bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment-Induced Neuropathy in Diabetes (TIND)—Developing a Disease Model in Type 1 Diabetic Rats
Authors: Baum Petra , Koj Severin , Klöting Nora , Blüher Matthias , Classen Joseph , Paeschke Sabine , Gericke Martin , Toyka Klaus V. , Nowicki Marcin , Kosacka Joanna
Published: February 2021

Treatment-induced neuropathy in diabetes (TIND) is defined by the occurrence of an acute neuropathy within 8 weeks of an abrupt decrease in glycated hemoglobin-A1c (HbA1c). The underlying pathogenic mechanisms are still incompletely understood with only one mouse model being explored to date. The aim of this study was to further explore the hypothesis that an abrupt insulin-induced fall in HbA1c may be the prime causal factor of developing TIND. BB/OKL (bio breeding/OKL, Ottawa Karlsburg Leipzig) diabetic rats were randomized in three groups, receiving insulin treatment by implanted subcutaneous osmotic insulin pumps for 3 months, as follows: Group one received 2 units per day; group two 1 unit per day: and group three 1 unit per day in the first month, followed by 2 units per day in the last two months. We serially examined blood glucose and HbA1c levels, motor- and sensory/mixed afferent conduction velocities (mNCV and csNCV) and peripheral nerve morphology, including intraepidermal nerve fiber density and numbers of Iba-1 (ionized calcium binding adaptor molecule 1) positive macrophages in the sciatic nerve. Only in BB/OKL rats of group three, with a rapid decrease in HbA1c of more than 2%, did we find a significant decrease in mNCV in sciatic nerves (81% of initial values) after three months of treatment as compared to those group three rats with a less marked decrease in HbA1c <2% (mNCV 106% of initial values, p ≤ 0.01). A similar trend was observed for sensory/mixed afferent nerve conduction velocities: csNCV were reduced in BB/OKL rats with a rapid decrease in HbA1c >2% (csNCV 90% of initial values), compared to those rats with a mild decrease <2% (csNCV 112% of initial values, p ≤ 0.01). Moreover, BB/OKL rats of group three with a decrease in HbA1c >2% showed significantly greater infiltration of macrophages by about 50% (p ≤ 0.01) and a decreased amount of calcitonin gene related peptide (CGRP) positive nerve fibers as compared to the animals with a milder decrease in HbA1c. We conclude that a mild acute neuropathy with inflammatory components was induced in BB/OKL rats as a consequence of an abrupt decrease in HbA1c caused by high-dose insulin treatment. This experimentally induced neuropathy shares some features with TIND in humans and may be further explored in studies into the pathogenesis and treatment of TIND.
Connexins during 500 Million Years—From Cyclostomes to Mammals
Authors: Mikalsen Svein-Ole , í Kongsstovu Sunnvør , Tausen Marni
Published: February 2021

It was previously shown that the connexin gene family had relatively similar subfamily structures in several vertebrate groups. Still, many details were left unclear. There are essentially no data between tunicates, which have connexins that cannot be divided into the classic subfamilies, and teleosts, where the subfamilies are easily recognized. There are also relatively few data for the groups that diverged between the teleosts and mammals. As many of the previously analyzed genomes have been improved, and many more genomes are available, we reanalyzed the connexin gene family and included species from all major vertebrate groups. The major results can be summarized as follows: (i) The same connexin subfamily structures are found in all Gnathostomata (jawed vertebrates), with some variations due to genome duplications, gene duplications and gene losses. (ii) In contrast to previous findings, birds do not have a lower number of connexins than other tetrapods. (iii) The cyclostomes (lampreys and hagfishes) possess genes in the alpha, beta, gamma and delta subfamilies, but only some of the genes show a phylogenetic affinity to specific genes in jawed vertebrates. Thus, two major evolutionary transformations have occurred in this gene family, from tunicates to cyclostomes and from cyclostomes to jawed vertebrates.
Transgenic Mice Overexpressing PG1 Display Corneal Opacity and Severe Inflammation in the Eye
Authors: Choi Min-Kyeung , Le Minh Thong , Cho Hye-Sun , Lee Juyoung , Jeon Hyoim , Cha Se-Yeoun , Na Manheum , Chun Taehoon , Kim Jin-Hoi , Song Hyuk , Park Chankyu
Published: February 2021

Antimicrobial peptides (AMPs) are of interest as alternatives to antibiotics or immunomodulators. We generated and characterized the phenotypes of transgenic mice overexpressing protegrin 1 (PG1), a potent porcine cathelicidin. No obvious differences were observed between PG1 transgenic and wild-type mice in terms of growth, development, general behaviour, and the major immune cell population. However, PG1 transgenic mice intranasally infected with Staphylococcus aureus resulted in a reduction in microscopic pulmonary injury, improved clearance of bacteria, and lower proinflammatory cytokine secretion, compared to those of wild-type mice. On the other hand, approximately 25% of PG1 transgenic mice (n = 54/215) showed corneal opacity and developed inflammation in the eye, resulting ultimately in phthisis bulbi. Immunohistochemical analyses revealed that PG1 and its activator, neutrophil elastase, localized to the basal cells of the cornea and glands in eyelids, respectively. In addition, apoptosis indicated by a Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive signal was detected from flat cells of the cornea. Our study suggests that the expression regulation or localization of AMPs such as PG1 is important to prevent their adverse effects. However, our results also showed that the cytotoxic effects of PG1 on cells could be tolerated in animals, except for the eyes.
HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells
Authors: Akbay Burkitkan , Germini Diego , Bissenbaev Amangeldy K. , Musinova Yana R. , Sheval Evgeny V. , Vassetzky Yegor , Dokudovskaya Svetlana
Published: February 2021

HIV-1 infects T cells, but the most frequent AIDS-related lymphomas are of B-cell origin. Molecular mechanisms of HIV-1-induced oncogenic transformation of B cells remain largely unknown. HIV-1 Tat protein may participate in this process by penetrating and regulating gene expression in B cells. Both immune and cancer cells can reprogram communications between extracellular signals and intracellular signaling pathways via the Akt/mTORC1 pathway, which plays a key role in the cellular response to various stimuli including viral infection. Here, we investigated the role of HIV-1 Tat on the modulation of the Akt/mTORC1 pathway in B cells. We found that HIV-1 Tat activated the Akt/mTORC1 signaling pathway; this leads to aberrant activation of activation-induced cytidine deaminase (AICDA) due to inhibition of the AICDA transcriptional repressors c-Myb and E2F8. These perturbations may ultimately lead to an increased genomic instability and proliferation that might cause B cell malignancies.
Neuroprotective Effects of Testosterone in the Hypothalamus of an Animal Model of Metabolic Syndrome
Authors: Sarchielli Erica , Comeglio Paolo , Filippi Sandra , Cellai Ilaria , Guarnieri Giulia , Marzoppi Alessandra , Cipriani Sarah , Vignozzi Linda , Morelli Annamaria , Maggi Mario
Published: February 2021

Metabolic syndrome (MetS) is known to be associated to inflammation and alteration in the hypothalamus, a brain region implicated in the control of several physiological functions, including energy homeostasis and reproduction. Previous studies demonstrated the beneficial effects of testosterone treatment (TTh) in counteracting some MetS symptoms in both animal models and clinical studies. This study investigated the effect of TTh (30 mg/kg/week for 12 weeks) on the hypothalamus in a high-fat diet (HFD)-induced animal model of MetS, utilizing quantitative RT-PCR and immunohistochemical analyses. The animal model recapitulates the human MetS features, including low testosterone/gonadotropin plasma levels. TTh significantly improved MetS-induced hypertension, visceral adipose tissue accumulation, and glucose homeostasis derangements. Within hypothalamus, TTh significantly counteracted HFD-induced inflammation, as detected in terms of expression of inflammatory markers and microglial activation. Moreover, TTh remarkably reverted the HFD-associated alterations in the expression of important regulators of energy status and reproduction, such as the melanocortin and the GnRH-controlling network. Our results suggest that TTh may exert neuroprotective effects on the HFD-related hypothalamic alterations, with positive outcomes on the circuits implicated in the control of energy metabolism and reproductive tasks, thus supporting a possible role of TTh in the clinical management of MetS.
Accelerated Wound Closure of Deep Partial Thickness Burns with Acellular Fish Skin Graft
Authors: Stone Randolph , Saathoff Emily C. , Larson David A. , Wall John T. , Wienandt Nathan A. , Magnusson Skuli , Kjartansson Hilmar , Natesan Shanmugasundaram , Christy Robert J.
Published: February 2021

Thermal injuries are caused by exposure to a variety of sources, and split thickness skin grafts are the gold standard treatment for severe burns; however, they may be impossible when there is no donor skin available. Large total body surface area burns leave patients with limited donor site availability and create a need for treatments capable of achieving early and complete coverage that can also retain normal skin function. In this preclinical trial, two cellular and tissue based products (CTPs) are evaluated on twenty-four 5 × 5 deep partial thickness (DPT) burn wounds. Using appropriate pain control methods, DPT burn wounds were created on six anesthetized Yorkshire pigs. Wounds were excised one day post-burn and the bleeding wound beds were subsequently treated with omega-3-rich acellular fish skin graft (FSG) or fetal bovine dermis (FBD). FSG was reapplied after 7 days and wounds healed via secondary intentions. Digital images, non-invasive measurements, and punch biopsies were acquired during rechecks performed on days 7, 14, 21, 28, 45, and 60. Multiple qualitative measurements were also employed, including re-epithelialization, contraction rates, hydration, laser speckle, and trans-epidermal water loss (TEWL). Each treatment produced granulated tissue (GT) that would be receptive to skin grafts, if desired; however, the FSG induced GT 7 days earlier. FSG treatment resulted in faster re-epithelialization and reduced wound size at day 14 compared to FBD (50.2% vs. 23.5% and 93.1% vs. 106.7%, p < 0.005, respectively). No differences in TEWL measurements were observed. The FSG integrated into the wound bed quicker as evidenced by lower hydration values at day 21 (309.7 vs. 2500.4 µS, p < 0.05) and higher blood flow at day 14 (4.9 vs. 3.1 fold change increase over normal skin, p < 0.005). Here we show that FSG integrated faster without increased contraction, resulting in quicker wound closure without skin graft application which suggests FSG improved burn wound healing over FBD.
Fall Detection from Electrocardiogram (ECG) Signals and Classification by Deep Transfer Learning
Authors: Butt Fatima Sajid , La Blunda Luigi , Wagner Matthias F. , Schäfer Jörg , Medina-Bulo Inmaculada , Gómez-Ullate David
Published: February 2021

Fall is a prominent issue due to its severe consequences both physically and mentally. Fall detection and prevention is a critical area of research because it can help elderly people to depend less on caregivers and allow them to live and move more independently. Using electrocardiograms (ECG) signals independently for fall detection and activity classification is a novel approach used in this paper. An algorithm has been proposed which uses pre-trained convolutional neural networks AlexNet and GoogLeNet as a classifier between the fall and no fall scenarios using electrocardiogram signals. The ECGs for both falling and no falling cases were obtained as part of the study using eight volunteers. The signals are pre-processed using an elliptical filter for signal noises such as baseline wander and power-line interface. As feature extractors, frequency-time representations (scalograms) were obtained by applying a continuous wavelet transform on the filtered ECG signals. These scalograms were used as inputs to the neural network and a significant validation accuracy of 98.08% was achieved in the first model. The trained model is able to distinguish ECGs with a fall activity from an ECG with a no fall activity with an accuracy of 98.02%. For the verification of the robustness of the proposed algorithm, our experimental dataset was augmented by adding two different publicly available datasets to it. The second model can classify fall, daily activities and no activities with an accuracy of 98.44%. These models were developed by transfer learning from the domain of real images to the medical images. In comparison to traditional deep learning approaches, the transfer learning not only avoids “reinventing the wheel,” but also presents a lightweight solution to otherwise computationally heavy problems.
CrowdHeritage: Crowdsourcing for Improving the Quality of Cultural Heritage Metadata
Authors: Kaldeli Eirini , Menis-Mastromichalakis Orfeas , Bekiaris Spyros , Ralli Maria , Tzouvaras Vassilis , Stamou Giorgos
Published: February 2021

The lack of granular and rich descriptive metadata highly affects the discoverability and usability of cultural heritage collections aggregated and served through digital platforms, such as Europeana, thus compromising the user experience. In this context, metadata enrichment services through automated analysis and feature extraction along with crowdsourcing annotation services can offer a great opportunity for improving the metadata quality of digital cultural content in a scalable way, while at the same time engaging different user communities and raising awareness about cultural heritage assets. To address this need, we propose the CrowdHeritage open end-to-end enrichment and crowdsourcing ecosystem, which supports an end-to-end workflow for the improvement of cultural heritage metadata by employing crowdsourcing and by combining machine and human intelligence to serve the particular requirements of the cultural heritage domain. The proposed solution repurposes, extends, and combines in an innovative way general-purpose state-of-the-art AI tools, semantic technologies, and aggregation mechanisms with a novel crowdsourcing platform, so as to support seamless enrichment workflows for improving the quality of CH metadata in a scalable, cost-effective, and amusing way.
Tool to Retrieve Less-Filtered Information from the Internet
Authors: Nemoto Yuta , Klyuev Vitaly
Published: February 2021

While users benefit greatly from the latest communication technology, with popular platforms such as social networking services including Facebook or search engines such as Google, scientists warn of the effects of a filter bubble at this time. A solution to escape from filtered information is urgently needed. We implement an approach based on the mechanism of a metasearch engine to present less-filtered information to users. We develop a practical application named MosaicSearch to select search results from diversified categories of sources collected from multiple search engines. To determine the power of MosaicSearch, we conduct an evaluation to assess retrieval quality. According to the results, MosaicSearch is more intelligent compared to other general-purpose search engines: it generates a smaller number of links while providing users with almost the same amount of objective information. Our approach contributes to transparent information retrieval. This application helps users play a main role in choosing the information they consume.
Individualism or Collectivism: A Reinforcement Learning Mechanism for Vaccination Decisions
Authors: Wu Chaohao , Qiao Tong , Qiu Hongjun , Shi Benyun , Bao Qing
Published: February 2021

Previous studies have pointed out that it is hard to achieve the level of herd immunity for the population and then effectively stop disease propagation from the perspective of public health, if individuals just make vaccination decisions based on individualism. Individuals in reality often exist in the form of groups and cooperate in or among communities. Meanwhile, society studies have suggested that we cannot ignore the existence and influence of collectivism for studying individuals’ decision-making. Regarding this, we formulate two vaccination strategies: individualistic strategy and collectivist strategy. The former helps individuals taking vaccination action after evaluating their perceived risk and cost of themselves, while the latter focuses on evaluating their contribution to their communities. More significantly, we propose a reinforcement learning mechanism based on policy gradient. Each individual can adaptively pick one of these two strategies after weighing their probabilities with a two-layer neural network whose parameters are dynamically updated with his/her more and more vaccination experience. Experimental results on scale-free networks verify that the reinforcement learning mechanism can effectively improve the vaccine coverage level of communities. Moreover, communities can always get higher total payoffs with fewer costs paid, comparing that of pure individualistic strategy. Such performance mostly stems from individuals’ adaptively picking collectivist strategy. Our study suggests that public health authorities should encourage individuals to make vaccination decisions from the perspective of their local mixed groups. Especially, it is more worthy of noting that individuals with low degrees are more significant as their vaccination behaviors can more sharply improve vaccination coverage of their groups and greatly reduce epidemic size.
GNSS (GPS) Monitoring of Dynamic Deflections of Bridges: Structural Constraints and Metrological Limitations
Authors: Stiros Stathis C.
Published: February 2021

The advent of modern geodetic satellite techniques (GNSS, including GPS) permitted to observe dynamic deflections of bridges, initially of long flexible ones, and more recently of short, essentially stiff bridges with modal frequencies > 1 Hz, and with small SNR (signal-to-noise ratio), even SNR < 1. This was an enormous progress, but not without problems. Apart from monitoring results consistent with structural models, experimental data and serviceability criteria, there exist some apparently unexplained cases of stiff bridges for which there have been claimed apparent dynamic deflections too large for common healthy structures. Summarizing previous experience, this article: (i) discusses structural constraints, experimental evidence, and serviceability limits of bridges as constraints to GNSS monitoring; (ii) examines a representative case of careful monitoring of a reinforced concrete road bridge with reported excessive dynamic deflections; and (iii) explains such deflections as a result of a double process generated by large reflective surfaces of passing vehicles near the antenna; first corruption/distortion of the satellite signal because of high-frequency dynamic multipath, and second, shadowing of some satellites; this last effect leads to a modified observations system and to instantaneously changed coordinates and deflections. In order to recognize and avoid such bias in GNSS monitoring, a strategy based on practical rules and structural constraints is presented.
De Novo Transcriptomic Analyses Revealed Some Detoxification Genes and Related Pathways Responsive to Noposion Yihaogong® 5% EC (Lambda-Cyhalothrin 5%) Exposure in Spodoptera frugiperda Third-Instar Larvae
Authors: Hafeez Muhammad , Li Xiaowei , Zhang Zhijun , Huang Jun , Wang Likun , Zhang Jinming , Shah Sakhawat , Khan Muhammad Musa , Xu Fei , Fernández-Grandon G. Mandela , Zalucki Myron P. , Lu Yaobin
Published: February 2021

The fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is a polyphagous, invasive insect pest which causes significant losses in important crops wherever it has spread. The use of pesticides in agriculture is a key tool in the management of many important crop pests, including S. frugiperda, but continued use of insecticides has selected for various types of resistance, including enzyme systems that provide enhanced mechanisms of detoxification. In the present study, we analyzed the de novo transcriptome of S. frugiperda larvae exposed to Noposion Yihaogong® 5% emulsifiable concentrate (EC) insecticide focusing on detoxification genes and related pathways. Results showed that a total of 1819 differentially expressed genes (DEGs) were identified in larvae after being treated with Noposion Yihaogong® 5% EC insecticide, of which 863 were up- and 956 down-regulated. Majority of these differentially expressed genes were identified in numerous Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including metabolism of xenobiotics and drug metabolism. Furthermore, many of S. frugiperda genes involved in detoxification pathways influenced by lambda-cyhalothrin stress support their predicted role by further co-expression network analysis. Our RT-qPCR results were consistent with the DEG’s data of transcriptome analysis. The comprehensive transcriptome sequence resource attained through this study enriches the genomic platform of S. frugiperda, and the identified DEGs may enable greater molecular underpinnings behind the insecticide-resistance mechanism caused by lambda-cyhalothrin.
Magnitude and Spread of Bed Bugs (Cimex lectularius) throughout Ohio (USA) Revealed by Surveys of Pest Management Industry
Authors: Jones Susan C.
Published: February 2021

Bed bugs have recently re-emerged as human pests worldwide. In this study, two surveys queried licensed pest management companies in Ohio (Midwest USA) about their experiences managing bed bugs. A primary objective was to assess the magnitude and spread of bed bug infestations statewide based on companies’ treatment records from 2005 and 2011 (first survey) and 2016 (second survey). The survey response rates were 35.6% and 31.6%, respectively. Treatment data from 2005 indicated that Ohio’s bed bug problem likely started in the SW corner of the state in Hamilton County (includes city of Cincinnati), since it totaled five times more treatments (approximately 4500) than second-ranking, centrally located Franklin County (Columbus). In the first half of 2011, more than 15,000 treatments were performed in these two counties. In 2016, treatments reached nearly 38,000 in Franklin County and in NE Ohio in the three combined counties that include Cleveland-Akron-Canton. Bed bug problems expanded statewide during an 11 y period, with an estimated 100+ treatments in 7 counties in 2005, 45 counties in 2011, and nearly all 88 counties in 2016. Apartments/condos and single-family residences comprised the largest share of bed bug work. Residents misused many pesticides and household cleaners trying to eliminate bed bugs. Many also discarded unwrapped infested furniture, which may further spread these bugs. More public education is needed to stop such practices. This study shows that bed bug problems grow and spread quickly; federal, state, and local officials and the public should immediately deal with bed bugs.
Deep Learning-Assisted Short-Term Load Forecasting for Sustainable Management of Energy in Microgrid
Authors: Moradzadeh Arash , Moayyed Hamed , Zakeri Sahar , Mohammadi-Ivatloo Behnam , Aguiar A. Pedro
Published: February 2021

Nowadays, supplying demand load and maintaining sustainable energy are important issues that have created many challenges in power systems. In these types of problems, short-term load forecasting has been proposed as one of the management and energy supply modes in power systems. In this paper, after reviewing various load forecasting techniques, a deep learning method called bidirectional long short-term memory (Bi-LSTM) is presented for short-term load forecasting in a microgrid. By collecting relevant features available in the input data at the training stage, it is shown that the proposed procedure enjoys important properties, such as its great ability to process time series data. A microgrid in rural Sub-Saharan Africa, including household and commercial loads, was selected as the case study. The parameters affecting the formation of household and commercial load profiles are considered as input variables, and the total household and commercial load profiles of the microgrid are considered as the target. The Bi-LSTM network is trained by input variables to forecast the microgrid load on an hourly basis by recognizing the consumption pattern. Various performance evaluation indicators such as the correlation coefficient (R), mean squared error (MSE), and root mean squared error (RMSE) are utilized to analyze the forecast results. In addition, in a comparative approach, the performance of the proposed method is compared and evaluated with other methods used in similar studies. The results presented for the training phase show an accuracy of R = 99.81% for the Bi-LSTM network. The test and load forecasting stage are performed by the Bi-STLM network, with an accuracy of R = 99.34% and forecasting errors of MSE = 0.1042 and RMSE = 0.3243. The results confirm the high performance of the proposed Bi-LSTM technique, with a high correlation coefficient when compared to other methods used for short-term load forecasting.
Markers of Cellular Proliferation, Apoptosis, Estrogen/Progesterone Receptor Expression and Fibrosis in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids
Authors: Szydłowska Iwona , Grabowska Marta , Nawrocka-Rutkowska Jolanta , Piasecka Małgorzata , Starczewski Andrzej
Published: February 2021

There appear to be very few data on the exact mechanisms of a selective progesterone receptor modulator action in myomas. The aim of the study was to assess the effects of ulipristal acetate (UPA) on fibroids, especially on estrogen receptor (ER) and progesterone receptor (PR) immunoexpression, proliferation, apoptosis and tissue fibrosis, and to compare the above parameters in untreated (surgical attention only) and UPA-treated leiomyomas. UPA-treated patients were divided into three groups: (1) good response (≥25% reduction in volume of fibroid), (2) weak response (insignificant volume reduction) and (3) no response to treatment (no decrease or increase in fibroid volume). The study observed a significant decrease in the percentage of collagen volume fraction and ER and PR immunoexpression in the good response group, in the percentage of proliferating cell nuclear antigen (PCNA)- and Ki67-positive cells in the groups with good and weak reactions vs. control group; significantly higher apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells) in the good reaction group vs. control group. The results of the study indicate that a good response to UPA, manifested by a volume reduction of myoma, may be associated with a decrease in fibrosis, ER/PR and PCNA and Ki67 immunoexpression and an increase in cell apoptosis within the myoma.
Intrahematomal Ultrasound Enhances RtPA-Fibrinolysis in a Porcine Model of Intracerebral Hemorrhage
Authors: Masomi-Bornwasser Julia , Heimann Axel , Schneider Christian , Klodt Tristan , Elmehdawi Hammoud , Kronfeld Andrea , Krenzlin Harald , Tanyildizi Yasemin , Kreitner Karl-Friedrich , Kempski Oliver , Sommer Clemens , Ringel Florian , Keric Naureen
Published: February 2021

Catheter-based ultrasound-thrombolysis has been successfully used in a small clinical trial in order to enhance recombinant tissue plasminogen activator (rtPA)-fibrinolysis, for the treatment of spontaneous intracerebral hemorrhages (ICHs). The aim of this study was to investigate the ultra-early effects of ultrasound on hematoma and the surrounding brain tissue in a porcine ICH-model. To achieve this, 21 pigs with a right frontal ICH were randomly assigned to four groups: (1) drainage (n = 3), (2) drainage + rtPA (n = 6), (3) drainage + ultrasound (n = 6), and (4) drainage + ultrasound + rtPA (n = 6). The hematoma volume assessment was performed using cranial MRI before and after the treatments. Subsequently, the brain sections were analyzed using HE-staining and immunohistochemistry. The combined treatment using rtPA and ultrasound led to a significantly higher hematoma reduction (62 ± 5%) compared to the other groups (Group 1: 2 ± 1%; Group 2: 30 ± 12%; Group 3: 18 ± 8% (p < 0.0001)). In all groups, the MRI revealed an increase in diffusion restriction but neither hyper- or hypoperfusion, nor perihematomal edema. HE stains showed perihematomal microhemorrhages were equally distributed in each group, while edema was more pronounced within the control group. Immunohistochemistry did not reveal any ultra-early side effects. The combined therapy of drainage, rtPA and ultrasound is a safe and effective technique for hematoma-reduction and protection of the perihematomal tissue in regard to ultra-early effects.
Hemoadsorption during Cardiopulmonary Bypass in Patients with Endocarditis Undergoing Valve Surgery: A Retrospective Single-Center Study
Authors: Santer David , Miazza Jules , Koechlin Luca , Gahl Brigitta , Rrahmani Bejtush , Hollinger Alexa , Eckstein Friedrich S. , Siegemund Martin , Reuthebuch Oliver T.
Published: February 2021

Background: Aim of this study was to evaluate the outcomes of endocarditis patients undergoing valve surgery with the Cytosorb® hemoadsorption (HA) device during cardiopulmonary bypass. Methods: From 2009 until 2019, 241 patients had undergone valve surgery due to endocarditis at the Department of Cardiac Surgery, University Hospital of Basel. We compared patients who received HA during surgery (n = 41) versus patients without HA (n = 200), after applying inverse probability of treatment weighting. Results: In-hospital mortality, major adverse cardiac and cerebrovascular events and postoperative renal failure were similar in both groups. Demand for norepinephrine (88.4 vs. 52.8%; p = 0.001), milrinone (42.2 vs. 17.2%; p = 0.046), red blood cell concentrates (65.2 vs. 30.6%; p = 0.003), and platelets (HA vs. Control: 36.7 vs. 9.8%; p = 0.013) were higher in the HA group. In addition, a higher incidence of reoperation for bleeding (34.0 vs. 7.7 %; p = 0.011), and a prolonged length of in-hospital stay (15.2 (11.8 to 19.6) vs. 9.0 (7.1 to 11.3) days; p = 0.017) were observed in the HA group. Conclusions: No benefits of HA-therapy were observed in patients with infective endocarditis undergoing valve surgery.
The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies
Authors: Garcia-Sampedro Andres , Gaggia Gabriella , Ney Alexander , Mahamed Ismahan , Acedo Pilar
Published: February 2021

Pancreatic cancer is a devastating disease with very poor prognosis. Currently, surgery followed by adjuvant chemotherapy represents the only curative option which, unfortunately, is only available for a small group of patients. The majority of pancreatic cancer cases are diagnosed at advanced or metastatic stage when surgical resection is not possible and treatment options are limited. Thus, novel and more effective therapeutic strategies are urgently needed. Molecular profiling together with targeted therapies against key hallmarks of pancreatic cancer appear as a promising approach that could overcome the limitations of conventional chemo- and radio-therapy. In this review, we focus on the latest personalised and multimodal targeted therapies currently undergoing phase II or III clinical trials. We discuss the most promising findings of agents targeting surface receptors, angiogenesis, DNA damage and cell cycle arrest, key signalling pathways, immunotherapies, and the tumour microenvironment.
Enthesitis Related Arthritis in a Longitudinal Southeast Asian Registry: High Prevalence of HLA-B27, Different Sacroiliitis Risk Factors and Less Common Drug-Free Remission
Authors: Arkachaisri Thaschawee , Teh Kai Liang , Book Yun Xin , Hoh Sook Fun , Gao Xiaocong , Das Lena
Published: February 2021

Objective. To describe the clinical characteristics, predictors and treatment of children with Enthesitis Related Arthritis (ERA) in a Singapore longitudinal cohort over 11 years. Methods. ERA patients were recruited from our registry (2009–2019). Nonparametric descriptive statistics including median (interquartile range, IQR) were used to describe data. Kaplan–Meier survival and logistic/Cox regression analyses were used to estimate the probabilities and determine predictors of clinical variables, respectively. The significance level was set at <0.05. Results. One hundred and forty-six ERA patients (87% male, 82% Chinese) were included. Median onset age was 11.9 years (IQR 9.4–14.0) and median disease duration was 4.9 years (IQR 2.6–8.3). Family history of Human Leukocyte Antigen (HLA)-B27 associated diseases was positive in 7.5%. Acute uveitis occurred in 3.4%. Oligoarthritis was present in 89.7%. Hip, knee and ankle joints were among the most common joints involved. One-fourth had enthesitis at diagnosis (Achilles tendon entheses, 82.9%). Sacroiliitis occurred in 61%. Probabilities of sacroiliitis development were 0.364, 0.448 and 0.578 at 1, 2 and 5 years after onset, respectively. Negative HLA-B27, female, older age at onset and hip arthritis at diagnosis were associated with shorter time for sacroiliitis development (p = 0.001–0.049). Methotrexate (MTX) remained the most common disease modifying anti-rheumatic drug (DMARD) used (77.4%). However, 77.9% required anti-TNF (aTNF) therapy secondary to MTX failure. Among MTX-treated sacroiliitis patients, 85.3% failed, requiring aTNF, as compared to 63.2%patients without axial disease. Longer duration to diagnosis (p = 0.038) and MTX use (p = 0.007) predicted aTNF therapy. None had joint deformity. Conclusions. This study underscores differences in ERA clinical characteristics, predictors and treatment responses. Our ERA population had many unique findings but good functional outcomes.
Recurrent Gestational Diabetes Mellitus: A Narrative Review and Single-Center Experience
Authors: Egan Aoife M. , Enninga Elizabeth Ann L. , Alrahmani Layan , Weaver Amy L. , Sarras Michael P. , Ruano Rodrigo
Published: February 2021

Gestational diabetes mellitus (GDM) is a frequently observed complication of pregnancy and is associated with an elevated risk of adverse maternal and neonatal outcomes. Many women with GDM will go on to have future pregnancies, and these pregnancies may or may not be affected by GDM. We conducted a literature search, and based on data from key studies retrieved during the search, we describe the epidemiology of GDM recurrence. This includes a summary of the observed clinical risk factors of increasing maternal age, weight, ethnicity, and requirement for insulin in the index pregnancy. We then present our data from Mayo Clinic (January 2013–December 2017) which identifies a GDM recurrence rate of 47.6%, and illustrates the relevance of population-based studies to clinical practice. Lastly, we examine the available evidence on strategies to prevent GDM recurrence, and note that more research is needed to evaluate the effect of interventions before, during and after pregnancy.
Loss of Smell and Taste Can Accurately Predict COVID-19 Infection: A Machine-Learning Approach
Authors: Callejon-Leblic María A , Moreno-Luna Ramon , Del Cuvillo Alfonso , Reyes-Tejero Isabel M , Garcia-Villaran Miguel A , Santos-Peña Marta , Maza-Solano Juan M , Martín-Jimenez Daniel I , Palacios-Garcia Jose M , Fernandez-Velez Carlos , Gonzalez-Garcia Jaime , Sanchez-Calvo Juan M , Solanellas-Soler Juan , Sanchez-Gomez Serafin
Published: February 2021

The COVID-19 outbreak has spread extensively around the world. Loss of smell and taste have emerged as main predictors for COVID-19. The objective of our study is to develop a comprehensive machine learning (ML) modelling framework to assess the predictive value of smell and taste disorders, along with other symptoms, in COVID-19 infection. A multicenter case-control study was performed, in which suspected cases for COVID-19, who were tested by real-time reverse-transcription polymerase chain reaction (RT-PCR), informed about the presence and severity of their symptoms using visual analog scales (VAS). ML algorithms were applied to the collected data to predict a COVID-19 diagnosis using a 50-fold cross-validation scheme by randomly splitting the patients in training (75%) and testing datasets (25%). A total of 777 patients were included. Loss of smell and taste were found to be the symptoms with higher odds ratios of 6.21 and 2.42 for COVID-19 positivity. The ML algorithms applied reached an average accuracy of 80%, a sensitivity of 82%, and a specificity of 78% when using VAS to predict a COVID-19 diagnosis. This study concludes that smell and taste disorders are accurate predictors, with ML algorithms constituting helpful tools for COVID-19 diagnostic prediction.
Effectiveness and Safety of SGLT2 Inhibitors in Clinical Routine Treatment of Patients with Diabetes Mellitus Type 2
Authors: Hopf Maximilian , Kloos Christof , Wolf Gunter , Müller Ulrich Alfons , Müller Nicolle
Published: February 2021

The aim of this study was to investigate the effectiveness of SGLT2 inhibitors with regard to metabolic parameters and patient safety under routine ambulatory conditions. Retrospective longitudinal study of 95 patients with type 2 diabetes (diabetes duration 13.3 y; HbA1c 8.9%; eGFR 80.1 mL/min) receiving SGLT-2-inhibitors. Metabolic control and adverse event profile were evaluated. The mean follow-up time was 1.2 ± 0.8 years. The following changes were observed: HbA1c −1.0% ± 1.9 (p < 0.001), eGFR −7.0 mL/min ± 13.3 (p < 0.001), albuminuria −23.9 mg/g creatinine ± 144.5 (p = 0.118), bodyweight −3.0 kg ± 5.8 (p < 0.001), systolic blood pressure −6 mmHg ± 22 (p = 0.01), diastolic blood pressure −2 mmHg ± 14 (p = 0.243). 53 participants continuously applied the therapy. Twenty-eight participants discontinued SGLT-2-inhibitors due to various reasons: 20 participants because of genital- or urinary tract infections. One for dysuria, seven due to reduced eGFR below 45 mL/min. This study showed a considerable reduction of HbA1c and a modest reduction of eGFR, bodyweight and systolic blood pressure under clinical routine conditions. Genital infections occurred markedly more often than in randomized controlled trials. To apply SGLT-2-inhibitors more safely in clinical routine individual risks for genital and urinary tract infections should be considered and re-evaluated during therapy.
Clinical Significance of Velamentous Cord Insertion Prenatally Diagnosed in Twin Pregnancy
Authors: Lee Hyun-Mi , Lee SiWon , Park Min-Kyung , Han You Jung , Kim Moon Young , Boo Hye Yeon , Chung Jin Hoon
Published: February 2021

Background: The purpose of this study was to evaluate the prevalence of velamentous cord insertion (VCI) and the actual association between pathologically confirmed VCI and perinatal outcomes in twins based on the chorionicity. Methods: All twin pregnancies that received prenatal care at a specialty clinic for multiple pregnancies, from less than 12 weeks of gestation until delivery in a single institution between 2015 and 2018 were included in this retrospective cohort study. Results: A total of 941 twins were included in the study. The prevalence of VCI in dichorionic (DC) twins and monochorionic diamniotic (MCDA) twins was 5.8% and 7.8%, respectively (p = 0.251). In all study population, the prevalence of vasa previa and placenta accreta spectrum was higher in VCI group than that of non-VCI group (p = 0.008 and 0.022). In MCDA twins with VCI, birth weight, 1 and 5-min Apgar score were lower than DC twins with VCI (p = 0.010, 0.002 and 0.000). There was no significant association between VCI and selective fetal growth restriction (p = 0.486), twin-to-twin transfusion syndrome (p = 0.400), and birth-weight discordance (>20% and >25%) (p = 0.378 and 0.161) in MCDA twins. Conclusion: There was no difference in the incidence of VCI in twins based on the chorionicity. Moreover, VCI was not a risk factor for adverse perinatal outcomes excepting vasa previa and placenta accreta spectrum, which had a high incidence in twins with VCI.
Early Cortisol and Inflammatory Responses to Parental Cancer and Their Impact on Functional Impairment in Youth
Authors: Hayes Benjamin , Brent Jacob , Zhong Yongqi , Bazmi Shervin , Porta Giovanna , Bovbjerg Dana H. , Tarhini Ahmad , Kirkwood John M. , Brent David A. , Marsland Anna , Melhem Nadine M.
Published: February 2021

Purpose: Chronic stress is associated with increased risk for maladaptive psychological responses during childhood, adolescence, and young adulthood. Adults exposed to chronic stress during childhood exhibit dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity and inflammation. There are no studies examining the impact of stress on biological stress responses and functional impairment in adolescents and young adults early after the onset of a stressor. Methods: The sample consisted of 59 offspring, aged 11–25 years, 33 of parents diagnosed with cancer and 26 controls from families with no cancer or severe chronic illness in parents or siblings. Cancer patients and their families were recruited within an average of 62 days (SD = 35.9) and followed at 6 and 9 months later. Functional impairment was assessed and hair cortisol concentrations (HCC), salivary cortisol, and inflammatory markers were measured. Mixed regression analyses were conducted. Results: The stress group showed higher functional impairment (β = −5.5, 95% CI (−10.4, −0.06), p = 0.03, d= −0.40) and HCC (β = 10.5, 95% CI (−5.5, −0.50), p < 0.001, d = 1.43). However, HCC were reduced over time in the stress group (β= −0.3, 95% CI (−0.04, −0.01), p < 0.001, d = −1.08). Higher total cortisol output was associated with increased functional impairment over time (β = −3.0, 95% CI (−5.5, −0.5), p = 0.02, d = −0.60). Conclusions: Parental cancer is associated with early increase in cortisol, which was associated with increased functional impairment in offspring. Clinicians need to assess and monitor psychiatric symptoms and functioning in these offspring early on following parental cancer diagnosis.
Cardiac Filaminopathies: Illuminating the Divergent Role of Filamin C Mutations in Human Cardiomyopathy
Authors: Eden Matthias , Frey Norbert
Published: February 2021

Over the past decades, there has been tremendous progress in understanding genetic alterations that can result in different phenotypes of human cardiomyopathies. More than a thousand mutations in various genes have been identified, indicating that distinct genetic alterations, or combinations of genetic alterations, can cause either hypertrophic (HCM), dilated (DCM), restrictive (RCM), or arrhythmogenic cardiomyopathies (ARVC). Translation of these results from “bench to bedside” can potentially group affected patients according to their molecular etiology and identify subclinical individuals at high risk for developing cardiomyopathy or patients with overt phenotypes at high risk for cardiac deterioration or sudden cardiac death. These advances provide not only mechanistic insights into the earliest manifestations of cardiomyopathy, but such efforts also hold the promise that mutation-specific pathophysiology might result in novel “personalized” therapeutic possibilities. Recently, the FLNC gene encoding the sarcomeric protein filamin C has gained special interest since FLNC mutations were found in several distinct and possibly overlapping cardiomyopathy phenotypes. Specifically, mutations in FLNC were initially only linked to myofibrillar myopathy (MFM), but are now increasingly found in various forms of human cardiomyopathy. FLNC thereby represents another example for the complex genetic and phenotypic continuum of these diseases.
Predicting Factors Influencing Visual Function of the Eye in Patients with Unresolved Facial Nerve Palsy after Upper Eyelid Gold Weight Loading
Authors: Nowak-Gospodarowicz Izabela , Rękas Marek
Published: February 2021

Implantation of gold weights into the upper eyelid is a proven method of treating lagophthalmos and exposure keratopathy in patients with unresolved facial nerve palsy. The aim of this study was to evaluate the factors affecting visual acuity and corneal complications in patients after upper eyelid gold weight lid loading. Material and methods: This prospective consecutive clinical study was conducted in years 2012–2018. In total, 59 people (40 women, 19 men aged 55.5 ± 17.4 years) meeting the inclusion criteria were treated with gold weights. The ordered multinomial logit model was used to analyze the factors affecting best-corrected visual acuity (BCVA) and degree of exposure keratopathy after surgery. The influence of the following variables was analyzed: patient age, etiology and duration of the facial nerve palsy, history of the previous eyelid surgery, degree of lagophthalmos in mm, presence of Bell’s phenomenon, and corneal sensation, Schirmer test results. Results: Implantation of gold weights into the upper eyelid effectively reduced lagophthalmos and exposure keratopathy in the study group (p < 0.001). BCVA was maintained or better in 95% of patients after surgery. Patient age, presence of the Bell’s phenomenon, and corneal sensation significantly affected the final BCVA (p < 0.1). The presence of Bell’s phenomenon and corneal sensation had a positive effect on the degree of keratopathy after surgery (p < 0.1). In turn, patient age and history of tarsorrhaphy were significant negative prognostic factors of exposure keratopathy and BCVA after surgery (p < 0.05). Etiology and duration of facial nerve palsy, degree of corneal exposure in mm, and results of the Schirmer test did not have a significant impact on the outcome after surgery (p > 0.1). Conclusions: The results of our study may help to answer the question of how to direct ophthalmologists and other specialists who refer to ophthalmologists for management advice in patients with facial nerve palsy. Elderly patients with a history of tarsorrhaphy who present with poor Bell’s phenomenon and/or a lack of corneal sensation should be the first candidates for immediate correction of lagophthalmos.
The Benefits of Physical Activity in Individuals with Cardiovascular Risk Factors: A Longitudinal Investigation Using fNIRS and Dual-Task Walking
Authors: Talamonti Deborah , Vincent Thomas , Fraser Sarah , Nigam Anil , Lesage Frédéric , Bherer Louis
Published: February 2021

Cardiovascular fitness is linked to better executive functions, preserved gait speed, and efficient cortical activity. Older adults with cardiovascular risk factors (CVRFs) typically show poor cognitive performance, low physical fitness, and altered brain functioning compared with healthy individuals. In the current study, the impact of regular physical activity on cognition, locomotion, and brain functions was explored in a cohort of older adults with low or high CVRFs. Cortical activation of the frontal areas was investigated using functional Near-Infrared Spectroscopy (fNIRS) at baseline, at 6 months and at 12 months. Evoked cortical response and behavioral performance were assessed using the dual-task walking paradigm, consisting of three conditions: single cognitive task (2-back task), single walking task (walking), and dual-task (2-back whilst walking). Results show greater task-related cortical response at baseline in individuals with high CVRFs compared to those with low CVRFs. Moreover, participants with high CVRFs benefitted the most from participating in regular physical activity, as their cortical response decreased at the 12-month follow-up and became comparable to that of participants with low CVRFs. These changes were observed in conjunction with improved cognitive performance and stable gait speed throughout the 12-month period in both groups. Our findings provide evidence that participation in regular physical activity may be especially beneficial in individuals with CVRFs by promoting brain and cognitive health, thus potentially contributing to prevention of cognitive decline. Future research may explore whether such effects are maintained in the long-term in order to design ad-hoc interventions in this specific population.