bluuebunny/crossref_metadata_2025 huggingface dataset:
Shaping the Future of Rare Diseases after a Global Health Emergency: Organisational Points to Consider
Authors: Talarico Rosaria , Marinello Diana , Cannizzo Sara , Gaglioti Andrea , Ticciati Simone , Carta Claudio , Kodra Yllka , Azadegan Mojgan , Taruscio Domenica , Mosca Marta , Turchetti Giuseppe
Published: November 2020

The unexpected outbreak of the COVID-19 disease had significant and enormous repercussions on the healthcare systems, such as the need to reorganise healthcare organisations in order to concentrate resources needed to the care of COVID-19 patients and to respond in general to this health emergency. Due to these challenges, the care of several chronic conditions was in many cases discontinued and patients and healthcare professionals treating these conditions had to cope with this new scenario. This was the case of the world rare diseases (RDs) that had to face this global emergency despite the vulnerability of people with RDs and the well-known need for high expertise required to treat and manage them. The numerous lessons learned so far regarding health emergencies and RDs should represent the basis for the establishment of new healthcare policies and plans aimed at ensuring the preparedness of our health systems in providing appropriate care to people living with RDs in the case of eventual new emergencies. This paper aims at providing pragmatic considerations that might be useful in designing future actions to create or optimise existing organisational models for the care of RDs in case of future emergencies or any other situation that might threaten the provision of routine care. These policies and plans should benefit from the multi-stakeholder RDs networks (such as the European Reference Networks), that should join forces at European, national, and local levels to minimise the economic, organisational, and health-related impact and the negative effects of potential emergencies on the RDs community. In order to design and develop these policies and plans, a decalogue of points to consider were developed to ensure appropriate care for people living with RDs in the case of eventual future health emergencies.
Low Tongue Strength and the Number of Teeth Present Are Associated with Cognitive Decline in Older Japanese Dental Outpatients: A Cross-Sectional Study
Authors: Egashira Rui , Mizutani Shinsuke , Yamaguchi Masahiro , Kato Tomotaka , Umezaki Yojiro , Oku Saori , Tamai Keiko , Obata Toyoshi , Naito Toru
Published: November 2020

To mitigate the impact of dementia, initiating early intervention is important. This study aims to investigate the associations between deterioration in oral function and cognitive decline in older outpatients whose oral health was maintained in the dental clinic. This study included 50 outpatients aged ≥65 years. We used the Japanese version of the Montreal Cognitive Assessment (MoCA-J) to assess cognitive decline. Oral function was evaluated by tongue pressure, masticatory performance, and swallowing ability. A full-mouth periodontal examination was conducted, and the occlusal support and number of teeth were recorded. Odds ratios (ORs) and 95% confidence intervals (CIs) for cognitive decline (MoCA-J score ≤25 points) were calculated using logistic regression models. The age, number of teeth, tongue pressure, and masticatory performance were significantly correlated with cognitive decline (p < 0.05). Logistic regression analyses revealed that cognitive decline was independently associated with age (OR: 1.25; 95% CI: 1.03–1.52; p = 0.024), number of teeth (OR = 0.83; 95% CI: 0.76–1.00; p = 0.047), and lower tongue pressure (OR: 0.87; 95% CI: 0.77–0.98; p = 0.022). Lower tongue pressure and a small number of remaining teeth may be associated with cognitive decline in Japanese outpatients.
The Spatial Correlations of Health Resource Agglomeration Capacities and Their Influencing Factors: Evidence from China
Authors: Guo Qingbin , Luo Kang , Hu Ruodi
Published: November 2020

We measured the health resource agglomeration capacities of 31 Chinese provinces (or municipalities) in 2004–2018 based on the entropy weight method. Using a modified spatial gravity model, we constructed and analyzed the spatial correlation network of these health resource agglomeration capacities and their influencing factors through social network analysis. We found that: (i) China’s health resource agglomeration capacity had a gradual strengthening trend, with capacity weakening from east to west (strongest in the eastern region, second strongest in the central region, and weakest in the western region). (ii) The spatial network of such capacities became more densely connected, and the network density and level (efficiency) showed an upward (downward) trend. (iii) In terms of centrality, the high-ranking provinces (or municipalities) were Beijing, Shanghai, Jiangsu, Zhejiang, Guangdong, Shandong, Hunan, Hubei, Fujian, Anhui, Jiangxi, and Tianjin, while the low-ranking were Tibet, Qinghai, Gansu, Ningxia, Inner Mongolia, Heilongjiang, Yunnan, Guizhou, Xinjiang, Hainan, Shaanxi, and Shanxi. (iv) Block 1 (eight provinces or municipalities), including Beijing, Tianjin, and Hebei, had a “net spillover” effect in the spatial network of health resource agglomeration capacities; Block 2, (seven provinces or municipalities), including Shanghai, Jiangsu, and Zhejiang, had a “bidirectional spillover” effect in the spatial network; Block 3 (seven provinces or municipalities), including Anhui, Hubei, and Hunan, had a “mediator” effect in the network; and Block 4, (nine provinces or municipalities), including Sichuan, Guizhou, and Tibet, had a “net beneficial” effect in the network. (v) The economic development, urbanization wage, and financial health expenditure levels, and population size had significant positive correlations with the spatial network of health resource agglomeration capacities. Policy recommendations to enhance the radiating role of health resources in core provinces (or municipalities), rationally allocate health resources, and transform ideas to support public health resource services were provided.
Immune-Modulating Drug MP1032 with SARS-CoV-2 Antiviral Activity In Vitro: A potential Multi-Target Approach for Prevention and Early Intervention Treatment of COVID-19
Authors: Schumann Sara , Kaiser Astrid , Nicoletti Ferdinando , Mangano Katia , Fagone Paolo , van Wijk Eduard , Yan Yu , Schulz Petra , Ludescher Beate , Niedermaier Michael , von Wegerer Joerg , Rauch Pia , Setz Christian , Schubert Ulrich , Brysch Wolfgang
Published: November 2020

At least since March 2020, the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic and the multi-organ coronavirus disease 2019 (COVID-19) are keeping a firm grip on the world. Although most cases are mild, older patients and those with co-morbidities are at increased risk of developing a cytokine storm, characterized by a systemic inflammatory response leading to acute respiratory distress syndrome and organ failure. The present paper focuses on the small molecule MP1032, describes its mode of action, and gives rationale why it is a promising option for the prevention/treatment of the SARS-CoV-2-induced cytokine storm. MP1032 is a phase-pure anhydrous polymorph of 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt that exhibits good stability and bioavailability. The physiological action of MP1032 is based on a multi-target mechanism including localized, self-limiting reactive oxygen species (ROS) scavenging activities that were demonstrated in a model of lipopolysaccharide (LPS)-induced joint inflammation. Furthermore, its immune-regulatory and PARP-1-modulating properties, coupled with antiviral effects against SARS-CoV-2, have been demonstrated in various cell models. Preclinical efficacy was elucidated in LPS-induced endotoxemia, a model with heightened innate immune responses that shares many similarities to COVID-19. So far, during oral clinical development with three-month daily administrations, no serious adverse drug reactions occurred, highlighting the outstanding safety profile of MP1032.
Beyond Haemostasis and Thrombosis: Platelets in Depression and Its Co-Morbidities
Authors: Izzi Benedetta , Tirozzi Alfonsina , Cerletti Chiara , Donati Maria Benedetta , de Gaetano Giovanni , Hoylaerts Marc F. , Iacoviello Licia , Gialluisi Alessandro
Published: November 2020

Alongside their function in primary haemostasis and thrombo-inflammation, platelets are increasingly considered a bridge between mental, immunological and coagulation-related disorders. This review focuses on the link between platelets and the pathophysiology of major depressive disorder (MDD) and its most frequent comorbidities. Platelet- and neuron-shared proteins involved in MDD are functionally described. Platelet-related studies performed in the context of MDD, cardiovascular disease, and major neurodegenerative, neuropsychiatric and neurodevelopmental disorders are transversally presented from an epidemiological, genetic and functional point of view. To provide a complete scenario, we report the analysis of original data on the epidemiological link between platelets and depression symptoms suggesting moderating and interactive effects of sex on this association. Epidemiological and genetic studies discussed suggest that blood platelets might also be relevant biomarkers of MDD prediction and occurrence in the context of MDD comorbidities. Finally, this review has the ambition to formulate some directives and perspectives for future research on this topic.
Extracellular Vesicles, Influential Players of Intercellular Communication within Adult Neurogenic Niches
Authors: Losurdo Morris , Grilli Mariagrazia
Published: November 2020

Adult neurogenesis, involving the generation of functional neurons from adult neural stem cells (NSCs), occurs constitutively in discrete brain regions such as hippocampus, sub-ventricular zone (SVZ) and hypothalamus. The intrinsic structural plasticity of the neurogenic process allows the adult brain to face the continuously changing external and internal environment and requires coordinated interplay between all cell types within the specialized microenvironment of the neurogenic niche. NSC-, neuronal- and glia-derived factors, originating locally, regulate the balance between quiescence and self-renewal of NSC, their differentiation programs and the survival and integration of newborn cells. Extracellular Vesicles (EVs) are emerging as important mediators of cell-to-cell communication, representing an efficient way to transfer the biologically active cargos (nucleic acids, proteins, lipids) by which they modulate the function of the recipient cells. Current knowledge of the physiological role of EVs within adult neurogenic niches is rather limited. In this review, we will summarize and discuss EV-based cross-talk within adult neurogenic niches and postulate how EVs might play a critical role in the regulation of the neurogenic process.
Mechanistic Insights into the Allosteric Regulation of the Clr4 Protein Lysine Methyltransferase by Autoinhibition and Automethylation
Authors: Khella Mina S. , Bröhm Alexander , Weirich Sara , Jeltsch Albert
Published: November 2020

Clr4 is a histone H3 lysine 9 methyltransferase in Schizosaccharomyces pombe that is essential for heterochromatin formation. Previous biochemical and structural studies have shown that Clr4 is in an autoinhibited state in which an autoregulatory loop (ARL) blocks the active site. Automethylation of lysine residues in the ARL relieves autoinhibition. To investigate the mechanism of Clr4 regulation by autoinhibition and automethylation, we exchanged residues in the ARL by site-directed mutagenesis leading to stimulation or inhibition of automethylation and corresponding changes in Clr4 catalytic activity. Furthermore, we demonstrate that Clr4 prefers monomethylated (H3K9me1) over unmodified (H3K9me0) histone peptide substrates, similar to related human enzymes and, accordingly, H3K9me1 is more efficient in overcoming autoinhibition. Due to enzyme activation by automethylation, we observed a sigmoidal dependence of Clr4 activity on the AdoMet concentration, with stimulation at high AdoMet levels. In contrast, an automethylation-deficient mutant showed a hyperbolic Michaelis–Menten type relationship. These data suggest that automethylation of the ARL could act as a sensor for AdoMet levels in cells and regulate the generation and maintenance of heterochromatin accordingly. This process could connect epigenome modifications with the metabolic state of cells. As other human protein lysine methyltransferases (for example, PRC2) also use automethylation/autoinhibition mechanisms, our results may provide a model to describe their regulation as well.
Morphologic and Molecular Landscape of Pancreatic Cancer Variants as the Basis of New Therapeutic Strategies for Precision Oncology
Authors: Bazzichetto Chiara , Luchini Claudio , Conciatori Fabiana , Vaccaro Vanja , Di Cello Ilaria , Mattiolo Paola , Falcone Italia , Ferretti Gianluigi , Scarpa Aldo , Cognetti Francesco , Milella Michele
Published: November 2020

To date, pancreatic cancer is still one of the most lethal cancers in the world, mainly due to the lack of early diagnosis and personalized treatment strategies. In this context, the possibility and the opportunity of identifying genetic and molecular biomarkers are crucial to improve the feasibility of precision medicine. In 2019, the World Health Organization classified pancreatic ductal adenocarcinoma cancer (the most common pancreatic tumor type) into eight variants, according to specific histomorphological features. They are: colloid carcinoma, medullary carcinoma, adenosquamous carcinoma, undifferentiated carcinoma, including also rhabdoid carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, hepatoid carcinoma, and signet-ring/poorly cohesive cells carcinoma. Interestingly, despite the very low incidence of these variants, innovative high throughput genomic/transcriptomic techniques allowed the investigation of both somatic and germline mutations in each specific variant, paving the way for their possible classification according also to specific alterations, along with the canonical mutations of pancreatic cancer (KRAS, TP53, CDKN2A, SMAD4). In this review, we aim to report the current evidence about genetic/molecular profiles of pancreatic cancer variants, highlighting their role in therapeutic and clinical impact.
Curcumin-Loaded Nanoparticles Based on Amphiphilic Hyaluronan-Conjugate Explored as Targeting Delivery System for Neurodegenerative Disorders
Authors: Pepe Giuseppe , Calce Enrica , Verdoliva Valentina , Saviano Michele , Maglione Vittorio , Di Pardo Alba , De Luca Stefania
Published: November 2020

Identification of molecules able to promote neuroprotective mechanisms can represent a promising therapeutic approach to neurodegenerative disorders including Huntington’s disease. Curcumin is an antioxidant and neuroprotective agent, even though its efficacy is limited by its poor absorption, rapid metabolism, systemic elimination, and limited blood–brain barrier (BBB) permeability. Herein, we report on novel biodegradable curcumin-containing nanoparticles to favor the compound delivery and potentially enhance its brain bioavailability. The prepared hyaluronan-based materials able to self-assemble in stable spherical nanoparticles, consist of natural fatty acids chemically conjugated to the natural polysaccharide. The aim of this study is to provide a possible effective delivery system for curcumin with the expectation that, after having released the drug at the specific site, the biopolymer can degrade to nontoxic fragments before renal excretion, since all the starting materials are provided by natural resource. Our findings demonstrate that curcumin-encapsulated nanoparticles enter the cells and reduce their susceptibility to apoptosis in an in vitro model of Huntington’s disease.
Effect of Acute Sprint Exercise on Myokines and Food Intake Hormones in Young Healthy Men
Authors: Bilski Jan , Mazur-Bialy Agnieszka Irena , Surmiak Marcin , Hubalewska-Mazgaj Magdalena , Pokorski Janusz , Nitecki Jacek , Nitecka Ewa , Pokorska Joanna , Targosz Aneta , Ptak-Belowska Agata , A. Zoladz Jerzy , Brzozowski Tomasz
Published: November 2020

Physical exercise is known to influence hormonal mediators of appetite, but the effect of short-term maximal intensity exercise on plasma levels of appetite hormones and cytokines has been little studied. We investigated the effect of a 30 s Wingate Test, followed by a postprandial period, on appetite sensations, food intake, and appetite hormones. Twenty-six physically active young males rated their subjective feelings of hunger, prospective food consumption, and fatigue on visual analogue scales at baseline, after exercise was completed, and during the postprandial period. Blood samples were obtained for the measurement of nesfatin-1, ghrelin, leptin, insulin, pancreatic polypeptide (PP), human growth factor (hGH) and cytokine interleukin-6 (IL-6), irisin and plasma lactate concentrations, at 30 min before exercise, immediately (210 s) after exercise, and 30 min following a meal and at corresponding times in control sedentary males without ad libitum meal intake, respectively. Appetite perceptions and food intake were decreased in response to exercise. Plasma levels of irisin, IL-6, lactate, nesfatin-1 and ghrelin was increased after exercise and then it was returned to postprandial/control period in both groups. A significant rise in plasma insulin, hGH and PP levels after exercise was observed while meal intake potentiated this response. In conclusion, an acute short-term fatiguing exercise can transiently suppress hunger sensations and food intake in humans. We postulate that this physiological response involves exercise-induced alterations in plasma hormones and the release of myokines such as irisin and IL-6, and supports the notion of existence of the skeletal muscle–brain–gut axis. Nevertheless, the detailed relationship between acute exercise releasing myokines, appetite sensations and impairment of this axis leading to several diseases should be further examined.
Correction: Shi, H., et al. Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling. Int. J. Mol. Sci. 2020, 21, 6357
Authors: Shi Hui , Zhao Luping , Guo Xinlin , Fang Runping , Zhang Hui , Dong Guanjun , Fu Jia , Yan Fenglian , Zhang Junfeng , Ning Zhaochen , Ma Qun , Li Zhihua , Li Chunxia , Dai Jun , Si Chuanping , Xiong Huabao
Published: November 2020

The authors wish to make the following correction to this paper [...]
The Body’s Cellular and Molecular Response to Protein-Coated Medical Device Implants: A Review Focused on Fibronectin and BMP Proteins
Authors: Chen Yi-Fan , Goodheart Clyde , Rua Diego
Published: November 2020

Recent years have seen a marked rise in implantation into the body of a great variety of devices: hip, knee, and shoulder replacements, pacemakers, meshes, glucose sensors, and many others. Cochlear and retinal implants are being developed to restore hearing and sight. After surgery to implant a device, adjacent cells interact with the implant and release molecular signals that result in attraction, infiltration of the tissue, and attachment to the implant of various cell types including monocytes, macrophages, and platelets. These cells release additional signaling molecules (chemokines and cytokines) that recruit tissue repair cells to the device site. Some implants fail and require additional revision surgery that is traumatic for the patient and expensive for the payer. This review examines the literature for evidence to support the possibility that fibronectins and BMPs could be coated on the implants as part of the manufacturing process so that the proteins could be released into the tissue surrounding the implant and improve the rate of successful implantation.
Deciphering the Immunological Phenomenon of Adaptive Natural Killer (NK) Cells and Cytomegalovirus (CMV)
Authors: Barnes Samantha , Schilizzi Ophelia , Audsley Katherine M. , Newnes Hannah V. , Foley Bree
Published: November 2020

Natural killer (NK) cells play a significant and vital role in the first line of defense against infection through their ability to target cells without prior sensitization. They also contribute significantly to the activation and recruitment of both innate and adaptive immune cells through the production of a range of cytokines and chemokines. In the context of cytomegalovirus (CMV) infection, NK cells and CMV have co-evolved side by side to employ several mechanisms to evade one another. However, during this co-evolution the discovery of a subset of long-lived NK cells with enhanced effector potential, increased antibody-dependent responses and the potential to mediate immune memory has revolutionized the field of NK cell biology. The ability of a virus to imprint on the NK cell receptor repertoire resulting in the expansion of diverse, highly functional NK cells to this day remains a significant immunological phenomenon that only occurs in the context of CMV. Here we review our current understanding of the development of these NK cells, commonly referred to as adaptive NK cells and their current role in transplantation, infection, vaccination and cancer immunotherapy to decipher the complex role of CMV in dictating NK cell functional fate.
Wild Soybean Oxalyl-CoA Synthetase Degrades Oxalate and Affects the Tolerance to Cadmium and Aluminum Stresses
Authors: Xian Peiqi , Cai Zhandong , Cheng Yanbo , Lin Rongbin , Lian Tengxiang , Ma Qibin , Nian Hai
Published: November 2020

Acyl activating enzyme 3 (AAE3) was identified as being involved in the acetylation pathway of oxalate degradation, which regulates the responses to biotic and abiotic stresses in various higher plants. Here, we investigated the role of Glycine sojaAAE3 (GsAAE3) in Cadmium (Cd) and Aluminum (Al) tolerances. The recombinant GsAAE3 protein showed high activity toward oxalate, with a Km of 105.10 ± 12.30 μM and Vmax of 12.64 ± 0.34 μmol min−1 mg−1 protein, suggesting that it functions as an oxalyl–CoA synthetase. The expression of a GsAAE3–green fluorescent protein (GFP) fusion protein in tobacco leaves did not reveal a specific subcellular localization pattern of GsAAE3. An analysis of the GsAAE3 expression pattern revealed an increase in GsAAE3 expression in response to Cd and Al stresses, and it is mainly expressed in root tips. Furthermore, oxalate accumulation induced by Cd and Al contributes to the inhibition of root growth in wild soybean. Importantly, GsAAE3 overexpression increases Cd and Al tolerances in A. thaliana and soybean hairy roots, which is associated with a decrease in oxalate accumulation. Taken together, our data provide evidence that the GsAAE3-encoded protein plays an important role in coping with Cd and Al stresses.
Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action
Authors: Mlost Jakub , Bryk Marta , Starowicz Katarzyna
Published: November 2020

Cannabis has a long history of medical use. Although there are many cannabinoids present in cannabis, Δ9tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the two components found in the highest concentrations. CBD itself does not produce typical behavioral cannabimimetic effects and was thought not to be responsible for psychotropic effects of cannabis. Numerous anecdotal findings testify to the therapeutic effects of CBD, which in some cases were further supported by research findings. However, data regarding CBD’s mechanism of action and therapeutic potential are abundant and omnifarious. Therefore, we review the basic research regarding molecular mechanism of CBD’s action with particular focus on its analgesic potential. Moreover, this article describes the detailed analgesic and anti-inflammatory effects of CBD in various models, including neuropathic pain, inflammatory pain, osteoarthritis and others. The dose and route of the administration-dependent effect of CBD, on the reduction in pain, hyperalgesia or allodynia, as well as the production of pro and anti-inflammatory cytokines, were described depending on the disease model. The clinical applications of CBD-containing drugs are also mentioned. The data presented herein unravel what is known about CBD’s pharmacodynamics and analgesic effects to provide the reader with current state-of-art knowledge regarding CBD’s action and future perspectives for research.
Access Control in NB-IoT Networks: A Deep Reinforcement Learning Strategy
Authors: Hadjadj-Aoul Yassine , Ait-Chellouche Soraya
Published: November 2020

The Internet of Things (IoT) is a key enabler of the digital mutation of our society. Driven by various services and applications, Machine Type Communications (MTC) will become an integral part of our daily life, over the next few years. Meeting the ITU-T requirements, in terms of density, battery longevity, coverage, price, and supported mechanisms and functionalities, Cellular IoT, and particularly Narrowband-IoT (NB-IoT), is identified as a promising candidate to handle massive MTC accesses. However, this massive connectivity would pose a huge challenge for network operators in terms of scalability. Indeed, the connection to the network in cellular IoT passes through a random access procedure and a high concentration of IoT devices would, very quickly, lead to a bottleneck. The latter procedure needs, then, to be enhanced as the connectivity would be considerable. With this in mind, we propose, in this paper, to apply the access class barring (ACB) mechanism to regulate the number of devices competing for the access. In order to derive the blocking factor, we formulated the access problem as a Markov decision process that we were able to solve using one of the most advanced deep reinforcement learning techniques. The evaluation of the proposed access control, through simulations, shows the effectiveness of our approach compared to existing approaches such as the adaptive one and the Proportional Integral Derivative (PID) controller. Indeed, it manages to keep the proportion of access attempts close to the optimum, despite the lack of accurate information on the number of access attempts.
Can Generalist Predators Control Bemisia tabaci?
Authors: Kheirodin Arash , Simmons Alvin M. , Legaspi Jesusa C. , Grabarczyk Erin E. , Toews Michael D. , Roberts Phillip M. , Chong Juang-Horng , Snyder William E. , Schmidt Jason M.
Published: November 2020

The whitefly, Bemisia tabaci, has developed resistance to many insecticides, renewing interest in the biological control of this global pest. Generalist predators might contribute to whitefly suppression if they commonly occur in infested fields and generally complement rather than interfere with specialized natural enemies. Here, we review literature from the last 20 years, across US cropping systems, which considers the impacts of generalist predators on B. tabaci. Laboratory feeding trials and molecular gut content analysis suggest that at least 30 different generalist predator species willingly and/or regularly feed on these whiteflies. Nine of these predators appear to be particularly impactful, and a higher abundance of a few of these predator species has been shown to correlate with greater B. tabaci predation in the field. Predator species often occupy complementary feeding niches, which would be expected to strengthen biocontrol, although intraguild predation is also common and might be disruptive. Overall, our review suggests that a bio-diverse community of generalist predators commonly attacks B. tabaci, with the potential to exert substantial control in the field. The key challenge will be to develop reduced-spray plans so that generalist predators, and other more specialized natural enemies, are abundant enough that their biocontrol potential is realized.
History of the Biodiversity of Ladybirds (Coccinellidae) at the Black Sea Coast of the Russian Caucasus in the Last 120 Years—Does the Landscape Transformation and Establishment of Harmonia axyridis Have an Impact?
Authors: Bieńkowski Andrzej O. , Orlova-Bienkowskaja Marina J.
Published: November 2020

Studies of the history of regional insect fauna are important for understanding the changes in ecosystems. We analyzed the dynamics of ladybird fauna at the main sea resort of Russia over a period of 120 years to determine the following: (1) what species disappeared and what species appeared during landscape transformation; (2) what alien species introduced for pest control have been observed to date; and (3) whether the establishment of the global invader Harmonia axyridis (Coccinellidae) caused the extinction of some ladybird species in the Caucasus. We examined specimens collected by us and 54 other collectors including specimens from old museum collections and detected 62 species, 50 of which were collected in recent years (2011–2020). Landscape transformation and recreational use have caused not a decrease but an increase in ladybird biodiversity. Twenty-nine of 34 species recorded before 1930 have been observed in the region to date. Twenty-three other species have spontaneously spread to the region between 1930 and 2020 because of the creation of suitable anthropogenic habitats or because of unintentional introduction. Rodolia cardinalis, Cryptolaemus montrouzieri, Lindorus lophanthae, and Serangium montazerii were released for pest control, and they occur in gardens and streets but not in natural habitats. Harmonia axyridis, which appeared approximately 10 years ago, is abundant in urban and natural habitats, but there is no evidence that it caused the elimination of any ladybird species.
Non-Intrusive Load Monitoring of Residential Water-Heating Circuit Using Ensemble Machine Learning Techniques
Authors: Rehman Attique Ur , Lie Tek Tjing , Vallès Brice , Tito Shafiqur Rahman
Published: November 2020

The recent advancement in computational capabilities and deployment of smart meters have caused non-intrusive load monitoring to revive itself as one of the promising techniques of energy monitoring. Toward effective energy monitoring, this paper presents a non-invasive load inference approach assisted by feature selection and ensemble machine learning techniques. For evaluation and validation purposes of the proposed approach, one of the major residential load elements having solid potential toward energy efficiency applications, i.e., water heating, is considered. Moreover, to realize the real-life deployment, digital simulations are carried out on low-sampling real-world load measurements: New Zealand GREEN Grid Database. For said purposes, MATLAB and Python (Scikit-Learn) are used as simulation tools. The employed learning models, i.e., standalone and ensemble, are trained on a single household’s load data and later tested rigorously on a set of diverse households’ load data, to validate the generalization capability of the employed models. This paper presents a comprehensive performance evaluation of the presented approach in the context of event detection, feature selection, and learning models. Based on the presented study and corresponding analysis of the results, it is concluded that the proposed approach generalizes well to the unseen testing data and yields promising results in terms of non-invasive load inference.
An Outbreak of Clostridium (Clostridioides) difficile Infections within an Acute and Long-Term Care Wards Due to Moxifloxacin-Resistant PCR Ribotype 176 Genotyped as PCR Ribotype 027 by a Commercial Assay
Authors: Novakova Elena , Kotlebova Nina , Gryndlerova Anezka , Novak Martin , Vladarova Michala , Wilcox Mark , Kuijper Ed , Krutova Marcela
Published: November 2020

We aimed to characterize Clostridioides difficile isolates cultured during a six-month single-center study from stool samples of patients with C. difficile infection (CDI) genotyped by the Xpert®C. difficile/Epi assay by polymerase chain reaction (PCR) ribotyping, toxin genes’ detection and multi-locus variable number tandem repeats analysis (MLVA). The susceptibility to metronidazole, vancomycin and moxifloxacin was determined by agar dilution. In addition, the presence of Thr82Ile in the GyrA and a single nucleotide deletion at position (Δ117) in the tcdC gene were investigated. Between January 1 and June 30, 2016, of 114 CDIs, 75 cases were genotyped as presumptive PCR ribotype (RT) 027 infections using a commercial assay. C. difficile isolates cultured from presumptive RT027 stool samples belonged to RT176. These isolates carried genes for toxin A (tcdA), B (tcdB), binary (cdtA/B) and had Δ117 in the tcdC gene. Using MLVA, the 71/75 isolates clustered into two clonal complexes (CCs). Of these, 39 isolates (54.9%) were from patients hospitalized in acute care and 32 isolates (45.1%) were isolated from patients hospitalized in the long-term care department. All isolates were susceptible to metronidazole and vancomycin, and 105 isolates were resistant to moxifloxacin (92%) carrying Thr83Ile in the GyrA. An outbreak of RT176 CDIs, suspected as RT027, was recognized in a Slovakian hospital. In order to monitor the emergence and spread of RT027-variants, the identification of a presumptive RT027 CDI should be confirmed at a strain level by PCR ribotyping.
Impact of Air Pollution and Weather on Dry Eye
Authors: Mandell Jordan T. , Idarraga Maria , Kumar Naresh , Galor Anat
Published: November 2020

Air pollution has broad effects on human health involving many organ systems. The ocular surface is an excellent model with which to study the effects of air pollution on human health as it is in constant contact with the environment, and it is directly accessible, facilitating disease monitoring. Effects of air pollutants on the ocular surface typically manifest as dry eye (DE) symptoms and signs. In this review, we break down air pollution into particulate matter (organic and inorganic) and gaseous compounds and summarize the literature regarding effects of various exposures on DE. Additionally, we examine the effects of weather (relative humidity, temperature) on DE symptoms and signs. To do so, we conducted a PubMed search using key terms to summarize the existing literature on the effects of air pollution and weather on DE. While we tried to focus on the effect of specific exposures on specific aspects of DE, environmental conditions are often studied concomitantly, and thus, there are unavoidable interactions between our variables of interest. Overall, we found that air pollution and weather conditions have differential adverse effects on DE symptoms and signs. We discuss these findings and potential mitigation strategies, such as air purifiers, air humidifiers, and plants, that may be instituted as treatments at an individual level to address environmental contributors to DE.
Predictors and Biomarkers of Subclinical Leaflet Thrombosis after Transcatheter Aortic Valve Implantation
Authors: Pieniak Katarzyna , Jędrzejczyk Szymon , Domaszk Olaf , Grodecki Kajetan , Rymuza Bartosz , Huczek Zenon , Kochman Janusz , Filipiak Krzysztof J. , Gąsecka Aleksandra
Published: November 2020

Transcatheter aortic valve implantation (TAVI) is a recent revolutionary treatment for high-risk patients with severe aortic stenosis who are not suitable for surgery, expanding to intermediate and low-risk patients. Valve leaflet thrombosis (LT) is a potentially fatal complication after TAVI. The incidence of subclinical LT is as high as 25% among patients in the first year after TAVI. Subclinical LT may evolve into symptomatic thrombosis or lead to premature bioprosthesis degeneration, increasing the risk of neurological complications. Because imaging-based methods have limited sensitivity to detect subclinical LT, there is an urgent need for predictors and biomarkers that would make it possible to predict LT after TAVI. Here, we summarize recent data regarding (i) patient-related, (ii) procedure-related, (iii) blood-based and (iv) imaging predictors and biomarkers which might be useful for the early diagnosis of subclinical LT after TAVI. Prevention of LT might offer an opportunity to improve risk stratification and tailor therapy after TAVI.
Pre-Hospital Management of Critically Ill Patients with SARS-CoV-2 Infection: A Retrospective Multicenter Study
Authors: Le Borgne Pierrick , Oberlin Mathieu , Bassand Adrien , Abensur Vuillaume Laure , Gottwalles Yannick , Noizet Marc , Gennai Stéphane , Baicry Florent , Jaeger Deborah , Girerd Nicolas , Lefebvre François , Bilbault Pascal , Chouihed Tahar
Published: November 2020

Introduction: The COVID-19 outbreak had a major impact on healthcare systems worldwide. Our study aims to describe the characteristics and therapeutic emergency mobile service (EMS) management of patients with vital distress due to COVID-19, their in-hospital care pathway and their in-hospital outcome. Methods: This retrospective and multicentric study was conducted in the six main centers of the French Greater East region, an area heavily impacted by the pandemic. All patients requiring EMS dispatch and who were admitted straight to the intensive care unit (ICU) were included. Clinical data from their pre-hospital and hospital management were retrieved. Results: We included a total of 103 patients (78.6% male, median age 68). In the initial stage, patients were in a critical condition (median oxygen saturation was 72% (60–80%)). In the field, 77.7% (CI 95%: 71.8–88.3%) were intubated. Almost half of our population (45.6%, CI 95%: 37.1–56.9%) had clinical Phenotype 1 (silent hypoxemia), while the remaining half presented Phenotype 2 (acute respiratory failure). In the ICU, a great number had ARDS (77.7%, CI 95% 71.8–88.3% with a PaO2/FiO2 < 200). In-hospital mortality was 33% (CI 95%: 24.6–43.3%). The two phenotypes showed clinical and radiological differences (respiratory rate, OR = 0.98, p = 0.02; CT scan lesion extension >50%, OR = 0.76, p < 0.03). However, no difference was found in terms of overall in-hospital mortality (OR = 1.07, p = 0.74). Conclusion: The clinical phenotypes appear to be very distinguishable in the pre-hospital field, yet no difference was found in terms of mortality. This leads us to recommend an identical management in the initial phase, despite the two distinct presentations.
Determining the Minimal Clinical Important Difference for Medication Quantification Scale III and Morphine Milligram Equivalents in Patients with Failed Back Surgery Syndrome
Authors: Goudman Lisa , Smedt Ann De , Forget Patrice , Moens Maarten
Published: November 2020

The Medication Quantification Scale III (MQS) is a tool to represent the negative impact of medication. A reduction in medication can serve as an indicator to evaluate treatment success. However, no cut-off value has yet been determined to evaluate whether a decrease in medication is clinically relevant. Therefore, the objective is to estimate the thresholds for the MQS and morphine milligram equivalents (MMEs) that best identify a clinically relevant important improvement for patients. Data from the Discover registry, in which patients with failed back surgery syndrome were treated with high-dose spinal cord stimulation, were used. Patient satisfaction was utilized to evaluate a clinically important outcome 12 months after stimulation. Anchor-based and distribution-based methods were applied to determine the minimal clinical important difference (MCID). Distribution-based methods revealed a value of 4.28 for the MQS and 33.61 for the MME as MCID. Anchor-based methods indicated a percentage change score of 41.2% for the MQS and 28.2% for the MME or an absolute change score of 4.72 for the MQS and 22.65 for the MME. For assessing a treatment outcome, we recommend using the percentage change score, which better reflects a clinically important outcome and is not severely influenced by high medication intake at baseline.
The Role of Liver Imaging in Hereditary Hemorrhagic Telangiectasia
Authors: Harwin Joelle , Sugi Mark D. , Hetts Steven W. , Conrad Miles B. , Ohliger Michael A.
Published: November 2020

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by spontaneous epistaxis, telangiectasia, and visceral vascular malformations. Hepatic vascular malformations are common, though a minority are symptomatic. Symptoms are dependent on the severity and exact type of shunting caused by the hepatic malformation: Arteriosystemic shunting leads to manifestations of high output cardiac failure, and arterioportal shunting leads to portal hypertension. Radiologic imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), is an important tool for assessing liver involvement. Doppler ultrasonography is the first-line screening modality for HHT-related liver disease, and it has a standardized scale. Imaging can determine whether shunting is principally to the hepatic vein or the portal vein, which can be a key determinant of patients’ symptoms. Liver-related complications can be detected, including manifestations of portal hypertension, focal liver masses as well as ischemic cholangiopathy. Ultrasound and MRI also have the ability to quantify blood flow through the liver, which in the future may be used to determine prognosis and direct antiangiogenic therapy.
Investigating Ethnic Disparity in Living-Donor Kidney Transplantation in the UK: Patient-Identified Reasons for Non-Donation among Family Members
Authors: Wong Katie , Owen-Smith Amanda , Caskey Fergus , MacNeill Stephanie , Tomson Charles , Dor Frank , Ben-Shlomo Yoav , Bouacida Soumeya , Idowu Dela , Bailey Pippa
Published: November 2020

There is ethnic inequity in access to living-donor kidney transplants in the UK. This study asked kidney patients from Black, Asian and minority ethnic groups why members of their family were not able to be living kidney donors. Responses were compared with responses from White individuals. This questionnaire-based mixed-methods study included adults transplanted between 1/4/13–31/3/17 at 14 UK hospitals. Participants were asked to indicate why relatives could not donate, selecting all options applicable from: Age; Health; Weight; Location; Financial/Cost; Job; Blood group; No-one to care for them after donation. A box entitled ‘Other—please give details’ was provided for free-text entries. Multivariable logistic regression was used to analyse the association between the likelihood of selecting each reason for non-donation and the participant’s self-reported ethnicity. Qualitative responses were analysed using inductive thematic analysis. In total, 1240 questionnaires were returned (40% response). There was strong evidence that Black, Asian and minority ethnic group individuals were more likely than White people to indicate that family members lived too far away to donate (adjusted odds ratio (aOR) = 3.25, 95% Confidence Interval (CI) 2.30–4.58), were prevented from donating by financial concerns (aOR = 2.95, 95% CI 2.02–4.29), were unable to take time off work (aOR = 1.88, 95% CI 1.18–3.02), were “not the right blood group” (aOR = 1.65, 95% CI 1.35–2.01), or had no-one to care for them post-donation (aOR = 3.73, 95% CI 2.60–5.35). Four qualitative themes were identified from responses from Black, Asian and minority ethnic group participants: ‘Burden of disease within the family’; ‘Differing religious interpretations’; ‘Geographical concerns’; and ‘A culture of silence’. Patients perceive barriers to living kidney donation in the UK Black, Asian and minority ethnic population. If confirmed, these could be targeted by interventions to redress the observed ethnic inequity.
An Original ELISA-Based Multiplex Method for the Simultaneous Detection of 5 SARS-CoV-2 IgG Antibodies Directed against Different Antigens
Authors: Gillot Constant , Douxfils Jonathan , Cadrobbi Julie , Laffineur Kim , Dogné Jean-Michel , Elsen Marc , Eucher Christine , Melchionda Sabrina , Modaffarri Élise , Tré-Hardy Marie , Favresse Julien
Published: November 2020

Strategies to detect SARS-CoV-2 are increasingly being developed. Among them, serological methods have been developed. Nevertheless, although these may present an interesting clinical performance, they are often directed against only one antigen. This study aims at evaluating the clinical performance of an innovative multiplex immunoassay (i.e., CoViDiag assay) detecting simultaneously the presence of antibodies directed against N, S1, S2, RBD and NTD antigens. Sensitivity was evaluated in 135 samples obtained from 94 rRT-PCR confirmed coronavirus disease 2019 (COVID-19) patients. Non-SARS-CoV-2 sera (n = 132) collected before the COVID-19 pandemic with potential cross-reactions to the SARS-CoV-2 immunoassay were included in the specificity analysis. The antibody signature was also studied in hospitalized and non-hospitalized patients. The specificity of the CoViDiag assay was excellent for all antibodies (99.2 to 100%) using adapted cut-offs. None of the false positive samples were positive for more than one antibody. The sensitivity obtained from samples collected 14 days since symptom onset varied from 92.0 to 100.0% depending on the antibody considered. Among samples collected more than 14 days after symptom onset, 12.8, 66.3, 3.5, 9.3, 5.8 and 2.3% were positive for 5, 4, 3, 2, 1 or 0 antibodies, respectively. A trend toward higher antibody titers was observed in hospitalized patient in the early days since symptom onset. However, no significant difference was observed compared to non-hospitalized patients after 14 days since symptom onset. The clinical performance of the CoViDiag 5 IgG assay is sufficient to recommend its use for the detection and the characterization of the antibody signature following SARS-CoV-2 infection. The combination of several antigens in the same test improves the overall specificity and sensitivity of the test. Further research is needed to investigate whether this strategy may be of interest to identify severe disease outcome in patients with SARS-CoV-2 infection.
Optimal Examination Sites for Periodontal Disease Evaluation: Applying the Item Response Theory Graded Response Model
Authors: Nomura Yoshiaki , Morozumi Toshiya , Fukuda Mitsuo , Hanada Nobuhiro , Kakuta Erika , Kobayashi Hiroaki , Minabe Masato , Nakamura Toshiaki , Nakayama Yohei , Nishimura Fusanori , Noguchi Kazuyuki , Numabe Yukihiro , Ogata Yorimasa , Saito Atsushi , Sato Soh , Sekino Satoshi , Sugano Naoyuki , Sugaya Tsutomu , Suzuki Fumihiko , Takahashi Keiso , Takai Hideki , Takashiba Shogo , Umeda Makoto , Yoshie Hiromasa , Yoshimura Atsutoshi , Yoshinari Nobuo , Nakagawa Taneaki
Published: November 2020

Periodontal examination data have a complex structure. For epidemiological studies, mass screenings, and public health use, a simple index that represents the periodontal condition is necessary. Periodontal indices for partial examination of selected teeth have been developed. However, the selected teeth vary between indices, and a justification for the selection of examination teeth has not been presented. We applied a graded response model based on the item response theory to select optimal examination teeth and sites that represent periodontal conditions. Data were obtained from 254 patients who participated in a multicenter follow-up study. Baseline data were obtained from initial follow-up. Optimal examination sites were selected using item information calculated by graded response modeling. Twelve sites—maxillary 2nd premolar (palatal-medial), 1st premolar (palatal-distal), canine (palatal-medial), lateral incisor (palatal-central), central incisor (palatal-distal) and mandibular 1st premolar (lingual, medial)—were selected. Mean values for clinical attachment level, probing pocket depth, and bleeding on probing by full mouth examinations were used for objective variables. Measuring the clinical parameters of these sites can predict the results of full mouth examination. For calculating the periodontal index by partial oral examination, a justification for the selection of examination sites is essential. This study presents an evidence-based partial examination methodology and its modeling.