bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide DNA Methylation Profiles in Community Members Exposed to the World Trade Center Disaster
Authors: Arslan Alan , Tuminello Stephanie , Yang Lei , Zhang Yian , Durmus Nedim , Snuderl Matija , Heguy Adriana , Zeleniuch-Jacquotte Anne , Shao Yongzhao , Reibman Joan
Published: July 2020

The primary goal of this pilot study was to assess feasibility of studies among local community members to address the hypothesis that complex exposures to the World Trade Center (WTC) dust and fumes resulted in long-term epigenetic changes. We enrolled 18 WTC-exposed cancer-free women from the WTC Environmental Health Center (WTC EHC) who agreed to donate blood samples during their standard clinical visits. As a reference WTC unexposed group, we randomly selected 24 age-matched cancer-free women from an existing prospective cohort who donated blood samples before 11 September 2001. The global DNA methylation analyses were performed using Illumina Infinium MethylationEpic arrays. Statistical analyses were performed using R Bioconductor package. Functional genomic analyses were done by mapping the top 5000 differentially expressed CpG sites to the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway database. Among cancer-free subjects, we observed substantial methylation differences between WTC-exposed and unexposed women. The top 15 differentially methylated gene probes included BCAS2, OSGIN1, BMI1, EEF1A2, SPTBN5, CHD8, CDCA7L, AIDA, DDN, SNORD45C, ZFAND6, ARHGEF7, UBXN8, USF1, and USP12. Several cancer-related pathways were enriched in the WTC-exposed subjects, including endocytosis, mitogen-activated protein kinase (MAPK), viral carcinogenesis, as well as Ras-associated protein-1 (Rap1) and mammalian target of rapamycin (mTOR) signaling. The study provides preliminary data on substantial differences in DNA methylation between WTC-exposed and unexposed populations that require validation in further studies.
Predicting Crash Injury Severity with Machine Learning Algorithm Synergized with Clustering Technique: A Promising Protocol
Authors: Assi Khaled , Rahman Syed Masiur , Mansoor Umer , Ratrout Nedal
Published: July 2020

Predicting crash injury severity is a crucial constituent of reducing the consequences of traffic crashes. This study developed machine learning (ML) models to predict crash injury severity using 15 crash-related parameters. Separate ML models for each cluster were obtained using fuzzy c-means, which enhanced the predicting capability. Finally, four ML models were developed: feed-forward neural networks (FNN), support vector machine (SVM), fuzzy C-means clustering based feed-forward neural network (FNN-FCM), and fuzzy c-means based support vector machine (SVM-FCM). Features that were easily identified with little investigation on crash sites were used as an input so that the trauma center can predict the crash severity level based on the initial information provided from the crash site and prepare accordingly for the treatment of the victims. The input parameters mainly include vehicle attributes and road condition attributes. This study used the crash database of Great Britain for the years 2011–2016. A random sample of crashes representing each year was used considering the same share of severe and non-severe crashes. The models were compared based on injury severity prediction accuracy, sensitivity, precision, and harmonic mean of sensitivity and precision (i.e., F1 score). The SVM-FCM model outperformed the other developed models in terms of accuracy and F1 score in predicting the injury severity level of severe and non-severe crashes. This study concluded that the FCM clustering algorithm enhanced the prediction power of FNN and SVM models.
Perception of Health Conditions and Test Availability as Predictors of Adults’ Mental Health during the COVID-19 Pandemic: A Survey Study of Adults in Malaysia
Authors: Dai Huiyang , Zhang Stephen X. , Looi Kim Hoe , Su Rui , Li Jizhen
Published: July 2020

Research identifying adults’ mental health during the coronavirus disease 2019 (COVID-19) pandemic relies solely on demographic predictors without examining adults’ health condition as a potential predictor. This study aims to examine individuals’ perception of health conditions and test availability as potential predictors of mental health—insomnia, anxiety, depression, and distress—during the COVID-19 pandemic. An online survey of 669 adults in Malaysia was conducted during 2–8 May 2020, six weeks after the Movement Control Order (MCO) was issued. We found adults’ perception of health conditions had curvilinear relationships (horizontally reversed J-shaped) with insomnia, anxiety, depression, and distress. Perceived test availability for COVID-19 also had curvilinear relationships (horizontally reversed J-shaped) with anxiety and depression. Younger adults reported worse mental health, but people from various religions and ethnic groups did not differ significantly in reported mental health. The results indicated that adults with worse health conditions had more mental health problems, and the worse degree deepened for unhealthy people. Perceived test availability negatively predicted anxiety and depression, especially for adults perceiving COVID-19 test unavailability. The significant predictions of perceived health condition and perceived COVID-19 test availability suggest a new direction for the literature to identify the psychiatric risk factors directly from health-related variables during a pandemic.
Shared Control of an Electric Wheelchair Considering Physical Functions and Driving Motivation
Authors: Xi Lele , Shino Motoki
Published: July 2020

Individuals with severe physical impairments have difficulties operating electric wheelchairs (EWs), especially in situations where fine steering abilities are required. Automatic driving partly solves the problem, although excessive reliance on automatic driving is not conducive to maintaining their residual physical functions and may cause more serious diseases in the future. The objective of this study was to develop a shared control system that can be adapted to different environments by completely utilizing the operating ability of the user while maintaining the motivation of the user to drive. The operating characteristics of individuals with severe physical impairments were first analyzed to understand their difficulties when operating EWs. Subsequently, a novel reinforcement learning-based shared control method was proposed to adjust the control weight between the user and the machine to meet the requirements of fully exploiting the operating abilities of the users while assisting them when necessary. Experimental results showed that the proposed shared control system gradually adjusted the control weights between the user and the machine, providing safe operation of the EW while ensuring full use of the control signals from the user. It was also found that the shared control results were deeply affected by the types of users.
Overexpressed BSR1-Mediated Enhancement of Disease Resistance Depends on the MAMP-Recognition System
Authors: Kanda Yasukazu , Nishizawa Yoko , Kamakura Takashi , Mori Masaki
Published: July 2020

Plant plasma membrane-localized receptors recognize microbe-associated molecular patterns (MAMPs) and activate immune responses via various signaling pathways. Receptor-like cytoplasmic kinases (RLCKs) are considered key signaling factors in plant immunity. BROAD-SPECTRUM RESISTANCE 1 (BSR1), a rice RLCK, plays a significant role in disease resistance. Overexpression of BSR1 confers strong resistance against fungal and bacterial pathogens. Our recent study revealed that MAMP-triggered immune responses are mediated by BSR1 in wild-type rice and are hyperactivated in BSR1-overexpressing rice. It was suggested that hyperactivated immune responses were responsible for the enhancement of broad-spectrum disease resistance; however, this remained to be experimentally validated. In this study, we verified the above hypothesis by disrupting the MAMP-recognition system in BSR1-overexpressing rice. To this end, we knocked out OsCERK1, which encodes a well-characterized MAMP-receptor-like protein kinase. In the background of BSR1 overaccumulation, the knockout of OsCERK1 nearly abolished the enhancement of blast resistance. This finding indicates that overexpressed BSR1-mediated enhancement of disease resistance depends on the MAMP-triggered immune system, corroborating our previously suggested model.
Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair
Authors: Selig Mischa , Lauer Jasmin C. , Hart Melanie L. , Rolauffs Bernd
Published: July 2020

Since material stiffness controls many cell functions, we reviewed the currently available knowledge on stiffness sensing and elucidated what is known in the context of clinical and experimental articular cartilage (AC) repair. Remarkably, no stiffness information on the various biomaterials for clinical AC repair was accessible. Using mRNA expression profiles and morphology as surrogate markers of stiffness-related effects, we deduced that the various clinically available biomaterials control chondrocyte (CH) phenotype well, but not to equal extents, and only in non-degenerative settings. Ample evidence demonstrates that multiple molecular aspects of CH and mesenchymal stromal cell (MSC) phenotype are susceptible to material stiffness, because proliferation, migration, lineage determination, shape, cytoskeletal properties, expression profiles, cell surface receptor composition, integrin subunit expression, and nuclear shape and composition of CHs and/or MSCs are stiffness-regulated. Moreover, material stiffness modulates MSC immuno-modulatory and angiogenic properties, transforming growth factor beta 1 (TGF-β1)-induced lineage determination, and CH re-differentiation/de-differentiation, collagen type II fragment production, and TGF-β1- and interleukin 1 beta (IL-1β)-induced changes in cell stiffness and traction force. We then integrated the available molecular signaling data into a stiffness-regulated CH phenotype model. Overall, we recommend using material stiffness for controlling cell phenotype, as this would be a promising design cornerstone for novel future-oriented, cell-instructive biomaterials for clinical high-quality AC repair tissue.
Endocytosis of Connexin 36 is Mediated by Interaction with Caveolin-1
Authors: Kotova Anna , Timonina Ksenia , Zoidl Georg R.
Published: July 2020

The gap junctional protein connexin 36 (Cx36) has been co-purified with the lipid raft protein caveolin-1 (Cav-1). The relevance of an interaction between the two proteins is unknown. In this study, we explored the significance of Cav-1 interaction in the context of intracellular and membrane transport of Cx36. Coimmunoprecipitation assays and Förster resonance energy transfer analysis (FRET) were used to confirm the interaction between the two proteins in the Neuro 2a cell line. We found that the Cx36 and Cav-1 interaction was dependent on the intracellular calcium levels. By employing different microscopy techniques, we demonstrated that Cav-1 enhances the vesicular transport of Cx36. Pharmacological interventions coupled with cell surface biotinylation assays and FRET analysis revealed that Cav-1 regulates membrane localization of Cx36. Our data indicate that the interaction between Cx36 and Cav-1 plays a role in the internalization of Cx36 by a caveolin-dependent pathway.
Transformation of Riccia fluitans, an Amphibious Liverwort Dynamically Responding to Environmental Changes
Authors: Althoff Felix , Zachgo Sabine
Published: July 2020

The colonization of land by streptophyte algae, ancestors of embryophyte plants, was a fundamental event in the history of life on earth. Bryophytes are early diversifying land plants that mark the transition from freshwater to terrestrial ecosystems. The amphibious liverwort Riccia fluitans can thrive in aquatic and terrestrial environments and thus represents an ideal organism to investigate this major transition. Therefore, we aimed to establish a transformation protocol for R. fluitans to make it amenable for genetic analyses. An Agrobacterium transformation procedure using R. fluitans callus tissue allows to generate stably transformed plants within 10 weeks. Furthermore, for comprehensive studies spanning all life stages, we demonstrate that the switch from vegetative to reproductive development can be induced by both flooding and poor nutrient availability. Interestingly, a single R. fluitans plant can consecutively adapt to different growth environments and forms distinctive and reversible features of the thallus, photosynthetically active tissue that is thus functionally similar to leaves of vascular plants. The morphological plasticity affecting vegetative growth, air pore formation, and rhizoid development realized by one genotype in response to two different environments makes R. fluitans ideal to study the adaptive molecular mechanisms enabling the colonialization of land by aquatic plants.
Biomechanics of Cell Membrane
Authors: Leporatti Stefano , Toca-Herrera José L.
Published: July 2020

This Special Issue is focused on measuring and characterizing the mechanical and adhesive properties of cells and membranes [...]
Peroxidan Plays a Tumor-Promoting Role in Oral Squamous Cell Carcinoma
Authors: Kurihara-Shimomura Miyako , Sasahira Tomonori , Shimomura Hiroyuki , Kirita Tadaaki
Published: July 2020

Despite dramatic progress in cancer diagnosis and treatment, the five-year survival rate of oral squamous cell carcinoma (OSCC) is still only about 50%. Thus, the need for elucidating the molecular mechanisms underlying OSCC is urgent. We previously identified the peroxidasin gene (PXDN) as one of several novel genes associated with OSCC. Although the PXDN protein is known to act as a tumor-promoting factor associated with the Warburg effect, its function and role in OSCC are poorly understood. In this study, we investigated the expression, function, and relationship with the Warburg effect of PXDN in OSCC. In immunohistochemical analysis of OSCC specimens, we observed that elevated PXDN expression correlated with lymph node metastasis and a diffuse invasion pattern. High PXDN expression was confirmed as an independent predictor of poor prognosis by multivariate analysis. The PXDN expression level correlated positively with that of pyruvate kinase (PKM2) and heme oxygenase-1 (HMOX1) and with lactate and ATP production. No relationship between PXDN expression and mitochondrial activation was observed, and PXDN expression correlated inversely with reactive oxygen species (ROS) production. These results suggest that PXDN might be a tumor progression factor causing a Warburg-like effect in OSCC.
Extracellular Vesicle Membrane-Associated Proteins: Emerging Roles in Tumor Angiogenesis and Anti-Angiogenesis Therapy Resistance
Authors: Ko Song Yi , Naora Honami
Published: July 2020

The tumor vasculature is essential for tumor growth and metastasis, and is a prime target of several anti-cancer agents. Increasing evidence indicates that tumor angiogenesis is stimulated by extracellular vesicles (EVs) that are secreted or shed by cancer cells. These EVs encapsulate a variety of biomolecules with angiogenic properties, and have been largely thought to stimulate vessel formation by transferring this luminal cargo into endothelial cells. However, recent studies have revealed that EVs can also signal to recipient cells via proteins on the vesicular surface. This review discusses and integrates emerging insights into the diverse mechanisms by which proteins associate with the EV membrane, the biological functions of EV membrane-associated proteins in tumor angiogenesis, and the clinical significance of these proteins in anti-angiogenic therapy.
DNA Methyltransferase 1 (DNMT1) Acts on Neurodegeneration by Modulating Proteostasis-Relevant Intracellular Processes
Authors: Bayer Cathrin , Pitschelatow Georg , Hannemann Nina , Linde Jenice , Reichard Julia , Pensold Daniel , Zimmer-Bensch Geraldine
Published: July 2020

The limited regenerative capacity of neurons requires a tightly orchestrated cell death and survival regulation in the context of longevity, as well as age-associated and neurodegenerative diseases. Subordinate to genetic networks, epigenetic mechanisms, such as DNA methylation and histone modifications, are involved in the regulation of neuronal functionality and emerge as key contributors to the pathophysiology of neurodegenerative diseases. DNA methylation, a dynamic and reversible process, is executed by DNA methyltransferases (DNMTs). DNMT1 was previously shown to act on neuronal survival in the aged brain, whereby a DNMT1-dependent modulation of processes relevant for protein degradation was proposed as an underlying mechanism. Properly operating proteostasis networks are a mandatory prerequisite for the functionality and long-term survival of neurons. Malfunctioning proteostasis is found, inter alia, in neurodegenerative contexts. Here, we investigated whether DNMT1 affects critical aspects of the proteostasis network by a combination of expression studies, live cell imaging, and protein biochemical analyses. We found that DNMT1 negatively impacts retrograde trafficking and autophagy, with both being involved in the clearance of aggregation-prone proteins by the aggresome–autophagy pathway. In line with this, we found that the transport of GFP-labeled mutant huntingtin (HTT) to perinuclear regions, proposed to be cytoprotective, also depends on DNMT1. Depletion of Dnmt1 accelerated perinuclear HTT aggregation and improved the survival of cells transfected with mutant HTT. This suggests that mutant HTT-induced cytotoxicity is at least in part mediated by DNMT1-dependent modulation of degradative pathways.
Long Non-Coding RNAs in Atrial Fibrillation: Pluripotent Stem Cell-Derived Cardiomyocytes as a Model System
Authors: Bektik Emre , Cowan Douglas B. , Wang Da-Zhi
Published: July 2020

Atrial fibrillation (AF) is a type of sustained arrhythmia in humans often characterized by devastating alterations to the cardiac conduction system as well as the structure of the atria. AF can lead to decreased cardiac function, heart failure, and other complications. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the cardiovascular system, including AF; however, a large group of lncRNAs is not conserved between mouse and human. Furthermore, AF has complex networks showing variations in mechanisms in different species, making it challenging to utilize conventional animal models to investigate the functional roles and potential therapeutic benefits of lncRNAs for AF. Fortunately, pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) offer a reliable platform to study lncRNA functions in AF because of certain electrophysiological and molecular similarities with native human CMs. In this review, we first summarize the broad aspects of lncRNAs in various heart disease settings, then focus on their potential roles in AF development and pathophysiology. We also discuss current uses of PSCs in AF research and describe how these studies could be developed into novel therapeutics for AF and other cardiovascular diseases.
Moderate High Caloric Maternal Diet Impacts Dam Breast Milk Metabotype and Offspring Lipidome in a Sex-Specific Manner
Authors: Alexandre-Gouabau Marie-Cécile , David-Sochard Agnès , Royer Anne-Lise , Parnet Patricia , Paillé Vincent
Published: July 2020

Lactation is a critical period during which maternal sub- or over-nutrition affect milk composition and offspring development that can have lasting health effects. The consequences of moderate high-fat, high-simple carbohydrate diet (WD) consumption by rat dams, during gestation and lactation, on milk composition and offspring blood lipidome and its growth, at weaning, were investigated by using a comprehensive lipidomic study on mass-spectrometric platform combined to targeted fatty- and free amino-acids analysis. This holistic approach allowed clear-cut differences in mature milk-lipidomic signature according to maternal diet with a similar content of protein, lactose and leptin. The lower WD-milk content in total fat and triglycerides (TGs), particularly in TGs-with saturated medium-chain, and higher levels in both sphingolipid (SL) and TG species with unsaturated long-chain were associated to a specific offspring blood-lipidome with decreased levels in TGs-containing saturated fatty acid (FA). The sexual-dimorphism in the FA-distribution in TG (higher TGs-rich in oleic and linoleic acids, specifically in males) and SL species (increased levels in very long-chain ceramides, specifically in females) could be associated with some differences that we observed between males and females like a higher total body weight gain in females and an increased preference for fatty taste in males upon weaning.
Functional Alterations in the Olfactory Neuronal Circuit Occur before Hippocampal Plasticity Deficits in the P301S Mouse Model of Tauopathy: Implications for Early Diagnosis and Translational Research in Alzheimer’s Disease
Authors: Ahnaou Abdallah , Rodriguez-Manrique Daniela , Biermans Ria , Embrechts Sofie , Manyakov Nikolay V. , Drinkenburg Wilhelmus H.
Published: July 2020

Alzheimer’s disease (AD) is characterized by neuronal loss and impaired synaptic transmission, ultimately leading to cognitive deficits. Early in the disease, the olfactory track seems most sensitive to tauopathy, while most plasticity studies focused on the hippocampal circuits. Functional network connectivity (FC) and long-term potentiation (LTP), considered as the plasticity substrate of learning and memory, were longitudinally assessed in mice of the P301S model of tauopathy following the course (time and location) of progressively neurodegenerative pathology (i.e., at 3, 6, and 9 months of age) and in their wild type (WT) littermates. Using in vivo local field potential (LFP) recordings, early (at three months) dampening in the gamma oscillatory activity and impairments in the phase-amplitude theta-gamma coupling (PAC) were found in the olfactory bulb (OB) circuit of P301S mice, which were maintained through the whole course of pathology development. In contrast, LFP oscillatory activity and PAC indices were normal in the entorhinal cortex, hippocampal CA1 and CA3 nuclei. Field excitatory postsynaptic potential (fEPSP) recordings from the Shaffer collateral (SC)-CA1 hippocampal stratum pyramidal revealed a significant altered synaptic LTP response to high-frequency stimulation (HFS): at three months of age, no significant difference between genotypes was found in basal synaptic activity, while signs of a deficit in short term plasticity were revealed by alterations in the fEPSPs. At six months of age, a slight deviance was found in basal synaptic activity and significant differences were observed in the LTP response. The alterations in network oscillations at the OB level and impairments in the functioning of the SC-CA1 pyramidal synapses strongly suggest that the progression of tau pathology elicited a brain area, activity-dependent disturbance in functional synaptic transmission. These findings point to early major alterations of neuronal activity in the OB circuit prior to the disturbance of hippocampal synaptic plasticity, possibly involving tauopathy in the anomalous FC. Further research should determine whether those early deficits in the OB network oscillations and FC are possible mechanisms that potentially promote the emergence of hippocampal synaptic impairments during the progression of tauopathy.
Building a Persuasive Virtual Dietitian
Authors: Anselma Luca , Mazzei Alessandro
Published: July 2020

This paper describes the Multimedia Application for Diet Management (MADiMan), a system that supports users in managing their diets while admitting diet transgressions. MADiMan consists of a numerical reasoner that takes into account users’ dietary constraints and automatically adapts the users’ diet, and of a natural language generation (NLG) system that automatically creates textual messages for explaining the results provided by the reasoner with the aim of persuading users to stick to a healthy diet. In the first part of the paper, we introduce the MADiMan system and, in particular, the basic mechanisms related to reasoning, data interpretation and content selection for a numeric data-to-text NLG system. We also discuss a number of factors influencing the design of the textual messages produced. In particular, we describe in detail the design of the sentence-aggregation procedure, which determines the compactness of the final message by applying two aggregation strategies. In the second part of the paper, we present the app that we developed, CheckYourMeal!, and the results of two human-based quantitative evaluations of the NLG module conducted using CheckYourMeal! in a simulation. The first evaluation, conducted with twenty users, ascertained both the perceived usefulness of graphics/text and the appeal, easiness and persuasiveness of the textual messages. The second evaluation, conducted with thirty-nine users, ascertained their persuasive power. The evaluations were based on the analysis of questionnaires and of logged data of users’ behaviour. Both evaluations showed significant results.
Effect of Temperature on Life History and Parasitization Behavior of Trichogramma achaeae Nagaraja and Nagarkatti (Hym.: Trichogrammatidae)
Authors: del Pino Modesto , Gallego Juan Ramón , Hernández Suárez Estrella , Cabello Tomás
Published: July 2020

Trichogramma achaeae Nagaraja and Nagarkatti (Hymenoptera: Trichogrammatidae) is currently used as biological control agent for several lepidopteran pests. Knowledge of thermal requirements is essential to optimize its rearing procedures and inundative releases. The biological characteristics and two-sex life table parameters of T. achaeae were determined at five constant temperatures (15, 20, 25, 30, and 35 °C) using Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) eggs. T. achaeae was able to develop and survive from 15 °C to 30 °C, but not at 35 °C. Temperature significantly affected the preadult development time and adult longevity, decreasing when temperature increased from 15 °C to 30 °C. Temperature significantly altered the sex ratio, being female biased between 15 °C and 25 °C. Age-stage, two-sex life table analysis indicated that net reproductive rate (R0) was highest at 20 °C. Both the intrinsic rate of increase (r) and finite rate of increase (λ) increased with increasing temperature, while the mean generation time (T) decreased significantly. In addition, functional response of T. achaeae was studied, being significantly affected by temperature and host egg density, displaying a Holling type-I at 15 °C and a Holling type-II at 25 °C. The relevance of these results is discussed for the use of T. achaeae as biological control agent.
Long-Term Prevalence of Sensory Chemotherapy-Induced Peripheral Neuropathy for 5 Years after Adjuvant FOLFOX Chemotherapy to Treat Colorectal Cancer: A Multicenter Cross-Sectional Study
Authors: Selvy Marie , Pereira Bruno , Kerckhove Nicolas , Gonneau Coralie , Feydel Gabrielle , Pétorin Caroline , Vimal-Baguet Agnès , Melnikov Sergey , Kullab Sharif , Hebbar Mohamed , Bouché Olivier , Slimano Florian , Bourgeois Vincent , Lebrun-Ly Valérie , Thuillier Frédéric , Mazard Thibault , Tavan David , Benmammar Kheir Eddine , Monange Brigitte , Ramdani Mohamed , Péré-Vergé Denis , Huet-Penz Floriane , Bedjaoui Ahmed , Genty Florent , Leyronnas Cécile , Busserolles Jérôme , Trevis Sophie , Pinon Vincent , Pezet Denis , Balayssac David
Published: July 2020

(1) Background: Oxaliplatin is among the most neurotoxic anticancer drugs. Little data are available on the long-term prevalence and consequences of chemotherapy-induced peripheral neuropathy (CIPN), even though the third largest population of cancer survivors is made up of survivors of colorectal cancer. (2) Methods: A multicenter, cross-sectional study was conducted in 16 French centers to assess the prevalence of CIPN, as well as its consequences (neuropathic pain, anxiety, depression, and quality of life) in cancer survivors during the 5 years after the end of adjuvant oxaliplatin chemotherapy. (3) Results: Out of 406 patients, the prevalence of CIPN was 31.3% (95% confidence interval: 26.8–36.0). Little improvement in CIPN was found over the 5 years, and 36.5% of patients with CIPN also had neuropathic pain. CIPN was associated with anxiety, depression, and deterioration of quality of life. None of the patients with CIPN were treated with duloxetine (recommendation from American Society of Clinical Oncology), and only 3.2%, 1.6%, and 1.6% were treated with pregabalin, gabapentin, and amitriptyline, respectively. (4) Conclusions: Five years after the end of chemotherapy, a quarter of patients suffered from CIPN. The present study showed marked psychological distress and uncovered a failure in management in these patients.
High Effectiveness of a 14-Day Concomitant Therapy for Helicobacter pylori Treatment in Primary Care. An Observational Multicenter Study
Authors: Olmedo Llum , Azagra Rafael , Aguyé Amada , Pascual Marta , Calvet Xavier , Gené Emili
Published: July 2020

Background: The current cure rates with triple therapy combining a proton-pump inhibitor, amoxicillin and clarithromycin are unacceptably low. Aims: To evaluate the efficacy of a 14-day concomitant therapy as an empirical first-line treatment for curing Helicobacter pylori (Hp) infection in primary care. Methods: Patients from six primary care centers in Catalonia -Spain- were included consecutively. Hp status pre and post treatment was assessed according to local clinical practice protocol. A 14-day concomitant therapy (amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg plus omeprazole 20 mg, all drugs administered twice daily) was prescribed. Adherence to therapy and adverse events were assessed by personal interview. Results: 112 patients were enrolled. Mean age was 46.7 ± 16.1 years. Main indication for treatment was non-investigated dyspepsia (83%). Hp eradication was achieved in 100 of the 112 patients. Eradication rates were 89.3% (95% CI: 81.7–94.1) by intention-to-treat (ITT) analysis and 91.7% (95% CI; 84.6–95.9) per protocol (PP). No major side effects were reported; 104 (92.8%) patients complete the treatment. Forty-seven patients (42%) complained of mild side effects (metallic taste, nausea). Low adherence to treatment (p = 0.004) and significant adverse events (p = 0.004) were the variables associated with treatment failure. Conclusions: In primary care, a 14-day concomitant therapy is highly effective and well tolerated.
Effect of Manual Therapy and Splint Therapy in People with Temporomandibular Disorders: A Preliminary Study
Authors: Espí-López Gemma Victoria , Arnal-Gómez Anna , Cuerda del Pino Alba , Benavent-Corai José , Serra-Añó Pilar , Inglés Marta
Published: July 2020

Background: Isolated manual therapy techniques (MT) have shown beneficial effects in patients with temporomandibular disorders (TMD) but the effect of the combination of such techniques, together with the well-stablished splint therapy (ST) remains to be elucidated. Objective: This study was conducted to ascertain whether a combined program of MT techniques, including intraoral treatment, plus traditional ST improves pain and clinical dysfunction in subjects with TMD. Methods: A preliminary trial was conducted. 16 participants were assigned to either the MT plus ST-Experimental Group (EG, n = 8) or the ST alone—Control Group (CG, n = 8). Forty-five minute sessions of combined MT techniques were performed, once a week for four weeks. Three evaluations were conducted: baseline, post-treatment, and one-month follow-up. Outcome measures were pain perception, pain pressure threshold (PPT), TMD dysfunction, and perception of change after treatment. Results: EG showed significant reduction on pain, higher PPT, significant improvement of dysfunction and significantly positive perception of change after treatment (p < 0.05 all). Additionally, such positive effects were maintained at follow-up with a high treatment effect (R2 explaining 26.6–33.2% of all variables). Conclusion: MT plus ST showed reduction on perceived pain (3 points decrease), higher PPT (of at least 1.0 kg/cm2), improvement of disability caused by pain (4.4 points decrease), and positive perception of change (EG: 50% felt “much improvement”), compared to ST alone.
T Helper Cell Infiltration in Osteoarthritis-Related Knee Pain and Disability
Authors: Nees Timo Albert , Rosshirt Nils , Zhang Jiji Alexander , Platzer Hadrian , Sorbi Reza , Tripel Elena , Reiner Tobias , Walker Tilman , Schiltenwolf Marcus , Lorenz Hanns-Martin , Tretter Theresa , Moradi Babak , Hagmann Sébastien
Published: July 2020

Despite the growing body of literature demonstrating a crucial role of T helper cell (Th) responses in the pathogenesis of osteoarthritis (OA), only few clinical studies have assessed interactions between Th cells and OA—related symptoms. Yet, the inclusion of clinical data in the interpretation of cellular analyses of Th cell infiltration is essential to reveal the mechanisms underlying the complex pathophysiology of OA pain and disability. Thus, the aim of the study was to analyze the infiltration pattern of Th cells in systemic (peripheral blood) and joint-derived (synovial membrane and fluid) samples from patients with knee OA in relation to OA-induced pain and disability. Therefore, radiographic OA severity, knee pain and function of 47 OA patients undergoing knee arthroplasty were evaluated prior to surgery. In parallel, samples of peripheral blood (PB), synovial membrane (SM) and synovial fluid (SF) were harvested and analyzed for different Th subsets using flow cytometry. According to surface marker expression Th cells (CD3+ CD4+ CD8−) were assigned to the Th subsets Th1 (CXCR3+, CCR5+), Th2 (CCR3+, CCR4+) and Th17 (CD161+, CCR6+). Interestingly, infiltration of the SM with all Th subtypes (Th1, Th2, Th17) significantly correlated with OA-induced disability. Most importantly, synovial CCR5+ and CCR3+ Th cell infiltration was associated with OA-related knee pain and disability. Furthermore, higher percentage rates of CXCR3+ Th cells in all tissue samples (PB, SM, SF) showed significant associations with OA severity. In contrast, increasing percentage rates of CD161+ Th cells in SM samples corresponded to a better functional outcome. In conclusion, the current study provides an extensive profile of the Th cell infiltration pattern in PB, SF and SM from patients with clinically relevant knee OA. Th cell infiltration of the SM might play a crucial role not only in the pathogenesis of OA but also in the development of OA-related knee pain and disability.
Comparison of BRAF Mutation Screening Strategies in a Large Real-Life Series of Advanced Melanoma Patients
Authors: Colombino Maria , Rozzo Carla , Paliogiannis Panagiotis , Casula Milena , Manca Antonella , Doneddu Valentina , Fedeli Maria Antonietta , Sini Maria Cristina , Palomba Grazia , Pisano Marina , Ascierto Paolo A. , Caracò Corrado , Lissia Amelia , Cossu Antonio , Palmieri Giuseppe
Published: July 2020

Malignant melanoma (MM) is one of the deadliest skin cancers. BRAF mutation status plays a predominant role in the management of MM patients. The aim of this study was to compare BRAF mutational testing performed by conventional nucleotide sequencing approaches with either real-time polymerase chain reaction (rtPCR) or next-generation sequencing (NGS) assays in a real-life, hospital-based series of advanced MM patients. Consecutive patients with AJCC (American Joint Committee on Cancer) stage IIIC and IV MM from Sardinia, Italy, who were referred for molecular testing, were enrolled into the study. Initial screening was performed to assess the mutational status of the BRAF and NRAS genes, using the conventional methodologies recognized by the nationwide guidelines, at the time of the molecular classification, required by clinicians: at the beginning, Sanger-based sequencing (SS) and, after, pyrosequencing. The present study was then focused on BRAF mutation detecting approaches only. BRAF wild-type cases with available tissue and adequate DNA were further tested with rtPCR (Idylla™) and NGS assays. Globally, 319 patients were included in the study; pathogenic BRAF mutations were found in 144 (45.1%) cases examined with initial screening. The rtPCR detected 11 (16.2%) and 3 (4.8%) additional BRAF mutations after SS and pyrosequencing, respectively. NGS detected one additional BRAF-mutated case (2.1%) among 48 wild-type cases previously tested with pyrosequencing and rtPCR. Our study evidenced that rtPCR and NGS were able to detect additional BRAF mutant cases in comparison with conventional sequencing methods; therefore, we argue for the preferential utilization of the aforementioned assays (NGS and rtPCR) in clinical practice, to eradicate false-negative cases and improve the accuracy of BRAF detection.
Small Cell Lung Cancer from Traditional to Innovative Therapeutics: Building a Comprehensive Network to Optimize Clinical and Translational Research
Authors: Subbiah Shanmuga , Nam Arin , Garg Natasha , Behal Amita , Kulkarni Prakash , Salgia Ravi
Published: July 2020

Small cell lung cancer (SCLC) is an aggressive, complex disease with a distinct biology that contributes to its poor prognosis. Management of SCLC is still widely limited to chemotherapy and radiation therapy, and research recruitment still poses a considerable challenge. Here, we review the current standard of care for SCLC and advances made in utilizing immunotherapy. We also highlight research in the development of targeted therapies and emphasize the importance of a team-based approach to make clinical advances. Building an integrative network between an academic site and community practice sites optimizes biomarker and drug target discovery for managing and treating a difficult disease like SCLC.
Estimation of Longshore Sediment Transport Using Video Monitoring Shoreline Data
Authors: Oh Jung-Eun , Chang Yeon S. , Jeong Weon Mu , Kim Ki Hyun , Ryu Kyong Ho
Published: July 2020

Video monitoring systems (VMS) have been used for beach status observation but are not effective for examining detailed beach processes as they only measure changes to the shoreline and backshore. Here, we extracted longshore sediment transport (LST) from VMS in order to investigate long- and short-term littoral processes on a pocket beach. LST estimated by applying one-line theory, wave power, and the oblique angle of incident waves were used to understand shoreline changes caused by severe winter storms. The estimated LST showed good agreement with the shoreline changes because the sediments were trapped at one end of the pocket beach and the alongshore direction of transported sediments was corresponded to the direction of LST. The results also showed that the beach that was severely eroded during storms was also rapidly recovered following the evolution of LST, which indicates that the LST may play a role in the recovery process while the erosion was mainly caused by the cross-shore transport due to storm waves. After the beach was nourished, beach changes became more active, even under lower wave energy conditions, owing to the equilibrium process. The analysis presented in this study could be applied to study inhomogeneous beach processes at other sites.
Chromatin Structure and Drug Resistance in Candida spp.
Authors: O’Kane Callum J. , Weild Rachel , M. Hyland Edel
Published: July 2020

Anti-microbial resistance (AMR) is currently one of the most serious threats to global human health and, appropriately, research to tackle AMR garnishes significant investment and extensive attention from the scientific community. However, most of this effort focuses on antibiotics, and research into anti-fungal resistance (AFR) is vastly under-represented in comparison. Given the growing number of vulnerable, immunocompromised individuals, as well as the positive impact global warming has on fungal growth, there is an immediate urgency to tackle fungal disease, and the disturbing rise in AFR. Chromatin structure and gene expression regulation play pivotal roles in the adaptation of fungal species to anti-fungal stress, suggesting a potential therapeutic avenue to tackle AFR. In this review we discuss both the genetic and epigenetic mechanisms by which chromatin structure can dictate AFR mechanisms and will present evidence of how pathogenic yeast, specifically from the Candida genus, modify chromatin structure to promote survival in the presence of anti-fungal drugs. We also discuss the mechanisms by which anti-chromatin therapy, specifically lysine deacetylase inhibitors, influence the acquisition and phenotypic expression of AFR in Candida spp. and their potential as effective adjuvants to mitigate against AFR.
Research on Urban and Rural Coordination Development and Its Driving Force Based on the Space-time Evolvement Taking Guangdong Province as an Example
Authors: Tang Daizhong , Li Baorui , Qiu Yuan , Zhao Linlin
Published: July 2020

Based on the background of the change in the urban–rural relationship in Guangdong Province, this paper constructs an analysis framework of urban and rural coordination development. Using the data of 19 administrative units above prefecture level in Guangdong Province, this paper studies the space–time evolution of urban and rural coordination development during 2000–2015 through Principal Component Analysis (PCA) and Exploratory Spatial Data Analysis (ESDA) and explores the influencing factors and driving forces behind it. It is found that there is club convergence in the urban and rural coordination development in Guangdong Province. This kind of convergence is reflected in the findings that the east bank of the Pearl River estuary is the best area for the urban and rural coordination development where Guangzhou, Dongguan, Shenzhen is the core and the level of urban and rural coordination development in the east, west and north of Guangdong Province is relatively low, which also reflects a geographical polarization feature. Based on the analysis of the factors that promote the urban and rural coordination development in the main years of 2000–2015, it can be concluded that location, economic development and urbanization level are the most important driving forces, followed by industrial structure. This research can be used as a decision-making reference for urban and rural coordination development and new countryside construction in China in the New Era.
Erratum: Chen, Z. and Etsion, I. Recent Development in Modeling of Coated Spherical Contact. Materials 2020, 13, 460
Authors: Chen Zhou , Etsion Izhak
Published: July 2020

The authors wish to make the following corrections to this paper [...]
Face Masks and Respirators in the Fight Against the COVID-19 Pandemic: A Review of Current Materials, Advances and Future Perspectives
Authors: O’Dowd Kris , Nair Keerthi M. , Forouzandeh Parnia , Mathew Snehamol , Grant Jamie , Moran Ruth , Bartlett John , Bird Jerry , Pillai Suresh C.
Published: July 2020

The outbreak of COVID-19 has spread rapidly across the globe, greatly affecting how humans as a whole interact, work and go about their daily life. One of the key pieces of personal protective equipment (PPE) that is being utilised to return to the norm is the face mask or respirator. In this review we aim to examine face masks and respirators, looking at the current materials in use and possible future innovations that will enhance their protection against SARS-CoV-2. Previous studies concluded that cotton, natural silk and chiffon could provide above 50% efficiency. In addition, it was found that cotton quilt with a highly tangled fibrous nature provides efficient filtration in the small particle size range. Novel designs by employing various filter materials such as nanofibres, silver nanoparticles, and nano-webs on the filter surfaces to induce antimicrobial properties are also discussed in detail. Modification of N95/N99 masks to provide additional filtration of air and to deactivate the pathogens using various technologies such as low- temperature plasma is reviewed. Legislative guidelines for selecting and wearing facial protection are also discussed. The feasibility of reusing these masks will be examined as well as a discussion on the modelling of mask use and the impact wearing them can have. The use of Artificial Intelligence (AI) models and its applications to minimise or prevent the spread of the virus using face masks and respirators is also addressed. It is concluded that a significant amount of research is required for the development of highly efficient, reusable, anti-viral and thermally regulated face masks and respirators.
Strong Interactions between Austenite and the Matrix of Medium-Mn Steel during Intercritical Annealing
Authors: Zhou Tianpeng , Wang Cunyu , Wang Chang , Cao Wenquan , Chen Zejun
Published: July 2020

The effects of heat treatment on the microstructure evolution was studied in regards to austenite nucleation and grain growth. It was found that the austenite nucleation and matrix recrystallization kinetics of samples annealed at 675 °C for different times were revealed, implying a strong interaction between the ferrite matrix and austenite. The recrystallization of the matrix during annealing provided favorable conditions for austenite nucleation and growth, and the formation of austenite during this process reduced the matrix recrystallization kinetics, thus delaying the recrystallization process of the matrix around the austenite grains. The statistical results for the austenite grain size under different annealing temperatures indicated that the average grain size of the austenite slightly increases with increasing of the annealing temperature, but the austenite with the largest grain size grows faster at the same temperature. This difference is attributed to the strict Kurdjumov Sachs (KS) orientation relationship (OR) between the austenite grains and the matrix, because the growth of austenite with a strict KS OR with the matrix is often inhibited during annealing. In contrast, the austenite maintains a non-strict KS OR with the matrix and can grow preferentially with increasing annealing temperature and time.
Effect of Supplementary Materials on the Autogenous Shrinkage of Cement Paste
Authors: Lu Tianshi , Li Zhenming , Huang Hao
Published: July 2020

In recent years more and more attention has been given to autogenous shrinkage due to the increasing use of high-performance concrete, which always contains supplementary materials. With the addition of supplementary materials—e.g., fly ash and blast furnace slag—internal relative humidity, chemical shrinkage and mechanical properties of cement paste will be affected. These properties significantly influence the autogenous shrinkage of cement paste. In this study, three supplementary materials—i.e., silica fume, fly ash and blast furnace slag—are investigated. Measurements of final setting time, internal relative humidity, chemical shrinkage, compressive strength and autogenous deformation of the cement pastes with and without supplementary materials are presented. Two water-binder ratios, 0.3 and 0.4, are considered. The effects of different supplementary materials on autogenous shrinkage of cement paste are discussed.