bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Contrast-Enhanced Ultrasound with Sonazoid for Evaluating the Radiotherapy Efficacy for Hepatocellular Carcinoma
Authors: Funaoka Akihiro , Numata Kazushi , Takeda Atsuya , Saigusa Yusuke , Tsurugai Yuichirou , Nihonmatsu Hiromi , Chuma Makoto , Fukuda Hiroyuki , Okada Masahiro , Nakano Masayuki , Maeda Shin
Published: March 2021

Radiotherapy is one of the available curative therapies for hepatocellular carcinoma (HCC). We investigate the use of contrast-enhanced ultrasound using Sonazoid (SCEUS) in evaluating the efficacy of radiotherapy for HCC. We enrolled 59 patients with 59 HCCs in this retrospective study. Tumor size and tumor vascularity were evaluated using SCEUS before and 1, 3, 7, 10, and 13 months after radiotherapy. The median follow-up period was 44.5 months (range: 16–82 months). Of the HCCs, 95% (56/59) had no local recurrence, while 5% (3/59) did. At 13 months after radiotherapy, in cases with no local recurrence, SCEUS showed a reduction in tumor vascularity in all cases, while tumor size reduction (>30% reduction, compared with pre-radiotherapy) was observed in 82.1% (46/56). In all three cases of local recurrence, vascularity and tumor size reduction were not observed during the follow-up period and residual HCCs were demonstrated pathologically. Compared with cases with local recurrence, tumor size reduction and reduction in tumor vascularity (p < 0.001) were significantly greater in cases with no local recurrence at 13 months after radiotherapy. SCEUS may be useful in evaluating radiotherapy efficacy for HCC.
Development of a Pandemic Awareness STEM Outreach Curriculum: Utilizing a Computational Thinking Taxonomy Framework
Authors: Gilchrist Pamela O. , Alexander Alonzo B. , Green Adrian J. , Sanders Frieda E. , Hooker Ashley Q. , Reif David M.
Published: March 2021

Computational thinking is an essential skill in the modern global workforce. The current public health crisis has highlighted the need for students and educators to have a deeper understanding of epidemiology. While existing STEM curricula has addressed these topics in the past, current events present an opportunity for new curricula that can be designed to present epidemiology, the science of public health, as a modern topic for students that embeds the problem-solving and mathematics skills of computational thinking practices authentically. Using the Computational Thinking Taxonomy within the informal education setting of a STEM outreach program, a curriculum was developed to introduce middle school students to epidemiological concepts while developing their problem-solving skills, a subset of their computational thinking and mathematical thinking practices, in a contextually rich environment. The informal education setting at a Research I Institution provides avenues to connect diverse learners to visually engaging computational thinking and data science curricula to understand emerging teaching and learning approaches. This paper documents the theory and design approach used by researchers and practitioners to create a Pandemic Awareness STEM Curriculum and future implications for teaching and learning computational thinking practices through engaging with data science.
A Comparison of Provision and Access to Inclusive Education for Children with Disabilities in a Metropolitan City and a Rural District in Telangana State, India
Authors: Rose Richard , Narayan Jayanthi , Matam Shankar , Reddy Sambram Prathima
Published: March 2021

In response to international agreements, recent Indian legislation has raised expectations that all children, regardless of need or ability, should gain access to formal education that is inclusive and addresses their social and learning needs. Initiatives designed to support the implementation of this legislation have been undertaken in several parts of India. Reports related to such initiatives have largely focused upon developments in large urban connotations, with studies in rural areas being less in evidence. This paper reports a small-scale study conducted in Telangana a state in the south-central part of India. Through the application of semi-structured interviews data were obtained to enable a comparison to be made of the experiences of two purposive samples of families of children with disabilities and special educational needs, and the professionals who support them. The first sample was located in Hyderabad, a large metropolitan city, the capital of Telangana State. The second was situated in villages in Sangareddy, a single rural district of the same state. Interviews were conducted either in English or in Telugu, the state language with all interviews transcribed and subjected to thematic analysis. The findings, which will be used to support further development in the area, reveal a willingness on the part of professionals to support the education and social welfare needs of children with special educational needs and their families and an awareness of current national legislation aimed at achieving this objective. A disparity exists between the availability of professional support services available to families and children, with those living in the rural district experiencing greater difficulty in accessing appropriate support than their counterparts in the metropolitan city. The lack of opportunities for training and professional development is perceived to be a major obstacle to the progress of inclusive education as required by national legislation in both locations. Recommendations are made for further research that is closely allied to changes in practice, for the development of professional development of teachers and other professionals, and for the development of centralised provision in rural areas to address the needs of families.
Performance Analysis and Design Considerations of the Shallow Underwater Optical Wireless Communication System with Solar Noises Utilizing a Photon Tracing-Based Simulation Platform
Authors: Wang Xiaozheng , Zhang Minglun , Zhou Hongyu , Ren Xiaomin
Published: March 2021

The performance of the underwater optical wireless communication (UOWC) system is highly affected by seawater´s inherent optical properties and the solar radiation from sunlight, especially for a shallow environment. The multipath effect and degradations in signal-to-noise ratio (SNR) due to absorption, scattering, and ambient noises can significantly limit the viable communication range, which poses key challenges to its large-scale commercial applications. To this end, this paper proposes a unified model for underwater channel characterization and system performance analysis in the presence of solar noises utilizing a photon tracing algorithm. Besides, we developed a generic simulation platform with configurable parameters and self-defined scenarios via MATLAB. Based on this platform, a comprehensive investigation of underwater channel impairments was conducted including temporal and spatial dispersion, illumination distribution pattern, and statistical attenuation with various oceanic types. The impact of ambient noise at different operation depths on the bit error rate (BER) performance of the shallow UOWC system was evaluated under typical specifications. Simulation results revealed that the multipath dispersion is tied closely to the multiple scattering phenomenon. The delay spread and ambient noise effect can be mitigated by considering a narrow field of view (FOV) and it also enables the system to exhibit optimal performance on combining with a wide aperture.
Enhancing Power System Frequency with a Novel Load Shedding Method Including Monitoring of Synchronous Condensers’ Power Injections
Authors: Sauhats Antans , Utans Andrejs , Silinevics Jurijs , Junghans Gatis , Guzs Dmitrijs
Published: March 2021

Under-frequency load shedding (UFLS) is a classic and a commonly accepted measure used to mitigate the frequency disturbances in case of loss-of-generation incidents in AC power grids. Triggering of UFLS is classically done at frequency thresholds when system frequency collapse is already close to happening. The renewed interest for synchronous condensers due to the global trends on massive commissioning of non-synchronous renewable power generation leading to reduction of system inertia gives an opportunity to rethink the approach used to trigger load-shedding activation. This question is especially relevant for the Baltic states facing a desynchronization from Russian power grid and a necessity to operate in an isolated island mode. The main goal of this paper is to introduce a predictive load shedding (LS) method without usage of either frequency or ROCOF measurements based on the monitoring of active power injections of synchronous condensers and to prove the efficiency of the concept through several sets of case study simulations. The paper shows that the proposed approach can provide a greatly improved frequency stability of the power system. The results are analyzed and discussed, the way forward for the practical implementation of the concept is sketched.
Molecular and Metabolic Subtypes in Sporadic and Inherited Clear Cell Renal Cell Carcinoma
Authors: Czyzyk-Krzeska Maria F. , Landero Figueroa Julio A. , Gulati Shuchi , Cunningham John T. , Meller Jarek , ShamsaeI Behrouz , Vemuri Bhargav , Plas David R.
Published: March 2021

The promise of personalized medicine is a therapeutic advance where tumor signatures obtained from different omics platforms, such as genomics, transcriptomics, proteomics, and metabolomics, in addition to environmental factors including metals and metalloids, are used to guide the treatments. Clear cell renal carcinoma (ccRCC), the most common type of kidney cancer, can be sporadic (frequently) or genetic (rare), both characterized by loss of the von Hippel-Lindau (VHL) gene that controls hypoxia inducible factors. Recently, several genomic subtypes were identified with different prognoses. Transcriptomics, proteomics, metabolomics and metallomic data converge on altered metabolism as the principal feature of the disease. However, in view of multiple biochemical alterations and high level of tumor heterogeneity, identification of clearly defined subtypes is necessary for further improvement of treatments. In the future, single-cell combined multi-omics approaches will be the next generation of analyses gaining deeper insights into ccRCC progression and allowing for design of specific signatures, with better prognostic/predictive clinical applications.
The Role of Epigenetics in Congenital Heart Disease
Authors: Lim Tingsen Benson , Foo Sik Yin Roger , Chen Ching Kit
Published: March 2021

Congenital heart disease (CHD) is the most common birth defect among newborns worldwide and contributes to significant infant morbidity and mortality. Owing to major advances in medical and surgical management, as well as improved prenatal diagnosis, the outcomes for these children with CHD have improved tremendously so much so that there are now more adults living with CHD than children. Advances in genomic technologies have discovered the genetic causes of a significant fraction of CHD, while at the same time pointing to remarkable complexity in CHD genetics. For this reason, the complex process of cardiogenesis, which is governed by multiple interlinked and dose-dependent pathways, is a well investigated process. In addition to the sequence of the genome, the contribution of epigenetics to cardiogenesis is increasingly recognized. Significant progress has been made dissecting the epigenome of the heart and identified associations with cardiovascular diseases. The role of epigenetic regulation in cardiac development/cardiogenesis, using tissue and animal models, has been well reviewed. Here, we curate the current literature based on studies in humans, which have revealed associated and/or causative epigenetic factors implicated in CHD. We sought to summarize the current knowledge on the functional role of epigenetics in cardiogenesis as well as in distinct CHDs, with an aim to provide scientists and clinicians an overview of the abnormal cardiogenic pathways affected by epigenetic mechanisms, for a better understanding of their impact on the developing fetal heart, particularly for readers interested in CHD research.
Health- and Age-Related Workplace Factors as Predictors of Preferred, Expected, and Actual Retirement Timing: Findings from a Swedish Cohort Study
Authors: Sousa-Ribeiro Marta , Bernhard-Oettel Claudia , Sverke Magnus , Westerlund Hugo
Published: March 2021

To address the challenges of demographic aging, governments and organizations encourage extended working lives. This study investigates how individual health- and age-related workplace factors contribute to preferred, expected and actual retirement timing, as well as to the congruency between preferences vs. expectations, and preferences vs. actual retirement. We used data from a representative Swedish longitudinal sample comprising 4058 workers aged 50–64, with follow-up data regarding actual retirement timing available for 1164 respondents. Multinomial logistic regression analyses suggest that later preferred, expected, and actual retirement timing were, to different extent, influenced by better health, an age-friendly workplace and feeling positive regarding the future at work. Emotional exhaustion, age-related inequalities at work and experiencing aging as an obstacle increased the likelihood of preferring to retire earlier than one expected to, over retiring at the time one expected to. Those with better health and positive work prospects were less likely to prefer retiring earlier than they expected to, and more likely to being “pulled toward working until 65 and beyond”, compared to being “pulled toward early retirement”. Experiencing aging as an obstacle decreased the chances of being “pulled toward working until 65 and beyond”. The results provide insights on how to facilitate extended working lives.
Maladaptive Perfectionism and Internet Addiction among Chinese College Students: A Moderated Mediation Model of Depression and Gender
Authors: Yang Wenjie , Morita Nobuaki , Zuo Zhijuan , Kawaida Kyoko , Ogai Yasukazu , Saito Tamaki , Hu Wenyan
Published: March 2021

The association between perfectionism and addictive behaviors has been examined in previous literature; however, few pieces of research have investigated the mediating and moderating mechanisms underlying this relationship. Using a sample of 2016 Chinese college students, the present study examined the mediator of depression between maladaptive perfectionism and Internet addiction and the moderator of gender in such associations. The findings indicated that maladaptive perfectionism was directly related to students’ Internet addiction and indirectly predicted students’ Internet addiction via the mediator of depression. Gender moderated the direct effect, rather than the indirect effect, of maladaptive perfectionism on Internet addiction. Even though males reported a lower score on Internet addiction compared to females, the effect of maladaptive perfectionism on Internet addiction was stronger for males than for females. These findings revealed the psychological mechanisms from perfectionism to Internet addiction, which contributed to the theoretical development in addiction research and provided implications for interventions to reduce Internet addiction among Chinese college students.
Exploring Private Sector Engagement for Faecal Sludge Emptying and Transport Business in Khulna, Bangladesh
Authors: Singh Shirish , Gupta Ankita , Alamgir Muhammed , Brdjanovic Damir
Published: March 2021

In Khulna, Bangladesh, mechanical faecal sludge (FS) emptying and transport (E&T) service is provided by community development committees (CDCs) and the Khulna City Corporation (KCC). Without considering capital expenditure and depreciation, financial analysis for one year revealed that a CDC-1 m3 vacutug made a profit of Bangladeshi taka (BDT) 145,780 (USD $1746) whereas a KCC-2 m3 vacutug was in the loss of BDT 218,179 (USD $2613). There is a need to engage the private sector for sustainable service provision. Some of the key elements of enabling the environment for private sector engagement are policy/strategy, institutional and regulatory framework, implementation capacity, and financial viability. Existing policy/strategy/frameworks acknowledged the need and suggested plans for private sector engagement, and decentralised authority to city corporations. With increasing private-public partnership projects and collaboration in the sanitation sector, capacity of the KCC and the private sector are increasing. Financial viability of the FS E&T business is primarily dependent on the number of trips and the emptying fee. For the E&T business to be financially viable, a 2 m3 vacutug should make six trips/day (internal rate of return (IRR)—13%, discount rate—6.5%) with an emptying fee of BDT 750 (USD $9)/m3. Despite the lack of operative guidelines for faecal sludge management (FSM), enabling the environment for private sector engagement in FS E&T business in Khulna seems favourable.
Does Lung Ultrasound Have a Role in the Clinical Management of Pregnant Women with SARS COV2 Infection?
Authors: Porpora Maria Grazia , Merlino Lucia , Masciullo Luisa , D’Alisa Rossella , Brandolino Gabriella , Galli Cecilia , De Luca Casimiro , Pecorini Francesco , Fonsi Giovanni Battista , Mingoli Andrea , Franchi Cristiana , Oliva Alessandra , Manganaro Lucia , Mastroianni Claudio Maria , Piccioni Maria Grazia
Published: March 2021

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is a major health threat. Pregnancy can lead to an increased susceptibility to viral infections. Although chest computed tomography (CT) represents the gold standard for the diagnosis of SARS-CoV-2 pneumonia, lung ultrasound (LUS) could be a valid alternative in pregnancy. The objectives of this prospective study were to assess the role of LUS in the diagnosis of lung involvement and in helping the physicians in the management of affected patients. Thirty pregnant women with SARS-CoV-2 infection were admitted at the obstetrical ward of our Hospital. Mean age was 31.2 years, mean gestational age 33.8 weeks. Several LUS were performed during hospitalization. The management of the patients was decided according to the LUS score and the clinical conditions. Mean gestational age at delivery was at 37.7 weeks, preterm birth was induced in 20% of cases for a worsening of the clinical conditions. No neonatal complications occurred. In 9 cases with a high LUS score, a chest CT was performed after delivery. CT confirmed the results of LUS, showing a significant positive correlation between the two techniques. LUS seems a safe alternative to CT in pregnancy and may help in the management of these patients.
Effects of Season of Birth and Meteorological Parameters on Serum Bilirubin Levels during the Early Neonatal Period: A Retrospective Chart Review
Authors: Iijima Shigeo , Baba Toru , Kondo Miyuki , Fujita Tomoka , Ohishi Akira
Published: March 2021

To establish whether serum bilirubin levels vary in healthy term neonates according to seasonal variations and meteorological factors, we retrospectively studied 3344 healthy term neonates born between 2013 and 2018. Total serum bilirubin (TSB) levels were measured on the fourth day after birth. The monthly and seasonal variations in TSB levels and clinical and meteorological effects on TSB levels were assessed. In the enrolled neonates, the median TSB level was 195 µmol/L. The TSB level peaked in December and was the lowest in July, but the variation was not statistically significant. The TSB level was significantly higher in the cold (October to March) than in the warm season (April to September; p = 0.01). The comparison between seasonal differences according to sex showed TSB levels were significantly higher in the cold than in the warm season in male infants (p = 0.001), whereas no significant difference was observed in female infants. A weakly negative but significant association existed between TSB levels and the mean daily air temperature (r = −0.07, p = 0.007) in only the male population; the female population showed no significant correlation between TSB levels and meteorological parameters. The season of birth is an etiological factor in neonatal jaundice, with an additional influence from sex.
Maternal Prenatal Hair Cortisol Is Associated with Child Wheeze among Mothers and Infants with Tobacco Smoke Exposure and Who Face High Socioeconomic Adversity
Authors: Scherman Ashley , Spindel Eliot R. , Park Byung , Tepper Robert , Erikson David W. , Morris Cynthia , McEvoy Cindy T.
Published: March 2021

The association of co-occurring prenatal stress and tobacco exposures on childhood wheezing and asthma are not well established. In this study, we compared maternal prenatal hair cortisol concentration (HCC) to the maternal report of infant wheezing (y/n) in the first year of life among mother–infant dyads exposed to tobacco smoke and socioeconomic adversity. Data were obtained from the Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function study. Maternal adversity was defined by the level of education, household income, and health insurance provider. Hair was collected at delivery, representing average circulating third-trimester cortisol levels. HCC was log transformed and dichotomized into high/low cortisol groups that were placed into a multivariate model predicting wheeze. Subjects (n = 132) were primarily White with ≤high school education and receiving government-provided health insurance. Forty-five percent of infants wheezed. Average HCC was 3.39 pg/mg hair. Women with HCC > 3.55 pg/mg were more than twice as likely to report having a child who wheezed (odds ratio 2.56, 95% confidence interval 1.22–5.40; p = 0.01), adjusting for insurance provider and maternal asthma. Among this sample of dyads with prenatal smoke exposure, elevated maternal HCC was associated with child wheeze that was not diminished after consideration of covariates.
Health Reporting Characteristics among Journalists in Nepal Utilizing a One Health Framework
Authors: Schwind Jessica S. , Norman Stephanie A. , Rahman Munshi Khaledur , Richmond Holly L. , Dixit Sameer M. , Rajbhandari Rajesh M. , Wagner Sarah K. , Karmacharya Dibesh
Published: March 2021

Journalists play a crucial role in the dissemination of health-related information. In developing countries, such as Nepal, the media are integral in shaping the national agenda and informing the public of important health issues. With an increasing need for a collaborative effort to attain optimal health for people, animals, and the environment, the One Health approach was used to characterize health reporting in Nepal. A comprehensive survey was administered to health journalists regarding their public, animal, and environmental health reporting habits. Seventy-one journalists completed the survey across three study sites. Many journalists indicated a history of reporting across all three sectors but did not routinely focus on health reporting in general. The majority of journalists perceived the quality and overall coverage of health-related topics increased over the last five years. However, few journalists reported receiving specialized training in any health sector. Although the overall quality of health reporting in the Nepali media showed improvements, many journalists acknowledged a lack of understanding of common health topics and a desire to learn more skills related to accurate health reporting. One Health provides a conceptual framework for understanding and promoting health communication through mass media to benefit humans, animals, and ecosystems.
PSMA-D4 Radioligand for Targeted Therapy of Prostate Cancer: Synthesis, Characteristics and Preliminary Assessment of Biological Properties
Authors: Garnuszek Piotr , Karczmarczyk Urszula , Maurin Michał , Sikora Arkadiusz , Zaborniak Jolanta , Pijarowska-Kruszyna Justyna , Jaroń Antoni , Wyczółkowska Monika , Wojdowska Wioletta , Pawlak Dariusz , Lipiński Piotr F. J. , Mikołajczak Renata
Published: March 2021

A new PSMA ligand (PSMA-D4) containing the Glu-CO-Lys pharmacophore connected with a new linker system (L-Trp-4-Amc) and chelator DOTA was developed for radiolabeling with therapeutic radionuclides. Herein we describe the synthesis, radiolabeling, and preliminary biological evaluation of the novel PSMA-D4 ligand. Synthesized PSMA-D4 was characterized using TOF-ESI-MS, NMR, and HPLC methods. The novel compound was subject to molecular modeling with GCP-II to compare its binding mode to analogous reference compounds. The radiolabeling efficiency of PSMA-D4 with 177Lu, 90Y, 47Sc, and 225Ac was chromatographically tested. In vitro studies were carried out in PSMA-positive LNCaP tumor cells membranes. The ex vivo tissue distribution profile of the radioligands and Cerenkov luminescence imaging (CLI) was studied in LNCaP tumor-bearing mice. PSMA-D4 was synthesized in 24% yield and purity >97%. The radio complexes were obtained with high yields (>97%) and molar activity ranging from 0.11 to 17.2 GBq mcmol−1, depending on the radionuclide. In vitro assays confirmed high specific binding and affinity for all radiocomplexes. Biodistribution and imaging studies revealed high accumulation in LNCaP tumor xenografts and rapid clearance of radiocomplexes from blood and non-target tissues. These render PSMA-D4 a promising ligand for targeted therapy of prostate cancer (PCa) metastases.
Mitochondrial Mistranslation in Brain Provokes a Metabolic Response Which Mitigates the Age-Associated Decline in Mitochondrial Gene Expression
Authors: Shcherbakov Dimitri , Juskeviciene Reda , Cortés Sanchón Adrián , Brilkova Margarita , Rehrauer Hubert , Laczko Endre , Böttger Erik C.
Published: March 2021

Mitochondrial misreading, conferred by mutation V338Y in mitoribosomal protein Mrps5, in-vivo is associated with a subtle neurological phenotype. Brain mitochondria of homozygous knock-in mutant Mrps5V338Y/V338Y mice show decreased oxygen consumption and reduced ATP levels. Using a combination of unbiased RNA-Seq with untargeted metabolomics, we here demonstrate a concerted response, which alleviates the impaired functionality of OXPHOS complexes in Mrps5 mutant mice. This concerted response mitigates the age-associated decline in mitochondrial gene expression and compensates for impaired respiration by transcriptional upregulation of OXPHOS components together with anaplerotic replenishment of the TCA cycle (pyruvate, 2-ketoglutarate).
Palmitic Acid Impairs Myogenesis and Alters Temporal Expression of miR-133a and miR-206 in C2C12 Myoblasts
Authors: da Paixão Ailma O. , Bolin Anaysa Paola , Silvestre João G. , Rodrigues Alice Cristina
Published: March 2021

Palmitic acid (PA), a saturated fatty acid enriched in high-fat diet, has been implicated in the development of sarcopenic obesity. Herein, we chose two non-cytotoxic concentrations to better understand how excess PA could impact myotube formation or diameter without inducing cell death. Forty-eight hours of 100 µM PA induced a reduction of myotube diameter and increased the number of type I fibers, which was associated with increased miR-206 expression. Next, C2C12 myotube growth in the presence of PA was evaluated. Compared to control cells, 150 µM PA reduces myoblast proliferation and the expression of MyoD and miR-206 and miR-133a expression, leading to a reduced number and diameter of myotubes. PA (100 µM), despite not affecting proliferation, impairs myotube formation by reducing the expression of Myf5 and miR-206 and decreasing protein synthesis. Interestingly, 100 and 150 µM PA-treated myotubes had a higher number of type II fibers than control cells. In conclusion, PA affects negatively myotube diameter, fusion, and metabolism, which may be related to myomiRs. By providing new insights into the mechanisms by which PA affects negatively skeletal muscle, our data may help in the discovery of new targets to treat sarcopenic obesity.
Supplementing with L-Tryptophan Increases Medium Protein and Alters Expression of Genes and Proteins Involved in Milk Protein Synthesis and Energy Metabolism in Bovine Mammary Cells
Authors: Conejos Jay Ronel V. , Ghassemi Nejad Jalil , Kim Jung-Eun , Moon Jun-Ok , Lee Jae-Sung , Lee Hong-Gu
Published: March 2021

The objective of this study was to investigate the effects of supplementing with L-tryptophan (L-Trp) on milk protein synthesis using an immortalized bovine mammary epithelial (MAC-T) cell line. Cells were treated with 0, 0.3, 0.6, 0.9, 1.2, and 1.5 mM of supplemental L-Trp, and the most efficient time for protein synthesis was determined by measuring cell, medium, and total protein at 0, 24, 48, 72, and 96 h. Time and dose tests showed that the 48 h incubation time and a 0.9 mM dose of L-Trp were the optimal values. The mechanism of milk protein synthesis was elucidated through proteomic analysis to identify the metabolic pathway involved. When L-Trp was supplemented, extracellular protein (medium protein) reached its peak at 48 h, whereas intracellular cell protein reached its peak at 96 h with all L-Trp doses. β-casein mRNA gene expression and genes related to milk protein synthesis, such as mammalian target of rapamycin (mTOR) and ribosomal protein 6 (RPS6) genes, were also stimulated (p < 0.05). Overall, there were 51 upregulated and 59 downregulated proteins, many of which are involved in protein synthesis. The results of protein pathway analysis showed that L-Trp stimulated glycolysis, the pentose phosphate pathway, and ATP synthesis, which are pathways involved in energy metabolism. Together, these results demonstrate that L-Trp supplementation, particularly at 0.9 mM, is an effective stimulus in β-casein synthesis by stimulating genes, proteins, and pathways related to protein and energy metabolism.
Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook
Authors: Qayyum Naila , Haseeb Muhammad , Kim Moon Suk , Choi Sangdun
Published: March 2021

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.
Increased Presence of Complement Factors and Mast Cells in Alveolar Bone and Tooth Resorption
Authors: Luntzer Kathrin , Lackner Ina , Weber Birte , Mödinger Yvonne , Ignatius Anita , Gebhard Florian , Mihaljevic Susann-Yvonne , Haffner-Luntzer Melanie , Kalbitz Miriam
Published: March 2021

Periodontitis is the inflammatory destruction of the tooth-surrounding and -supporting tissue, resulting at worst in tooth loss. Another locally aggressive disease of the oral cavity is tooth resorption (TR). This is associated with the destruction of the dental mineralized tissue. However, the underlying pathomechanisms remain unknown. The complement system, as well as mast cells (MCs), are known to be involved in osteoclastogenesis and bone loss. The complement factors C3 and C5 were previously identified as key players in periodontal disease. Therefore, we hypothesize that complement factors and MCs might play a role in alveolar bone and tooth resorption. To investigate this, we used the cat as a model because of the naturally occurring high prevalence of both these disorders in this species. Teeth, gingiva samples and serum were collected from domestic cats, which had an appointment for dental treatment under anesthesia, as well as from healthy cats. Histological analyses, immunohistochemical staining and the CH-50 and AH-50 assays revealed increased numbers of osteoclasts and MCs, as well as complement activity in cats with TR. Calcifications score in the gingiva was highest in animals that suffer from TR. This indicates that MCs and the complement system are involved in the destruction of the mineralized tissue in this condition.
Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives
Authors: Kretschmer Nadine , Hufner Antje , Durchschein Christin , Popodi Katrin , Rinner Beate , Lohberger Birgit , Bauer Rudolf
Published: March 2021

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGloTM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.
Fine Morphology of Antennal and Ovipositor Sensory Structures of the Gall Chestnut Wasp, Dryocosmus kuriphilus
Authors: Sevarika Milos , Rossi Stacconi Marco Valerio , Romani Roberto
Published: March 2021

Dryocosmus kuriphilus is a gall-inducing insect, which can cause significant damage on plants of the genus Castanea Mill., 1754. Antennae and ovipositor are the main sensory organs involved in the location of suitable oviposition sites. Antennal sensilla are involved in the host plant location, while ovipositor sensilla assess the suitability of the ovipositional bud. On both organs, diverse sensillar organs are present. Here, the distribution and ultrastructural organization of the sensilla were investigated by scanning and transmission electron microscopy. The antennae of D. kuriphilus are filiform and composed of 14 antennomeres, with the distal flagellomere bearing the highest number of sensilla. On the antennae, 6 sensilla types were found; sensilla chaetica, campaniformia, coeloconica-I, coeloconica-II, trichoidea and placoidea. The sensilla placoidea and trichoidea were the most abundant types. On the external walls of the ovipositor, gustatory and mechanoreceptive sensilla were observed. Internally, the egg channel hosted two additional sensory structures. The putative functional role of each sensilla in the context of insect’s ecology is discussed as well as the ovipositional mechanism used by this insect.
MCP-1 Predicts Recurrent Cardiovascular Events in Patients with Persistent Inflammation
Authors: Blanco-Colio Luis M. , Méndez-Barbero Nerea , Pello Lázaro Ana María , Aceña Álvaro , Tarín Nieves , Cristóbal Carmen , Martínez-Milla Juan , González-Lorenzo Óscar , Martín-Ventura José Luis , Huelmos Ana , Gutiérrez-Landaluce Carlos , López-Castillo Marta , Kallmeyer Andrea , Cánovas Ester , Alonso Joaquín , López Bescós Lorenzo , Egido Jesús , Lorenzo Óscar , Tuñón José
Published: March 2021

Clinical data indicate that patients with C-reactive protein (CRP) levels higher than 2 mg per liter suffer from persistent inflammation, which is associated with high risk of cardiovascular disease (CVD). We determined whether a panel of biomarkers associated with CVD could predict recurrent events in patients with low or persistent inflammation and coronary artery disease (CAD). We followed 917 patients with CAD (median 4.59 ± 2.39 years), assessing CRP, galectin-3, monocyte chemoattractant protein-1 (MCP-1), N-terminal fragment of brain natriuretic peptide (NT-proBNP) and troponin-I plasma levels. The primary outcome was the combination of cardiovascular events (acute coronary syndrome, stroke or transient ischemic event, heart failure or death). Patients with persistent inflammation (n = 343) showed higher NT-proBNP and MCP-1 plasma levels compared to patients with CRP < 2 mg/L. Neither MCP-1 nor NT-proBNP was associated with primary outcome in patients with CRP < 2 mg/L. However, NT-proBNP and MCP-1 plasma levels were associated with increased risk of the primary outcome in patients with persistent inflammation. When patients were divided by type of event, MCP-1 was associated with an increased risk of acute ischemic events. A significant interaction between MCP-1 and persistent inflammation was found (synergy index: 6.17 (4.39–7.95)). In conclusion, MCP-1 plasma concentration is associated with recurrent cardiovascular events in patients with persistent inflammation.
Duration of Bisphosphonate Drug Holidays in Osteoporosis Patients: A Narrative Review of the Evidence and Considerations for Decision-Making
Authors: Hayes Kaleen N. , Winter Elizabeth M. , Cadarette Suzanne M. , Burden Andrea M.
Published: March 2021

Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and the potential for rare adverse events associated with long-term use (atypical femoral fractures and osteonecrosis of the jaw), a drug holiday of two to three years is recommended for most patients after long-term bisphosphonate therapy. The recommendation for a drug holiday up to three years is derived primarily from extensions of pivotal trials with alendronate and zoledronate and select surrogate marker studies. However, certain factors may modify the duration of bisphosphonate effects on a drug holiday and warrant consideration when determining an appropriate time off-therapy. In this narrative review, we recall what is currently known about drug holidays and discuss what we believe to be the primary considerations and areas for future research regarding drug holiday duration: total bisphosphonate exposure, type of bisphosphonate used, bone mineral density and falls risk, and patient sex and body weight.
Partial Lipodystrophy and LMNA p.R545H Variant
Authors: Magno Silvia , Ceccarini Giovanni , Barison Andrea , Fabiani Iacopo , Giacomina Alessandro , Gilio Donatella , Pelosini Caterina , Rubegni Anna , Emdin Michele , Gatti Gian Luca , Santorelli Filippo Maria , Sessa Maria Rita , Santini Ferruccio
Published: March 2021

Laminopathies are disorders caused by LMNA gene mutations, which selectively affect different tissues and organ systems, and present with heterogeneous clinical and pathological traits. The molecular mechanisms behind these clinical differences and tissue specificity have not been fully clarified. We herein examine the case of a patient carrying a heterozygous LMNA c.1634G>A (p.R545H) variant with a mild, transient myopathy, who was referred to our center for the suspicion of lipodystrophy. At physical examination, an abnormal distribution of subcutaneous fat was noticed, with fat accumulation in the anterior regions of the neck, resembling the fat distribution pattern of familial partial lipodystrophy type 2 (FPLD2). The R545H missense variant has been found at very low allelic frequency in public databases, and in silico analysis showed that this amino acid substitution is predicted to have a damaging role. Other patients carrying the heterozygous LMNA p.R545H allele have shown a marked clinical heterogeneity in terms of phenotypic body fat distribution and severity of organ system involvement. These findings indicate that the LMNA p.R545H heterozygous variant exhibits incomplete penetrance and highly variable expressivity. We hypothesized that additional genetic factors, epigenetic mechanisms, or environmental triggers might explain the variable expressivity of phenotypes among various patients.
Cancer Patients’ Prehospital Emergency Care: Post Hoc Analysis from the French Prospective Multicenter Study EPICANCER
Authors: Peyrony Olivier , Fontaine Jean-Paul , Trabattoni Eloïse , Nakad Lionel , Charreyre Sylvain , Picaud Adrien , Bosc Juliane , Viglino Damien , Jacquin Laurent , Laribi Saïd , Pereira Laurent , Thiriez Sylvain , Paquet Anne-Laure , Tanneau Alexandre , Azoulay Elie , Chevret Sylvie ,   Initiatives de Recherche aux Urgences (IRU-SFMU) Research Group
Published: March 2021

Background: Very little data are available concerning the prehospital emergency care of cancer patients. The objective of this study is to report the trajectories and outcomes of cancer patients attended by prehospital emergency services. Methods: This was an ancillary study from a three-day cross-sectional prospective multicenter study in France. Adult patients with cancer were included if they called the emergency medical dispatch center Service d’Aide Médicale Urgente (SAMU). The study was registered on ClinicalTrials.gov (NCT03393260, accessed on 8th January 2018). Results: During the study period, 1081 cancer patients called the SAMU. The three most frequent reasons were dyspnea (20.2%), neurological disorder (15.4%), and fatigue (13.1%). Among those patients, 949 (87.8%) were directed to the hospital, among which 802 (90.8%) were directed to an emergency department (ED) and 44 (5%) were transported directly to an intensive care unit (ICU). A mobile intensive care unit (MICU) was dispatched 213 (31.6%) times. The decision to dispatch an MICU seemed generally based on the patient’s reason for seeking emergency care and the presence of severity signs rather than on the malignancy or the patient general health status. Among the patients who were directed to the ED, 98 (16.1%) were deceased on day 30. Mortality was 15.4% for those patients directed to the ED but who were not admitted to the ICU in the next 7 days, 28.2% for those who were admitted to ICU in the next 7 days, and 56.1% for those patients transported by the MICU directly to the ICU. Conclusion: Cancer patients attending prehospital emergency care were most often directed to EDs. Patients who were directly transported to the ICU had a high mortality rate, raising the question of improving triage policies.
The Biochemical Diagnosis of Acromegaly
Authors: Akirov Amit , Masri-Iraqi Hiba , Dotan Idit , Shimon Ilan
Published: March 2021

Background: The diagnosis of acromegaly still poses a clinical challenge, and prolonged diagnostic delay is common. The most important assays for the biochemical diagnosis and management of acromegaly are growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Objective: Discuss the role of IGF-1, basal serum GH, and nadir GH after oral glucose tolerance test (OGTT) for the diagnosis, management, and treatment of patients with acromegaly. Methods: We performed a narrative review of the published data on the biochemical diagnosis and monitoring of acromegaly. An English-language search for relevant studies was conducted on PubMed from inception to 1 January 2021. The reference lists of relevant studies were also reviewed. Results: Serum IGF-1 levels, basal GH values, and nadir GH after OGTT play a major role in the diagnosis, management, and treatment of patients with acromegaly. Measurement of IGF-1 levels is the key factor in the diagnosis and monitoring of acromegaly, but basal and nadir GH following OGTT are also important. However, several factors may significantly influence the concentrations of these hormones, including assay methods, physiologic and pathologic factors. In some cases, discordant GH and IGF-1 levels may be challenging and usually requires additional data and monitoring. Conclusion: New GH and IGF-1 standards are much more precise and provide more accurate tools to diagnose and monitor patients with acromegaly. However, all these biochemical tools have their limitations, and these should be taken under consideration, along with the history, clinical features and imaging studies, when assessing patients for acromegaly.
Environmental Regulations on the Spatial Spillover of the Sustainable Development Capability of Chinese Clustered Ports
Authors: He Xinhua , Liu Wenjun , Hu Ruiqi , Hu Wenfa
Published: March 2021

For years, China has adopted environmental regulations in developing ports to improve their sustainability. Based on the data of Chinese ports from 2009 to 2018, this paper presents a data envelopment analysis model with subdividing input-output indicator weights and develops it further in two stages with the weight preference and the slacks-based measure, respectively. After assessing the sustainable development capability (SDC) of Chinese ports and their spatial correlation, it revealed that Chinese ports are clustered in several regions and their SDC has spilled over into their neighbors. Further study revealed the SDC is affected by environmental regulations in different ways: as a key measure among regulations to improve the SDC, voluntary regulation has a spatial spillover effect, but neither the mandatory regulation nor public media regulation can significantly improve the SDC. This suggests that the port authority should enact environmental regulations based on the port spatial difference and the port should expand its operation scale and market size and recruit more top talent, which is good for improving its productivity and reducing its carbon emissions.
Bacillus megaterium-Mediated Synthesis of Selenium Nanoparticles and Their Antifungal Activity against Rhizoctonia solani in Faba Bean Plants
Authors: Hashem Amr H. , Abdelaziz Amer M. , Askar Ahmed A. , Fouda Hossam M. , Khalil Ahmed M. A. , Abd-Elsalam Kamel A. , Khaleil Mona M.
Published: March 2021

Rhizoctonia root-rot disease causes severe economic losses in a wide range of crops, including Vicia faba worldwide. Currently, biosynthesized nanoparticles have become super-growth promoters as well as antifungal agents. In this study, biosynthesized selenium nanoparticles (Se-NPs) have been examined as growth promoters as well as antifungal agents against Rhizoctonia solani RCMB 031001 in vitro and in vivo. Se-NPs were synthesized biologically by Bacillus megaterium ATCC 55000 and characterized by using UV-Vis spectroscopy, XRD, dynamic light scattering (DLS), and transmission electron microscopy (TEM) imaging. TEM and DLS images showed that Se-NPs are mono-dispersed spheres with a mean diameter of 41.2 nm. Se-NPs improved healthy Vicia faba cv. Giza 716 seed germination, morphological, metabolic indicators, and yield. Furthermore, Se-NPs exhibited influential antifungal activity against R. solani in vitro as well as in vivo. Results revealed that minimum inhibition and minimum fungicidal concentrations of Se-NPs were 0.0625 and 1 mM, respectively. Moreover, Se-NPs were able to decrease the pre-and post-emergence of R. solani damping-off and minimize the severity of root rot disease. The most effective treatment method is found when soaking and spraying were used with each other followed by spraying and then soaking individually. Likewise, Se-NPs improve morphological and metabolic indicators and yield significantly compared with infected control. In conclusion, biosynthesized Se-NPs by B. megaterium ATCC 55000 are a promising and effective agent against R. solani damping-off and root rot diseases in Vicia faba as well as plant growth inducer.