bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Identification of Sex-Biased Biomarker MicroRNAs and Genes Associated with Immune Infiltration in Breast Cancer
Authors: Li Eric W. , Bai Yongsheng
Published: April 2021

MicroRNAs (miRNAs) perform their functions through targeting messenger RNAs (mRNAs). X chromosome-located (X-linked) miRNAs have a broad role in cell lineage determination, immune regulation, and oncogenesis. The regulating roles of miRNAs in cancer and immunity are often altered when aberrant expression happens. Sex-biased genes could contribute to cancer sex bias in the context of their expression change due to targeting miRNAs. How biological roles and associations with immune cell abundance levels for sex-biased gene-miRNA pairs in gender-related cancer (e.g., breast cancer) change due to the alteration of their expression pattern to identify candidate therapeutic markers has not been investigated thoroughly. Upon analyzing anti-correlated genes and miRNAs within significant clusters of 12 The Cancer Genome Atlas (TCGA) cancer types and the list of sex-biased genes and miRNAs reported from previous studies, 125 sex-biased genes (11 male-biased and 114 female-biased) were identified in breast cancer (BC). Seventy-three sex-biased miRNAs (40 male-biased and 33 female-biased) were identified across 5 out of 12 cancers (head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and lung adenocarcinoma (LUAD)). Correlation between the BC sex-biased genes and tumor infiltrating immune cell types was further evaluated. We found eight genes having high correlation with immune infiltration. Fifteen candidate female-biased BC genes targeted by 3 X-linked miRNAs (has-mir-18hashsa-mir-221, and hsa-mir-224) were pinpointed in this study. Our computational result indicates that many identified female-biased genes which have positive associations with immune cell abundance levels could serve as alternative therapeutic markers. Our analysis suggests that female-biased expression of BC candidate genes is likely influenced by their targeting miRNA(s).
The T Cell Receptor (TRB) Locus in Tursiops truncatus: From Sequence to Structure of the Alpha/Beta Heterodimer in the Human/Dolphin Comparison
Authors: Linguiti Giovanna , Kossida Sofia , Pierri Ciro Leonardo , Jabado-Michaloud Joumana , Folch Geraldine , Massari Serafina , Lefranc Marie-Paule , Ciccarese Salvatrice , Antonacci Rachele
Published: April 2021

The bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and, similarly to other cetaceans, represents the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary, and expression study of T. truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3′ end, its uniqueness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rearranged T cell receptor α (TRA) and TRB cDNA from the peripheral blood of one of the two specimens, and the human/dolphin amino acids multi-sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the complementarity-determining region according to IMGT numbering (CDR-IMGT) of the dolphin variable V-alpha and beta domains were identified. According to comparative modelization, the atom pair contact sites analysis between the human MH1 grove (G) domains and the T cell receptor (TR) V domains confirms conservation of the structure of the dolphin TR/pMH.
Kinematics of Deformable Blocks: Application to the Opening of the Tyrrhenian Basin and the Formation of the Apennine Chain
Authors: Turco Eugenio , Macchiavelli Chiara , Penza Giulia , Schettino Antonio , Pierantoni Pietro Paolo
Published: April 2021

We describe the opening of back-arc basins and the associated formation of accretionary wedges through the application of techniques of deformable plate kinematics. These methods have proven to be suitable to describe complex tectonic processes, such as those that are observed along the Africa–Europe collision belt. In the central Mediterranean area, these processes result from the passive subduction of the lithosphere belonging to the Alpine Tethys and Ionian Ocean. In particular, we focus on the opening of the Tyrrhenian basin and the contemporary formation of the Apennine chain. We divide the area of the Apennine Chain and the Tyrrhenian basin into deformable polygons that are identified on the basis of sets of extensional structures that are coherent with unique Euler pole grids. The boundaries between these polygons coincide with large tectonic lineaments that characterize the Tyrrhenian–Apennine area. The tectonic style along these structures reflects the variability of relative velocity vectors between two adjacent blocks. The deformation of tectonic elements is accomplished, allowing different rotation velocities of lines that compose these blocks about the same stable stage poles. The angular velocities of extension are determined on the basis of the stratigraphic records of syn-rift sequences, while the rotation angles are obtained by crustal balancing.
Hospitalization for Short-Term Diabetes-Related Complications: Focus on Patients Aged over 85 Years
Authors: Di Martino Giuseppe , Di Giovanni Pamela , Cedrone Fabrizio , Meo Francesca , Scampoli Piera , Romano Ferdinando , Staniscia Tommaso
Published: April 2021

(1) Background: The prevalence of diabetes in elderly people is frequently high. When occurring in the elderly, diabetes is often accompanied by complications and comorbidities, at least one in 60% and four or more in 40% of older people with diabetes. As far as short-term complications among the elderly are concerned, hypoglycemia and hyperglycemic crises prove to be frequent. The aim of this study was to investigate the difference in hospitalization for short-term diabetes complications in patients below and over 85 years of age. (2) Methods: Data were collected from hospital discharge records (HDRs) of all hospital admissions that occurred in Abruzzo Region, Italy, from 2006 to 2015. Only diabetic patients aged over 65 years were included. Outcomes included were diabetic ketoacidosis, hyperosmolar coma, hypoglycemic shock, iatrogenic hypoglycemic coma, and other diabetic comas. (3) Results: During the study period, 144,376 admissions were collected, 116,305 (80.56%) of which referred to patients below 85 years. Those aged over 85 years were significantly associated to all short-term diabetes-related complications with the exception of ketoacidosis. (4) Conclusions: In older diabetic patients, the avoidance of short-term diabetes complications are a greater concern than in younger patients. Diabetes management among very elderly patients should be tailored accordingly to patient characteristics.
Mobile Health to Improve Adherence and Patient Experience in Heart Transplantation Recipients: The mHeart Trial
Authors: Gomis-Pastor Mar , Mirabet Perez Sonia , Roig Minguell Eulalia , Brossa Loidi Vicenç , Lopez Lopez Laura , Ros Abarca Sandra , Galvez Tugas Elisabeth , Mas-Malagarriga Núria , Mangues Bafalluy Mª Antonia
Published: April 2021

Non-adherence after heart transplantation (HTx) is a significant problem. The main objective of this study was to evaluate if a mHealth strategy is more effective than standard care in improving adherence and patients’ experience in heart transplant recipients. Methods: This was a single-center, randomized controlled trial (RCT) in adult recipients >1.5 years post-HTx. Participants were randomized to standard care (control group) or to the mHeart Strategy (intervention group). For patients randomized to the mHeart strategy, multifaceted theory-based interventions were provided during the study period to optimize therapy management using the mHeart mobile application. Patient experience regarding their medication regimens were evaluated in a face-to-face interview. Medication adherence was assessed by performing self-reported questionnaires. A composite adherence score that included the SMAQ questionnaire, the coefficient of variation of drug levels and missing visits was also reported. Results: A total of 134 HTx recipients were randomized (intervention N = 71; control N = 63). Mean follow-up was 1.6 (SD 0.6) years. Improvement in adherence from baseline was significantly higher in the intervention group versus the control group according to the SMAQ questionnaire (85% vs. 46%, OR = 6.7 (2.9; 15.8), p-value < 0.001) and the composite score (51% vs. 23%, OR = 0.3 (0.1; 0.6), p-value = 0.001). Patients’ experiences with their drug therapy including knowledge of their medication timing intakes (p-value = 0.019) and the drug indications or uses that they remembered (p-value = 0.003) significantly improved in the intervention versus the control group. Conclusions: In our study, the mHealth-based strategy significantly improved adherence and patient beliefs regarding their medication regimens among the HTx population. The mHeart mobile application was used as a feasible tool for providing long-term, tailor-made interventions to HTx recipients to improve the goals assessed.
Effect of Pre-Harvest Supplemental UV-A/Blue and Red/Blue LED Lighting on Lettuce Growth and Nutritional Quality
Authors: Hooks Triston , Masabni Joseph , Sun Ling , Niu Genhua
Published: April 2021

Blue light and ultra-violet (UV) light have been shown to influence plant growth, morphology, and quality. In this study, we investigated the effects of pre-harvest supplemental lighting using UV-A and blue (UV-A/Blue) light and red and blue (RB) light on growth and nutritional quality of lettuce grown hydroponically in two greenhouse experiments. The RB spectrum was applied pre-harvest for two days or nights, while the UV-A/Blue spectrum was applied pre-harvest for two or four days or nights. All pre-harvest supplemental lighting treatments had a same duration of 12 h with a photon flux density (PFD) of 171 μmol m−2 s−1. Results of both experiments showed that pre-harvest supplemental lighting using UV A/Blue or RB light can increase the growth and nutritional quality of lettuce grown hydroponically. The enhancement of lettuce growth and nutritional quality by the pre-harvest supplemental lighting was more effective under low daily light integral (DLI) compared to a high DLI and tended to be more effective when applied during the night, regardless of spectrum.
Cultivation Conditions Change Aroma Volatiles of Strawberry Fruit
Authors: Li Yunduan , Zhang Yuanyuan , Liu Xincheng , Xiao Yuwei , Zhang Zuying , Shi Yanna , Kong Wenbing , Yang Xiaofang , Jiang Guihua , Zhang Bo , Chen Kunsong
Published: April 2021

Volatile compounds principally contribute to flavor of strawberry (Fragaria × ananassa) fruit. Besides to genetics, cultivation conditions play an important role in fruit volatile formation. Compared to soil culture as control, effects of substrate culture on volatile compounds of two strawberry cultivars (‘Amaou’ and ‘Yuexin’) were investigated. GC-MS analysis revealed significant difference in volatile contents of ‘Amaou’ strawberry caused by substrate culture. No significant effect was observed for cultivar ‘Yuexin’. For ‘Amaou’ strawberry from soil culture produced higher volatile contents compared with substrate culture. This difference is contributed by high contents of esters, lactones, ketones, aldehydes, terpenes, hydrocarbons, acids, furans and phenols in ‘Amaou’ strawberry fruit from soil culture. Furanones, beta-linalool, trans-Nerolidol and esters are major contributor to strawberry aroma, whose contents are higher in soil culture planted fruit when compared to substrate culture. Moreover, strawberry fruit from soil culture had higher transcripts related to volatile biosynthesis were observed, including FaQR, FaOMT, FaNES1, FaSAAT and FaAAT2.
Treatment Compliance of Multidrug Resistant Tuberculosis in Uzbekistan: Does Practice Follow Policy?
Authors: Usmanova Ruzilya , Parpieva Nargiza , Davtyan Hayk , Denisiuk Olga , Gadoev Jamshid , Alaverdyan Sevak , Dumchev Kostyantyn , Liverko Irina , Abdusamatova Barno
Published: April 2021

Compliance with treatment guidelines is essential to achieve successful outcomes in tuberculosis patients. Thus, we assessed if multidrug-resistant tuberculosis treatment practices from 2012–2018 in Uzbekistan were compliant with national guidelines in terms of regimens prescribed, weight-based drug dosages used, and documentation of treatment changes (such as prolongation of intensive phase, change of drugs, and their reasons) in the treatment card and Consilium form. A total of 1481 patients were included. Of them, only 25% received standardized regimens as per guidelines and the remaining received individualized regimens. There was an increasing trend in using standardized regimens from 2% in 2012 to 44% in 2018. Compliance to recommended weight-based drug dosages was observed in 85% of the patients during the intensive phase and 84% in the continuation phase—ranged 71–91% over the years. Prolongation of the intensive phase was done in 42% of patients. The treatment was changed in 44% of patients during the intensive phase and 34% of patients during the continuation phase. The documentation of treatment changes was suboptimal (42–75%) during the initial years (2012–2014); however, it improved significantly during later years (86–100%). Future research should explore reasons for non-compliance so that the quality of patient care can be improved.
Chemical Characterization and Quantification of Silver Nanoparticles (Ag-NPs) and Dissolved Ag in Seafood by Single Particle ICP-MS: Assessment of Dietary Exposure
Authors: Grasso Alfina , Ferrante Margherita , Arena Giovanni , Salemi Rossella , Zuccarello Pietro , Fiore Maria , Copat Chiara
Published: April 2021

This study provides a first insight on the chemical characterization and quantification of silver nanoparticles (AgNPs) and dissolved Ag in processed canned seafood products, where food-grade edible silver (E174) is not intentionally added nor is the nanoparticle contained in the food contact material. The aim was to evaluate the bioaccumulation potential of AgNPs and to contribute to the assessment of AgNPs and ionic Ag human dietary intake from processed seafood. It is known how seafood, and in particular pelagic fish, is a precious nutritional source of unsaturated fatty acids, protein, and different micronutrients. Nevertheless, it may cause possible health problems due to the intake of toxic compounds coming from environmental pollution. Among emerging contaminants, AgNPs are widely applied in several fields such as biomedicine, pharmaceutical, food industry, health care, drug-gene delivery, environmental study, water treatments, and many others, although its primary application is in accordance with its antimicrobial property. As a consequence, AgNPs are discharged into the aquatic environment, where the colloidal stability of these NPs is altered by chemical and physical environmental parameters. Its toxicity was demonstrated in in-vitro and in-vivo studies, although some findings are controversial because toxicity depends by several factors such as size, concentration, chemical composition, surface charge, Ag+ ions released, and hydrophobicity. The new emerging technique called single-particle inductively coupled plasma mass spectrometry (spICP-MS) was applied, which allows the determination of nanoparticle number-based concentration and size distribution, as well as the dissolved element. Our findings highlighted comparable mean sizes across all species analysed, although AgNPs concentrations partly follow a trophic level-dependent trend. The low mean size detected could be of human health concern, since, smaller is the diameter higher is the toxicity. Dietary intake from a meal calculated for adults and children seems to be very low. Although seafood consumption represents only a small part of the human total diet, our findings represent a first important step to understand the AgNPs dietary exposure of the human population. Further studies are needed to characterize and quantify AgNPs in a large number of food items, both processing and not, and where AgNPs are added at the industrial level. They will provide a realistic exposure assessment, useful to understand if AgNPs toxicity levels observed in literature are close to those estimable through food consumption and implement data useful for risk assessors in developing AgNPs provisional tolerable daily intake.
Measuring Nature Contact: A Narrative Review
Authors: Holland Isabel , DeVille Nicole V. , Browning Matthew H. E. M. , Buehler Ryan M. , Hart Jaime E. , Hipp J. Aaron , Mitchell Richard , Rakow Donald A. , Schiff Jessica E. , White Mathew P. , Yin Jie , James Peter
Published: April 2021

While many studies suggest evidence for the health benefits of nature, there is currently no standardized method to measure time spent in nature or nature contact, nor agreement on how best to define nature contact in research. The purpose of this review is to summarize how nature contact has been measured in recent health research and provide insight into current metrics of exposure to nature at individual and population scales. The most common methods include surrounding greenness, questionnaires, and global positioning systems (GPS) tracking. Several national-level surveys exist, though these are limited by their cross-sectional design, often measuring only a single component of time spent in nature, and poor links to measures of health. In future research, exposure assessment combining the quantifying (e.g., time spent in nature and frequency of visits to nature) and qualifying (e.g., greenness by the normalized difference of vegetation index (NDVI) and ratings on perception by individuals) aspects of current methods and leveraging innovative methods (e.g., experience sampling methods, ecological momentary assessment) will provide a more comprehensive understanding of the health effects of nature exposure and inform health policy and urban planning.
Joint-Preserving Surgery for Forefoot Deformities in Patients with Rheumatoid Arthritis: A Literature Review
Authors: Yano Koichiro , Ikari Katsunori , Tobimatsu Haruki , Tominaga Ayako , Okazaki Ken
Published: April 2021

The combination of first metatarsophalangeal joint arthrodesis and resection arthroplasty of all lesser metatarsal heads has been historically considered the golden standard treatment for rheumatoid forefoot deformities. However, as recent improved management of rheumatoid arthritis have reduced progression of joint destruction, the surgical treatments for rheumatoid forefoot deformities have gradually changed from joint-sacrificing surgery, such as arthrodesis and resection arthroplasty, to joint-preserving surgery. The aim of this literature review was to provide current evidence for joint-preserving surgery for rheumatoid forefoot deformities. We focused on the indications, specific outcomes, and postsurgical complications of joint-preserving surgery in this review.
It’s Sunny, Be Healthy? An International Comparison of the Influence of Sun Exposure and Latitude Lines on Self-Rated Health
Authors: Jaworeck Sandra , Kriwy Peter
Published: April 2021

The positive impact of sunshine on self-rated health is well known. For the first time, the relationship between sunshine and self-rated health is examined in the context of latitude lines in international comparison. The further people live from the equator, the lower sun exposure (UVB exposure) and the more often they experience a vitamin D deficiency. UVB exposure decreases with degrees of latitudinal lines, and in addition to that, sunshine duration is shorter in northern countries. In order to consider the connection, sunshine duration and degree of latitude lines were manually enriched from the German Meteorological Service (Deutscher Wetterdienst) to the International Social Survey Programs (2011): Health and Health Care and analyzed with a logistic multilevel model, as well as the inclusion of sunshine duration as a mediator. If sunshine hours, as well as latitude lines, are considered separately in models, both show a statistically significant effect. Together in one model, the sunshine hours lose their relationship and additionally there is no mediation. This suggests that the location of the region is the decisive component when considering self-rated health. Furthermore, an interaction between age and sunshine hours as well as latitude lines is also shown.
Implementing a Novel Facility-Community Intervention for Strengthening Integration of Infant Nutrition and Family Planning in Mara and Kagera, Tanzania
Authors: Cooper Chelsea M. , Drake Mary , Kavle Justine A. , Nyoni Joyce , Lemwayi Ruth , Mabuga Lemmy , Pfitzer Anne , Makungu Mary , Massawe Elizabeth , George John
Published: April 2021

Tanzania has high fertility, low contraceptive prevalence and low exclusive breastfeeding (EBF). The Lake Zone, including Mara and Kagera regions, leads the country in total fertility; use of the lactational amenorrhea method (LAM) is negligible. This pre-/post-study explored the effects of a multi-level facility and community intervention (service delivery support, community engagement, media and LAM tracking) to integrate maternal and infant nutrition and postpartum family planning (FP) within existing health contacts. Mixed methods were used, including service statistics, exit interviews, patient-tracking tools for community health workers, client self-tracking tools, supervision data, focus group discussions and in-depth interviews. Results are presented using the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) implementation science framework. The intervention reached primarily the second and fourth wealth quintiles, increased FP and EBF at six weeks postpartum. LAM was very acceptable, provided an entry point for FP conversations and for addressing misconceptions, and reinforced EBF practices. Partners felt encouraged to support spousal nutrition, breastfeeding and FP. Higher adoption in Kagera may be influenced by performance-based financing. The intervention was implemented with generally high fidelity. Maintenance data reflected stakeholder interest in continuing the intervention. A multi-level facility and community intervention was feasible to implement and likely contributed to improved EBF practices and FP uptake, including LAM use.
Developmental Language Disorder (DLD) in Young People Leaving Care in England: A Study Profiling the Language, Literacy and Communication Abilities of Young People Transitioning from Care to Independence
Authors: Clegg Judy , Crawford Ellen , Spencer Sarah , Matthews Danielle
Published: April 2021

Research indicates children and young people in care have a high prevalence of Developmental Language Disorder (DLD) as part of a complex set of vulnerabilities. This study describes the profile of language, literacy and communication abilities of a cohort of care leavers. The language, literacy and communication abilities of 44 young people leaving care between the ages of 16 and 26 years were assessed using standardized measures. Demographic data about the young people was collected along with a survey to key staff to capture their perceptions and experiences of the language and communication abilities of these young people. Ninety percent of the care leavers’ language abilities were below average and over 60% met criteria for DLD in combination with literacy difficulties, developmental disorders and social, emotional and mental health difficulties (SEMH). The implications of unidentified DLD on the lives of young people leaving care is discussed. Earlier identification of DLD is advocated to enable services to intervene to facilitate more positive outcomes and life chances for this very vulnerable population.
The Dark Triad of Personality in the Context of Health Behaviors: Ally or Enemy?
Authors: Dębska Małgorzata , Dębski Paweł , Polechoński Jacek , Rozpara Michał , Tomik Rajmund
Published: April 2021

The main aim of this manuscript was to present a preliminary verification of the relations between the Dark Triad of personality traits and health-oriented behaviors in university students. The study involved 143 healthy students (94 female and 49 male) from the Silesian Voivodeship (Poland). The diagnosis of the elements of the Dark Triad of personality was carried out using a psychological examination based on the following tests: TriPM-41, Mach IV, NPI. The intensity of the health behaviors was examined using the Health Behavior Inventory developed by Z. Juczyński. The Health Behavior Inventory is positively correlated with narcissism and its self-sufficiency component and negatively with psychopathic disinhibition. For the Health Behavior Inventory’s subscales, a positive relationship was observed between Positive Mental Attitude and narcissism, most of its components, and psychopathic boldness. The analysis of correlations with the division of the subjects into the Dark Triad traits ≤Me and >Me revealed that a significant positive correlation between the general intensity of the health behaviors and the intensity of narcissism mainly concerns university students with a lower level of this trait and its components. Therefore, it can be presumed that narcissism, although considered as a socially aversive trait, is associated with pro-health behaviors.
Reprogramming: Emerging Strategies to Rejuvenate Aging Cells and Tissues
Authors: Alle Quentin , Le Borgne Enora , Milhavet Ollivier , Lemaitre Jean-Marc
Published: April 2021

Aging is associated with a progressive and functional decline of all tissues and a striking increase in many “age-related diseases”. Although aging has long been considered an inevitable process, strategies to delay and potentially even reverse the aging process have recently been developed. Here, we review emerging rejuvenation strategies that are based on reprogramming toward pluripotency. Some of these approaches may eventually lead to medical applications to improve healthspan and longevity.
The Methyl Ester of 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic Acid Reduces Endometrial Lesions Development by Modulating the NFkB and Nrf2 Pathways
Authors: Siracusa Rosalba , D’Amico Ramona , Cordaro Marika , Peritore Alessio Filippo , Genovese Tiziana , Gugliandolo Enrico , Crupi Rosalia , Impellizzeri Daniela , Cuzzocrea Salvatore , Fusco Roberta , Di Paola Rosanna
Published: April 2021

Endometriosis is a common gynecological disease. Here, we aimed to investigate the anti-fibrotic, anti-inflammatory, and anti-oxidative role of the methyl ester of 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO-Me) on endometriosis. An endometriosis rat model was constructed by intraperitoneally injecting recipient rats with an equivalent of tissue from the uterus of a donor animal. Endometriosis was allowed to develop for seven days. CDDO-Me was administered on the 7th day and for the next 7 days. On day 14, rats were sacrificed, and peritoneal fluid and endometriotic implants were collected. CDDO-Me displayed antioxidant activity by activating the Nfr2 pathway and the expression of antioxidant mediators such as NQO-1 and HO-1. Moreover, it reduced lipid peroxidation and increased glutathione (GSH) levels and superoxide dismutase (SOD) activity. CDDO-Me also showed anti-inflammatory activity by decreasing the expression of pro-inflammatory cytokines in peritoneal fluids and NFkB activation. It, in turn, reduced cyclooxygenase-2 (COX-2) expression in the endometriotic loci and prostaglandin E2 (PGE2) levels in the peritoneal fluids, leading to increased apoptosis and reduced angiogenesis. The reduced oxidative stress and pro-inflammatory microenvironment decreased implants diameter, area, and volume. In particular, CDDO-Me administration reduced the histopathological signs of endometriosis and inflammatory cells recruitment into the lesions, as shown by toluidine blue staining and myeloperoxidase (MPO) activity. CDDO-Me strongly suppressed α-SMA and fibronectin expression and collagen deposition, reducing endometriosis-associated fibrosis. In conclusion, CDDO-Me treatment resulted in a coordinated and effective suppression of endometriosis by modulating the Nrf2 and NFkB pathways.
Generation of a Novel Transgenic Zebrafish for Studying Adipocyte Development and Metabolic Control
Authors: Mao Yousheng , Hong Kwang-Heum , Liao Weifang , Li Li , Kim Seong-Jin , Xiong Yinyi , Nam In-Koo , Choe Seong-Kyu , Kwak Seong-Ae
Published: April 2021

Zebrafish have become a popular animal model for studying various biological processes and human diseases. The metabolic pathways and players conserved among zebrafish and mammals facilitate the use of zebrafish to understand the pathological mechanisms underlying various metabolic disorders in humans. Adipocytes play an important role in metabolic homeostasis, and zebrafish adipocytes have been characterized. However, a versatile and reliable zebrafish model for long-term monitoring of adipose tissues has not been reported. In this study, we generated stable transgenic zebrafish expressing enhanced green fluorescent protein (EGFP) in adipocytes. The transgenic zebrafish harbored adipose tissues that could be detected using GFP fluorescence and the morphology of single adipocyte could be investigated in vivo. In addition, we demonstrated the applicability of this model to the long-term in vivo imaging of adipose tissue development and regulation based on nutrition. The transgenic zebrafish established in this study may serve as an excellent tool to advance the characterization of white adipose tissue in zebrafish, thereby aiding the development of therapeutic interventions to treat metabolic diseases in humans.
Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling
Authors: Takahashi Satoshi , Noro Rintaro , Seike Masahiro , Zeng Chao , Matsumoto Masaru , Yoshikawa Akiko , Nakamichi Shinji , Sugano Teppei , Hirao Mariko , Matsuda Kuniko , Hamada Michiaki , Gemma Akihiko
Published: April 2021

(1) Background: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable problem for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are complex. Long non-coding RNAs (lncRNAs) may play an important role in cancer development and metastasis. However, the biological process between lncRNAs and drug resistance to EGFR-mutated lung cancer remains largely unknown. (2) Methods: Osimertinib- and afatinib-resistant EGFR-mutated lung cancer cells were established using a stepwise method. A microarray analysis of non-coding and coding RNAs was performed using parental and resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells and evaluated by bioinformatics analysis through medical-industrial collaboration. (3) Results: Colorectal neoplasia differentially expressed (CRNDE) and DiGeorge syndrome critical region gene 5 (DGCR5) lncRNAs were highly expressed in EGFR-TKI-resistant cells by microarray analysis. RNA-protein binding analysis revealed eukaryotic translation initiation factor 4A3 (eIF4A3) bound in an overlapping manner to CRNDE and DGCR5. The CRNDE downregulates the expression of eIF4A3, mucin 1 (MUC1), and phospho-EGFR. Inhibition of CRNDE activated the eIF4A3/MUC1/EGFR signaling pathway and apoptotic activity, and restored sensitivity to EGFR-TKIs. (4) Conclusions: The results showed that CRNDE is associated with the development of resistance to EGFR-TKIs. CRNDE may be a novel therapeutic target to conquer EGFR-mutant NSCLC.
Evaluating Oxygen Tensions Related to Bone Marrow and Matrix for MSC Differentiation in 2D and 3D Biomimetic Lamellar Scaffolds
Authors: Sayin Esen , Baran Erkan Türker , Elsheikh Ahmed , Mudera Vivek , Cheema Umber , Hasirci Vasif
Published: April 2021

The physiological O2 microenvironment of mesenchymal stem cells (MSCs) and osteoblasts and the dimensionality of a substrate are known to be important in regulating cell phenotype and function. By providing the physiologically normoxic environments of bone marrow (5%) and matrix (12%), we assessed their potential to maintain stemness, induce osteogenic differentiation, and enhance the material properties in the micropatterned collagen/silk fibroin scaffolds that were produced in 2D or 3D. Expression of osterix (OSX) and vascular endothelial growth factor A (VEGFA) was significantly enhanced in the 3D scaffold in all oxygen environments. At 21% O2, OSX and VEGFA expressions in the 3D scaffold were respectively 13,200 and 270 times higher than those of the 2D scaffold. Markers for assessing stemness were significantly more pronounced on tissue culture polystyrene and 2D scaffold incubated at 5% O2. At 21% O2, we measured significant increases in ultimate tensile strength (p < 0.0001) and Young’s modulus (p = 0.003) of the 3D scaffold compared to the 2D scaffold, whilst 5% O2 hindered the positive effect of cell seeding on tensile strength. In conclusion, we demonstrated that the 3D culture of MSCs in collagen/silk fibroin scaffolds provided biomimetic cues for bone progenitor cells toward differentiation and enhanced the tensile mechanical properties.
Plant-Origin Stabilizer as an Alternative of Natural Additive to Polymers Used in Packaging Materials
Authors: Plota Angelika , Masek Anna
Published: April 2021

Over the past 25 years, cannabis plants have gained major popularity in the research community. This study aimed to evaluate the antioxidant capacity and stabilization efficiency of cannabidiol (CBD) extract in two different polymers: polylactide (PLA) and ethylene–norbornene copolymer (Topas) that are used in packaging materials more often. The research technology included weathering in a special chamber, surface free energy and color change measurements, surface morphology and Fourier-transform infrared spectroscopy (FTIR) analysis, thermogravimetry, and determination of the oxidation induction time or temperature (OIT) values, based on which the effectiveness of the cannabidiol extract could be estimated. Obtained results showed that the addition of CBD to polymer mixtures significantly increased their resistance to oxidation, and it can be used as a natural stabilizer for polymeric products. Moreover, samples with cannabidiol changed their coloration as a result of weathering. Therefore, this natural additive can also be considered as a colorimetric indicator of aging that informs about the changes in polymeric materials during their lifetime. On the other hand, surface properties of samples with cannabidiol content did not alter much compared to pure Topas and PLA.
Cell-Mediated Therapies to Facilitate Operational Tolerance in Liver Transplantation
Authors: Ellias Samia D. , Larson Ellen L. , Taner Timucin , Nyberg Scott L.
Published: April 2021

Cell therapies using immune cells or non-parenchymal cells of the liver have emerged as potential treatments to facilitate immunosuppression withdrawal and to induce operational tolerance in liver transplant (LT) recipients. Recent pre-clinical and clinical trials of cellular therapies including regulatory T cells, regulatory dendritic cells, and mesenchymal cells have shown promising results. Here we briefly summarize current concepts of cellular therapy for induction of operational tolerance in LT recipients.
Long-Term Neurological Outcomes of Adult Patients with Phenylketonuria before and after Newborn Screening in Japan
Authors: Yamada Kenji , Yamaguchi Seiji , Yokoyama Kazunori , Aoki Kikumaro , Taketani Takeshi
Published: April 2021

Japanese newborn screening (NBS) for phenylketonuria (PKU) was initiated in 1977. We surveyed the neurological outcomes of Japanese adult patients with PKU to investigate the long-term effects and of and issues with NBS. Eighty-five patients with PKU aged over 19 years who continued to be treated with a phenylalanine-free amino acid formula were investigated by administering questionnaires regarding clinical characteristics, such as mental ability, education status, and therapeutic condition. Of the 85 subjects, 68 patients were detected by NBS (NBS group), while the other 17 were clinically diagnosed before the initiation of NBS (pre-NBS group). Further, 10 of the 68 NBS patients presented intellectual and/or psychiatric disabilities, 5 of whom had a history of treatment discontinuation; in contrast, 12 of the 17 pre-NBS patients presented with neuropsychiatric symptoms. Regarding social outcomes, almost all patients in the NBS group could live an independent life, while over half of the patients in the pre-NBS group were not employed or lived in nursing-care facilities. Neurological outcomes are obviously improved by NBS in Japan. However, some patients, even those detected by NBS, developed neuropsychiatric symptoms due to treatment disruption. Lifelong and strict management is essential to maintain good neurological and social prognoses for patients with PKU.
Metal-Rich Metallaboranes: Synthesis, Structures and Bonding of Bi- and Trimetallic Open-Faced Cobaltaboranes
Authors: Pathak Kriti , Nandi Chandan , Halet Jean-François , Ghosh Sundargopal
Published: April 2021

Synthesis, isolation, and structural characterization of unique metal rich diamagnetic cobaltaborane clusters are reported. They were obtained from reactions of monoborane as well as modified borohydride reagents with cobalt sources. For example, the reaction of [Cp*CoCl]2 with [LiBH4·THF] and subsequent photolysis with excess [BH3·THF] (THF = tetrahydrofuran) at room temperature afforded the 11-vertex tricobaltaborane nido-[(Cp*Co)3B8H10] (1, Cp* = η5-C5Me5). The reaction of Li[BH2S3] with the dicobaltaoctaborane(12) [(Cp*Co)2B6H10] yielded the 10-vertex nido-2,4-[(Cp*Co)2B8H12] cluster (2), extending the library of dicobaltadecaborane(14) analogues. Although cluster 1 adopts a classical 11-vertex-nido-geometry with one cobalt center and four boron atoms forming the open pentagonal face, it disobeys the Polyhedral Skeletal Electron Pair Theory (PSEPT). Compound 2 adopts a perfectly symmetrical 10-vertex-nido framework with a plane of symmetry bisecting the basal boron plane resulting in two {CoB3} units bridged at the base by two boron atoms and possesses the expected electron count. Both compounds were characterized in solution by multinuclear NMR and IR spectroscopies and by mass spectrometry. Single-crystal X-ray diffraction analyses confirmed the structures of the compounds. Additionally, density functional theory (DFT) calculations were performed in order to study and interpret the nature of bonding and electronic structures of these complexes.
Potential Global Distribution of Daktulosphaira vitifoliae under Climate Change Based on MaxEnt
Authors: Ji Wei , Gao Gary , Wei Jiufeng
Published: April 2021

Grape phylloxera, Daktulosphaira vitifoliae, is a small, invasive, sap-sucking pest that is widely present in most viticulture regions all over the world. It is originally from North America and feeds on grapevine roots and leaves. In the current study, the potential distribution area of the leaf-feeding population was investigated with MaxEnt based on population occurrence data under different environmental variables. Results suggested that under current climatic conditions, Europe, East and North China, Japan, the Eastern USA, Uruguay, and the Southeast of South America are highly suitable areas for the occurrence of phylloxera leaf populations. The results showed that isothermality and precipitation of coldest quarter were major factors which contribute more than 60% of the model under current climate conditions. Our results provide important information for governmental decision makers and famers to develop control and management strategies against D. vitifoliae, and can also be used as a reference for studies on other invasive pest.
Sexual Dimorphism and Morphological Modularity in Acanthoscelides obtectus (Say, 1831) (Coleoptera: Chrysomelidae): A Geometric Morphometric Approach
Authors: Budečević Sanja , Savković Uroš , Đorđević Mirko , Vlajnić Lea , Stojković Biljana
Published: April 2021

Sexual dimorphism and specific patterns of development contribute in a great manner to the direction and degree of the sexual differences in body size and shape in many insects. Using a landmark-based geometric morpohometrics approach, we investigated sex-specific morphological size and shape variation in the seed beetle, Acanthoscelides obtectus. We also tested the functional hypothesis of the two morphological modules—thorax and abdomen in both sexes. Female-biased sexual dimorphism in size was shown, while differences in shape were reflected in the wider thorax and abdomen and shorter abdomen in females in comparison to males. The functional hypothesis of a two-module body was confirmed only in females before correction for size, and in both sexes after the allometry correction. Our results indicate that reproductive function has the central role in forming the patterns of modularity. We hypothesize that high morphological integration of the abdomen in females results from intense stabilizing selection, while the more relaxed integration in males is driven by the higher intensity of sexual selection.
Neurogenic Bowel Dysfunction in Children and Adolescents
Authors: Mosiello Giovanni , Safder Shaista , Marshall David , Rolle Udo , Benninga Marc A.
Published: April 2021

Neurogenic/neuropathic bowel dysfunction (NBD) is common in children who are affected by congenital and acquired neurological disease, and negatively impacts quality of life. In the past, NBD received less attention than neurogenic bladder, generally being considered only in spina bifida (the most common cause of pediatric NBD). Many methods of conservative and medical management of NBD are reported, including relatively recently Transanal Irrigation (TAI). Based on the literature and personal experience, an expert group (pediatric urologists/surgeons/gastroenterologists with specific experience in NBD) focused on NBD in children and adolescents. A statement document was created using a modified Delphi method. The range of causes of pediatric NBD are discussed in this paper. The various therapeutic approaches are presented to improve clinical management. The population of children and adolescents with NBD is increasing, due both to the higher survival rate and better diagnosis. While NBD is relatively predictable in producing either constipation or fecal incontinence, or both, its various effects on each patient will depend on a wide range of underlying causes and accompanying comorbidities. For this reason, management of NBD should be tailored individually with a combined multidisciplinary therapy appropriate for the status of the affected child and caregivers.
Individual Lymphocyte Sensitivity to Steroids as a Reliable Biomarker for Clinical Outcome after Steroid Withdrawal in Japanese Renal Transplantation
Authors: Okihara Masaaki , Takeuchi Hironori , Kikuchi Yukiko , Akashi Isao , Kihara Yu , Konno Osamu , Iwamoto Hitoshi , Oda Takashi , Tanaka Sachiko , Unezaki Sakae , Hirano Toshihiko
Published: April 2021

Recently, steroid reduction/withdrawal regimens have been attempted to minimize the side effects of steroids in renal transplantation. However, some recipients have experienced an increase/resumption of steroid administrations and acute graft rejection (AR). Therefore, we investigated the relationship between the individual lymphocyte sensitivity to steroids and the clinical outcome after steroid reduction/withdrawal. We cultured peripheral blood mononuclear cells (PBMCs) isolated from 24 recipients with concanavalin A (Con A) in the presence of methylprednisolone (MPSL) or cortisol (COR) for four days, and the 50% of PBMC proliferation (IC50) values and the PBMC sensitivity to steroids were calculated. Regarding the experience of steroid increase/resumption and incidence of AR within one year of steroid reduction/withdrawal, the IC50 values of these drugs before transplantation in the clinical event group were significantly higher than those in the event-free group. The cumulative incidence of steroid increase/resumption and AR in the PBMC high-sensitivity groups to these drugs before transplantation were significantly lower than those in the low-sensitivity groups. These observations suggested that an individual’s lymphocyte sensitivity to steroids could be a reliable biomarker to predict the clinical outcome after steroid reduction/withdrawal and to select the patients whose dose of steroids can be decreased and/or withdrawn after transplantation.
Neurogenic Bowel in Acute Rehabilitation Following Spinal Cord Injury: Impact of Laxatives and Opioids
Authors: Round Andrew M. , Joo Min Cheol , Barakso Carolyn M. , Fallah Nader , Noonan Vanessa K. , Krassioukov Andrei V.
Published: April 2021

Objective: To explore the association between bowel dysfunction and use of laxatives and opioids in an acute rehabilitation setting following spinal cord injury (SCI). Methods: Data was collected regarding individuals with acute traumatic/non-traumatic SCI over a two-year period (2012–2013) during both the week of admission and discharge of their inpatient stay. Results: An increase in frequency of bowel movement (BM) (p = 0.003) and a decrease in frequency of fecal incontinence (FI) per week (p < 0.001) between admission and discharge was found across all participants. There was a reduction in the number of individuals using laxatives (p = 0.004) as well as the number of unique laxatives taken (p < 0.001) between admission and discharge in our cohort. The number of individuals using opioids and the average dose of opioids in morphine milligram equivalents (MME) from admission to discharge were significantly reduced (p = 0.001 and p = 0.02, respectively). There was a positive correlation between the number of laxatives and frequency of FI at discharge (r = 0.194, p = 0.014), suggesting that an increase in laxative use results in an increased frequency of FI. Finally, there was a significant negative correlation between average dose of opioids (MME) and frequency of BM at discharge, confirming the constipating effect of opioids (r = −0.20, p = 0.009).
New Perspective for Soft Tissue Closure in Medication-Related Osteonecrosis of the Jaw (MRONJ) Using Barbed Sutures
Authors: Laimer Johannes , Hechenberger Martin , Lercher Johanna Maria , Born Eva , Schomaker Michael , Puntscher Sibylle , Siebert Uwe , Bruckmoser Emanuel
Published: April 2021

The aim of this study was to compare the effectiveness of barbed versus smooth sutures for soft tissue closure of exposed jawbone sites in medication-related osteonecrosis of the jaw (MRONJ) patients. Exposed necrotic jawbone sites surgically managed by intraoral soft tissue closure were evaluated. Either barbed sutures (Stratafix™ or V-Loc™) together with Prolene® or Vicryl® sutures were used. We estimated the effect of barbed sutures (BS) with Prolene® compared to smooth sutures (Vicryl®) on the hazard rate of intraoral soft tissue dehiscence using a multivariate Cox regression model within a target trial framework, adjusting for relevant confounders. In total, 306 operations were performed in 188 sites. In the primary analysis 182 sites without prior surgery were included. Of these, 113 sites developed a dehiscence during follow-up. 84 sites were operated using BS and Prolene®. A total of 222 sites were operated with Vicryl® (control group). In the BS group, the median time to event (i.e., dehiscence) was 148 days (interquartile range (IQR), 42–449 days) compared to 15 days (IQR, 12–52 days) in the control group. The hazard rate of developing intraoral dehiscence was 0.03 times (95%-confidence interval (CI): 0.01; 0.14, p < 0.001) lower for BS patients compared to the control group. Within the limits of a retrospective study, BS showed a high success rate and are therefore recommended for soft tissue closure of exposed jawbone sites in MRONJ patients. Additional studies are warranted to further evaluate this novel application of BS.