bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cost Decision Model Supporting Treatment Strategy Selection in BRCA1/2 Mutation Carriers in Breast Cancer
Authors: Carbonara Nunzia , La Forgia Daniele , Pellegrino Roberta , Ressa Cosmo , Tommasi Stefania
Published: August 2021

In this paper, a cost decision-making model that compares the healthcare costs for diverse treatment strategies is built for BRCA-mutated women with breast cancer. Moreover, this model calculates the cancer treatment costs that could potentially be prevented, if the treatment strategy with the lowest total cost, along the entire lifetime of the patient, is chosen for high-risk women with breast cancer. The benchmark of the healthcare costs for diverse treatment strategies is selected in the presence of uncertainty, i.e., considering, throughout the lifetime of the patient, the risks and complications that may arise in each strategy and, therefore, the costs associated with the management of such events. Our results reveal a clear economic advantage of adopting the cost decision-making model for benchmarking the healthcare costs for various treatment strategies for BRCA-mutated women with breast cancer. The cost savings were higher when all breast cancer patients underwent counseling and genetic testing before deciding on any diagnostic-therapeutic path, with a probability of obtaining savings of over 75%.
Molecular Dysregulation in Autism Spectrum Disorder
Authors: Gill Pritmohinder S. , Clothier Jeffery L. , Veerapandiyan Aravindhan , Dweep Harsh , Porter-Gill Patricia A. , Schaefer G. Bradley
Published: August 2021

Autism Spectrum Disorder (ASD) comprises a heterogeneous group of neurodevelopmental disorders with a strong heritable genetic component. At present, ASD is diagnosed solely by behavioral criteria. Advances in genomic analysis have contributed to numerous candidate genes for the risk of ASD, where rare mutations and s common variants contribute to its susceptibility. Moreover, studies show rare de novo variants, copy number variation and single nucleotide polymorphisms (SNPs) also impact neurodevelopment signaling. Exploration of rare and common variants involved in common dysregulated pathways can provide new diagnostic and therapeutic strategies for ASD. Contributions of current innovative molecular strategies to understand etiology of ASD will be explored which are focused on whole exome sequencing (WES), whole genome sequencing (WGS), microRNA, long non-coding RNAs and CRISPR/Cas9 models. Some promising areas of pharmacogenomic and endophenotype directed therapies as novel personalized treatment and prevention will be discussed.
Precision Medicine into Clinical Practice: A Web-Based Tool Enables Real-Time Pharmacogenetic Assessment of Tailored Treatments in Psychiatric Disorders
Authors: Zampatti Stefania , Fabrizio Carlo , Ragazzo Michele , Campoli Giulia , Caputo Valerio , Strafella Claudia , Pellicano Clelia , Cascella Raffaella , Spalletta Gianfranco , Petrosini Laura , Caltagirone Carlo , Termine Andrea , Giardina Emiliano
Published: August 2021

The management of neuropsychiatric disorders involves different pharmacological treatments. In order to perform efficacious drug treatments, the metabolism of CYP genes can help to foresee potential drug–drug interactions. The NeuroPGx software is an open-source web-based tool for genotype/diplotype/phenotype interpretation for neuropharmacogenomic purposes. The software provides information about: (i) the genotypes of evaluated SNPs (single nucleotide polymorphisms); (ii) the main diplotypes in CYP genes and corresponding metabolization phenotypes; (iii) the list of neuropsychiatric drugs with recommended dosage adjustment (according to CPIC and DPWG guidelines); (iv) the list of possible (rare) diplotypes and corresponding metabolization phenotypes. The combined application of NeuroPGx software to the OpenArray technology results in an easy, quick, and highly automated device ready to be used in routine clinical practice.
Association of Breast Tumour Expression of Cannabinoid Receptors CBR1 and CBR2 with Prognostic Factors and Survival in Breast Cancer Patients
Authors: Morin-Buote Jessica , Ennour-Idrissi Kaoutar , Poirier Éric , Lemieux Julie , Furrer Daniela , Burguin Anna , Durocher Francine , Diorio Caroline
Published: August 2021

Cannabinoid receptors (CBR) are potential therapeutic targets for breast cancer. However, the role of CBR in breast cancer survival remains poorly understood. Data from a prospective cohort of 522 women diagnosed with invasive breast cancer between 2010 and 2012 were analysed. Clinical and pathological features were retrieved from electronic medical records. CBR expression was measured by immunohistochemistry. Adjusted partial Spearman correlations and multivariate Cox models were used to estimate associations with breast cancer prognostic factors and survival, respectively. The median follow-up was 92.0 months (range 7.0–114.0). CBR expression was heterogenous in tumours. Cytoplasmic expression of CBR1 was positively correlated with lymph node invasion (rs = 0.110; p = 0.0155) and positive status of the human epidermal growth factor receptor 2 (HER2) (rs = 0.168; p = 0.0002), while nuclear CBR2 was negatively correlated with grade (rs = −0.171; p = 0.0002) and positively correlated with oestrogen receptor and progesterone receptor-positive status (rs = 0.173; p = 0.0002 and rs = 0.121; p = 0.0084, respectively). High cytoplasmic expression of CBR2 was associated, with 13% higher locoregional and distant recurrences (HR = 1.13 [0.97–1.33]), though this association did not reach statistical significance. Although the few events occurring during follow-up may have limited the detection of significant associations, these results indicate that CBR expression in breast cancer deserves further investigation.
Ways to Address Perinatal Mast Cell Activation and Focal Brain Inflammation, including Response to SARS-CoV-2, in Autism Spectrum Disorder
Authors: Theoharides Theoharis C.
Published: August 2021

The prevalence of autism spectrum disorder (ASD) continues to increase, but no distinct pathogenesis or effective treatment are known yet. The presence of many comorbidities further complicates matters, making a personalized approach necessary. An increasing number of reports indicate that inflammation of the brain leads to neurodegenerative changes, especially during perinatal life, “short-circuiting the electrical system” in the amygdala that is essential for our ability to feel emotions, but also regulates fear. Inflammation of the brain can result from the stimulation of mast cells—found in all tissues including the brain—by neuropeptides, stress, toxins, and viruses such as SARS-CoV-2, leading to the activation of microglia. These resident brain defenders then release even more inflammatory molecules and stop “pruning” nerve connections, disrupting neuronal connectivity, lowering the fear threshold, and derailing the expression of emotions, as seen in ASD. Many epidemiological studies have reported a strong association between ASD and atopic dermatitis (eczema), asthma, and food allergies/intolerance, all of which involve activated mast cells. Mast cells can be triggered by allergens, neuropeptides, stress, and toxins, leading to disruption of the blood–brain barrier (BBB) and activation of microglia. Moreover, many epidemiological studies have reported a strong association between stress and atopic dermatitis (eczema) during gestation, which involves activated mast cells. Both mast cells and microglia can also be activated by SARS-CoV-2 in affected mothers during pregnancy. We showed increased expression of the proinflammatory cytokine IL-18 and its receptor, but decreased expression of the anti-inflammatory cytokine IL-38 and its receptor IL-36R, only in the amygdala of deceased children with ASD. We further showed that the natural flavonoid luteolin is a potent inhibitor of the activation of both mast cells and microglia, but also blocks SARS-CoV-2 binding to its receptor angiotensin-converting enzyme 2 (ACE2). A treatment approach should be tailored to each individual patient and should address hyperactivity/stress, allergies, or food intolerance, with the introduction of natural molecules or drugs to inhibit mast cells and microglia, such as liposomal luteolin.
Second-Generation 3D Automated Breast Ultrasonography (Prone ABUS) for Dense Breast Cancer Screening Integrated to Mammography: Effectiveness, Performance and Detection Rates
Authors: Gatta Gianluca , Cappabianca Salvatore , La Forgia Daniele , Massafra Raffaella , Fanizzi Annarita , Cuccurullo Vincenzo , Brunese Luca , Tagliafico Alberto , Grassi Roberto
Published: August 2021

In our study, we added a three-dimensional automated breast ultrasound (3D ABUS) to mammography to evaluate the performance and cancer detection rate of mammography alone or with the addition of 3D prone ABUS in women with dense breasts. Our prospective observational study was based on the screening of 1165 asymptomatic women with dense breasts who selected independent of risk factors. The results evaluated include the cancers detected between June 2017 and February 2019, and all surveys were subjected to a double reading. Mammography detected four cancers, while mammography combined with a prone Sofia system (3D ABUS) doubled the detection rate, with eight instances of cancer being found. The diagnostic yield difference was 3.4 per 1000. Mammography alone was subjected to a recall rate of 14.5 for 1000 women, while mammography combined with 3D prone ABUS resulted in a recall rate of 26.6 per 1000 women. We also observed an additional 12.1 recalls per 1000 women screened. Integrating full-field digital mammography (FFDM) with 3D prone ABUS in women with high breast density increases and improves breast cancer detection rates in a significant manner, including small and invasive cancers, and it has a tolerable impact on recall rate. Moreover, 3D prone ABUS performance results are comparable with the performance results of the supine 3D ABUS system.
Filtration-Histogram Based Magnetic Resonance Texture Analysis (MRTA) for the Distinction of Primary Central Nervous System Lymphoma and Glioblastoma
Authors: MacIver Claire L. , Busaidi Ayisha Al , Ganeshan Balaji , Maynard John A. , Wastling Stephen , Hyare Harpreet , Brandner Sebastian , Markus Julia E. , Lewis Martin A. , Groves Ashley M. , Cwynarski Kate , Thust Stefanie C.
Published: August 2021

Primary central nervous system lymphoma (PCNSL) has variable imaging appearances, which overlap with those of glioblastoma (GBM), thereby necessitating invasive tissue diagnosis. We aimed to investigate whether a rapid filtration histogram analysis of clinical MRI data supports the distinction of PCNSL from GBM. Ninety tumours (PCNSL n = 48, GBM n = 42) were analysed using pre-treatment MRI sequences (T1-weighted contrast-enhanced (T1CE), T2-weighted (T2), and apparent diffusion coefficient maps (ADC)). The segmentations were completed with proprietary texture analysis software (TexRAD version 3.3). Filtered (five filter sizes SSF = 2–6 mm) and unfiltered (SSF = 0) histogram parameters were compared using Mann-Whitney U non-parametric testing, with receiver operating characteristic (ROC) derived area under the curve (AUC) analysis for significant results. Across all (n = 90) tumours, the optimal algorithm performance was achieved using an unfiltered ADC mean and the mean of positive pixels (MPP), with a sensitivity of 83.8%, specificity of 8.9%, and AUC of 0.88. For subgroup analysis with >1/3 necrosis masses, ADC permitted the identification of PCNSL with a sensitivity of 96.9% and specificity of 100%. For T1CE-derived regions, the distinction was less accurate, with a sensitivity of 71.4%, specificity of 77.1%, and AUC of 0.779. A role may exist for cross-sectional texture analysis without complex machine learning models to differentiate PCNSL from GBM. ADC appears the most suitable sequence, especially for necrotic lesion distinction.
Regional Spatial Structure and Land Use: Evidence from Bogotá and 17 Municipalities
Authors: Dominguez Andres , Sierra Hernán , Cuervo Ballesteros Nicolás
Published: August 2021

The expansion of urban areas and the growth of the urban population are challenges faced by different territorial administrations across the world. In this context, the objective of this document is to analyze land occupation and the distribution of land uses in Bogotá and 17 municipalities. Therefore, a methodology is proposed in which an accessibility indicator models the spatial structure of the territory based on employment concentrations (the sum of the number of jobs weighted by the distance between each pair of municipalities). Then, the analysis of land use is carried out using a multinomial model, with the accessibility indicator as its principal explanatory variable. In such a way, it is possible to estimate the effects associated with the location decisions of economic agents in the territory. The results will enable policy makers to identify location and relocation patterns; we found evidence of a greater probability of commercial uses within urban areas and a relocation of industrial activity towards rural areas in some municipalities.
How Do Observable Characteristics of Post-Mining Forests Affect Their Attractiveness for Recreation?
Authors: Braun Kohlová Markéta , Nepožitková Petra , Melichar Jan
Published: August 2021

Afforestation is a popular practice of the recovery of landscape affected by open-cast coal mining. We investigated what impact the observable characteristics of restored forests have on their attractiveness for recreation framed as a one hour walk in a respective type of forest. In this study, we elaborate on some of the observable characteristics which have been previously found in the literature to affect the perceived attractiveness of outdoor environments. Environmental preference data were collected online using a quasi-representative sample of affected and control populations of the Czech Republic (N = 869). The questionnaire employed visual representations of typical reclaimed forest sites on spoil heaps in the Sokolov mining district. A mediation analysis revealed that forests growing in post-mining areas are perceived more negatively than the typical commercial spruce forest due to their lower permeability, lower level of stewardship, and perceived low safety. However, there are differences in observed characteristics also between different types of restored forests, even when controlling the effect of forest age. The results show for forestry practice that while some of the observed characteristics change by themselves with the increasing age of the forest (permeability, perceived safety, and naturalness of successional forests), improvement in others requires targeted after-care (perceived stewardship). In any case, our results are promising in that they imply that the recreational value of restored forests in post-mining areas may further increase in the future.
Applying SBM-GPA Model to Explore Urban Land Use Efficiency Considering Ecological Development in China
Authors: Cui Xufeng , Huang Sisi , Liu Cuicui , Zhou Tingting , Shan Ling , Zhang Fengyuan , Chen Min , Li Fei , de Vries Walter T.
Published: August 2021

Rapid urban sprawl is a key characteristic of the current urban land use changes in China. It leads, however, to inefficient land use and spatial imbalance. This paper conducts a quantitative analysis of the urban land use efficiency (ULUE) at a provincial scale in China, based on the SBM-GPA integration model, and using the datasets of 31 province-level regions (provinces, municipalities and autonomous regions) in Chinese mainland from 2008 to 2017. The analysis demonstrates that: (1) the proportion of provinces reaching the production frontiers is low, but there are possibilities to improve for the ULUE; (2) the provincial ULUE strongly correlates to the type of agglomeration characteristics, and the degree of agglomeration tends to increase year by year; (3) there are three types of clusters of provincial ULUE values: high, medium, and low; (4) the gravity center of the provincial ULUE is located in Henan Province, where values are relatively stable and limited changes occur. The novelty of this research is that it applies spatial modeling to characterize and analyze ULUE spatial and temporal variations and clusters in China. Practically, this can better support decision making in urban land use management.
Driving Forces for the Spatial Reconstruction of Rural Settlements in Mountainous Areas Based on Structural Equation Models: A Case Study in Western China
Authors: Zhong Jia , Liu Shaoquan , Huang Min , Cao Sha , Yu Hui
Published: August 2021

Rural settlement development in mountainous areas is the key to eliminating global hunger and poverty. The spatial reconstruction of rural settlements in mountainous areas can promote rural development in mountainous areas. In this study, the Panxi area—a typical mountainous area in China—was chosen as the study area. The driving forces for the spatial reconstruction of rural settlements in mountainous areas were explored from the perspective of peasant households by combining participatory rural appraisal (PRA) with structural equation modeling (SEM). Results showed that: (1) 62.03% of the 266 peasant households included were willing to have spatial reconstruction, indicating that most peasant households in mountainous areas have a very strong intention towards the spatial reconstruction of rural settlements. (2) Infrastructure, medical conditions, living environment, farming culture, and dietary habits significantly influenced the reconstruction intention of peasant households. In contrast, development opportunities, place attachment, language, and living mode each had a slight influence. (3) Geological disasters were the main driving force for the spatial reconstruction of rural settlements in mountainous areas, whilst the driving force of living cohesion was the smallest. This study provides insights for future planning and construction of rural settlements in the Panxi area and spatial reconstruction practices. It has important practical significance for overcoming poverty and realizing rural revitalization in mountainous areas.
Hydrological Responses to Land Use Land Cover Changes in the Fincha’a Watershed, Ethiopia
Authors: Kenea Urgessa , Adeba Dereje , Regasa Motuma , Nones Michael
Published: August 2021

Land use land cover (LULC) changes are highly pronounced in African countries, as they are characterized by an agriculture-based economy and a rapidly growing population. Understanding how land use/cover changes (LULCC) influence watershed hydrology will enable local governments and policymakers to formulate and implement effective and appropriate response strategies to minimize the undesirable effects of future land use/cover change or modification and sustain the local socio-economic situation. The hydrological response of the Ethiopia Fincha’a watershed to LULCC that happened during 25 years was investigated, comparing the situation in three reference years: 1994, 2004, and 2018. The information was derived from Landsat sensors, respectively Landsat 5 TM, Landsat 7 ETM, and Landsat 8 OLI/TIRS. The various LULC classes were derived via ArcGIS using a supervised classification system, and the accuracy assessment was done using confusion matrixes. For all the years investigated, the overall accuracies and the kappa coefficients were higher than 80%, with 2018 as the more accurate year. The analysis of LULCC revealed that forest decreased by 20.0% between the years 1994–2004, and it decreased by 11.8% in the following period 2004–2018. Such decline in areas covered by forest is correlated to an expansion of cultivated land by 16.4% and 10.81%, respectively. After having evaluated the LULCC at the basin scale, the watershed was divided into 18 sub-watersheds, which contained 176 hydrologic response units (HRUs), having a specific LULC. Accounting for such a detailed subdivision of the Fincha’a watershed, the SWAT model was firstly calibrated and validated on past data, and then applied to infer information on the hydrological response of each HRU on LULCC. The modelling results pointed out a general increase of average water flow, both during dry and wet periods, as a consequence of a shift of land coverage from forest and grass towards settlements and build-up areas. The present analysis pointed out the need of accounting for past and future LULCC in modelling the hydrological responses of rivers at the watershed scale.
Ontology-Based Probabilistic Estimation for Assessing Semantic Similarity of Land Use/Land Cover Classification Systems
Authors: Zhou Xiran , Xie Xiao , Xue Yong , Xue Bing
Published: August 2021

To accurately and formally represent the historical trajectory and present the current situation of land use/land cover (LULC), numerous types of classification standards for LULC have been developed by different nations, institutes, organizations, etc.; however, these land cover classification systems and legends generate polysemy and ambiguity in integration and sharing. The approaches for dealing with semantic heterogeneity have been developed in terms of semantic similarity. Generally speaking, these approaches lack domain ontologies, which might be a significant barrier to implementing these approaches in terms of semantic similarity assessment. In this paper, we propose an ontological approach to assess the similarity of the domain of LULC classification systems and standards. We develop domain ontologies to explicitly define the descriptions and codes of different LULC classification systems and standards as semantic information, and formally organize this semantic information as rules for logical reasoning. Then, we utilize a Bayes algorithm to create a conditional probabilistic model for computing the semantic similarity of terms in two separate LULC land cover classification systems. The experiment shows that semantic similarity can be effectively measured by integrating a probabilistic model based on the content of ontology.
Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer
Authors: Nordeen Steven K. , Su Lih-Jen , Osborne Gregory A. , Hayman Perry M. , Orlicky David J. , Wessells Veronica M. , van Bokhoven Adrie , Flaig Thomas W.
Published: August 2021

Since the Nobel Prize-winning work of Huggins, androgen ablation has been a mainstay for treatment of recurrent prostate cancer. While initially effective for most patients, prostate cancers inevitably develop the ability to survive, grow, and metastasize further, despite ongoing androgen suppression. Here, we briefly review key preclinical studies over decades and include illustrative examples from our own laboratories that suggest prostate cancer cells titrate androgen signaling to optimize growth. Such laboratory-based studies argue that adaptations that allow growth in a low-androgen environment render prostate cancer sensitive to restoration of androgens, especially at supraphysiologic doses. Based on preclinical data as well as clinical observations, trials employing high-dose testosterone (HDT) therapy have now been conducted. These trials suggest a clinical benefit in cancer response and quality of life in a subset of castration-resistant prostate cancer patients. Laboratory studies also suggest that HDT may yet be optimized further to improve efficacy or durability of response. However, laboratory observations suggest that the cancer will inevitably adapt to HDT, and, as with prior androgen deprivation, disease progression follows. Nonetheless, the adaptations made to render tumors resistant to hormonal manipulations may reveal vulnerabilities that can be exploited to prolong survival and provide other clinical benefits.
Human Responses and Adaptation in a Changing Climate: A Framework Integrating Biological, Psychological, and Behavioural Aspects
Authors: Cianconi Paolo , Hanife Batul , Grillo Francesco , Zhang Kai , Janiri Luigi
Published: August 2021

Climate change is one of the biggest challenges of our times. Its impact on human populations is not yet completely understood. Many studies have focused on single aspects with contradictory observations. However, climate change is a complex phenomenon that cannot be adequately addressed from a single discipline’s perspective. Hence, we propose a comprehensive conceptual framework on the relationships between climate change and human responses. This framework includes biological, psychological, and behavioural aspects and provides a multidisciplinary overview and critical information for focused interventions. The role of tipping points and regime shifts is explored, and a historical perspective is presented to describe the relationship between climate evolution and socio-cultural crisis. Vulnerability, resilience, and adaptation are analysed from an individual and a community point of view. Finally, emergent behaviours and mass effect phenomena are examined that account for mental maladjustment and conflicts.
The Ideal Time for Iron Administration in Anemia Secondary to Blood Loss—An Experimental Animal Model
Authors: Tiglis Mirela , Peride Ileana , Petcu Lucian Cristian , Neagu Tiberiu Paul , Niculae Andrei , Totan Alexandra , Zurac Sabina Andrada , Checherita Ionel Alexandru , Grintescu Ioana Marina
Published: August 2021

Background: Anemia and iron deficiency are two of the main public health problems worldwide, associated with negative outcomes in surgical patients. This experimental study aimed to create a model of acute iron deficiency with anemia through blood loss and extensive surgery. Afterwards, intravenous iron was administered to correct the iron deficiency and to improve the hematological parameters in distinct moments regarding the surgical time. To assess the optimum time for therapeutic intervention, experimental subjects were compared, performing clinical, paraclinical, and histological examinations, as well. Methods: Male rats (n = 35), aged 11–13 months, were randomly designated into six groups. Anemia and iron deficiency were obtained through a 15% blood volume loss, followed by major surgical intervention (femur fracture and osteosynthesis using Kirschner wire). Therapeutic intervention was obtained with an intravenous ferric carboxymaltose infusion, as follows: group II: intraoperative (n = 7), group III: 48 h after surgery (n = 7), group IV: 48 h before surgery (n = 5), and group V: seven days before surgery (n = 6). Group I (n = 5) was left anemic, while group 0 (n = 5) was nonanemic without therapeutic intervention. Results and Discussion: In group I, serum iron lower than in group 0 (27.04 ± 6.92 μg/dL versus 60.5 ± 2.34 μg/dL), as well as hemoglobin (10.4 ± 0.54 g/dL versus 14.32 ± 2.01 g/dL) and ferritin values (22.52 ± 0.53 ng/mL versus 29.86 ± 3.97 ng/mL), validated the experimental model. Regarding wound healing after surgical trauma, we observed that neovascularization was more significant in group III, followed by group V, with fewer neutrophils, a well-represented and rich in lymphomonocytes inflammatory infiltrate associated with the biggest collagen fiber dimensions. The periosteal reaction and callus area presented thicker trabeculae in groups II and III compared to the anemic group. Conclusions: This original experimental study assessed the effect of perioperative intravenous iron administration at a specific time by comparing the weight, hematological, and iron status-defining parameters, as well as histological characteristics of the included subjects. The present findings highlight that correcting the iron deficiency in emergency settings through intravenous iron administration intraoperatively or 48 h postoperatively could determine the improved bioumoral parameters, as well as a better evolution of the postoperative wound and bone healing compared to the anemic group or subjects that received therapeutic intervention 48 h before surgery.
Influencing Factors and Molecular Pathogenesis of Sarcopenia and Osteosarcopenia in Chronic Liver Disease
Authors: Saeki Chisato , Tsubota Akihito
Published: August 2021

The liver plays a pivotal role in nutrient/energy metabolism and storage, anabolic hormone regulation, ammonia detoxification, and cytokine production. Impaired liver function can cause malnutrition, hyperammonemia, and chronic inflammation, leading to an imbalance between muscle protein synthesis and proteolysis. Patients with chronic liver disease (CLD) have a high prevalence of sarcopenia, characterized by progressive loss of muscle mass and function, affecting health-related quality of life and prognosis. Recent reports have revealed that osteosarcopenia, defined as the concomitant occurrence of sarcopenia and osteoporosis, is also highly prevalent in patients with CLD. Since the differentiation and growth of muscles and bones are closely interrelated through mechanical and biochemical communication, sarcopenia and osteoporosis often progress concurrently and affect each other. Osteosarcopenia further exacerbates unfavorable health outcomes, such as vertebral fracture and frailty. Therefore, a comprehensive assessment of sarcopenia, osteoporosis, and osteosarcopenia, and an understanding of the pathogenic mechanisms involving the liver, bones, and muscles, are important for prevention and treatment. This review summarizes the molecular mechanisms of sarcopenia and osteosarcopenia elucidated to data in hopes of promoting advances in treating these musculoskeletal disorders in patients with CLD.
The Female Pelvic Floor Fascia Anatomy: A Systematic Search and Review
Authors: Roch Mélanie , Gaudreault Nathaly , Cyr Marie-Pierre , Venne Gabriel , Bureau Nathalie J. , Morin Mélanie
Published: August 2021

The female pelvis is a complex anatomical region comprising the pelvic organs, muscles, neurovascular supplies, and fasciae. The anatomy of the pelvic floor and its fascial components are currently poorly described and misunderstood. This systematic search and review aimed to explore and summarize the current state of knowledge on the fascial anatomy of the pelvic floor in women. Methods: A systematic search was performed using Medline and Scopus databases. A synthesis of the findings with a critical appraisal was subsequently carried out. The risk of bias was assessed with the Anatomical Quality Assurance Tool. Results: A total of 39 articles, involving 1192 women, were included in the review. Although the perineal membrane, tendinous arch of pelvic fascia, pubourethral ligaments, rectovaginal fascia, and perineal body were the most frequently described structures, uncertainties were identified in micro- and macro-anatomy. The risk of bias was scored as low in 16 studies (41%), unclear in 3 studies (8%), and high in 20 studies (51%). Conclusions: This review provides the best available evidence on the female anatomy of the pelvic floor fasciae. Future studies should be conducted to clarify the discrepancies highlighted and accurately describe the pelvic floor fasciae.
Enhancement of Transgene Expression by Mild Hypothermia Is Promoter Dependent in HEK293 Cells
Authors: Jang Min Ho , Min Honggi , Lee Jae Seong
Published: August 2021

Mild hypothermia has been widely used to enhance transgene expression and improve the cellular productivity of mammalian cells. This study investigated mild hypothermia-responsive exogenous promoters in human embryonic kidney 293 (HEK293) cells using site-specific integration of various promoter sequences, including CMV, EF1α, SV40, and TK promoters, into the well-known genomic safe harbor site, AAVS1. EGFP expression driven by the CMV promoter increased up to 1.5-fold at 32 °C versus 37 °C under stable expression, while others showed no hypothermic response. Integration of short CMV variants revealed that the CMV-enhancer region is responsible for the positive hypothermic response. CMV-enhancer-specific transcription factors (TFs) were then predicted through in silico analysis and RNA-sequencing analysis, resulting in the selection of one TF, NKX3-1. At 37 °C, overexpression of NKX3-1 in recombinant HEK293 cells expressing EGFP through the CMV promoter (CMV-EGFP) increased EGFP expression up to 1.6-fold, compared with that in CMV-EGFP, the expression level of which was comparable to that of CMV-EGFP at 32 °C. Taken together, this work demonstrates promoter-dependent hypothermia responses in HEK293 cells and emphasizes interactions between endogenous TFs and promoter sequences.
Effect of Aspirin on Mitochondrial Dysfunction and Stress in the Pancreas and Heart of Goto-Kakizaki Diabetic Rats
Authors: John Annie , Amiri Layla , Shafarin Jasmin , Howarth Frank Christopher , Raza Haider
Published: August 2021

Our previous study in Goto-Kakizaki (GK) type 2 diabetic rats provided significant evidence that aspirin treatment improves pancreatic β-cell function by reducing inflammatory responses and improving glucose tolerance. In the present study, we aimed to elucidate the mechanism of action of aspirin on the pathophysiology and progression of type 2 diabetic complications in the heart and pancreas of insulin-resistant GK rats. Aspirin treatment demonstrated a reduction in mitochondrial reactive oxygen species (ROS) production and lipid peroxidation, accompanied by improved redox homeostasis. Furthermore, the recovery of metabolic and mitochondrial functions, as well as cytochrome P450 enzyme activities, which were altered in the pancreas and heart of GK rats, were observed. Aspirin treatment brought the activity of CYP 2E1 to the control level in both tissues, whereas the CYP 3A4 level decreased only in the pancreas. This suggests the tissue-specific differential metabolism of substrates in these rats. The recovery of redox homeostasis could be the key target in the improvement of oxidative-stress-dependent alterations in mitochondrial functions which, in turn, facilitated improved energy metabolism in these tissues in the aspirin-treated GK rats. These results may have implications in determining the therapeutic use of aspirin, either alone or in combination with other clinically approved therapies, in insulin-resistant type 2 diabetes.
Crosstalk between Autophagy and Inflammatory Processes in Cancer
Authors: Lee Eun-Ji , Kim Hyun-Jeong , Choi Min Sik , Chang Ji-Eun
Published: August 2021

Inflammation is an adaptive response to tissue injury, which is a critical process in order to restore tissue functionality and homeostasis. The association between inflammation and cancer has been a topic of interest for many years, not only inflammatory cells themselves but also the chemokines and cytokines they produce, which affect cancer development. Autophagy is an intracellular self-degradative process providing elimination of damaged or dysfunctional organelles under stressful conditions such as nutrient deficiency, hypoxia, or chemotherapy. Interestingly, the signaling pathways that are involved in cancer-associated inflammation may regulate autophagy as well. These are (1) the toll-like receptor (TLR) signaling cascade, (2) the reactive oxygen species (ROS) signaling pathway, (3) the inflammatory cytokine signaling pathway, and (4) the IκB kinase (IKK)/Nuclear factor-κB (NF-κB) signaling axis. Moreover, the studies on the context-specific functions of autophagy during inflammatory responses in cancer will be discussed here. On that basis, we focus on autophagy inhibitors and activators regulating inflammatory process in cancer as useful candidates for enhancing anticancer effects. This review summarizes how the autophagic process regulates these key inflammatory processes and vice versa in various cancers.
Effects of 24 h Compression Interventions with Different Garments on Recovery Markers during Running
Authors: Carvalho Jean , Kunzler Marcos Roberto , Priego-Quesada Jose Ignacio , Aparicio Inmaculada , Pérez-Soriano Pedro , Machado Álvaro Sosa , Carpes Felipe Pivetta
Published: August 2021

Compression and temperature manipulation are discussed as strategies to improve performance markers and recovery in sports. Here, we investigate the effects of compression stockings made with fabric, either combined or not with heating and cooling substances, on variables related to running performance and recovery. Ten trained runners (mean ± standard deviation age 45 ± 9 years old, body mass 69 ± 7 kg, height 166 ± 4 cm) with no experience of using compression garments performed an intense running session of 10 km, then wore a stocking for 24 h (randomized; without compression, compression, compression with camphor, and compression with menthol), and were evaluated on the following day, after running 5 km. The different types of compression stockings used 24 h before exercise did not affect running kinematics (p > 0.14), skin temperature (p > 0.05), heart rate (p > 0.12; mean value of maximal heart rate 156 bpm), comfort perception (p = 0.13; mean value of 7/10 points), or perception of recovery (p = 0.13; mean value of 7/10 points). In general, there were no effects of 24 h pre-exercise lower leg compression, including those treated with menthol and camphor applications on running kinematics, skin temperature, heart rate, or recovery perception in athletes undertaking consecutive running exercises.
Resorbable Mg2+-Containing Phosphates for Bone Tissue Repair
Authors: Kazakova Gilyana , Safronova Tatiana , Golubchikov Daniil , Shevtsova Olga , Rau Julietta V.
Published: August 2021

Materials based on Mg2+-containing phosphates are gaining great relevance in the field of bone tissue repair via regenerative medicine methods. Magnesium ions, together with condensed phosphate ions, play substantial roles in the process of bone remodeling, affecting the early stage of bone regeneration through active participation in the process of osteosynthesis. In this paper we provide a comprehensive overview of the usage of biomaterials based on magnesium phosphate and magnesium calcium phosphate in bone reconstruction. We consider the role of magnesium ions in angiogenesis, which is an important process associated with osteogenesis. Finally, we summarize the biological properties of calcium magnesium phosphates for regeneration of bone.
Effect of TRC and F/TRC Strengthening on the Cracking Behaviour of RC Beams in Bending
Authors: Rossi Edoardo , Randl Norbert , Mészöly Tamás , Harsányi Peter
Published: August 2021

The increasing demand on the performance of existing structures, together with their degradation, is among the main drivers towards the development of innovative strengthening solutions. While such solutions are generally aimed at increasing the load-bearing capacity of structural elements, serviceability limit states also play an important role in ensuring the performance and durability of the structure. An experimental campaign was performed to assess the cracking behaviour of reinforced concrete beams strengthened with different typologies of Textile-Reinforced Concrete. The specimens were monitored using Digital Image Correlation (DIC) technology in order to obtain a quantitative evaluation of the evolution of the crack pattern throughout the whole test. Results show the beneficial effects of this retrofitting strategy both at ultimate limit states and serviceability limit states, provide detailed insights on the progression of damage in the specimens and highlight how different parameters impact the cracking behaviour of the tested elements.
New Coordination Polymers of Selected Lanthanides with 1,2-Phenylenediacetate Linker: Structures, Thermal and Luminescence Properties
Authors: Łyszczek Renata , Rusinek Iwona , Ostasz Agnieszka , Sienkiewicz-Gromiuk Justyna , Vlasyuk Dmytro , Groszek Marcin , Lipke Agnieszka , Pavlyuk Oleksiy
Published: August 2021

Solvothermal reactions of lanthanide (III) salts with 1,2-phenylenediacetic acid in N,N′-dimethylformamide (DMF) solvent lead to the formation of the metal complexes of the general formula Ln2(1,2-pda)3(DMF)2, where Ln(III) = Pr(1), Sm(2), Eu(3), Tb(4), Dy(5), and Er(6), 1,2-pda = [C6H4(CH2COO)2]2−. The compounds were characterized by elemental analysis, powder and single-crystal X-ray diffraction methods, thermal analysis methods (TG-DSC and TG-FTIR), infrared and luminescence spectroscopy. They exhibit structural similarity in the two groups (Pr, Sm, and Eu; Tb, Dy, and Er), which was reflected in their thermal behaviours and spectroscopic properties. Single-crystal X-ray diffraction studies reveal that Sm(2) and Eu(3) complexes form 2D coordination polymers with four crystallographically independent metal centers. Every second lanthanide ion is additionally coordinated by two DMF molecules. The 1,2-phenylenediacetate linker shows different denticity being: penta- and hexadentate while carboxylate groups exhibit bidentate-bridging, bidentate-chelating, and three-dentate bridging-chelating modes. The infrared spectra reflect divergence between these two groups of complexes. The complexes of lighter lanthanides contain in the structure coordinated DMF molecules, while in the structures of heavier complexes, DMF molecules appear in the inner and outer coordination sphere. Both carboxylate groups are deprotonated and engaged in the coordination of metal centers but in different ways in such groups of complexes. In the groups, the thermal decomposition of the isostructural complexes occurs similarly. Pyrolysis of complexes takes place with the formation of such gaseous products as DMF, carbon oxides, ortho-xylene, ethers, water, carboxylic acids, and esters. The complexes of Eu and Tb exhibit characteristic luminescence in the VIS region, while the erbium complex emits NIR wavelength.
A Novel Flow Model of Strain Hardening and Softening for Use in Tensile Testing of a Cylindrical Specimen at Room Temperature
Authors: Razali Mohd Kaswandee , Joun Man Soo , Chung Wan Jin
Published: August 2021

We develop a new flow model based on the Swift method, which is both versatile and accurate when used to describe flow stress in terms of strain hardening and damage softening. A practical issue associated with flow stress at room temperature is discussed in terms of tensile testing of a cylindrical specimen; we deal with both material identification and finite element predictions. The flow model has four major components, namely the stress before, at, and after the necking point and around fracture point. The Swift model has the drawback that not all major points of stress can be covered simultaneously. A term of strain to the third or fourth power (the “second strain hardening exponent”), multiplied and thus controlled by a second strain hardening parameter, can be neglected at small strains. Any effect of the second strain hardening exponent on the identification of the necking point is thus negligible. We use this term to enhance the flexibility and accuracy of our new flow model, which naturally couples flow stress with damage using the same hardening constant as a function of damage. The hardening constant becomes negative when damage exceeds a critical value that causes a drastic drop in flow stress.
Behaviour of Microwave-Heated Al4SiC4 at 2.45 GHz
Authors: Fujii Takashi , Oshita Akio , Kashimura Keiichiro
Published: August 2021

The ongoing development of high-temperature processes with the use of microwaves requires new microwave absorbers that are useful at these temperatures. In this study, we propose Al4SiC4 powders as important and efficient microwave absorbers. We investigated both the behavioural microwave heating and electrical permittivity characteristics of Al4SiC4 powders with various particle sizes at 2.45 GHz. The TE103 single-mode cavity indicated that Al4SiC4 powder samples yielded different heating behaviours and dielectric constants for each particle size compared with SiC. By microwave heating ∅50 mm × 5 mm disks of Al4SiC4 and SiC, we demonstrate that for specific sizes, Al4SiC4 can be heated at a higher temperature than SiC. Finally, the results of the two-dimensional two-colour thermometer show that an energy concentration appears at the interface of the microwave-heated Al4SiC4. These phenomena, which are inconsistent in individual physical property values, can be explained without contradicting microwave heating physics.
Spark Plasma Sintering of AlN/Al Functionally Graded Materials
Authors: Xiu Ziyang , Ju Boyu , Liu Saiyue , Song Yiwei , Du Jindan , Li Zhimin , Zhou Chang , Yang Wenshu , Wu Gaohui
Published: August 2021

In this paper, six-layer AlN/Al gradient composites were prepared by a spark plasma sintering process to study the influences of sintering temperature and holding time on the microstructure and mechanical properties. The well-bonded interface enables the composite to exhibit excellent thermal and mechanical properties. The hardness and thermal expansion properties of the composite exhibit a gradient property. The hardness increased with the volume fraction of AlN while the CTE decreased as the volume fraction of AlN. The thermal expansion reaches the lowest value of 13–14 ppm/K, and the hardness reaches the maximum value of 1.25 GPa, when the target volume fraction of AlN is 45%. The simulation results show that this gradient material can effectively reduce the thermal stress caused by the mismatch of the thermal expansion coefficient as a transmitter and receiver (T/R) module. This paper attempts to provide experimental support for the preparation of gradient Al matrix composites.
Evaluation of the Protection Ability of a Magnesium Hydroxide Coating against the Bio-Corrosion of Concrete Sewer Pipes, by Using Short and Long Duration Accelerated Acid Spraying Tests
Authors: Merachtsaki Domna , Tsardaka Eirini-Chrysanthi , Anastasiou Eleftherios , Zouboulis Anastasios
Published: August 2021

The Microbiologically Induced Corrosion (MIC) of concrete sewer pipes is a commonly known problem that can lead to the destruction of the system, creating multiple public health issues and the need for costly repair investments. The present study focuses on the development of a magnesium hydroxide coating, with optimized properties to protect concrete against MIC. The anti-corrosion properties of the respective coating were evaluated by using short and long duration accelerated sulfuric acid spraying tests. The coating presented satisfying adhesion ability, based on pull-off and Scanning Electron Microscopy (SEM) analysis measurements. The surface pH of the coated concrete was maintained at the alkaline region (i.e., >8.0) throughout the duration of all acid spraying tests. The consumption of the coating, due to the reaction (neutralization) with sulfuric acid, was confirmed by the respective mass and thickness measurements. The protection ability of this coating was also evaluated by recording the formation of gypsum (i.e., the main corrosion product of concrete) during the performed tests, by X-ray Diffraction (XRD) analysis and by the Attenuated Total Reflectance (ATR) measurements. Finally, a long duration acid spraying test was additionally used to evaluate the behavior of the coating, simulating better the conditions existing in a real sewer pipe, and the obtained results showed that this coating is capable of offering prolonged protection to the concrete substrate.