bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Aspiration Pneumonia among Elderly Patients in a Community-Based Integrated Care Unit: A Retrospective Cohort Study
Authors: Uno Isao , Kubo Takaaki
Published: December 2021

We aimed to clarify the physical factors associated with the incidence of aspiration pneumonia in a community-based integrated care unit. This retrospective cohort study included 412 patients aged 65 years or older admitted to a community-based integrated care unit. A new diagnosis of aspiration pneumonia made by the attending physician based on physical examination, imaging findings, and blood test data after 48 h of admission was considered as an incidence of aspiration pneumonia. Basic patient information, activities of daily living, swallowing function, nutritional status, cognitive function, oral health-related factors, and energy intake were retrospectively investigated. We classified the patients into a pneumonia group and a non-pneumonia group, and examined the factors associated with the development of aspiration pneumonia. The mean age was 86.9 ± 8.1 years, and the pneumonia group comprised 49 participants. Comparison between the groups showed significant differences in oral environment, denture use, cognitive functional independence measure, and discharge to home. In multivariate logistic regression analysis, oral environment (odds ratio (OR) = 0.229, 95% confidence interval (CI): 0.070–0.753, p = 0.015) and use of dentures (OR = 0.360, 95% CI: 0.172–0.754, p = 0.007) were independently associated with aspiration pneumonia. Oral care and the use of dentures may be effective in preventing aspiration pneumonia.
Low Back Pain in Elderly from Belém-Pa, Brazil: Prevalence and Association with Functional Disability
Authors: Sato Elaine Miyuka , Magalhães Mauricio Oliveira , Jenkins Beatriz Coelho , da Silva Ferreira Lays , da Silva Hallyson Andrey Raposo , Farias Furtado Paulo Renan , Soares Ferreira Eder Gabriel , dos Santos Emmanuele Celina Souza , Callegari Bianca , Pasqual Marques Amélia
Published: December 2021

Background: This cross-sectional study aimed to determine the prevalence of low back pain (LBP) in the elderly population living in Belém-Pará and to assess the spectrum of problems related to these diseases including the demographic, socioeconomic, occupational characteristics and disability in this population. Methods: Three structured questionnaires were applied in a randomly selected representative sample of 512 elderly people aged ≥60 years. Results: LBP prevalence in the elderly population was 55.7%. Among then, 56.1% had pain at the time of the interview (punctual prevalence), 91.7% had LBP in the last 365 days (prevalence in the last year), and 85.3% at some point in life (prevalence at some point in life). Overall, most studies are above average. LBP was positively associated with hypertension and the influence of the physical and mental health on their social activities ranged from slightly to extreme. LBP was negatively associated with characteristics, such as education (over 11 years), class A or B income, physical activity, high satisfaction with previous work, and excellent self-perceived health, corroborating to the literature. Conclusions: Greater intensity of pain and functional disability were associated with the presence of comorbidities, smoking habits, and low physical activity. LBP prevalence was high, above the national average, mainly affecting the underprivileged classes related to several modifiable factors, highlighting the importance of preventive and interventionist actions for healthy aging.
Evaluation of Student Satisfaction with Ubiquitous-Based Tests in Women’s Health Nursing Course
Authors: An Mi-Young , Kim Yun-Mi
Published: December 2021

Learning evaluation using ubiquitous-based tests may be essential during a public health crisis, such as the COVID-19 pandemic, during which theoretical classes and clinical practice are conducted online. However, students may not be as familiar with ubiquitous-based tests as they are with paper-based tests. This survey study aimed to evaluate students’ satisfaction with ubiquitous-based tests and compare the evaluation results of a paper-based test with that of a ubiquitous-based test in nursing education. For the midterm exam of the Women’s Health Nursing course, a paper-based test was conducted, while a ubiquitous-based test using a tablet computer was used for the final exam. The Ubiquitous-Based Test Usefulness and Satisfaction tool, which has a five-point Likert-type response scale, was employed to evaluate the post-test usefulness and satisfaction scores of the ubiquitous-based test. The mean score of the ubiquitous-based test usefulness was 4.01 ± 0.67. There was a significant difference in satisfaction levels between the ubiquitous-based and the paper-based test (t = −3.36, p = 0.001). Specifically, the evaluation scores were not affected by different evaluation methods. Study participants deemed the ubiquitous-based test highly useful and satisfactory, suggesting that such tests may be a future-oriented evaluation method, potentially replacing paper-based tests.
Transfer of Development Rights and Cultural Heritage Preservation: A Case Study at Athens Historic Triangle, Greece
Authors: Perperidou Dionysia-Georgia , Siori Stavroula , Doxobolis Vasileios , Lampropoulou Fotini , Katsios Ioannis
Published: December 2021

History and the modern world co-exist in Greece’s landscape. The urban spaces of Greek cities contain structures from ancient history alongside contemporary constructions, but intense urban development from the 1960s onwards, as in the historic center of Athens, has led to imbalances with respect to cultural heritage protection. The 1975 Greek Constitution defined the preservation and protection of the cultural environment as a constitutional mandate, and severe restrictions on the exploitation of private properties deemed to be of historical or architectural importance were imposed. Property owners were deprived of their property development rights (DRs), whereas the preservation and conservation of protected constructions became costly, resulting in abandoned buildings and a downgraded urban environment. As the debate over cultural heritage protection and urban regeneration is more topical than ever, the recent legal reintroduction of the transfer of development rights (TDRs) provides new opportunities for property exploitation with respect to cultural heritage protection legislation. Herein is presented a methodological framework on the classification and 3D visualization and representation of DRs and TDRs in relation to the cultural heritage protective framework and its implementation in a selected area of Athens’ historic center. Legal and technical aspects that affect 3D DRs and TDRs are emphasized as key elements in the successful implementation of the TDR process.
An Archaeometric Investigation of Gems and Glass Beads Decorating the Double-Arm Reliquary Cross from Liège, Belgium
Authors: Bruni Yannick , Hatert Frédéric , Demaude Merry , Delmelle Nicolas , George Philippe , Maquet Julien
Published: December 2021

In 1914, a magnificent reliquary cross dating from the early XIIIth century was discovered in a safe from the Liège Cathedral. This double-arm cross shows a wooden structure, covered by gold-coated copper on the front, and by carved silver plates on the back. Its total length is 34 cm, and it is covered by filigrees, gems, glass beads, and pearls on its front. The reliquary cross was analysed by Raman spectrometry and X-ray fluorescence spectrometry (pXRF) to determine the mineralogical and chemical compositions of gems, glass beads, and metals that have been used to decorate it. The results confirm the identification of twenty-five turquoises from Egypt, one garnet from Sri Lanka, as well as six quartz and one opal whose origin is difficult to certify. Twelve glass beads, showing green, blue, or amber tints, were also identified. Their compositions either correspond to soda lime glasses with natron or to potash–lead glasses similar to those of Central Europe. Moreover, a small polished red cross and a green stone appear to be constituted by nice doublets, composed of coloured glass covered by quartz. The filigrees contain Au and Cu, while carved plates covering the edges and the back of the cross are made of silver.
Women’s Trade-Offs between Fertility and Employment during Industrialisation
Authors: Moore Fhionna , Lumb Ethan , Starkey Charlotte , McIntosh James , Benjamin Jaime , Macleod Mairi , Krams Indrikis
Published: December 2021

Modelling fertility decline in post-industrial populations in the context of life history theory has allowed us to better understand the environmental pressures that shape reduced family size. One such pressure, which has received relatively little attention from ecologists, is the movement of women into the labour market. Analyses of effects of employment on fertility in contemporary developing or post-demographic transition populations are limited by the widespread use of modern contraceptives: while uptake of these methods may be a mechanism by which reduced fertility is enacted, their use may obscure effects of employment on fertility. Here, we investigated the impact of women’s employment on family size during a period of the movement of women into the workforce but prior to the use of modern contraceptives. We analysed the effects of women’s employment on family size using census records from 1901 for a regional-level analysis of parishes in Scotland, and for 1851–1901 for an individual-level analysis of the Scottish city of Dundee. Women in employment had fewer children than those not in employment. Income was inversely related with family size, and this was independent of the effects of women’s employment on family size. We suggest that female employment contributes to the evolution of smaller family sizes and that this takes place in the context of prevailing and emerging gender roles, and in interaction with opportunities for employment and wealth.
Molecular Hydrogen as Medicine: An Assessment of Administration Methods
Authors: Russell Grace , Nenov Alexander , Kisher Hesham , Hancock John T.
Published: December 2021

Since the late 18th century, molecular hydrogen (H2) has been shown to be well tolerated, firstly in animals, and then in humans. However, although research into the beneficial effects of molecular hydrogen in both plant and mammalian physiology is gaining momentum, the idea of utilising this electrochemically neutral and non-polar diatomic compound for the benefit of health has yet to be widely accepted by regulatory bodies worldwide. Due to the precise mechanisms of H2 activity being as yet undefined, the lack of primary target identification, coupled with difficulties regarding administration methods (e.g., dosage and dosage frequencies, long-term effects of treatment, and the patient’s innate antioxidant profile), there is a requirement for H2 research to evidence how it can reasonably and most effectively be incorporated into medical practice. This review collates and assesses the current information regarding the many routes of molecular hydrogen administration in animals and humans, whilst evaluating how targeted delivery methods could be integrated into a modern healthcare system.
The Role of Bedload Transport in the Development of a Proglacial River Alluvial Fan (Case Study: Scott River, Southwest Svalbard)
Authors: Kociuba Waldemar
Published: December 2021

This study, which was conducted between 2010 and 2013, presents the results of direct, continuous measurements of the bedload transport rate at the mouth section of the Scott River catchment (NW part of Wedel-Jarlsberg Land, Svalbard). In four consecutive melt seasons, the bedload flux was analyzed at two cross-sections located in the lower reaches of the gravel-bed proglacial river. The transported bedload was measured using two sets of River Bedload Traps (RBTs). Over the course of 130 simultaneous measurement days, a total of 930 bedload samples were collected. During this period, the river discharged about 1.32 t of bedload through cross-section I (XS I), located at the foot of the alluvial fan, and 0.99 t through cross-section II (XS II), located at the river mouth running into the fjord. A comparison of the bedload flux showed a distinctive disproportion between cross-sections. Specifically, the average daily bedload flux QB was 130 kg day−1 (XS I) and 81 kg day−1 (XS II) at the individual cross-profiles. The lower bedload fluxes that were recorded at specified periods in XS II, which closed the catchment at the river mouth from the alluvial cone, indicated an active role of aggradation processes. Approximately 40% of all transported bedload was stored at the alluvial fan, mostly in the active channel zone. However, comparative Geomorphic Change Detection (GCD) analyses of the alluvial fan, which were performed over the period between August 2010 and August 2013, indicated a general lowering of the surface (erosion). It can be assumed that the melt season’s average flows in the active channel zone led to a greater deposition of bedload particles than what was discharged with high intensity during floods (especially the bankfull stage, effectively reshaping the whole surface of the alluvial fan). This study documents that the intensity of bedload flux was determined by the frequency of floods. Notably, the highest daily rates recorded in successive seasons accounted for 12–30% of the total bedload flux. Lastly, the multi-seasonal analysis showed a high spatio-temporal variability of the bedload transport rates, which resulted in changes not only in the channel but also on the entire surface of the alluvial fan morphology during floods.
Reliability and Accuracy of Alternative Default Prediction Models: Evidence from Slovakia
Authors: Rybárová Daniela , Majdúchová Helena , Štetka Peter , Luščíková Darina
Published: December 2021

The aim of this paper is to assess the reliability of alternative default prediction models in local conditions, with subsequent comparison with other generally known and globally disseminated default prediction models, such as Altman’s Z-score, Quick Test, Creditworthiness Index, and Taffler’s Model. The comparison was carried out on a sample of 90 companies operating in the Slovak Republic over a period of 3 years (2016, 2017, and 2018) with a narrower focus on three sectors: construction, retail, and tourism, using alternative default prediction models, such as CH-index, G-index, Binkert’s Model, HGN2 Model, M-model, Gulka’s Model, Hurtošová’s Model, Model of Delina and Packová, and Binkert’s Model. To verify the reliability of these models, tests of the significance of statistical hypotheses were used, such as type I and type II error. According to research results, the highest reliability and accuracy was achieved by an alternative local Model of Delina and Packová. The least reliable results within the list of models were reported by the most globally disseminated model, Altman’s Z-score. Significant differences between sectors were identified.
Estimation of Agricultural Dykelands Cultivated in Nova Scotia Using Land Property Boundaries and Crop Inventory
Authors: Bilodeau Mathieu F. , Esau Travis J. , Farooque Aitazaz A. , Zaman Qamar U. , Heung Brandon
Published: December 2021

Dykelands are agricultural ground protected from coastal inundation by dyke infra-structure and constitute some of the most agriculturally productive lands in Nova Scotia. Between 2015 and 2019, Canada’s Annual Crop Inventory was used to characterize and estimate hectares of agricultural dykelands cultivated in Nova Scotia. The number of hectares of wheat, barley, corn, forages and soybeans were compiled for each year and compared to the previous year. This was accomplished using GIS software, satellite images, and geodata from the Nova Scotia’s Land Property Database. Results revealed that from 2015 to 2019, an average of 56% of the dykelands’ total surface was dedicated to the production of field crops (wheat, barley, corn, soybeans) and forage. Results also highlighted the importance of forage production on the dykelands. Forage was the largest commodity grown, representing around 80% of the total crop land area of the agricultural dykelands. Corn and soybeans were the second and third crops of abundance, constituting 12 and 4% of the total crop land area, respectively. This study represents the first attempt to document the number of hectares of the principal crops grown on Nova Scotia’s dykelands using crop inventory and property boundaries. Given the predictions of rising sea levels and the overtopping risks that the dykelands face, this study will facilitate more suitable land-use policies by providing stakeholders with an accurate quantitative assessment of the utilization of agricultural dykelands.
Real-Time Web Map Construction Based on Multiple Cameras and GIS
Authors: Zhang Xingguo , Shi Xinyu , Luo Xiaoyue , Sun Yinping , Zhou Yingdi
Published: December 2021

Previous VideoGIS integration methods mostly used geographic homography mapping. However, the related processing techniques were mainly for independent cameras and the software architecture was C/S, resulting in large deviations in geographic video mapping for small scenes, a lack of multi-camera video fusion, and difficulty in accessing real-time information with WebGIS. Therefore, we propose real-time web map construction based on the object height and camera posture (RTWM-HP for short). We first consider the constraint of having a similar height for each object by constructing an auxiliary plane and establishing a high-precision homography matrix (HP-HM) between the plane and the map; thus, the accuracy of geographic video mapping can be improved. Then, we map the objects in the multi-camera video with overlapping areas to geographic space and perform the object selection with the multi-camera (OS-CDD) algorithm, which includes the confidence of the object, the distance, and the angle between the objects and the center of the cameras. Further, we use the WebSocket technology to design a hybrid C/S and B/S software framework that is suitable for WebGIS integration. Experiments were carried out based on multi-camera videos and high-precision geospatial data in an office and a parking lot. The case study’s results show the following: (1) The HP-HM method can achieve the high-precision geographic mapping of objects (such as human heads and cars) with multiple cameras; (2) the OS-CDD algorithm can optimize and adjust the positions of the objects in the overlapping area and achieve a better map visualization effect; (3) RTWM-HP can publish real-time maps of objects with multiple cameras, which can be browsed in real time through point layers and hot-spot layers through WebGIS. The methods can be applied to some fields, such as person or car supervision and the flow analysis of customers or traffic passengers.
Smart Design for Evacuation Signage Layout for Exhibition Halls in Exhibition Buildings Based on Visibility
Authors: Wan Zhanzhi , Zhou Tiejun , Tang Zhili , Pan Yin , Zhang Lingfei
Published: December 2021

The reasonable placement of evacuation signage is an important means to improve the efficiency of evacuation in the exhibition halls of exhibition buildings. The booths in exhibition halls are arranged and changed frequently for different exhibitions, which means that the evacuation paths are not fixed. Most people are also unfamiliar with the exhibition hall environment. In case of fire, earthquake, or other emergencies, people need to quickly escape to the safety exit, adhering to the guidance of evacuation signage. Existing evacuation signs are located according to the standards and the experience of the designers, and the locations of the signs are fixed and do not change with the changes in the booth layout, which means that the signage can be easily obscured by the booths, affecting the signage identification. Based on the visibility of evacuation signage, a smart design method of evacuation signage layout is proposed in this paper that can be adapted to different forms of booth arrangements in exhibition halls. This method establishes a key goal of achieving the full coverage of the visibility range of evacuation passages with the minimum number of evacuation signs. In the context of the actual visibility range of evacuation signage being blocked by booths in a three-dimensional space, this method finds the optimal number and best locations of evacuation signs by using a genetic algorithm. Finally, a case is given to verify the effectiveness of the method. This smart design for evacuation signage layout can enhance the guidance ability of evacuation signage in exhibition halls and improve the efficiency of evacuation.
Synaptamide Improves Cognitive Functions and Neuronal Plasticity in Neuropathic Pain
Authors: Tyrtyshnaia Anna , Bondar Anatoly , Konovalova Sophia , Manzhulo Igor
Published: December 2021

Neuropathic pain arises from damage or dysfunction of the peripheral or central nervous system and manifests itself in a wide variety of sensory symptoms and cognitive disorders. Many studies demonstrate the role of neuropathic pain-induced neuroinflammation in behavioral disorders. For effective neuropathic pain treatment, an integrative approach is required, which simultaneously affects several links of pathogenesis. One promising candidate for this role is synaptamide (N-docosahexaenoylethanolamine), which is an endogenous metabolite of docosahexaenoic acid. In this study, we investigated the activity of synaptamide on mice behavior and hippocampal plasticity in neuropathic pain induced by spared nerve injury (SNI). We found a beneficial effect of synaptamide on the thermal allodynia and mechanical hyperalgesia dynamics. Synaptamide prevented working and long-term memory impairment. These results are probably based on the supportive effect of synaptamide on SNI-impaired hippocampal plasticity. Nerve ligation caused microglia activation predominantly in the contralateral hippocampus, while synaptamide inhibited this effect. The treatment reversed dendritic tree degeneration, dendritic spines density reduction on CA1-pyramidal neurons, neurogenesis deterioration, and hippocampal long-term potentiation (LTP) impairment. In addition, synaptamide inhibits changes in the glutamatergic receptor expression. Thus, synaptamide has a beneficial effect on hippocampal functioning, including synaptic plasticity and hippocampus-dependent cognitive processes in neuropathic pain.
Cytotoxic Aβ Protofilaments Are Generated in the Process of Aβ Fibril Disaggregation
Authors: Kaku Toshisuke , Tsukakoshi Kaori , Ikebukuro Kazunori
Published: December 2021

Significant research on Alzheimer’s disease (AD) has demonstrated that amyloid β (Aβ) oligomers are toxic molecules against neural cells. Thus, determining the generation mechanism of toxic Aβ oligomers is crucial for understanding AD pathogenesis. Aβ fibrils were reported to be disaggregated by treatment with small compounds, such as epigallocatechin gallate (EGCG) and dopamine (DA), and a loss of fibril shape and decrease in cytotoxicity were observed. However, the characteristics of intermediate products during the fibril disaggregation process are poorly understood. In this study, we found that cytotoxic Aβ aggregates are generated during a moderate disaggregation process of Aβ fibrils. A cytotoxicity assay revealed that Aβ fibrils incubated with a low concentration of EGCG and DA showed higher cytotoxicity than Aβ fibrils alone. Atomic force microscopy imaging and circular dichroism spectrometry showed that short and narrow protofilaments, which were highly stable in the β-sheet structure, were abundant in these moderately disaggregated samples. These results indicate that toxic Aβ protofilaments are generated during disaggregation from amyloid fibrils, suggesting that disaggregation of Aβ fibrils by small compounds may be one of the possible mechanisms for the generation of toxic Aβ aggregates in the brain.
Downregulation of MMP-9 Enhances the Anti-Migratory Effect of Cyclophosphamide in MDA-MB-231 and MCF-7 Breast Cancer Cell Lines
Authors: Izdebska Magdalena , Zielińska Wioletta , Krajewski Adrian , Hałas-Wiśniewska Marta , Mikołajczyk Klaudia , Gagat Maciej , Grzanka Alina
Published: December 2021

Metastasis is one of the most urgent issues in breast cancer patients. One of the factors necessary in the migration process is the remodeling of the extracellular matrix (ECM). Metalloproteinases (MMPs) can break down the elements of the ECM, which facilitates cell movement. Many highly aggressive tumors are characterized by high levels of MMPs. In the case of breast cancer, the association between MMP-9 and the migration potential and invasiveness of cells has been demonstrated. In addition, reports indicating increased migration of breast cancer cells after the administration of the commonly used cytostatic cyclophosphamide (CP) are particularly disturbing. Hence, our research aimed to assess the effect of CP treatment on MDA-MB-231 and MCF-7 cells and how this response is influenced by the downregulation of the MMP-9 level. The obtained results suggest that CP causes a decrease in the survival of breast cancer cells of various invasiveness, and the downregulation of MMP-9 enhances this effect, mainly by inducing apoptosis. Moreover, in the group of MMP-9 siRNA-transfected CP-treated cells, a more severe reduction in invasion and migration of cells of both lines was observed, as indicated by the migration and invasion transwell assays and Wound healing assay. Hence, we suggest that CP alone may not result in satisfactory therapeutic effects. On the other hand, the use of combination therapy targeting MMP-9, together with the CP, could improve the effectiveness of the treatment. Additionally, we confirmed a relationship between the levels of MMP-9 and cytokeratin 19 (CK19).
Lessons Learned from the Studies of Roots Shaded from Direct Root Illumination
Authors: Lacek Jozef , García-González Judith , Weckwerth Wolfram , Retzer Katarzyna
Published: December 2021

The root is the below-ground organ of a plant, and it has evolved multiple signaling pathways that allow adaptation of architecture, growth rate, and direction to an ever-changing environment. Roots grow along the gravitropic vector towards beneficial areas in the soil to provide the plant with proper nutrients to ensure its survival and productivity. In addition, roots have developed escape mechanisms to avoid adverse environments, which include direct illumination. Standard laboratory growth conditions for basic research of plant development and stress adaptation include growing seedlings in Petri dishes on medium with roots exposed to light. Several studies have shown that direct illumination of roots alters their morphology, cellular and biochemical responses, which results in reduced nutrient uptake and adaptability upon additive stress stimuli. In this review, we summarize recent methods that allow the study of shaded roots under controlled laboratory conditions and discuss the observed changes in the results depending on the root illumination status.
Therapeutic Modulation of the Host Defense by Hemoadsorption with CytoSorb®—Basics, Indications and Perspectives—A Scoping Review
Authors: Köhler Thomas , Schwier Elke , Praxenthaler Janina , Kirchner Carmen , Henzler Dietrich , Eickmeyer Claas
Published: December 2021

The “normal” immune response to an insult triggers a highly regulated response determined by the interaction of various immunocompetent cells with pro- and anti-inflammatory cytokines. Under pathologic conditions, the massive elevation of cytokine levels (“cytokine storm”) could not be controlled until the recent development of hemoadsorption devices that are able to extract a variety of different DAMPs, PAMPs, and metabolic products from the blood. CytoSorb® has been approved for adjunctive sepsis therapy since 2011. This review aims to summarize theoretical knowledge, in vitro results, and clinical findings to provide the clinician with pragmatic guidance for daily practice. English-language and peer-reviewed literature identified by a selective literature search in PubMed and published between January 2016 and May 2021 was included. Hemoadsorption can be used successfully as adjunct to a complex therapeutic regimen for various conditions. To the contrary, this nonspecific intervention may potentially worsen patient outcomes in complex immunological processes. CytoSorb® therapy appears to be safe and useful in various diseases (e.g., rhabdomyolysis, liver failure, or intoxications) as well as in septic shock or cytokine release syndrome, although a conclusive assessment of treatment benefit is not possible and no survival benefit has yet been demonstrated in randomized controlled trials.
Transmission Electron Microscopy as a Powerful Tool to Investigate the Interaction of Nanoparticles with Subcellular Structures
Authors: Malatesta Manuela
Published: December 2021

Nanomedical research necessarily involves the study of the interactions between nanoparticulates and the biological environment. Transmission electron microscopy has proven to be a powerful tool in providing information about nanoparticle uptake, biodistribution and relationships with cell and tissue components, thanks to its high resolution. This article aims to overview the transmission electron microscopy techniques used to explore the impact of nanoconstructs on biological systems, highlighting the functional value of ultrastructural morphology, histochemistry and microanalysis as well as their fundamental contribution to the advancement of nanomedicine.
Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD
Authors: Mavromati Maria , Jornayvaz François R.
Published: December 2021

Thyroid hormones control lipid metabolism by exhibiting specific effects on the liver and adipose tissue in a coordinated manner. Different diseases of the thyroid gland can result in hypothyroidism. Hypothyroidism is frequently associated with dyslipidemia. Hypothyroidism-associated dyslipidemia subsequently results in intrahepatic accumulation of fat, leading to nonalcoholic fatty liver disease (NAFLD), which leads to the development of hepatic insulin resistance. The prevalence of NAFLD in the western world is increasing, and evidence of its association with hypothyroidism is accumulating. Since hypothyroidism has been identified as a modifiable risk factor of NAFLD and recent data provides evidence that selective thyroid hormone receptor β (THR-β) agonists are effective in the treatment of dyslipidemia and NAFLD, interest in potential therapeutic options for NAFLD targeting these receptors is growing. In this review, we summarize current knowledge regarding clinical and molecular data exploring the association of hypothyroidism, dyslipidemia and NAFLD.
Revisiting the Role of Ser982 Phosphorylation in Stoichiometry Shift of the Electrogenic Na+/qHCO3− Cotransporter NBCe1
Authors: Alsufayan Thamer A. , Myers Evan J. , Quade Bianca N. , Brady Clayton T. , Marshall Aniko , Haque Nayem , Duffey Michael E. , Parker Mark D.
Published: December 2021

In most cell types and heterologous expression systems, the electrogenic sodium-bicarbonate cotransporter NBCe1 operates with a 1Na+–2HCO3− stoichiometry that, given typical transmembrane electrochemical gradients, promotes Na+ and HCO3− influx. However, NBCe1 in the kidney mediates HCO3− efflux (HCO3− reabsorption), a direction that has been predicted to be favored only if NBCe1 operates with a 1:3 stoichiometry. The phosphorylation state of Ser982 in the cytosolic carboxy-terminal domain of NBCe1 has been reported to be a key determinant of the transporter stoichiometry, with non-phosphorylated Ser982 favoring a 1:3 stoichiometry. Conversely, phosphoproteomic data from renal cortical preparations have revealed the presence of NBCe1 peptides including phosphoserine982 (pSer982) and/or pSer985 although it was not known what proportion of NBCe1 molecules were phosphorylated. In the present study, we report the generation, characterization, and application of a novel phosphospecific antibody raised against NBCe1/pSer982 and show that, contrary to expectations, Ser982 is more prevalently phosphorylated in murine kidneys (in which NBCe1 mediates HCO3− efflux) than in murine colons (in which NBCe1 mediates HCO3− influx). Using phosphomimetic mutants of murine NBCe1 expressed in Xenopus oocytes, we found no evidence that the phosphorylation state of Ser982 or Ser985 alone influences the transport stoichiometry or conductance. Furthermore, we found that the phosphorylation of NBCe1/Ser982 is enhanced in murine kidneys following a 24 h induction of metabolic acidosis. We conclude that the phosphorylation status of Ser982 is not a key determinant of NBCe1 stoichiometry but correlates with presumed NBCe1 activity.
Risk Mitigation of Immunogenicity: A Key to Personalized Retinal Gene Therapy
Authors: Varin Juliette , Morival Clément , Maillard Noémien , Adjali Oumeya , Cronin Therese
Published: December 2021

Gene therapy (GT) for ocular disorders has advanced the most among adeno-associated virus (AAV)-mediated therapies, with one product already approved in the market. The bank of retinal gene mutations carefully compiled over 30 years, the small retinal surface that does not require high clinical vector stocks, and the relatively immune-privileged environment of the eye explain such success. However, adverse effects due to AAV-delivery, though rare in the retina have led to the interruption of clinical trials. Risk mitigation, as the key to safe and efficient GT, has become the focus of ‘bedside-back-to-bench’ studies. Herein, we overview the inflammatory adverse events described in retinal GT trials and analyze which components of the retinal immunological environment might be the most involved in these immune responses, with a focus on the innate immune system composed of microglial surveillance. We consider the factors that can influence inflammation in the retina after GT such as viral sensors in the retinal tissue and CpG content in promoters or transgene sequences. Finally, we consider options to reduce the immunological risk, including dose, modified capsids or exclusion criteria for clinical trials. A better understanding and mitigation of immune risk factors inducing host immunity in AAV-mediated retinal GT is the key to achieving safe and efficient GT.
β-Cell Pathophysiology: A Review of Advanced Optical Microscopy Applications
Authors: Ferri Gianmarco , Pesce Luca , Tesi Marta , Marchetti Piero , Cardarelli Francesco
Published: December 2021

β-cells convert glucose (input) resulting in the controlled release of insulin (output), which in turn has the role to maintain glucose homeostasis. β-cell function is regulated by a complex interplay between the metabolic processing of the input, its transformation into second-messenger signals, and final mobilization of insulin-containing granules towards secretion of the output. Failure at any level in this process marks β-cell dysfunction in diabetes, thus making β-cells obvious potential targets for therapeutic purposes. Addressing quantitatively β-cell (dys)function at the molecular level in living samples requires probing simultaneously the spatial and temporal dimensions at the proper resolution. To this aim, an increasing amount of research efforts are exploiting the potentiality of biophysical techniques. In particular, using excitation light in the visible/infrared range, a number of optical-microscopy-based approaches have been tailored to the study of β-cell-(dys)function at the molecular level, either in label-free mode (i.e., exploiting intrinsic autofluorescence of cells) or by the use of organic/genetically-encoded fluorescent probes. Here, relevant examples from the literature are reviewed and discussed. Based on this, new potential lines of development in the field are drawn.
Differential Effects of Low and High Radiation Dose Rates on Mouse Spermatogenesis
Authors: Bae Min Ji , Kang Min Kook , Kye Yong Uk , Baek Jeong-Hwa , Sim Ye-Ji , Lee Hae-June , Kang Yeong-Rok , Jo Wol Soon , Kim Joong Sun , Lee Chang Geun
Published: December 2021

The adverse effects of radiation are proportional to the total dose and dose rate. We aimed to investigate the effects of radiation dose rate on different organs in mice. The mice were subjected to low dose rate (LDR, ~3.4 mGy/h) and high dose rate (HDR, ~51 Gy/h) radiation. LDR radiation caused severe tissue toxicity, as observed in the histological analysis of testis. It adversely influenced sperm production, including sperm count and motility, and induced greater sperm abnormalities. The expression of markers of early stage spermatogonial stem cells, such as Plzf, c-Kit, and Oct4, decreased significantly after LDR irradiation, compared to that following exposure of HDR radiation, in qPCR analysis. The compositional ratios of all stages of spermatogonia and meiotic cells, except round spermatid, were considerably reduced by LDR in FACS analysis. Therefore, LDR radiation caused more adverse testicular damage than that by HDR radiation, contrary to the response observed in other organs. Therefore, the dose rate of radiation may have differential effects, depending on the organ; it is necessary to evaluate the effect of radiation in terms of radiation dose, dose rate, organ type, and other conditions.
Verification of the Impact of Blood Glucose Level on Liver Carcinogenesis and the Efficacy of a Dietary Intervention in a Spontaneous Metabolic Syndrome Model
Authors: Ichimura-Shimizu Mayuko , Kageyama Takeshi , Oya Takeshi , Ogawa Hirohisa , Matsumoto Minoru , Sumida Satoshi , Kakimoto Takumi , Miyakami Yuko , Nagatomo Ryosuke , Inoue Koichi , Cheng Chunmei , Tsuneyama Koichi
Published: December 2021

Metabolic syndrome (MS) is a risk factor for type 2 diabetes mellitus, vascular inflammation, atherosclerosis, and renal, liver, and heart diseases. Non-alcoholic steatohepatitis (NASH) is a progressive representative liver disease and may lead to the irreversible calamities of cirrhosis and hepatocellular carcinoma. Metabolic disorders such as hyperglycemia have been broadly reported to be related to hepatocarcinogenesis in NASH; however, direct evidence of a link between hyperglycemia and carcinogenesis is still lacking. Tsumura Suzuki Obese Diabetic (TSOD) mice spontaneously develop metabolic syndrome, including obesity, insulin resistance, and NASH-like liver phenotype, and eventually develop hepatocellular carcinomas. TSOD mice provide a spontaneous human MS-like model, even with significant individual variations. In this study, we monitored mice in terms of their changes in blood glucose levels, body weights, and pancreatic and liver lesions over time. As a result, liver carcinogenesis was delayed in non-hyperglycemic TSOD mice compared to hyperglycemic mice. Moreover, at the termination point of 40 weeks, liver tumors appeared in 18 of 24 (75%) hyperglycemic TSOD mice; in contrast, they only appeared in 5 of 24 (20.8%) non-hyperglycemic mice. Next, we investigated three kinds of oligosaccharide that could lower blood glucose levels in hyperglycemic TSOD mice. We monitored the levels of blood and urinary glucose and assessed pancreatic lesions among the experimental groups. As expected, significantly lower levels of blood and urinary glucose and smaller deletions of Langerhans cells were found in TSOD mice fed with milk-derived oligosaccharides (galactooligosaccharides and lactosucrose). At the age of 24 weeks, mild steatohepatitis was found in the liver but there was no evidence of liver carcinogenesis. Steatosis in the liver was alleviated in the milk-derived oligosaccharide-administered group. Taken together, suppressing the increase in blood glucose level from a young age prevented susceptible individuals from diabetes and the onset of NAFLD/NASH, as well as carcinogenesis. Milk-derived oligosaccharides showed a lowering effect on blood glucose levels, which may be expected to prevent liver carcinogenesis.
Gut-Microbial Metabolites, Probiotics and Their Roles in Type 2 Diabetes
Authors: Zhai Lixiang , Wu Jiayan , Lam Yan Y. , Kwan Hiu Yee , Bian Zhao-Xiang , Wong Hoi Leong Xavier
Published: December 2021

Type 2 diabetes (T2D) is a worldwide prevalent metabolic disorder defined by high blood glucose levels due to insulin resistance (IR) and impaired insulin secretion. Understanding the mechanism of insulin action is of great importance to the continuing development of novel therapeutic strategies for the treatment of T2D. Disturbances of gut microbiota have been widely found in T2D patients and contribute to the development of IR. In the present article, we reviewed the pathological role of gut microbial metabolites including gaseous products, branched-chain amino acids (BCAAs) products, aromatic amino acids (AAAs) products, bile acids (BA) products, choline products and bacterial toxins in regulating insulin sensitivity in T2D. Following that, we summarized probiotics-based therapeutic strategy for the treatment of T2D with a focus on modulating gut microbiota in both animal and human studies. These results indicate that gut-microbial metabolites are involved in the pathogenesis of T2D and supplementation of probiotics could be beneficial to alleviate IR in T2D via modulation of gut microbiota.
Integrated Physiological, Transcriptomic, and Metabolomic Analyses Revealed Molecular Mechanism for Salt Resistance in Soybean Roots
Authors: Jin Jie , Wang Jianfeng , Li Keke , Wang Shengwang , Qin Juan , Zhang Guohong , Na Xiaofan , Wang Xiaomin , Bi Yurong
Published: December 2021

Salinity stress is a threat to yield in many crops, including soybean (Glycine max L.). In this study, three soybean cultivars (JD19, LH3, and LD2) with different salt resistance were used to analyze salt tolerance mechanisms using physiology, transcriptomic, metabolomic, and bioinformatic methods. Physiological studies showed that salt-tolerant cultivars JD19 and LH3 had less root growth inhibition, higher antioxidant enzyme activities, lower ROS accumulation, and lower Na+ and Cl- contents than salt-susceptible cultivar LD2 under 100 mM NaCl treatment. Comparative transcriptome analysis showed that compared with LD2, salt stress increased the expression of antioxidant metabolism, stress response metabolism, glycine, serine and threonine metabolism, auxin response protein, transcription, and translation-related genes in JD19 and LH3. The comparison of metabolite profiles indicated that amino acid metabolism and the TCA cycle were important metabolic pathways of soybean in response to salt stress. In the further validation analysis of the above two pathways, it was found that compared with LD2, JD19, and LH3 had higher nitrogen absorption and assimilation rate, more amino acid accumulation, and faster TCA cycle activity under salt stress, which helped them better adapt to salt stress. Taken together, this study provides valuable information for better understanding the molecular mechanism underlying salt tolerance of soybean and also proposes new ideas and methods for cultivating stress-tolerant soybean.
The Receptor AT1 Appears to Be Important for the Maintenance of Bone Mass and AT2 Receptor Function in Periodontal Bone Loss Appears to Be Regulated by AT1 Receptor
Authors: Lima Maria Laura de Souza , Martins Agnes Andrade , Medeiros Caroline Addison Carvalho Xavier de , Guerra Gerlane Coelho Bernardo , Santos Robson , Bader Michael , Pirih Flavia Q. , Araújo Júnior Raimundo Fernandes de , Brito Gerly Anne de Castro , Leitão Renata Ferreira de Carvalho , Silva Rafaela Alcindo , Barbosa Stphannie Jamyla de Araújo , Melo Rômulo Camilo de Oliveira , Araújo Aurigena Antunes de
Published: December 2021

A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors on periodontitis. Methods: Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR. Results: The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (p < 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L. Conclusions: Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1.
Homodimeric and Heterodimeric Interactions among Vertebrate Basic Helix–Loop–Helix Transcription Factors
Authors: Torres-Machorro Ana Lilia
Published: December 2021

The basic helix–loop–helix transcription factor (bHLH TF) family is involved in tissue development, cell differentiation, and disease. These factors have transcriptionally positive, negative, and inactive functions by combining dimeric interactions among family members. The best known bHLH TFs are the E-protein homodimers and heterodimers with the tissue-specific TFs or ID proteins. These cooperative and dynamic interactions result in a complex transcriptional network that helps define the cell’s fate. Here, the reported dimeric interactions of 67 vertebrate bHLH TFs with other family members are summarized in tables, including specifications of the experimental techniques that defined the dimers. The compilation of these extensive data underscores homodimers of tissue-specific bHLH TFs as a central part of the bHLH regulatory network, with relevant positive and negative transcriptional regulatory roles. Furthermore, some sequence-specific TFs can also form transcriptionally inactive heterodimers with each other. The function, classification, and developmental role for all vertebrate bHLH TFs in four major classes are detailed.
Sequence Does Not Matter: The Biomedical Applications of DNA-Based Coatings and Cores
Authors: Batasheva Svetlana , Fakhrullin Rawil
Published: December 2021

Biomedical applications of DNA are diverse but are usually associated with specific recognition of target nucleotide sequences or proteins and with gene delivery for therapeutic or biotechnological purposes. However, other aspects of DNA functionalities, like its nontoxicity, biodegradability, polyelectrolyte nature, stability, thermo-responsivity and charge transfer ability that are rather independent of its sequence, have recently become highly appreciated in material science and biomedicine. Whereas the latest achievements in structural DNA nanotechnology associated with DNA sequence recognition and Watson–Crick base pairing between complementary nucleotides are regularly reviewed, the recent uses of DNA as a raw material in biomedicine have not been summarized. This review paper describes the main biomedical applications of DNA that do not involve any synthesis or extraction of oligo- or polynucleotides with specified sequences. These sequence-independent applications currently include some types of drug delivery systems, biocompatible coatings, fire retardant and antimicrobial coatings and biosensors. The reinforcement of DNA properties by DNA complexation with nanoparticles is also described as a field of further research.