bluuebunny/crossref_metadata_2025 huggingface dataset:
Unravelling the Role of Socioeconomic Forces in the Early Stage of COVID-19 Pandemic: A Global Analysis
Authors: Rontos Kostas , Syrmali Maria-Eleni , Salvati Luca
Published: June 2021

The COVID-19 pandemic has rapidly evolved into an acute health crisis with extensive socioeconomic and demographic consequences. The severity of the COVID-19 pandemic requires a refined (and more comprehensive) understanding of virus dissemination over space, transmission mechanisms, clinical features, and risk factors. In line with this assumption, the present study illustrates a comparative, empirical analysis of the role of socioeconomic and demographic dimensions in the early stages of the COVID-19 pandemic grounded on a large set of indicators comparing the background context across a global sample of countries. Results indicate that—in addition to epidemiological factors—basic socioeconomic forces significantly shaped contagions as well as hospitalization and death rates across countries. As a response to the global crisis driven by the COVID-19 pandemic, all-embracing access to healthcare services should be strengthened along with the development of sustainable health systems supported by appropriate resources and skills. The empirical findings of this study have direct implications for the coordination of on-going, global efforts aimed at containing COVID-19 (and other, future) pandemics.
The Application of the Adult Self-Report and the Adult Behavior Checklist Form to Chinese Adults: Syndrome Structure, Inter-Informant Agreement, and Cultural Comparison
Authors: Liu Jianghong , Dong Fanghong , Lee Christopher M. , Reyes Jenny , Ivanova Masha
Published: June 2021

Given the global public health burden of mental illness, there is a critical need for culturally validated psychopathology assessment tools that perform well in diverse societies. This study examines the psychometric properties of the Adult Self-Report (ASR) and Adult Behavioral Checklist (ABCL) from the Achenbach System of Empirically Based Assessments in adults in China. Chinese adults (N = 1276) and their spouses completed the ASR and ABCL, respectively. We conducted confirmatory factor analysis on 99 ASR items and 93 ABCL items. Estimators of model fit confirmed that both measures demonstrated excellent fit (e.g., root mean square error of approximation = 0.016 and 0.018, respectively). Syndrome loadings on both measures were satisfactory but generally higher on the ASR. Neither gender nor education had significant effects, but there were informant x gender effects on most problem scales. Cross-informant agreement correlations between the ASR and ABCL were medium to large. Findings from this novel sample of Chinese adults are consistent with previous validation studies supporting the dimensionality, syndrome structure, gender differences, and inter-informant agreement of the ASR and ABCL. Our findings contribute to the cross-cultural understanding of mental health assessment and offer a psychometrically sound approach to measuring adult psychopathology in Chinese populations.
MoSIoT: Modeling and Simulating IoT Healthcare-Monitoring Systems for People with Disabilities
Authors: Meliá Santiago , Nasabeh Shahabadin , Luján-Mora Sergio , Cachero Cristina
Published: June 2021

The need to remotely monitor people with disabilities has increased due to growth in their number in recent years. The democratization of Internet of Things (IoT) devices facilitates the implementation of healthcare-monitoring systems (HMSs) that are capable of supporting disabilities and diseases. However, to achieve their full potential, these devices must efficiently address the customization demanded by different IoT HMS scenarios. This work introduces a new approach, called Modeling Scenarios of Internet of Things (MoSIoT), which allows healthcare experts to model and simulate IoT HMS scenarios defined for different disabilities and diseases. MoSIoT comprises a set of models based on the model-driven engineering (MDE) paradigm, which first allows simulation of a complete IoT HMS scenario, followed by generation of a final IoT system. In the current study, we used a real scenario defined by a recognized medical publication for a patient with Alzheimer’s disease to validate this proposal. Furthermore, we present an implementation based on an enterprise cloud architecture that provides the simulation data to a commercial IoT hub, such as Azure IoT Central.
Recent Insights into the Interplay of Alpha-Synuclein and Sphingolipid Signaling in Parkinson’s Disease
Authors: Motyl Joanna A. , Strosznajder Joanna B. , Wencel Agnieszka , Strosznajder Robert P.
Published: June 2021

Molecular studies have provided increasing evidence that Parkinson’s disease (PD) is a protein conformational disease, where the spread of alpha-synuclein (ASN) pathology along the neuraxis correlates with clinical disease outcome. Pathogenic forms of ASN evoke oxidative stress (OS), neuroinflammation, and protein alterations in neighboring cells, thereby intensifying ASN toxicity, neurodegeneration, and neuronal death. A number of evidence suggest that homeostasis between bioactive sphingolipids with opposing function—e.g., sphingosine-1-phosphate (S1P) and ceramide—is essential in pro-survival signaling and cell defense against OS. In contrast, imbalance of the “sphingolipid biostat” favoring pro-oxidative/pro-apoptotic ceramide-mediated changes have been indicated in PD and other neurodegenerative disorders. Therefore, we focused on the role of sphingolipid alterations in ASN burden, as well as in a vast range of its neurotoxic effects. Sphingolipid homeostasis is principally directed by sphingosine kinases (SphKs), which synthesize S1P—a potent lipid mediator regulating cell fate and inflammatory response—making SphK/S1P signaling an essential pharmacological target. A growing number of studies have shown that S1P receptor modulators, and agonists are promising protectants in several neurological diseases. This review demonstrates the relationship between ASN toxicity and alteration of SphK-dependent S1P signaling in OS, neuroinflammation, and neuronal death. Moreover, we discuss the S1P receptor-mediated pathways as a novel promising therapeutic approach in PD.
Multidiscipline Immunotherapy-Based Rational Combinations for Robust and Durable Efficacy in Brain Metastases from Renal Cell Carcinoma
Authors: Lee Hye-Won
Published: June 2021

Advanced imaging techniques for diagnosis have increased awareness on the benefits of brain screening, facilitated effective control of extracranial disease, and prolonged life expectancy of metastatic renal cell carcinoma (mRCC) patients. Brain metastasis (BM) in patients with mRCC (RCC-BM) is associated with grave prognoses, a high degree of morbidity, dedicated assessment, and unresponsiveness to conventional systemic therapeutics. The therapeutic landscape of RCC-BM is rapidly changing; however, survival outcomes remain poor despite standard surgery and radiation, highlighting the unmet medical needs and the requisite for advancement in systemic therapies. Immune checkpoint inhibitors (ICIs) are one of the most promising strategies to treat RCC-BM. Understanding the role of brain-specific tumor immune microenvironment (TIME) is important for developing rationale-driven ICI-based combination strategies that circumvent tumor intrinsic and extrinsic factors and complex positive feedback loops associated with resistance to ICIs in RCC-BM via combination with ICIs involving other immunological pathways, anti-antiangiogenic multiple tyrosine kinase inhibitors, and radiotherapy; therefore, novel combination approaches are being developed for synergistic potential against RCC-BM; however, further prospective investigations with longer follow-up periods are required to improve the efficacy and safety of combination treatments and to elucidate dynamic predictive biomarkers depending on the interactions in the brain TIME.
The Role of Nuclear Factor of Activated T Cells 5 in Hyperosmotic Stress-Exposed Human Lens Epithelial Cells
Authors: Kim Gyu-Nam , Hah Young-Sool , Seong Hyemin , Yoo Woong-Sun , Choi Mee-Young , Cho Hee-Young , Yun Seung Pil , Kim Seong-Jae
Published: June 2021

We investigated the role of nuclear factor of activated T cells 5 (NFAT5) under hyperosmotic conditions in human lens epithelial cells (HLECs). Hyperosmotic stress decreased the viability of human lens epithelial B-3 cells and significantly increased NFAT5 expression. Hyperosmotic stress-induced cell death occurred to a greater extent in NFAT5-knockout (KO) cells than in NFAT5 wild-type (NFAT5 WT) cells. Bcl-2 and Bcl-xl expression was down-regulated in NFAT5 WT cells and NFAT5 KO cells under hyperosmotic stress. Pre-treatment with a necroptosis inhibitor (necrostatin-1) significantly blocked hyperosmotic stress-induced death of NFAT5 KO cells, but not of NFAT5 WT cells. The phosphorylation levels of receptor-interacting protein kinase 1 (RIP1) and RIP3, which indicate the occurrence of necroptosis, were up-regulated in NFAT5 KO cells, suggesting that death of these cells is predominantly related to the necroptosis pathway. This finding is the first to report that necroptosis occurs when lens epithelial cells are exposed to hyperosmolar conditions, and that NFAT5 is involved in this process.
A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia
Authors: Martínez-Rubio Álvaro , Chulián Salvador , Blázquez Goñi Cristina , Ramírez Orellana Manuel , Pérez Martínez Antonio , Navarro-Zapata Alfonso , Ferreras Cristina , Pérez-García Victor M. , Rosa María
Published: June 2021

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients’ experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.
The Role of lncRNAs in the Stem Phenotype of Pancreatic Ductal Adenocarcinoma
Authors: Melendez-Zajgla Jorge , Maldonado Vilma
Published: June 2021

Pancreatic ductal adenocarcinoma is one of the deadliest tumors. This neoplasia is characterized by an important cellular and phenotypic heterogeneity. In particular, it has been shown that at least two subtypes can be found: basal-like, which presents stem-like properties, and classical. Cancer stem cells have been isolated and characterized from these tumors, showing their dependance on general and tissue-specific stem transcription factors and signaling pathways. Nevertheless, little is known about their tissue microenvironment and cell non-autonomous regulators, such as long-non-coding RNAs. (lncRNAs). In this review, we summarize the current knowledge about the positive and negative effects of lncRNAs in the stemness phenotype of pancreatic ductal adenocarcinoma cancer (PDAC).
pHEMA: An Overview for Biomedical Applications
Authors: Zare Mina , Bigham Ashkan , Zare Mohamad , Luo Hongrong , Rezvani Ghomi Erfan , Ramakrishna Seeram
Published: June 2021

Poly(2-hydroxyethyl methacrylate) (pHEMA) as a biomaterial with excellent biocompatibility and cytocompatibility elicits a minimal immunological response from host tissue making it desirable for different biomedical applications. This article seeks to provide an in-depth overview of the properties and biomedical applications of pHEMA for bone tissue regeneration, wound healing, cancer therapy (stimuli and non-stimuli responsive systems), and ophthalmic applications (contact lenses and ocular drug delivery). As this polymer has been widely applied in ophthalmic applications, a specific consideration has been devoted to this field. Pure pHEMA does not possess antimicrobial properties and the site where the biomedical device is employed may be susceptible to microbial infections. Therefore, antimicrobial strategies such as the use of silver nanoparticles, antibiotics, and antimicrobial agents can be utilized to protect against infections. Therefore, the antimicrobial strategies besides the drug delivery applications of pHEMA were covered. With continuous research and advancement in science and technology, the outlook of pHEMA is promising as it will most certainly be utilized in more biomedical applications in the near future. The aim of this review was to bring together state-of-the-art research on pHEMA and their applications.
Neuroprotective Metabolites of Hericium erinaceus Promote Neuro-Healthy Aging
Authors: Roda Elisa , Priori Erica Cecilia , Ratto Daniela , De Luca Fabrizio , Di Iorio Carmine , Angelone Paola , Locatelli Carlo Alessandro , Desiderio Anthea , Goppa Lorenzo , Savino Elena , Bottone Maria Grazia , Rossi Paola
Published: June 2021

Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.
Sinking Our Teeth in Getting Dental Stem Cells to Clinics for Bone Regeneration
Authors: Shoushrah Sarah Hani , Transfeld Janis Lisa , Tonk Christian Horst , Büchner Dominik , Witzleben Steffen , Sieber Martin A. , Schulze Margit , Tobiasch Edda
Published: June 2021

Dental stem cells have been isolated from the medical waste of various dental tissues. They have been characterized by numerous markers, which are evaluated herein and differentiated into multiple cell types. They can also be used to generate cell lines and iPSCs for long-term in vitro research. Methods for utilizing these stem cells including cellular systems such as organoids or cell sheets, cell-free systems such as exosomes, and scaffold-based approaches with and without drug release concepts are reported in this review and presented with new pictures for clarification. These in vitro applications can be deployed in disease modeling and subsequent pharmaceutical research and also pave the way for tissue regeneration. The main focus herein is on the potential of dental stem cells for hard tissue regeneration, especially bone, by evaluating their potential for osteogenesis and angiogenesis, and the regulation of these two processes by growth factors and environmental stimulators. Current in vitro and in vivo publications show numerous benefits of using dental stem cells for research purposes and hard tissue regeneration. However, only a few clinical trials currently exist. The goal of this review is to pinpoint this imbalance and encourage scientists to pick up this research and proceed one step further to translation.
Characterization of the Mitochondrial Genome of a Wheat AL-Type Male Sterility Line and the Candidate CMS Gene
Authors: Hao Miaomiao , Yang Wenlong , Lu Weiwen , Sun Linhe , Shoaib Muhammad , Sun Jiazhu , Liu Dongcheng , Li Xin , Zhang Aimin
Published: June 2021

Heterosis utilization is very important in hybrid seed production. An AL-type cytoplasmic male sterile (CMS) line has been used in wheat-hybrid seed production, but its sterility mechanism has not been explored. In the present study, we sequenced and verified the candidate CMS gene in the AL-type sterile line (AL18A) and its maintainer line (AL18B). In the late uni-nucleate stage, the tapetum cells of AL18A showed delayed programmed cell death (PCD) and termination of microspore at the bi-nucleate stage. As compared to AL18B, the AL18A line produced 100% aborted pollens. The mitochondrial genomes of AL18A and AL18B were sequenced using the next generation sequencing such as Hiseq and PacBio. It was found that the mitochondrial genome of AL18A had 99% similarity with that of Triticum timopheevii, AL18B was identical to that of Triticum aestivum cv. Chinese Yumai. Based on transmembrane structure prediction, 12 orfs were selected as candidate CMS genes, including a previously suggested orf256. Only the lines harboring orf279 showed sterility in the transgenic Arabidopsis system, indicating that orf279 is the CMS gene in the AL-type wheat CMS lines. These results provide a theoretical basis and data support to further analyze the mechanism of AL-type cytoplasmic male sterility in wheat.
Adeno-Associated Viral Vectors as Versatile Tools for Parkinson’s Research, Both for Disease Modeling Purposes and for Therapeutic Uses
Authors: Fajardo-Serrano Ana , Rico Alberto J. , Roda Elvira , Honrubia Adriana , Arrieta Sandra , Ariznabarreta Goiaz , Chocarro Julia , Lorenzo-Ramos Elena , Pejenaute Alvaro , Vázquez Alfonso , Lanciego José Luis
Published: June 2021

It is without any doubt that precision medicine therapeutic strategies targeting neurodegenerative disorders are currently witnessing the spectacular rise of newly designed approaches based on the use of viral vectors as Trojan horses for the controlled release of a given genetic payload. Among the different types of viral vectors, adeno-associated viruses (AAVs) rank as the ones most commonly used for the purposes of either disease modeling or for therapeutic strategies. Here, we reviewed the current literature dealing with the use of AAVs within the field of Parkinson’s disease with the aim to provide neuroscientists with the advice and background required when facing a choice on which AAV might be best suited for addressing a given experimental challenge. Accordingly, here we will be summarizing some insights on different AAV serotypes, and which would be the most appropriate AAV delivery route. Next, the use of AAVs for modeling synucleinopathies is highlighted, providing potential readers with a landscape view of ongoing pre-clinical and clinical initiatives pushing forward AAV-based therapeutic approaches for Parkinson’s disease and related synucleinopathies.
Proteomics of Homeobox7 Enhanced Salt Tolerance in Mesembryanthemum crystallinum
Authors: Zhang Xuemei , Tan Bowen , Zhu Dan , Dufresne Daniel , Jiang Tingbo , Chen Sixue
Published: June 2021

Mesembryanthemum crystallinum (common ice plant) is a halophyte species that has adapted to extreme conditions. In this study, we cloned a McHB7 transcription factor gene from the ice plant. The expression of McHB7 was significantly induced by 500 mM NaCl and it reached the peak under salt treatment for 7 days. The McHB7 protein was targeted to the nucleus. McHB7-overexpressing in ice plant leaves through Agrobacterium-mediated transformation led to 25 times more McHB7 transcripts than the non-transformed wild type (WT). After 500 mM NaCl treatment for 7 days, the activities of superoxide dismutase (SOD) and peroxidase (POD) and water content of the transgenic plants were higher than the WT, while malondialdehyde (MDA) was decreased in the transgenic plants. A total of 1082 and 1072 proteins were profiled by proteomics under control and salt treatment, respectively, with 22 and 11 proteins uniquely identified under control and salt stress, respectively. Among the 11 proteins, 7 were increased and 4 were decreased after salt treatment. Most of the proteins whose expression increased in the McHB7 overexpression (OE) ice plants under high salinity were involved in transport regulation, catalytic activities, biosynthesis of secondary metabolites, and response to stimulus. The results demonstrate that the McHB7 transcription factor plays a positive role in improving plant salt tolerance.
Aetiology and Pathogenesis of Cutaneous Melanoma: Current Concepts and Advances
Authors: Strashilov Strahil , Yordanov Angel
Published: June 2021

Melanoma develops from malignant transformations of the pigment-producing melanocytes. If located in the basal layer of the skin epidermis, melanoma is referred to as cutaneous, which is more frequent. However, as melanocytes are be found in the eyes, ears, gastrointestinal tract, genitalia, urinary system, and meninges, cases of mucosal melanoma or other types (e.g., ocular) may occur. The incidence and morbidity of cutaneous melanoma (cM) are constantly increasing worldwide. Australia and New Zealand are world leaders in this regard with a morbidity rate of 54/100,000 and a mortality rate of 5.6/100,000 for 2015. The aim of this review is to consolidate and present the data related to the aetiology and pathogenesis of cutaneous melanoma, thus rendering them easier to understand. In this article we will discuss these problems and the possible impacts on treatment for this disease.
Molecular Physiology of Anaerobic Phototrophic Purple and Green Sulfur Bacteria
Authors: Kushkevych Ivan , Procházka Jiří , Gajdács Márió , Rittmann Simon K.-M. R. , Vítězová Monika
Published: June 2021

There are two main types of bacterial photosynthesis: oxygenic (cyanobacteria) and anoxygenic (sulfur and non-sulfur phototrophs). Molecular mechanisms of photosynthesis in the phototrophic microorganisms can differ and depend on their location and pigments in the cells. This paper describes bacteria capable of molecular oxidizing hydrogen sulfide, specifically the families Chromatiaceae and Chlorobiaceae, also known as purple and green sulfur bacteria in the process of anoxygenic photosynthesis. Further, it analyzes certain important physiological processes, especially those which are characteristic for these bacterial families. Primarily, the molecular metabolism of sulfur, which oxidizes hydrogen sulfide to elementary molecular sulfur, as well as photosynthetic processes taking place inside of cells are presented. Particular attention is paid to the description of the molecular structure of the photosynthetic apparatus in these two families of phototrophs. Moreover, some of their molecular biotechnological perspectives are discussed.
Short-Term Strength Exercise Reduces Hepatic Insulin Resistance in Obese Mice by Reducing PTP1B Content, Regardless of Changes in Body Weight
Authors: da Cruz Rodrigues Kellen Cristina , Martins Pereira Rodrigo , Peruca Guilherme Francisco , Torres Barbosa Lucas Wesley , Ramos Sant’Ana Marcella , Rosetto Muñoz Vitor , Morelli Ana Paula , Moreira Simabuco Fernando , Sanchez Ramos da Silva Adelino , Esper Cintra Dennys , Rochete Ropelle Eduardo , Pauli José Rodrigo , de Moura Leandro Pereira
Published: June 2021

Obesity is closely related to insulin resistance and type 2 diabetes genesis. The liver is a key organ to glucose homeostasis since insulin resistance in this organ increases hepatic glucose production (HGP) and fasting hyperglycemia. The protein-tyrosine phosphatase 1B (PTP1B) may dephosphorylate the IR and IRS, contributing to insulin resistance in this organ. Aerobic exercise is a great strategy to increase insulin action in the liver by reducing the PTP1B content. In contrast, no study has shown the direct effects of strength training on the hepatic metabolism of PTP1B. Therefore, this study aims to investigate the effects of short-term strength exercise (STSE) on hepatic insulin sensitivity and PTP1B content in obese mice, regardless of body weight change. To achieve this goal, obese Swiss mice were submitted to a strength exercise protocol lasting 15 days. The results showed that STSE increased Akt phosphorylation in the liver and enhanced the control of HGP during the pyruvate tolerance test. Furthermore, sedentary obese animals increased PTP1B content and decreased IRS-1/2 tyrosine phosphorylation; however, STSE was able to reverse this scenario. Therefore, we conclude that STSE is an important strategy to improve the hepatic insulin sensitivity and HGP by reducing the PTP1B content in the liver of obese mice, regardless of changes in body weight.
Potential Molecular Targets for Treating Neuropathic Orofacial Pain Based on Current Findings in Animal Models
Authors: Nagakura Yukinori , Nagaoka Shogo , Kurose Takahiro
Published: June 2021

This review highlights potential molecular targets for treating neuropathic orofacial pain based on current findings in animal models. Preclinical research is currently elucidating the pathophysiology of the disease and identifying the molecular targets for better therapies using animal models that mimic this category of orofacial pain, especially post-traumatic trigeminal neuropathic pain (PTNP) and primary trigeminal neuralgia (PTN). Animal models of PTNP and PTN simulate their etiologies, that is, trauma to the trigeminal nerve branch and compression of the trigeminal root entry zone, respectively. Investigations in these animal models have suggested that biological processes, including inflammation, enhanced neuropeptide-mediated pain signal transmission, axonal ectopic discharges, and enhancement of interactions between neurons and glial cells in the trigeminal pathway, are underlying orofacial pain phenotypes. The molecules associated with biological processes, whose expressions are substantially altered following trigeminal nerve damage or compression of the trigeminal nerve root, are potentially involved in the generation and/or exacerbation of neuropathic orofacial pain and can be potential molecular targets for the discovery of better therapies. Application of therapeutic candidates, which act on the molecular targets and modulate biological processes, attenuates pain-associated behaviors in animal models. Such therapeutic candidates including calcitonin gene-related peptide receptor antagonists that have a reasonable mechanism for ameliorating neuropathic orofacial pain and meet the requirements for safe administration to humans seem worth to be evaluated in clinical trials. Such prospective translation of the efficacy of therapeutic candidates from animal models to human patients would help develop better therapies for neuropathic orofacial pain.
Novel TTLL5 Variants Associated with Cone-Rod Dystrophy and Early-Onset Severe Retinal Dystrophy
Authors: Smirnov Vasily , Grunewald Olivier , Muller Jean , Zeitz Christina , Obermaier Carolin D. , Devos Aurore , Pelletier Valérie , Bocquet Béatrice , Andrieu Camille , Bacquet Jean-Louis , Lebredonchel Elodie , Mohand-Saïd Saddek , Defoort-Dhellemmes Sabine , Sahel José-Alain , Dollfus Hélène , Zanlonghi Xavier , Audo Isabelle , Meunier Isabelle , Boulanger-Scemama Elise , Dhaenens Claire-Marie
Published: June 2021

Variants of the TTLL5 gene, which encodes tubulin tyrosine ligase-like family member five, are a rare cause of cone dystrophy (COD) or cone-rod dystrophy (CORD). To date, only a few TTLL5 patients have been clinically and genetically described. In this study, we report five patients harbouring biallelic variants of TTLL5. Four adult patients presented either COD or CORD with onset in the late teenage years. The youngest patient had a phenotype of early onset severe retinal dystrophy (EOSRD). Genetic analysis was performed by targeted next generation sequencing of gene panels and assessment of copy number variants (CNV). We identified eight variants, of which six were novel, including two large multiexon deletions in patients with COD or CORD, while the EOSRD patient harboured the novel homozygous p.(Trp640*) variant and three distinct USH2A variants, which might explain the observed rod involvement. Our study highlights the role of TTLL5 in COD/CORD and the importance of large deletions. These findings suggest that COD or CORD patients lacking variants in known genes may harbour CNVs to be discovered in TTLL5, previously undetected by classical sequencing methods. In addition, variable phenotypes in TTLL5-associated patients might be due to the presence of additional gene defects.
Genome-Wide Identification of the Nramp Gene Family in Spirodela polyrhiza and Expression Analysis under Cadmium Stress
Authors: Chen Yan , Zhao Xuyao , Li Gaojie , Kumar Sunjeet , Sun Zuoliang , Li Yixian , Guo Wenjun , Yang Jingjing , Hou Hongwei
Published: June 2021

Natural resistance-associated macrophage proteins (Nramps) are specific metal transporters in plants with different functions among various species. The evolutionary and functional information of the Nramp gene family in Spirodela polyrhiza has not been previously reported in detail. To identify the Nramp genes in S. polyrhiza, we performed genome-wide identification, characterization, classification, and cis-elements analysis among 22 species with 138 amino acid sequences. We also conducted chromosomal localization and analyzed the synteny relationship, promoter, subcellular localization, and expression patterns in S. polyrhiza. β-Glucuronidase staining indicated that SpNramp1 and SpNramp3 mainly accumulated in the root and joint between mother and daughter frond. Moreover, SpNramp1 was also widely displayed in the frond. SpNramp2 was intensively distributed in the root and frond. Quantitative real-time PCR results proved that the SpNramp gene expression level was influenced by Cd stress, especially in response to Fe or Mn deficiency. The study provides detailed information on the SpNramp gene family and their distribution and expression, laying a beneficial foundation for functional research.
Nesting, Sex Ratio and Natural Enemies of the Giant Resin Bee in Relation to Native Species in Europe
Authors: Straffon-Díaz Sara , Carisio Luca , Manino Aulo , Biella Paolo , Porporato Marco
Published: June 2021

Megachile sculpturalis (Smith, 1853) is the first exotic bee species in Europe. Its remarkably fast expansion across this continent is leading to a growing concern on the extent of negative impacts to the native fauna. To evaluate the interactions of exotic bees with local wild bees, we set up trap nests for above-ground nesting bees on a semi-urban area of north-western Italy. We aimed to investigate the interaction in artificial traps between the exotic and native wild bees and to assess offspring traits accounting for exotic bee fitness: progeny sex ratio and incidence of natural enemies. We found that the tunnels occupied by exotic bees were already cohabited by O. cornuta, and thus the cells of later nesting alien bees may block the native bee emergence for the next year. The progeny sex ratio of M. sculpturalis was strongly unbalanced toward males, indicating a temporary adverse population trend in the local invaded area. In addition, we documented the presence of three native natural enemies affecting the brood of the exotic bee. Our results bring out new insights on how the M. sculpturalis indirectly competes with native species and on its performance in new locations.
Fat Body—Multifunctional Insect Tissue
Authors: Skowronek Patrycja , Wójcik Łukasz , Strachecka Aneta
Published: June 2021

The biodiversity of useful organisms, e.g., insects, decreases due to many environmental factors and increasing anthropopressure. Multifunctional tissues, such as the fat body, are key elements in the proper functioning of invertebrate organisms and resistance factors. The fat body is the center of metabolism, integrating signals, controlling molting and metamorphosis, and synthesizing hormones that control the functioning of the whole body and the synthesis of immune system proteins. In fat body cells, lipids, carbohydrates and proteins are the substrates and products of many pathways that can be used for energy production, accumulate as reserves, and mobilize at the appropriate stage of life (diapause, metamorphosis, flight), determining the survival of an individual. The fat body is the main tissue responsible for innate and acquired humoral immunity. The tissue produces bactericidal proteins and polypeptides, i.e., lysozyme. The fat body is also important in the early stages of an insect’s life due to the production of vitellogenin, the yolk protein needed for the development of oocytes. Although a lot of information is available on its structure and biochemistry, the fat body is an interesting research topic on which much is still to be discovered.
Listening to Slugs: Acceptability and Consumption of Molluscicide Pellets by the Grey Field Slug, Deroceras reticulatum
Authors: de Silva Samantha Mirhaya , Chesmore David , Smith Jack , Port Gordon
Published: June 2021

Gastropod damage to crop plants has a significant economic impact on agricultural and horticultural industries worldwide, with the Grey Field Slug (Deroceras reticulatum (Müller)) considered the main mollusc pest in the United Kingdom and in many other temperate areas. The prevailing form of crop protection is pellets containing the active ingredient, metaldehyde. Metaldehyde can cause paralysis and death in the mollusc, depending on the amount ingested. The paralysing effects may result in reduced pellet consumption. A greater understanding of metaldehyde consumption may reveal an area that can be manipulated using novel molluscicide formulations. Novel pellet types included commercial metaldehyde pellets coated so that metaldehyde is released more slowly. In both laboratory and arena trials, an audio sensor was used to record individual slugs feeding on a variety of pellet types, including commercially available toxic pellets (metaldehyde and ferric phosphate) and novel metaldehyde formulations. The sensor was used to record the length of each bite and the total number of bites. There was no significant difference in the length of bites between pellet types in laboratory trials. Novel pellets were not consumed more than commercial pellet types. Commercial pellet types did not differ in consumption.
Safety, Fear and Neuromuscular Responses after a Resisted Knee Extension Performed to Failure in Patients with Severe Haemophilia
Authors: Calatayud Joaquín , Martín-Cuesta Jonathan , Carrasco Juan J. , Pérez-Alenda Sofía , Cruz-Montecinos Carlos , Andersen Lars L. , Querol-Giner Felipe , Casaña José
Published: June 2021

Background: low–moderate intensity strength training to failure increases strength and muscle hypertrophy in healthy people. However, no study assessed the safety and neuromuscular response of training to failure in people with severe haemophilia (PWH). The purpose of the study was to analyse neuromuscular responses, fear of movement, and possible adverse effects in PWH, after knee extensions to failure. Methods: twelve severe PWH in prophylactic treatment performed knee extensions until failure at an intensity of five on the Borg CR10 scale. Normalised values of amplitude (nRMS) and neuromuscular fatigue were determined using surface electromyography for the rectus femoris, vastus medialis, and vastus lateralis. After the exercise, participants were asked about their perceived change in fear of movement, and to report any possible adverse effects. Results: Patients reported no adverse effects or increased fear. The nRMS was maximal for all the muscles before failure, the median frequency decreased, and wavelet index increased during the repetitions. The vastus lateralis demonstrated a higher maximum nRMS threshold and earlier fatigue, albeit with a lower and more progressive overall fatigue. Conclusions: severe PWH with adequate prophylactic treatment can perform knee extensions to task failure using a moderate intensity, without increasing fear of movement, or adverse effects.
Plastic Changes in Pain and Motor Network Induced by Chronic Burn Pain
Authors: Joo So Young , Park Chang-hyun , Cho Yoon Soo , Seo Cheong Hoon , Ohn Suk Hoon
Published: June 2021

Musculoskeletal diseases with chronic pain are difficult to control because of their association with both central as well as the peripheral nervous system. In burn patients, chronic pain is one of the major complications that cause persistent discomfort. The peripheral mechanisms of chronic pain by burn have been greatly revealed through studies, but the central mechanisms have not been identified. Our study aimed to characterize the cerebral plastic changes secondary to electrical burn (EB) and non-electrical burn (NEB) by measuring cerebral blood volume (CBV). Sixty patients, twenty with electrical burn (EB) and forty with non-electrical burn (NEB), having chronic pain after burn, along with twenty healthy controls, participated in the study. Voxel-wise comparisons of relative CBV maps were made among EB, NEB, and control groups over the entire brain volume. The CBV was measured as an increase and decrease in the pain and motor network including postcentral gyrus, frontal lobe, temporal lobe, and insula in the hemisphere associated with burned limbs in the whole burn group. In the EB group, CBV was decreased in the frontal and temporal lobes in the hemisphere associated with the burned side. In the NEB group, the CBV was measured as an increase or decrease in the pain and motor network in the postcentral gyrus, precentral gyrus, and frontal lobe of the hemisphere associated with the burn-affected side. Among EB and NEB groups, the CBV changes were not different. Our findings provide evidence of plastic changes in pain and motor network in patients with chronic pain by burn.
Management of Dyslipidemia in Women and Men with Coronary Heart Disease: Results from POLASPIRE Study
Authors: Setny Małgorzata , Jankowski Piotr , Krzykwa Agnieszka , Kamiński Karol A. , Gąsior Zbigniew , Haberka Maciej , Czarnecka Danuta , Pająk Andrzej , Kozieł Paweł , Szóstak-Janiak Karolina , Sawicka Emilia , Stachurska Zofia , Kosior Dariusz A.
Published: June 2021

Cardiovascular diseases (CVDs) are the leading cause of death in Poland. Starting from 1992, a gradual decrease in mortality due to CVDs has been observed, which is less noticeable in women. Following this notion, we assessed sex differences in the implementation of ESC recommendations regarding lipid control and the use of statins as part of secondary CVDs prevention in 1236 patients with acute coronary syndrome or elective coronary revascularization within the last 6–24 months. During hospitalization women had more frequently abnormal TC levels than men (p = 0.035), with overall higher TC levels (p = 0.009) and lower HDL-C levels (p = 0.035). In the oldest group, they also had more frequently elevated LDL-C levels (p = 0.033). Similar relationships were found during the follow-up visit. In addition, women less often achieved the secondary lipid therapeutic goal for non-HDL-C (p = 0.009). At discharge from hospital women were less frequently prescribed statins (p = 0.001), which included high-intensity statins (p = 0.002). At the follow-up visit the use of high-intensity statins was still less frequent in women (p = 0.02). We conclude that women generally have less optimal lipid profiles than men and are less likely to receive high-intensity statins. There is a need for more organized care focused on the management of risk factors.
Arterioportal Fistulas (APFs) in Pediatric Patients: Single Center Experience with Interventional Radiological versus Conservative Management and Clinical Outcomes
Authors: Marra Paolo , Dulcetta Ludovico , Carbone Francesco Saverio , Agazzi Roberto , Muglia Riccardo , Bonaffini Pietro Andrea , Bonanomi Ezio , Colledan Michele , D’Antiga Lorenzo , Venturini Massimo , Sironi Sandro
Published: June 2021

Arterioportal fistulas (APFs) are uncommon vascular abnormalities with a heterogeneous etiology. In pediatric orthotopic liver transplantation (OLT), APFs are frequently iatrogenic, following percutaneous liver interventions. The aim of this study was to report the 10-year experience of a tertiary referral center for pediatric OLT in the interventional radiological (IR) and conservative management of acquired APFs. A retrospective search was performed to retrieve pediatric patients (<18 years old) with a diagnosis of APF at color Doppler ultrasound (CDUS) or computed tomography angiography (CTA) from 2010 to 2020. Criteria for IR treatment were the presence of hemodynamic alterations at CDUS (resistive index <0.5; portal flow reversal) or clinical manifestations (bleeding; portal hypertension). Conservatively managed patients served as a control population. Clinical and imaging follow-up was analyzed. Twenty-three pediatric patients (median age, 4 years; interquartile range = 11 years; 15 males) with 24 APFs were retrieved. Twenty patients were OLT recipients with acquired APFs (16 iatrogenic). Twelve out of twenty-three patients were managed conservatively. The remaining 11 underwent angiography with confirmation of a shunt in 10, who underwent a total of 16 embolization procedures (14 endovascular; 2 transhepatic). Technical success was reached in 12/16 (75%) procedures. Clinical success was achieved in 8/11 (73%) patients; three clinical failures resulted in one death and two OLTs. After a median follow-up time of 42 months (range 1–107), successfully treated patients showed an improvement in hemodynamic parameters at CDUS. Conservatively managed patients showed a stable persistence of the shunts in six cases, spontaneous resolution in four, reduction in one and mild shunt increase in one. In pediatric patients undergoing liver interventions, APFs should be investigated. Although asymptomatic in most cases, IR treatment of APFs should be considered whenever hemodynamic changes are found at CDUS.
Multidimensional Prognostic Index and Mortality in Intermediate Care Facilities: A Retrospective Study
Authors: Veronese Nicola , Vianello Stefano , Danesin Claudia , Tudor Florina , Pozzobon Gianfranco , Pilotto Alberto
Published: June 2021

Multidimensional prognostic index (MPI) is a frailty assessment tool used for stratifying prognosis in older hospitalized people, but data regarding older people admitted to intermediate care facilities (ICFs) are missing. The aim of this study is to evaluate whether MPI can predict mortality in older patients admitted to the ICFs. MPI was calculated using different domains explored by a standard comprehensive geriatric assessment and categorized into tertiles (MPI-1 ≤ 0.20, MPI-2 0.20–0.34, MPI-3 > 0.34). A Cox’s regression analysis, taking mortality as the outcome, was used, reporting the results as hazard ratios (HRs) with 95% confidence intervals (CIs). In total, 653 older patients were enrolled (mean age: 82 years, 59.1% females). Patients in MPI-2 (HR = 3.66; 95%CI: 2.45–5.47) and MPI-3 (HR = 6.22; 95%CI: 4.22–9.16) experienced a higher risk of mortality, compared to MPI-1. The accuracy of MPI in predicting mortality was good (area under the curve (AUC) = 0.74, 95%CI: 0.70–0.78). In conclusion, our study showed that prognostic stratification, as assessed by the MPI, was associated with a significantly different risk of mortality in older patients admitted to the ICFs, indicating the necessity of using a CGA-based tool for better managing older people in this setting as well.
First Report of the Marine Benthic Dinoflagellate Bysmatrum subsalsum from Korean Tidal Pools
Authors: Park Joon , Li Zhun , Kim Hyun , Kim Ki , Lee Kyun , Youn Joo , Kwak Kyeong , Shin Hyeon
Published: June 2021

Dense patches were observed in the tidal pools of the southern area of Korea. To clarify the causative organisms, the cells were collected and their morphological features were examined using light and scanning electron microscopy (SEM). In addition, after establishing strains for the cells the molecular phylogeny was inferred with concatenated small subunit (SSU) and large subunit (LSU) rRNA sequences. The cells were characterized by a nucleus in the hypotheca, strong reticulations in thecal plates, the separation of plates 2a and 3a, the tear-shaped apical pore complex, an elongated rectangular 1a plate and the absence of the right sulcal list. The thecal plate formula was Po, X, 4′, 3a, 7″, 6c, 4S, 5′′′, 2′′′′. Based on these morphological features, the cells were identified as Bysmatrum subsalsum. In the culture, the spherical cysts of B. subsalsum without thecal plates were observed. Molecular phylogeny revealed two ribotypes of B. subsalsum are identified; The Korean isolates were nested within the ribotype B consisting of the isolates from China, Malaysia and the French Atlantic, whereas the ribotype A includes only the isolates from the Mediterranean Sea. In the phylogeny, B. subsalsum and B. austrafrum were grouped. This can be supported by the morphological similarity between the two species, indicating that the two species may be conspecific, however B. subsalsum may distinguish from B. austrafrum, because of differences in the types of eyespots reported in previous studies. These findings support the idea that there is cryptic diversity within B. subsalsum.
Acoustic Monitoring of a Bottlenose Dolphin (Tursiops truncatus) Population: Trends in Presence and Foraging beyond the Limits of the Lower River Shannon SAC
Authors: Charish Rachel , Berrow Simon , O’Brien Joanne
Published: June 2021

The Shannon dolphins are a population of bottlenose dolphins resident year round within the Lower River Shannon SAC, Ireland, which has been designated to protect this relatively small, genetically discrete population. Although trends in habitat use and foraging have been studied within the estuary, little is known about the movements of the Shannon dolphins outside the boundaries of the SAC, and whether any other foraging hotspots exist for this population outside of the estuary. The purpose of this study was to explore the presence and foraging behavior of these dolphins in adjacent waters located 20–30 km to the southwest of the Lower River Shannon SAC. Static acoustic monitoring was carried out with C-PODs deployed in Ballyheigue Bay, Brandon Bay, and around the Maharees between May and November 2013. A GEE-GLM modelling approach was then used to analyze potential significant environmental predictors of presence and foraging by bottlenose dolphins at these sites. Brandon Bay was found to be a site of particular importance for the Shannon population, where dolphins were present on 92% of days monitored and foraging occurring on 20% of all monitored hours. The results of this study indicate that Brandon Bay is a potentially important habitat for the Shannon dolphins and further support designation of this site as a candidate SAC. However, long-term acoustic monitoring should be conducted at all sites to identify relative use of the areas at year-round and inter-annual scales.