a dose of aprepitant (>20 mg/kg/day) for a period of time according to the response to treatment is suggested). Aprepitant is currently used in clinical practice as an anti-nausea medication.
Relationships between Pulmonary Hypertension Risk, Clinical Profiles, and Outcomes in Dilated Cardiomyopathy
Authors: Dziewięcka Ewa , Wiśniowska-Śmiałek Sylwia , Karabinowska Aleksandra , Holcman Katarzyna , Gliniak Matylda , Winiarczyk Mateusz , Karapetyan Arman , Kaciczak Monika , Podolec Piotr , Kostkiewicz Magdalena , Hlawaty Marta , Leśniak-Sobelga Agata , Rubiś Paweł
Published: June 2020

Pulmonary hypertension (PH) in patients with heart failure (HF) contributes to a poorer prognosis. However, in those with dilated cardiomyopathy (DCM), the true prevalence and role of PH is unclear. Therefore, this study aimed to analyze the profile of DCM patients at various levels of PH risk, determined via echocardiography, and its impact on outcomes. The 502 DCM in- and out-patient records were retrospectively analyzed. Information on patient status was gathered after 45.9 ± 31.3 months. Patients were divided into 3 PH-risk groups based on results from echocardiography measurements: low (L, n = 239, 47.6%), intermediate (I, n = 153, 30.5%), and high (H, n = 110, 21.9%). Symptom duration, atrial fibrillation, ventricular tachyarrhythmia, ejection fraction, right atrial area, and moderate or severe mitral regurgitation were found to be independently associated with PH risk. During the follow-up period, 83 (16.5%) DCM patients died: 29 (12.1%) in L, 31 (20.3%) in I, and 23 (20.9%) in H. L-patients had a significantly lower risk of all-cause death (L to H: HR 0.55 (95%CI 0.32–0.98), p = 0.01), while no differences in prognosis were found between I and H. In conclusion, over one in five DCM patients had a high PH risk, and low PH risk was associated with better prognoses.
Non-Invasive Skin Cancer Diagnosis Using Hyperspectral Imaging for In-Situ Clinical Support
Authors: Leon Raquel , Martinez-Vega Beatriz , Fabelo Himar , Ortega Samuel , Melian Veronica , Castaño Irene , Carretero Gregorio , Almeida Pablo , Garcia Aday , Quevedo Eduardo , Hernandez Javier A. , Clavo Bernardino , M. Callico Gustavo
Published: June 2020

Skin cancer is one of the most common forms of cancer worldwide and its early detection its key to achieve an effective treatment of the lesion. Commonly, skin cancer diagnosis is based on dermatologist expertise and pathological assessment of biopsies. Although there are diagnosis aid systems based on morphological processing algorithms using conventional imaging, currently, these systems have reached their limit and are not able to outperform dermatologists. In this sense, hyperspectral (HS) imaging (HSI) arises as a new non-invasive technology able to facilitate the detection and classification of pigmented skin lesions (PSLs), employing the spectral properties of the captured sample within and beyond the human eye capabilities. This paper presents a research carried out to develop a dermatological acquisition system based on HSI, employing 125 spectral bands captured between 450 and 950 nm. A database composed of 76 HS PSL images from 61 patients was obtained and labeled and classified into benign and malignant classes. A processing framework is proposed for the automatic identification and classification of the PSL based on a combination of unsupervised and supervised algorithms. Sensitivity and specificity results of 87.5% and 100%, respectively, were obtained in the discrimination of malignant and benign PSLs. This preliminary study demonstrates, as a proof-of-concept, the potential of HSI technology to assist dermatologists in the discrimination of benign and malignant PSLs during clinical routine practice using a real-time and non-invasive hand-held device.
Low Expression of miR-20a-5p Predicts Benefit to Bevacizumab in Metastatic Breast Cancer Patients Treated within the TANIA Phase III Trial
Authors: Rinnerthaler Gabriel , Gampenrieder Simon Peter , Hackl Hubert , Steiner Markus , Monzo-Fuentes Claudia , Melchardt Thomas , Magnes Teresa , Huemer Florian , Westphal Theresa , Hufnagl Clemens , Hauser-Kronberger Cornelia , Egle Alexander , Greil Richard
Published: June 2020

Background: In metastatic breast cancer (MBC) patients, no biomarker predicting benefit to a bevacizumab-containing therapy has been established yet. MicroRNAs (miRNAs) are involved in angiogenesis and treatment resistance and therefore could be of predictive value. Methods: Profiling of 754 miRNAs was performed in tumor samples of 58 MBC patients treated with a bevacizumab-containing first-line regimen (learning set). Based on progression-free survival (PFS), patients were divided into responders (R) and non-responders (NR). Differentially expressed miRNAs between R and NR were analyzed in a cohort of 57 patients treated with first-line chemotherapy without bevacizumab (control set), to exclude miRNAs providing prognostic information. MiRNA candidates significantly associated with PFS in multivariate analysis were further validated in tumor samples of 203 patients treated within the phase III trial TANIA randomizing between chemotherapy either alone or with bevacizumab after progression on first-line bevacizumab. Results: Low expression of miR-20a-5p (multivariate p = 0.035) and miR-21-5p (multivariate p = 0.004) were significantly associated with longer PFS in the learning set, but not in the control set. In samples from the TANIA trial, low expression of miR-20a-5p was also significantly associated with longer PFS (hazard ration (HR) 0.60; 95%-CI 0.37–0.89; p = 0.012) and longer overall survival (OS; HR 0.54; 95%-CI 0.32–0.83; p = 0.007) in the bevacizumab arm but not in the chemotherapy-only arm (PFS: HR 0.73, p = 0.119; OS: HR 1.01; p = 0.964). For miR-21-5p no significant association with PFS or OS in both treatment arms was observed. Conclusion: MiR-20a-5p expression in breast cancer tissue was predictive for a greater benefit from bevacizumab-containing therapy in two independent cohorts.
Using Machine Learning to Predict ICU Transfer in Hospitalized COVID-19 Patients
Authors: Cheng Fu-Yuan , Joshi Himanshu , Tandon Pranai , Freeman Robert , Reich David L , Mazumdar Madhu , Kohli-Seth Roopa , Levin Matthew A. , Timsina Prem , Kia Arash
Published: June 2020

Objectives: Approximately 20–30% of patients with COVID-19 require hospitalization, and 5–12% may require critical care in an intensive care unit (ICU). A rapid surge in cases of severe COVID-19 will lead to a corresponding surge in demand for ICU care. Because of constraints on resources, frontline healthcare workers may be unable to provide the frequent monitoring and assessment required for all patients at high risk of clinical deterioration. We developed a machine learning-based risk prioritization tool that predicts ICU transfer within 24 h, seeking to facilitate efficient use of care providers’ efforts and help hospitals plan their flow of operations. Methods: A retrospective cohort was comprised of non-ICU COVID-19 admissions at a large acute care health system between 26 February and 18 April 2020. Time series data, including vital signs, nursing assessments, laboratory data, and electrocardiograms, were used as input variables for training a random forest (RF) model. The cohort was randomly split (70:30) into training and test sets. The RF model was trained using 10-fold cross-validation on the training set, and its predictive performance on the test set was then evaluated. Results: The cohort consisted of 1987 unique patients diagnosed with COVID-19 and admitted to non-ICU units of the hospital. The median time to ICU transfer was 2.45 days from the time of admission. Compared to actual admissions, the tool had 72.8% (95% CI: 63.2–81.1%) sensitivity, 76.3% (95% CI: 74.7–77.9%) specificity, 76.2% (95% CI: 74.6–77.7%) accuracy, and 79.9% (95% CI: 75.2–84.6%) area under the receiver operating characteristics curve. Conclusions: A ML-based prediction model can be used as a screening tool to identify patients at risk of imminent ICU transfer within 24 h. This tool could improve the management of hospital resources and patient-throughput planning, thus delivering more effective care to patients hospitalized with COVID-19.
Genotype-Related Clinical Characteristics and Myocardial Fibrosis and Their Association with Prognosis in Hypertrophic Cardiomyopathy
Authors: Kim Hyung Yoon , Park Jong Eun , Lee Sang-Chol , Jeon Eun-Seok , On Young Keun , Kim Sung Mok , Choe Yeon Hyeon , Ki Chang-Seok , Kim Jong-Won , Kim Kye Hun
Published: June 2020

Background: The spectrum of genetic variants and their clinical significance of Hypertrophic cardiomyopathy (HCM) have been poorly studied in Asian patients. The objectives of this study were to assess the spectrum of genetic variants and genotype–phenotype relationships within a Korean HCM population. Methods: Eighty-nine consecutive unrelated HCM patients were included. All patients underwent genotypic analysis for 23 HCM-associated genes. Clinical parameters including echocardiographic and cardiac magnetic resonance (CMR) parameters were evaluated. A composite of major adverse cardiac and cerebrovascular events was assessed. Results: Genetic variants were detected in 55 of 89 subjects. Pathogenic variants or likely pathogenic variants were identified in 27 of HCM patients in MYBPC3, TNNI3, MYH7, and MYL7. Variants of uncertain significance were identified in 28 patients. There were significant differences in the presence of non-sustained ventricular tachycardia (p = 0.030) and myocardial fibrosis on CMR (p = 0.029) in the detected compared to the not-detected groups. Event-free survival was superior in the not-detected group (p = 0.006). Conclusion: Genetic variants in patients with HCM are relatively common and are associated with adverse clinical events and myocardial fibrosis on CMR. Genotypic analysis may add important information to clinical variables in the assessment of long-term risk for HCM patients.
Well Differentiated Grade 3 Neuroendocrine Tumors of the Digestive Tract: A Narrative Review
Authors: Pellat Anna , Coriat Romain
Published: June 2020

The 2017 World Health Organization (WHO) classification of neuroendocrine neoplasms (NEN) of the digestive tract introduced a new category of tumors named well-differentiated grade 3 neuroendocrine tumors (NET G−3). These lesions show a number of mitosis, or a Ki−67 index higher than 20% with a well-differentiated morphology, therefore separating them from neuroendocrine carcinomas (NEC) which are poorly differentiated. It has become clear that NET G−3 show differences not only in morphology but also in genotype, clinical presentation, and treatment response. The incidence of digestive NET G−3 represents about one third of NEN G−3 with main tumor sites being the pancreas, the stomach and the colon. Treatment for NET G−3 is not yet standardized because of lack of data. In a non-metastatic setting, international guidelines recommend surgical resection, regardless of tumor grading. For metastatic lesion, chemotherapy is the main treatment with similar regimen as NET G−2. Sunitinib has also shown some positive results in a small sample of patients but this needs confirmation. Peptide receptor radionuclide therapy (PRRT) and immunotherapy could be future available treatments after ongoing studies. The goal of this review was to sum up the latest data on the epidemiology and management of digestive NET G−3.
Adjunctive Cilostazol to Dual Antiplatelet Therapy to Enhance Mobilization of Endothelial Progenitor Cell in Patients with Acute Myocardial Infarction: A Randomized, Placebo-Controlled EPISODE Trial
Authors: Park Yongwhi , Kim Jin Hyun , Kim Tae Ho , Koh Jin-Sin , Hwang Seok-Jae , Hwang Jin-Yong , Jeong Young-Hoon
Published: June 2020

Background: Endothelial progenitor cells (EPCs) have the potential to protect against atherothrombotic event occurrences. There are no data to evaluate the impact of cilostazol on EPC levels in high-risk patients. Methods: We conducted a randomized, double-blind, placebo-controlled trial to assess the effect of adjunctive cilostazol on EPC mobilization and platelet reactivity in patients with acute myocardial infarction (AMI). Before discharge, patients undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive cilostazol SR capsule (200-mg) a day (n = 30) or placebo (n = 30) on top of dual antiplatelet therapy (DAPT) with clopidogrel and aspirin. Before randomization (baseline) and at 30-day follow-up, circulating EPC levels were analyzed using flow cytometry and hemostatic measurements were evaluated by VerifyNow and thromboelastography assays. The primary endpoint was the relative change in EPC levels between baseline and 30-day. Results: At baseline, there were similar levels of EPC counts between treatments, whereas patients with cilostazol showed higher levels of EPC counts compared with placebo after 30 days. Cilostazol versus placebo treatment displayed significantly higher changes in EPC levels between baseline and follow-up (ΔCD133+/KDR+: difference 216%, 95% confidence interval (CI) 44~388%, p = 0.015; ΔCD34+/KDR+: difference 183%, 95% CI 25~342%, p = 0.024). At 30-day follow-up, platelet reactivity was lower in the cilostazol group compared with the placebo group (130 ± 45 versus 169 ± 62 P2Y12 Reaction Unit, p = 0.009). However, there were no significant correlations between the changes of EPC levels and platelet reactivity. Conclusion: Adjunctive cilostazol on top of clopidogrel and aspirin versus DAPT alone is associated with increased EPC mobilization and decreased platelet reactivity in AMI patients, suggesting its pleiotropic effects against atherothrombotic events (NCT04407312).
Thyroid Hormones and Functional Ovarian Reserve: Systemic vs. Peripheral Dysfunctions
Authors: Colella Marco , Cuomo Danila , Giacco Antonia , Mallardo Massimo , De Felice Mario , Ambrosino Concetta
Published: June 2020

Thyroid hormones (THs) exert pleiotropic effects in different mammalian organs, including gonads. Genetic and non-genetic factors, such as ageing and environmental stressors (e.g., low-iodine intake, exposure to endocrine disruptors, etc.), can alter T4/T3 synthesis by the thyroid. In any case, peripheral T3, controlled by tissue-specific enzymes (deiodinases), receptors and transporters, ensures organ homeostasis. Conflicting reports suggest that both hypothyroidism and hyperthyroidism, assessed by mean of circulating T4, T3 and Thyroid-Stimulating Hormone (TSH), could affect the functionality of the ovarian reserve determining infertility. The relationship between ovarian T3 level and functional ovarian reserve (FOR) is poorly understood despite that the modifications of local T3 metabolism and signalling have been associated with dysfunctions of several organs. Here, we will summarize the current knowledge on the role of TH signalling and its crosstalk with other pathways in controlling the physiological and premature ovarian ageing and, finally, in preserving FOR. We will consider separately the reports describing the effects of circulating and local THs on the ovarian health to elucidate their role in ovarian dysfunctions.
Effects of Different Types of Exercise Training on Pulmonary Arterial Hypertension: A Systematic Review
Authors: Waller Lena , Krüger Karsten , Conrad Kerstin , Weiss Astrid , Alack Katharina
Published: June 2020

Pulmonary arterial hypertension (PAH) represents a chronic progressive disease characterized by high blood pressure in the pulmonary arteries leading to right heart failure. The disease has been a focus of medical research for many years due to its worse prognosis and limited treatment options. The aim of this study was to systematically assess the effects of different types of exercise interventions on PAH. Electronic databases were searched until July 2019. MEDLINE database was used as the predominant source for this paper. Studies with regards to chronic physical activity in adult PAH patients are compared on retrieving evidence on cellular, physiological, and psychological alterations in the PAH setting. Twenty human studies and 12 rat trials were identified. Amongst all studies, a total of 628 human subjects and 614 rats were examined. Regular physical activity affects the production of nitric oxygen and attenuates right ventricular hypertrophy. A combination of aerobic, anaerobic, and respiratory muscle training induces the strongest improvement in functional capacity indicated by an increase of 6 MWD and VO2 peak. In human studies, an increase of quality of life was found. Exercise training has an overall positive effect on the physiological and psychological components of PAH. Consequently, PAH patients should be encouraged to take part in regular exercise training programs.
Follicle-Stimulating Hormone Treatment and Male Idiopathic Infertility: Effects on Sperm Parameters and Oxidative Stress Indices according to FSHR c. 2039 A/G and c. -29 G/A Genotypes
Authors: Mongioì Laura M. , Condorelli Rosita A. , Alamo Angela , Cannarella Rossella , Musso Nicolò , La Vignera Sandro , Calogero Aldo E.
Published: June 2020

Scientific evidence shows that the administration of follicle-stimulating hormone (FSH) to infertile patients with normal serum FSH concentrations improves sperm parameters in oligozoospermic men. The aim of this study was to evaluate the effects of highly purified urofollitropin (hpFSH) on conventional and bio-functional sperm parameters and on oxidative stress indices in patients with idiopathic infertility. We also evaluated the response to hpFSH on these parameters in relationship to FSHR c. 2039 A/G and FSHR c. -29 G/A genotypes. A prospective longitudinal study was conducted on 42 patients with idiopathic male infertility, 23 of whom underwent to FSHR c. 2039 A/G and FSHR c. -29 G/A genotyping. Each patient was asked to collect two semen samples before and after administration of 150 IU hpFSH three times a week for 16 weeks. Patients were divided into responders or non-responders based on whether their total sperm count had at least doubled or was less than double at the end of treatment, respectively. Responders showed a significantly higher semen volume, sperm concentration, spermatids, and leukocytes. Non-responders had a significant decrease of the percentage of spermatozoa in early apoptosis after hpFSH administration. Oxidative stress indexes did not differ significantly after FSH administration in both groups. Conventional and bio-functional sperm parameters did not differ in patients with FSHR c. 2039 GG and AA genotypes, and FSHR c. -29 GG genotype both before and after FSH administration. The FSHR c. 2039 and FSHR -29 G/A genotypes and allelic distribution did not differ between responders and non-responders. FSH showed to be capable of ameliorating sperm parameters in about half patients treated, therefore it may be helpful in patients with idiopathic infertility.
The Role of Digital Devices in Dentistry: Clinical Trends and Scientific Evidences
Authors: Spagnuolo Gianrico , Sorrentino Roberto
Published: June 2020

In recent years, digital technologies have significantlychanged the clinical approach to medicine and dentistry. Innovative operative techniques and restorative materials have paved the way to a significant active boost towards full digital workflows. Particularly, novel dental materials offer undeniable advantages such as optimal mechanical resistance, excellent esthetic and optical properties, and reliable accuracy and precision, widening the clinical scenario and allowing for innovative and less invasive restorative solutions.
Clinical Outcomes of Single Mosaic Embryo Transfer: High-Level or Low-Level Mosaic Embryo, Does It Matter?
Authors: Lin Pin-Yao , Lee Chun-I , Cheng En-Hui , Huang Chun-Chia , Lee Tsung-Hsien , Shih Hui-Hsin , Pai Yi-Ping , Chen Yi-Chun , Lee Maw-Sheng
Published: June 2020

Recently, reports showed that embryos identified as mosaic after preimplantation genetic testing for aneuploid (PGT-A) could result in live birth with lower pregnancy and higher pregnancy loss rates compared with euploid embryos. However, the effects of mosaicism level on reproductive outcomes remain controversial. This study aimed to examine the level of mosaicism on pregnancy outcomes. Single mosaic embryo transfer was offered to 108 women who only had mosaic embryos. Mosaic embryos were labeled by utilizing next generation sequencing (NGS) based PGT-A for day 5/6 trophectoderm (TE) biopsies. TE biopsies containing < 50% abnormal cells were classified as low-level mosaicism and ≥ 50% as high-level mosaicism. To further confirm the concordance of chromosome constitution between TE and inner cell mass (ICM), 41 remaining embryos designated as mosaic blastocysts donated for research were also analyzed. Comparable live birth rate (LBR) but higher miscarriage rate (MR) was found in the high-level group. (LBR: low vs. high: 44.5% vs. 36%; p = 0.45, MR: low vs. high: 5.1% vs. 30.7%; p = 0.012). Analyses of TE and ICM from the remaining mosaic blastocysts show a poor concordance. This preliminary study demonstrated that high-level mosaic embryos could result in comparable LBR but higher MR.
Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study
Authors: Pallio Giovanni , Irrera Natasha , Bitto Alessandra , Mannino Federica , Minutoli Letteria , Rottura Michelangelo , Pallio Socrate , Altavilla Domenica , Alibrandi Angela , Marciano Maria Concetta , Righi Maria , Mannucci Carmen , Arcoraci Vincenzo , Squadrito Francesco
Published: June 2020

Precise tacrolimus treatment in transplanted patients is achieved in the clinical setting by performing therapeutic drug monitoring (TDM) and consequently adjusting therapy. The aim of this study was to retrospectively analyze the variability in tacrolimus blood levels throughout 2 years of observation in 75 transplanted patients and to investigate if tacrolimus blood levels correlate with presence of genetic polymorphisms, thus modifying tacrolimus pharmacokinetics. CYP3A5*1 (G6986A), CYP3A4*1B (A392G), CYP3A4*22, ABCB1 (C3435T; C1236T; G2677A/T), SLCO1B1 (T521C), polymorphisms were analyzed. Based on the effect of their genotypes, patients were stratified into 5 groups: (1) reduced tacrolimus metabolism (RM), (2) increased metabolism (IM), (3) transporters polymorphisms (TM), (4) metabolism and transporter polymorphisms (AM) and (5) no mutations (Wild Type, WT). The percentage of the samples out of therapeutic range was significantly higher in the IM group than in the WT group (p = 0.001), as well as compared to the TM group (p = 0.004). Only IM pattern (p = 0.015) resulted as an independent predictor of number of tacrolimus blood levels out of therapeutic range. RM pattern (p = 0.006) was inversely related to the administered dose. Therefore, genotyping could become a standard practice before tacrolimus prescription thus decreasing side effects, increasing efficacy and reducing the economic burden for the national health system.
3D Digital Representation of Cadastral Data in Turkey—Apartments Case
Authors: Döner Fatih , Şirin Samet
Published: June 2020

With the widespread use of three-dimensional (3D) geographic information technologies, studies for 3D digital representation of property units in cadasters have increased in recent years. In Turkey, a project named 3D City Models and Cadasters was initiated by the General Directorate of Land Registries and Cadasters in 2018. With this project, which is planned to last four years, it aims to create 3D models of individual units (apartments) in buildings and provide visual representations of these individual units with legal information. Transition from the current 2D representation towards a 3D digital cadaster requires not only replacing analog drawings with 3D models but also examining the workflow for forming the property units. In this study, the process of registration of property rights for individual units is examined and possibilities and challenges for successful completion of the 3D cadaster project are evaluated from a legal, an organizational, and a technical point of view. Government plays a lead role by adopting the digital transformation as a state policy. However, new regulations and organizational settings may have to be introduced. Modeling and visualization alternatives for 3D data should be studied further.
Public Perception of Autonomous Mobility Using ML-Based Sentiment Analysis over Social Media Data
Authors: Bakalos Nikolaos , Papadakis Nikolaos , Litke Antonios
Published: June 2020

The purpose of this article is to present a framework for capturing and analyzing social media posts using a sentiment analysis tool to determine the views of the general public towards autonomous mobility. The paper presents the systems used and the results of this analysis, which was performed on social media posts from Twitter and Reddit. To achieve this, a specialized lexicon of terms was used to query social media content from the dedicated application programming interfaces (APIs) that the aforementioned social media platforms provide. The captured posts were then analyzed using a sentiment analysis framework, developed using state-of-the-art deep machine learning (ML) models. This framework provides labeling for the captured posts based on their content (i.e., classifies them as positive or negative opinions). The results of this classification were used to identify fears and autonomous mobility aspects that affect negative opinions. This method can provide a more realistic view of the general public’s perception of automated mobility, as it has the ability to analyze thousands of opinions and encapsulate the users’ opinion in a semi-automated way.
Synthesis of (R) and (S)-3-Chloro-5-(2,4-dimethylpiperazin-1-yl)-4H-1,2,6-thiadiazin-4-ones
Authors: Kalogirou Andreas , Asquith Christopher , Koutentis Panayiotis
Published: June 2020

The reaction of 3,5-dichloro-4H-1,2,6-thiadiazin-4-one with (R) and (S)-1,3-dimethylpiperazines (1 equiv), in THF, at ca. 20 °C gives (R) and (S)-3-chloro-5-(2,4-dimethylpiperazin-1-yl)-4H-1,2,6-thiadiazin-4-ones in 70% and 68% yields, respectively. The new compounds were fully characterized.
A Novel Electrochemical Process for Desulfurization in the CaO-SiO2-Al2O3 System
Authors: Lee Sang Hoon , Min Dong Joon
Published: June 2020

The effect of electric potential on the sulfide capacity of the CaO-SiO2-Al2O3 system was evaluated by applying voltages in the range of −1.5 to 1.5 V at 1823 K in a C/CO gas equilibrium. When the cathodic potential (−1.5 to 0 V) was applied, it was confirmed that the sulfur partition ratio increased based on the electrochemical reaction of sulfur (S + 2e− = S2−). However, the reversibility of the electrochemical resulfurization reaction (S2− = S + 2e−) in slag was not established in the reverse (anodic) potential region (0–1.5 V), yet the sulfur partition ratio increased. In particular, sulfur evaporation was observed in the anodic potential region. Therefore, in the present study, potential anodic electro-desulfurization mechanisms based on sulfur evaporation are proposed. To verify these mechanisms, sulfur evaporation is discussed in detail as a function of the thermodynamic stability of sulfur in the slag.
Feasibility Study of Digital Image Correlation in Determining Strains in Concrete Exposed to Fire
Authors: Mróz Katarzyna , Tekieli Marcin , Hager Izabela
Published: June 2020

Concrete is prone to spalling when exposed to fire. During fire tests, the strains of concrete elements are hard to identify, both from the fire-exposed face and the non-exposed face. This paper presents a field experiment which employed the original CivEng digital image correlation (DIC) method developed at the Cracow University of Technology to measure the strain fields of elements exposed to heating by a pin-point gas burner. The paper presents experimental proof that it is possible to analyze the deformation of both unheated and fire-exposed sides of heated concrete by the DIC method. The strain fields, crack patterns and modes of crack development are presented. The study shows the encouraging results of employing the DIC method to test concrete behavior under fire attack.
Geomaterials Evaluation: A New Application of Ashby Plots
Authors: Sun Fuqiang , Zhao Ya-Pu
Published: June 2020

The development of fossil energy resources and the occurrence of geological hazards call for a quick and effective identification of geological situations. In this study, we present rapid evaluations of geological structures from the pure point of view of material properties. For the first time, Ashby plots are applied to the evaluation of geomaterials such as rocks and coals. A series of case studies are presented and related Ashby plots are drawn. The stability of rocks facing natural hazards is analyzed and compared; the stability of coals formed in different periods in China is studied; and a new brittleness index for reservoir rocks is proposed. The Ashby plots show a strong vitality and a wide application prospect in geomaterial evaluation and geological engineering.
The Meshless Analysis of Scale-Dependent Problems for Coupled Fields
Authors: Sladek Jan , Sladek Vladimir , Wen Pihua H.
Published: June 2020

The meshless local Petrov–Galerkin (MLPG) method was developed to analyze 2D problems for flexoelectricity and higher-grade thermoelectricity. Both problems were multiphysical and scale-dependent. The size effect was considered by the strain and electric field gradients in the flexoelectricity, and higher-grade heat flux in the thermoelectricity. The variational principle was applied to derive the governing equations within the higher-grade theory of considered continuous media. The order of derivatives in the governing equations was higher than in their counterparts in classical theory. In the numerical treatment, the coupled governing partial differential equations (PDE) were satisfied in a local weak-form on small fictitious subdomains with a simple test function. Physical fields were approximated by the moving least-squares (MLS) scheme. Applying the spatial approximations in local integral equations and to boundary conditions, a system of algebraic equations was obtained for the nodal unknowns.