bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal Glucocorticoid Administration Accelerates Maturation in The Hepatocytes of Fetal Rats
Authors: Kobayashi Tsukasa , Takeba Yuko , Ohta Yuki , Ootaki Masanori , Kida Keisuke , Watanabe Minoru , Iiri Taroh , Matsumoto Naoki
Published: March 2021

Preterm and low birth weight infants often experience liver dysfunction after birth because the liver is immature. As such, prenatal glucocorticoid (GC) is clinically administered to pregnant women at risk of preterm birth for maturation of the cardiopulmonary function. However, the effects of prenatal GC administration on the liver remain unclear. We aimed to investigate the effects of prenatal GC administration regarding maturity of the liver in preterm rats. Dexamethasone (DEX) was administered to pregnant Wistar rats on gestational days 17 and 19 before cesarean section. Real time polymerase chain reaction (RT-PCR) was then used to analyze the mRNA levels (albumin, HNF4α, HGF, Thy-1, cyclin B, and CDK1) in the liver samples. Immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA) were used to analyze protein produced. Hepatocyte size enlarged because of growth and administration of prenatal DEX. Albumin, HNF4α, and hepatocyte growth factor (HGF) increased secondary to growth and administration of prenatal DEX. Cell cycle markers, Cyclin B, and CDK1 gradually decreased during growth and by administration of DEX. These results suggest that prenatal GC administration induces hepatocyte differentiation and achieves maturation via expression of HNF4α and HGF in premature fetuses.
High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer
Authors: Palafox Marta , Monserrat Laia , Bellet Meritxell , Villacampa Guillermo , Gonzalez-Perez Abel , Oliveira Mafalda , Brasó-Maristany Fara , Ibrahimi Nusaibah , Kannan Srinivasaraghavan , Mina Leonardo , Herrera-Abreu María Teresa , Ódena Andreu , Sánchez-Guixé Mónica , Capelán Marta , Azaro Analía , Bruna Alejandra , Rodriguez Olga , Guzmán Marta , Grueso Judit , Viaplana Cristina , Hernandez-Losa Javier , Su Faye , Lin Kui , Clarke Robert (B.) , Caldas Carlos , Joaquín Arribas , Michiels Stefan , García-Sanz Alicia , Turner Nicholas C. , Prat Aleix , Nuciforo Paolo , Dienstmann Rodgrigo , Verma Chandra , López-Bigas Núria , Scaltriti Maurizio , Arnedos Monica , Saura Cristina , Serra Violeta
Published: March 2021

Cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), combined with endocrine therapy (ET), have demonstrated higher antitumor activity than ET alone for the treatment of advanced estrogen receptor-positive (ER+) breast cancer (BC). Some ER+ BC are de novo resistant to CDK4/6i and others develop acquired resistance. Therapies for tumors after progression are needed. Here, we demonstrate that p16 overexpression is associated with reduced antitumor activity of CDK4/6i in patient-derived xenografts (PDX; n=37) and ER+ BC cell lines, and reduced response of early/advanced ER+HER2- BC patients (n=49) to CDK4/6i. We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome in ER+, CDK4/6i-treated BC PDX and patients. Combination of CDK4/6i ribociclib with PI3K inhibitor (PI3Ki) alpelisib showed antitumor activity in ER+ non-basal-like BC PDX, independently of PIK3CA or RB1 mutation (n=25). Our results offer new insights into predicting primary and acquired resistance to CDK4/6i and post-progression therapeutic strategies.
Unique Chemical Parameters and Microbial Activity Lead to Increased Archaeological Preservation within Vindolanda, UK.
Authors: Orr C. H , Williams R , Halldórsdóttir H , Birley A , Greene E , Nelson A , Ralebitso-Senior T.K , Taylor G
Published: March 2021

Waterlogged burial conditions impact upon artefact preservation. One major determinant of preservation is presence and behaviour of microorganisms, however, unravelling the mechanisms is challenging. In this study, we analysed elemental composition, bacterial diversity and community structure from excavation trenches at the Roman Site of Vindolanda, Northumberland, UK, using pXRF and 16s rRNA gene amplicon sequencing. Excavation trenches provide layers which can be classed as phosphorus sinks and which are strongly linked to the abundance of vivanite. The results indicated that microbial communities were dominant in Firmicutes, Bacteroidetes and Proteobacteria at a phylum level. Samples which also had visible vivianite presence showed that there were marked increases in Methylophilus. Methylophilus might be associated with favourable preservation in these anaerobic conditions. More research is needed to clearly link the presence of Methylophilus with vivianite production. The study emphasises the need for further integration of chemical and microbiome approaches, especially in good preservation areas, to explore microbial and chemical degradation mechanisms.
Association between cancer risk and HLA genotype can be explained by anti-tumor immunity
Authors: Toke Eniko , Miklos Istvan , Molnár Levente , Tóth József , Lorincz Orsolya , Csiszovszki Zsolt , Páles Péter , Pántya Katalin , Somogyi Eszter
Published: March 2021

Over recent decades, efforts to explain the heritability of developing cancer have focused on identifying high-risk genes and common genetic variants. However, no studies considered genetic factors regulating tumor-specific immune responses. By developing a novel human leukocyte antigen (HLA) score, determined by autologous HLA allele-binding epitopes of tumor-specific antigens, we showed that individuals with HLA allele sets supporting broader tumor-specific T cell responses have lower risk of developing melanoma. The risk ratio between the highest risk and most protected groups was 5.69 comparing the top and bottom 20% of the HLA score distribution (p < 0.05). Similar results were obtained for other cancers, including non-small cell lung, renal, and bladder cancers, but not colorectal cancer. Our findings suggest that subjects with a low HLA score have an increased genetic risk of developing certain cancers.
Ecological status assessment and Non-Indigenous Species in industrial and fishing harbours of the Gulf of Gabès (central Mediterranean Sea)
Authors: Mosbahi Nawfel , Pezy Jean-Philippe , Neifar Lassad , Dauvin Jean-Claude
Published: March 2021

This study from January to December 2018 was the first initiative of a Port Baseline Survey (PBS) aimed at assessing the impact of biological invasions in harbours of the Gulf of Gabès (GG). A total of 12 fishing and industrial harbours were seasonally prospected during 2018. A total of 174 macrobenthos taxa were recorded, belonging to eight zoological groups, with a dominance of crustaceans (32%), molluscs (31%) and polychaetes (20%). Among these taxa, 57 were Non-Indigenous Species (NIS) for Tunisian waters, while 27 species were recorded for the first time in GG harbours and three decapods ( Dyspanopeus sayi, Hippolyte prideauxiana and Pilumnus minutus ) and one amphipod ( Hamimaera hamigera ) were newly recorded from Tunisian waters. Two main categories of harbours are distinguished according to their macrobenthic communities and environmental features (essentially edaphic factors). The industrial harbours yield higher numbers of species and abundance of NIS than the fishing ports. The ALEX metric is used to evaluate the biological invasion status of the Gulf of Gabès harbours, showing that their status ranges from unaffected in fishing harbours to extremely affected in industrial harbours. Three biotic indices (AMBI, BO2A and BENTIX) are applied to assess the ecological status of harbours, which varies from moderate to good. ALEX and the other biotic indices are significantly correlated with harbour characteristics, maritime traffic and edaphic factors (organic matter and chemical contamination). The present study gives an overview of all available benthic data, the impact of biological invasions and the ecological quality status of harbours in the Gulf of Gabès. The results could be considered as providing important baseline data for the implementation of environmental policies and management plans in the future.
Anthropic Pollution Impacts on Groundwater Vulnerability Based on Modified DRASTIC-FAHP
Authors: Goodarzi Mohammad Reza , Niknam Amirreza R. , Jamali Vahid , Pourghasemi Hamid Reza , Kiani-Harchegani Mahboobeh
Published: March 2021

In arid and semi-arid regions such as Iran, groundwater is more important for humans and ecosystems than surface water. Different models of groundwater vulnerability assessment can be used to better manage water resources. The purpose of this study is to evaluate the qualitative vulnerability of groundwater resources in the Birjand Plain aquifer using the DRASTIC model and 7 hydrogeological components. DRASTIC model was also modified by adding a land use component (MDRASTIC) based on Analytical Hierarchy Process (AHP) and Fuzzy Analytic Hierarchy Process (FAHP) methods. After calculating the vulnerability index, the vulnerability of each method was mapped and the final index obtained from each method was classified into 4 different categories. Nitrate concentration was used to confirm the results and to analyze the sensitivity of a single parameter. Sensitivity analysis showed that the groundwater vulnerability is mainly affected by water depth and land use. To validate each of the models, their correlation with nitrate concentration was calculated and compared. To determine the correlation coefficient, simple linear regression method was performed and the Pearson and Spearman methods were used. According to the obtained Pearson correlation results, the DRASTIC, MDRASTIC, MDRASTIC-AHP, and MDRASTIC-FAHP models resulted in values of 0.550, 0.680, 0.778, and 0.794respectively. The results show a good correlation between the modified DRASTIC-FAHP model and nitrate concentration as an indicator of groundwater pollution.
Role of Environmental Surfaces and Hands of Healthcare Workers in Perpetuating Multi-Drug Resistant Pathogens in a Neonatal Intensive Care Unit
Authors: Elkady Marwa A. , Bakr Wafaa M.K. , Ghazal Hesham , Omran Eman A.
Published: March 2021

Neonates admitted to neonatal intensive care units are at a risk of developing healthcare associated infections, leading to increased risk of mortality. This study aimed to identify organisms causing such late-onset infections in neonates and determine whether these isolates were genetically identical to those from the surrounding environmental surfaces and hands of healthcare workers (HCWs). A cross-sectional study was carried out over a period of four months in a University neonatal intensive care unit. Samples were collected from all neonates with symptoms of late-onset infections (n=180). Fingerprint samples of 21 healthcare workers as well as 330 random environmental samples were also taken from the unit. Isolates from neonates, environment and fingerprints were subjected to protein electrophoresis followed by sequencing to detect genetic similarities. Almost half of neonatal samples were culture-positive (91/180, 50.6%), out of which, 72% of bacterial isolates (49/ 68) were multi-drug resistant. Klebsiella pneumoniae (32.6%) and Candida spp. (28.4%) were the commonest neonatal isolates. A cluster of four homologous Klebsiella pneumoniae strains was isolated from two neonates as well as an examining bed and a portal incubator. Another cluster was isolated from hands and three neonatal samples. Both clusters were multi-drug resistant Klebsiella pneumoniae. A homologous pair of each of Candida tropicalis and Candida glabrata was isolated from the blood of two neonates, and one neonatal and a crash cart sample, respectively. Overall, 8.8% (8/91) of neonatal samples were found to be homologous to other neonatal /environmental/ hand isolates, denoting perpetuation of pathogens between neonates themselves and also other reservoirs of infections. Conclusion: Hands of healthcare providers as well as surfaces are reservoirs of multi-drug resistant pathogens in the neonatal intensive care unit.
Structural basis for late maturation steps of the human mitoribosomal large subunit
Authors: Rorbach Joanna , Cipullo Miriam , Gesé Genís Valentín , Khawaja Anas , Hällberg Martin
Published: March 2021

Mitochondrial ribosomes (mitoribosomes) synthezise a critical set of proteins essential for oxidative phosphorylation. Therefore, their function is vital to cellular energy supply and mitoribosomal defects give rise to a large and diverse group of human diseases 1. The architecture of mitoribosomes is strikingly different from that of their bacterial and eukaryotic cytosolic counterparts and display high divergence between species 2–6. Mitoribosome biogenesis follows distinct molecular pathways that remain poorly understood. Here, we determined the cryo-EM structures of mitoribosomes isolated from human cell lines with either depleted or overexpressed mitoribosome assembly factor GTPBP5. This allowed us to capture consecutive steps during mitoribosomal large subunit (mt-LSU) biogenesis that involve normally short-lived assembly intermediates. Our structures provide important insights into the last steps of 16S rRNA folding, methylation and peptidyl transferase centre (PTC) completion, which require the coordinated action of nine assembly factors. We show that mammalian-specific MTERF4 contributes to the folding of 16S rRNA, allowing 16S rRNA methylation by MRM2, while GTPBP5 and NSUN4 promote fine-tuning rRNA rearrangments leading to PTC formation. Moreover, our structures reveal an unexpected role for the elongation factor mtEF-Tu in mt-LSU assembly, in which mt-EF-Tu interacts with GTPBP5 in a manner similar to its interaction with tRNA during translational elongation. Together, our approaches provide detailed understanding of the last stages of mt-LSU biogenesis that are unique to mammalian mitochondria.
Supercapacitance and Superinductance of TiN
and NbTiN films in the Vicinity of
Superconductor-to-Insulator Transition
Authors: Mironov Alexey , Silevitch Daniel , Postolova Svetlana , Burdastyh Maria , Proslier Thomas , Baturina Tatyana , Rosenbaum Thomas , Vinokur Valerii
Published: March 2021

We investigate the low temperature complex impedance of disordered insulating thin TiN and NbTiN films in the frequency
region 400 Hz–1MHz in close proximity to the superconductor-insulator transition. The frequency, temperature, and magnetic field dependence of the real and imaginary parts of the impedance indicate the response of superconducting
droplets resulting from self-induced electronic granularity. The impedance crosses over from capacitive to
inductive behavior as the sample is driven through the transition, characterized by a divergent dielectric response.
CircRNA Expression Patterns and circRNA-miRNA-mRNA Networks During CV-A16 Infection of SH-SY5Y Cells
Authors: Hu Yajie , Yang Ruian , Zhao Wei , Liu Chen , Tan Yan , Pu Dandan , Song Jie , Zhang Yunhui
Published: March 2021

Coxsackievirus A16 (CV-A16) has caused worldwide epidemics of hand, foot, and mouth disease (HFMD), particularly among infants and preschool children. Circular RNAs (circRNAs) are a recently identified class of noncoding RNA molecules that participate in the occurrence and development of numerous infectious diseases. To date, the function of circRNAs has been a heavily researched topic, and their role in CV-A16 infection has not been fully elucidated. In this study, the viral effects of CV-A16 on the cellular circRNA transcriptome were investigated using next-generation sequencing technology. In this study, a total of 8726, 8611 and 6826 circRNAs were identified in the control, CV-A16-12 h and CV-A16-24 h groups, respectively. Further analysis showed that 1769 and 1192 circRNAs were differentially expressed in the CV-A16-12 h and CV-A16-24 h groups, respectively. Moreover, the common differentially expressed circRNAs were screened out and used for functional annotation analysis, which demonstrated that the parent genes of differentially expressed circRNAs might be associated with the viral infection process, especially the “Immune system process” in GO analysis and the “Inflammation mediated by chemokine and cytokine signaling pathway” in KEGG analysis. Additionally, 6 dysregulated circRNAs were selected for validation and were verified to be consistent with the sequencing results. Additionally, we further constructed a circRNA-miRNA-mRNA regulatory network that suggested the putative function of circRNAs as cellular miRNA decoys to indirectly regulate gene expression during CV-A16 infection, especially the hsa_circ_0004447/hsa-miR-942-5p/MMP2, hsa_circ_0078617/hsa-miR-6780b-5p/MMP2 and hsa_circ_0078617/hsa-miR-5196-5p/MMP2 regulatory axes. Considering all of these results, to the best of our knowledge, this study is the first to present a comprehensive overview of circRNAs induced by CV-A16, and this research demonstrated that a network of enriched circRNAs and circRNA-associated competitive endogenous RNAs (ceRNAs) is involved in the regulation of CV-A16 infection, thereby helping to elucidate the mechanisms underlying CV-A16-host interactions.
Outcomes of Surgery for Giant Hepatic Hemangioma
Authors: Xie Qing-song , Chen Zi-xiang , Zhao Yi-jun , Gu Heng , Geng Xiao-ping , Liu Fu-bao
Published: March 2021

Background: The surgical indications for liver hemangioma remain unclear. Methods: Data from 152 patients with hepatic hemangioma who underwent hepatectomy between 2004 and 2019 were retrospectively reviewed. We analyzed characteristics including tumor size, surgical parameters, and variables associated with Kasabach–Merritt syndrome and compared the outcomes of laparoscopic and open hepatectomy. Here, we describe surgical techniques for giant hepatic hemangioma and report on two meaningful cases. Results: Most (63.8%) patients with hepatic hemangioma were asymptomatic. Most (86.4%) tumors from patients with Kasabach–Merritt syndrome were larger than 15 cm. Enucleation (30.9%), sectionectomy (28.9%), hemihepatectomy (25.7%), and the removal of more than half of the liver (14.5%) were performed through open (87.5%) and laparoscopic (12.5%) approaches. Laparoscopic hepatectomy is associated with an operative time, estimated blood loss, and major morbidity and mortality rate similar to those of open hepatectomy, but a shorter length of stay. 3D image reconstruction is an alternative for diagnosis and surgical planning for partial hepatectomy. Conclusion: The main indication for surgery is giant (>10 cm) liver hemangioma, with or without symptoms. Laparoscopic hepatectomy was an effective option for hepatic hemangioma treatment. For extremely giant hemangiomas, 3D image reconstruction was indispensable. Hepatectomy should be performed by experienced hepatic surgeons.
Model of Care and Chance of Spontaneous Vaginal Birth: A Prospective, Multicenter Matched-Pair Analysis From North Rhine-Westphalia
Authors: Tietjen Sophia L. , Puth Marie-Therese , Heep Andrea , Kocks Andreas , Gerzen Lydia , Schmid Matthias , Gembruch Ulrich , Merz Waltraut M.
Published: March 2021

BackgroundCompared to standard obstetric care, advantages of midwife-led models of care have been reported; these include a higher vaginal birth rate and less interventions. In Germany, 98.4% of women are giving birth in consultant-led obstetric units. We compared the outcome of birth planned in alongside midwifery units (AMU) in North Rhine-Westphalia (NRW) with a matched group of low-risk women who gave birth in standard obstetric care during the same period of time.MethodsA prospective, controlled, multicenter study was conducted. Six of the seven AMUs in NRW participated. Healthy women with a singleton term cephalic pregnancy booking for birth in AMU were eligible. For each woman in the study group a control was chosen who would have been eligible for birth in AMU but was booking for standard obstetric care at the same hospital at the same time; additionally, matching for parity was performed. Mode of birth was chosen as primary outcome parameter. Secondary endpoints included a composite outcome of abnormal third stage and / or postpartum hemorrhage; higher-order obstetric lacerations; and for the neonate, a composite outcome (5-minute Apgar <7 and / or umbilical cord arterial pH < 7.10 and / or transfer to specialist neonatal care). Statistical analysis was by intention to treat. A non-inferiority analysis was performed for the primary and all secondary endpoints.Results589 case-control pairs were recruited, corresponding to 13.6% of those assumed to be eligible; 198 cases were excluded. Final analysis was performed with 391 case-control pairs. Nulliparous women constituted 56.0% of cases. For the primary endpoint vaginal birth superiority was established for the study group (5.66, 90%-CI 1.26-10.04). Superiority was also confirmed for higher-order obstetric lacerations (2.33, 90%-CI 0.04-4.81). For the composite newborn outcome non-inferiority was established (1.28, 90%-CI 1.33-3.93). Non-inferiority was not present for the composite maternal outcome (-1.56, 90%-CI -5.86-2.75). The epidural anesthesia rate was lower (22.9% vs. 41.1%), and the length of hospital stay was shorter in the study group (p<0.001 for both).Transfer to standard obstetric care occurred in 51.2% of cases, with a strong association between parity and transfer (p<0.001). Request for regional anesthesia was the most common cause for transfer (47.1%). ConclusionOur comparison between care in AMU and standard obstetric care with respect to mode of birth and other outcomes confirmed the superiority of this model of care for low-risk women. Admission and transfer criteria were in place in all participating centers and strictly adhered to.
Development of non-enzymatic cholesterol electrochemical sensor based on CuO(NPs)-Polyaniline-Murexide composite
Authors: Hassine Chedia Ben Ali , Kahri Hamza , Barhoumi Houcine
Published: March 2021

In this study, a novel non-enzymatic sensor based on copper oxide nanoparticles (CuO), polyaniline nanofibers (PANI) and murexide (Mu) modified glassy carbon electrode was developed and used for the detection of cholesterol. Copper oxide nanoparticles were deposited on the glassy carbon electrode through electrodeposition and electrochemical oxidation followed by electrodeposition of PANI-Mu composite. The as prepared CuO-PANI-Mu sensor was characterized using electrochemical, optical and morphological methods such as cyclic voltammetry (CV), impedance spectroscopy (EIS), linear sweep voltammetry (LSV), UV-visible and scanning electron microscopy (SEM). The elaborated composite matrix was used for cholesterol detection employing the impedance spectroscopy method. As a result, good analytical performances were obtained for cholesterol quantification with good stability and high sensitivity (5575 Ω/M) with a wide linear range from 0.5nM to 50mM.
The Type of Gastrectomy and Modified Frailty Index as Useful Predictive Indicators for One-Year Readmission Due to Nutritional Difficulty in Patients Who Undergo Gastrectomy for Gastric Cancer.
Authors: Osaki Tomohiro , Saito Hiroaki , Miyauchi Wataru , Shishido Yuji , Miyatani Kozo , Matsunaga Tomoyuki , Tatebe Shigeru , Fujiwara Yoshiyuki
Published: March 2021

Background
Patients who undergo gastrectomy for gastric cancer are likely to have nutritional difficulty after surgery. Therefore, readmission due to nutritional difficulty is frequently observed in such patients. This study aimed to identify predictive indicators for readmission due to nutritional difficulty in patients who underwent gastrectomy for gastric cancer.
Methods
We retrospectively reviewed surgical outcomes in 516 consecutive patients who underwent gastrectomy for gastric cancer.
Results
The readmission rate within one year was 13.8%. Readmission due to nutritional difficulty was observed in 20 patients (3.9%), and nutritional difficulty was the second leading cause of readmission. Multivariate analysis revealed that the type of gastrectomy and the modified frailty index were independent predictive indicators of readmission due to nutritional difficulty. The readmission rates due to nutritional difficulty were 1.2%, 4.7%, and 11.5% in patients who underwent distal partial gastrectomy and had low modified frailty index, in those who underwent distal partial gastrectomy and had high modified frailty index or those who underwent either proximal partial or total gastrectomy and had low modified frailty index, and in those who underwent either proximal partial or total gastrectomy and had high modified frailty index, respectively (P = 0.0008).
Conclusions
Because the readmission rate due to nutritional difficulty is high in patients who underwent either total or proximal partial gastrectomy with high modified frailty index, intensive follow-up and nutritional support is needed to reduce readmission due to nutritional difficulty, which can help improve the patients’ quality of life and reduce additional medical costs.
Assessment of Microplastics in a Municipal Wastewater Treatment Plant With Tertiary Treatment: Removal Efficiencies and Loading Per Day Into the Environment
Authors: Bayo Javier , Olmos Sonia , López-Castellanos Joaquín
Published: March 2021

This study investigates the removal of microplastics from wastewater in an urban wastewater treatment plant located in Southeast Spain, including an oxidation ditch, rapid sand filtration, and ultraviolet disinfection. A total of 146.73 L of wastewater samples from influent and effluent were processed, following a density separation methodology, visual classification under a stereomicroscope, and FTIR analysis for polymer identification. Microplastics proved to be 72.41% of total microparticles collected, with a global removal rate of 64.26% after the tertiary treatment and within the average retention for European WWTPs. Three different shapes were identified: i.e., microfiber (79.65%), film (11.26%), and fragment (9.09%), without the identification of microbeads despite the proximity to a plastic compounding factory. Fibers were less efficiently removed (56.16%) than particulate microplastics (90.03%), suggesting that tertiary treatments clearly discriminate among forms, and reporting a daily emission of 1.6 x 107 microplastics to the environment. Year variability in microplastic burden was cushioned at the effluent, reporting a stable performance of the sewage plant. Eight different polymer families were identified, LDPE film being the most abundant form. Future efforts should be carried on source control, plastic waste management, improvement of legislation, and specific microplastic-targeted treatment units, especially for microfiber removal.
Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo.
Authors: Mensch Maria , Dunot Jade , Yishan Sandy , Harris Samuel , Blistein Aline , Avdiu Alban , Pousinha Paula A , Giudici Camilla , Busche Marc Aurel , Jedlicka Peter , Willem Michael , Marie Helene
Published: March 2021

Background
Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo.
Methods
With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging and in vivo electrophysiology.
Results
We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo.
Conclusions
These results give novel insights into the functional role of the recently discovered η-secretase-derived products, and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.
Clinical and Biochemical Predictors of Non-Alcoholic Fatty Liver Disease in Obese Children and Adolescents
Authors: Atwa Hoda , Ibrahim Ahmed , Abd-Allah Husseiny , Labib Jacklien
Published: March 2021

Background

Obesity and associated co-morbidities are growing worldwide, including non-alcoholic fatty liver disease (NAFLD), which become one of the leading causes of chronic liver diseases in both children and adults. The aim of this study is to investigate the clinical and biochemical predictors associated with NAFLD among obese children.
Materials and Methods

Ninety obese children and adolescents, aged 12–18 years, were enrolled in this study. All were subjected to anthropometric measurement; biochemical analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver function tests. Ultrasonography was used to diagnose NAFLD.
Results

The frequency of NAFLD was 38.9% among obese children 68.6% of them met the criteria of metabolic syndrome. Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver ultrasound (p < 0.05). Insulin resistance was significantly more common among NAFLD group (88.6% vs. 18.2%) (p < 001). Logistic regression analysis revealed that BMI and HOMA-IR are the independent predictors for NAFLD with (P 0.034 and 0.022) respectively
Conclusion

More than one third of obese children have NAFLD, which is closely linked to metabolic syndrome and insulin resistance.
“Higher Pedicle Screw Density Does Not Result in Improved Curve Correction in Lenke 2 Adolescent Idiopathic Scoliosis”
Authors: Skalak Timothy , Gagnier Joel , Caird Michelle S. , Farley Frances A. , Li Ying
Published: March 2021

Purpose: Higher pedicle screw density posterior spinal fusion (PSF) constructs have not been shown to result in improved curve correction in Lenke 1 and 5 adolescent idiopathic scoliosis (AIS) but do increase cost. The purpose of this study questioned whether higher screw density constructs improved curve correction and maintenance of correction in Lenke 2 AIS. Secondary goals were to identify predictive factors for correction and postoperative magnitude of curves in Lenke 2 AIS. Methods: We identified patients 11 to 17 years old who underwent primary PSF for Lenke 2 AIS between 2007 and 2017 who had minimum follow up of 2 years. Demographic and radiographic data were collected to perform regression and elimination analysis. Results: Thirty patients (21 Female, 9 male) were analyzed. Average age and SD at time of surgery was 14.0 ± 1.8 years (range, 11-17 years) and median follow-up was 2.8 years (IQR 2.1-4.0 years). Implant density did not predict final postoperative curve magnitude. Predictors of final postoperative curve magnitude were sex and preoperative curve magnitude. Predictors of percentage of correction of major curve were sex and age at the time of surgery. Predictors of final postoperative thoracic kyphosis were sex and percent flexibility preop. Females had lower final postoperative major curve magnitude, a higher percent curve correction, and lower postoperative thoracic kyphosis.Conclusions: Increased implant density is not predictive of postoperative curve magnitude in Lenke 2 AIS. Predictors of postoperative curve magnitude are sex and preoperative curve magnitude.Level of Evidence: Level III Retrospective Observational
Tailoring Growth of MOF199 on Hierarchical Surface of Bamboo and Its Antibacterial Property
Authors: Su Minglei , Zhang Rong , Li Jingpeng , Jin Xiaobei , Zhang Xiaofeng , Qin Daochun
Published: March 2021

Bamboo, as a fast-grown forest resource, could be functionalized by metal–organic frameworks (MOF) with various potential applications. However, the stability of MOF immobilized on bamboo surface remains to be improved. In this work, MOF199, as known as HKUST-1, was in situ anchoring on moso bamboo via regulating pretreatment of bamboo and a green two-step synthesis route. The two-step synthesis route could be completed under room temperature and both precursor solutions can be reused. The results indicated that, with the collaboration of delignification and carboxymethylation pretreatment of bamboo, a dense and well-dispersed MOF199 coating was successfully synthesized, the adhesion between MOF and bamboo surface was also improved. Besides, the quantity and size of MOF199 on bamboo can be tailored by adjusting the carboxyl groups of pretreated bamboo and the concentration of copper nitrate solution. More importantly, results show that the formation of carboxyl-copper (II) complex served as nucleation sites for the growth of MOF199 crystals is the key to prepare uniform MOF layers. The growth of MOF199 endow bamboo with good antibacterial activity against E. coli. This method provides a facile and practical strategy for designing MOF coated woody materials.
Sirt6 protects cardiomyocytes against doxorubicin-induced cardiotoxicity by inhibiting P53/Fas-dependent cell death and augmenting endogenous antioxidant defense mechanisms
Authors: Wu Sisi , Wang Xiaoxiao , Tong Mingming , Fu Li , Zhang Yanjing , Xu Jiayi , Chen Xuemei , Chen Hongying , Li Ruli , Wu Yao , Xin Juanjuan , Yan Xin , Li He , Lan Jie , Xue Kunyue , Li Xue , Zhuo Caili , Wei Jiang
Published: March 2021

Sirt6, a class III NAD+-dependent deacetylase of the sirtuin family, is a highly specific H3 deacetylase and plays important roles in regulating cellular growth and death. The induction of oxidative stress and death are the crucial mechanisms involved in cardiomyocyte damage and cardiac dysfunction in doxorubicin-induced cardiotoxocity, but the regulatory role of Sirt6 in the fate of DOX-impaired cardiomyocytes is poorly understood. In this study, we exposed heterozygous Sirt6 knockout (Sirt6+/−) mice and their littermates as well as cultured neonatal rat cardiomyocytes to DOX, then investigated how Sirt6 mitigates oxidative stress and myocardial injury in the DOX-treated myocardium. Sirt6 partial knockout or silencing worsened myocardial damage, cardiac remodeling, and oxidative stress in mice or cultured cardiomyocytes with DOX challenge. Cardiomyocytes infected with adenoviral constructs encoding Sirt6 showed reversal of this DOX-induced damage. Intriguingly, Sirt6 reduced oxidative stress injury by upregulating endogenous antioxidant levels, interacted with oxidative stress-stirred p53, and acted as a co-repressor of p53 in nuclei. Sirt6 was recruited by p53 to the promoter regions of the target genes Fas and FasL and further suppressed p53 transcription activity by reducing histone acetylation. Sirt6 inhibited Fas/FasL signaling and attenuated both Fas-FADD-caspase-8 apoptotic and Fas-RIP3 necrotic pathways. These results suggest that Sirt6 protects the heart against DOX-induced cardiotoxity by upregulating endogenous antioxidants, as well as suppressing oxidative stress and cell death signaling pathways dependent on ROS-stirred p53 transcriptional activation, thus reducing Fas-FasL–mediated apoptosis and necrosis.
Effect of whole-body cryotherapy on morphological, rheological, and biochemical blood indices in individuals with multiple sclerosis
Authors: Ptaszek Bartłomiej , Teległów Aneta , Adamiak Justyna , Głodzik Jacek , Podsiadło Szymon , Marchewka Jakub
Published: March 2021

The study aim was to examine the impact of 20 whole-body cryotherapy sessions on biochemical and rheological blood indices in multiple sclerosis individuals. The study group involved 15 women (mean age: 41.53 ± 6.98 years) with diagnosed multiple sclerosis who underwent whole-body cryotherapy sessions. The first control group consisted of 20 women (mean age: 40.45 ± 4.77 years) with multiple sclerosis who received no cryotherapy intervention. The second control group comprised 15 women (mean age: 38.47 ± 6.0 years) without neurological diseases or other chronic conditions who participated in cryotherapy sessions. For blood indices analysis, venous blood was collected twice: on the day of cryotherapy commencement and after the 20 cryotherapy sessions. Blood counts were determined with a hematology analyzer. A laser-optical rotational cell analyzer served to investigate erythrocyte aggregation and deformability. Total serum protein was measured, and proteinogram and fibrinogen values were established. Statistically significant differences were observed in red blood cells, hemoglobin, hematocrit, elongation index, total extent of aggregation, proteins (including fibrinogen). There was no significant effect of the 20 cryotherapy sessions on morphological, rheological, or biochemical blood indices in women with multiple sclerosis. The intervention had a positive impact on the rheological blood properties of healthy women.
Microsponges for controlled release and enhanced oral bioavailability of carbamazepine
Authors: Abdalla Karam F. , Osman Mohamed A. , Nouh Ahmed T. , Maghraby Gamal M. El
Published: March 2021

The oral absorption and hence the oral bioavailability of carbamazepine (CBZ) is variable even after administration of rapidly dissolving formulation. This problem was attributed to supersaturation of CBZ and transformation to the less soluble carbamazepine dihydrate (CBD). Accordingly, formulation of sustained release products of CBZ is a promising approach to overcome this problem. Microsponges is an emerging formulation which can help in this direction. The aim of this work was to optimize the composition of microsponges for better encapsulation and sustained release of CBZ for oral administration. CBZ microsponges were prepared using quasi emulsion solvent diffusion technique with varying composition of ethyl cellulose and polyvinyl alcohol (PVA). Microsponges were evaluated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction. Production yield, entrapment efficiency and surface morphology of microsponges were assessed in addition to drug release. Optimum formulation was administered orally to albino rabbits to evaluate the oral bioavailability with reference to unprocessed CBZ. The Instrumental analysis reflected the encapsulation of CBZ in amorphous or molecularly dispersed form in the microsponges. The size and entrapment efficiency of the microsponges increased with increasing polymer contents. This was associated with reduction in CBZ release. Optimum formulation enhanced the oral absorption of CBZ. This was manifested by 2.6-fold increase in the area under the plasma concentration versus time curve compared to that of unprocessed CBZ. The study introduced microsponges as promising carriers for sustained oral delivery of CBZ.
Pregnant Women Utilization of Dental Services: Still a Challenge in Low Resource Setting
Authors: Onwuka C , Onwuka CI , Iloghalu E , Udealor PC , Ezugwu EC , Menuba IE , Ugwu EO
Published: March 2021

Background: Poor oral health in pregnancy can be associated with poor pregnancy outcome, however, dental consultation among pregnant women appears to be low.Results: Only 36 (8.7%) of the respondents had dental consultations in index pregnancy for complaints such as tooth ache and decay (66.7%) and pains and swelling of the gum (33.3%). The commonest reason given for not visiting a dentist during the index pregnancy was the visit not being relevant to their pregnancy outcome (69.2%). After counseling them, only 249 (60.3%) agreed to have dental consultation during subsequent pregnancies. The relationship between visiting the dentist and place of residence (<0.001), occupation (0.019) and frequency of brushing/ changing of brush (0.005, <0.001 respectively) were statistically significant.Conclusion: The prevalence of dental consultations during pregnancy is very low. Pregnant women should be encouraged to have routine dental consultations with oral health counseling and check-up incorporated as part of routine antenatal care.
More rapid intensification of flash droughts with shorter onset timescales
Authors: Qing Yamin , Wang Shuo , Ancell Brian C. , Yang Zong-Liang
Published: March 2021

Flash droughts can cause more serious environmental and agricultural impacts than traditional droughts because of the sudden onset and rapid intensification. However, it remains unclear how rapidly flash droughts develop and intensify worldwide. Here, we present for the first time a comprehensive assessment of the onset development phase of flash droughts on a global scale. We find that humid and semi-humid regions are more vulnerable to flash droughts. And 56.8% of flash droughts are extremely fast-developing (timescale ≤ 15 days) and intensifying (intensification rate ≥ 12.5th percentile) droughts during 2000–2019. More importantly, the evolution of flash droughts is accelerating with a significantly shorter timescale and a faster intensification, implying that less time is left for early warning and impact preparation. Our findings suggest that urgent action is needed to upgrade existing drought monitoring systems for better capturing the more rapid onset and evolution of flash droughts.
Mab-Mig: Registry of the Spanish Neurological Society of Erenumab for Migraine Prevention. Three-Months Results
Authors: Belvís Robert , Irimia Pablo , Pozo-Rosich Patricia , González-Oria Carmen , Cano Antonio , Viguera Javier , Sánchez Belén , Molina Francisco , Río Margarita Sánchez del , Beltran Isabel , Oterino Agustín , Cuadrado Elisa , Gómez-Camello Angel , Alberte-Woodward  , Jurado Carmen , Oms Teresa , Ezpeleta David , de Terán Javier Díaz , Morollón Noemi , Latorre Germán , Torres-Ferrús Marta , Alpuente Alicia , Lamas Raquel , Toledano Carlos , Leira Rogelio , Santos-Lasaosa Sonia
Published: March 2021

Background

Erenumab was approved in Europe for migraine prevention in patients with ≥4 monthly migraine days (MMD). In Spain, Novartis started a personalized managed access program which allowed free access to erenumab before official reimbursement. The Headache Study Group of the Spanish Neurological Society started a registry to monitor real-world safety and efficacy, and all Spanish headache experts were invited to participate.

Methods

Patients fulfilled ICHD3 criteria for migraine and had ≥ 4MMD. Sociodemographic and clinical data were registered as well as MMD, headache frequency (MHD), prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and PROs: HIT6, MIDAS, and PGIC. A >50% reduction of MMD after 3 months was considered as response.

Results

We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 hospitals from February 2019 – to – June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Average of prior preventive treatment failure was >7 (BoNT/A had been used by 95.2%). Most patients (67,6%) started with erenumab 70mg. 61% of patients were also taking oral preventive drugs or getting simultaneous BoNT/A (27.6%). Responder rate was 37.1% and the mean reduction of MMD was -6.28 and MHD: -8.6. Regarding PROs: MIDAS: -35 p., HIT6: -11.6 p., PIGC: 4.7 p. Predictors of good response were: HIT6 score ( p =0.01), prior preventive treatment failures ( p =0.026), absence of MOH ( p =0.039), and simultaneous BoNT/A treatment ( p <0.001). 20% had adverse event, but only two of them were severe (0.9%) which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%).

Conclusion

In real-life, in a personalized managed access program, erenumab shows a good profile of efficacy and an excellent safety in migraine prevention in our cohort of refractory patients.
Stress tolerance enhancement via SPT15 base editing in Saccharomyces cerevisiae
Authors: Liu Yanfang , Lin Yuping , Guo Yufeng , Wu Fengli , Zhang Yuanyuan , Qi Xianni , Wang Zhen , Wang Qin-Hong
Published: March 2021

Background
Saccharomyces cerevisiae is widely used in traditional brewing and modern fermentation industries to produce biofuels, chemicals and other bioproducts, but challenged by various harsh industrial conditions, such as hyperosmotic, thermal and ethanol stresses. Thus, its stress tolerance enhancement has been attracting broad interests. Recently, CRISPR/Cas-based genome editing technology offers unprecedented tools to explore genetic modifications and performance improvement of S. cerevisiae.
Results
Here, we presented that the Target-AID (activation-induced cytidine deaminase) base editor of enabling C-to-T substitutions could be harnessed to generate in situ nucleotide changes on the S. cerevisiae genome, thereby introducing protein point mutation in cells. The general transcription factor gene SPT15 was targeted, and total 36 mutants with diversified stress tolerances were obtained. Among them, the 18 tolerant mutants against hyperosmotic, thermal and ethanol stresses showed more than 1.5-fold increases of fermentation capacities. These mutations were mainly enriched at the N-terminal region and the convex surface of the saddle-shaped structure of Spt15. Comparative transcriptome analysis of three most stress-tolerant (A140G, P169A and R238K) and two most stress-sensitive (S118L and L214V) mutants revealed common and distinctive impacted global transcription reprogramming and transcriptional regulatory hubs in response to stresses, and these five amino acid changes had different effects on the interactions of Spt15 with DNA and other proteins in the RNA Polymerase II transcription machinery according to protein structure alignment analysis.
Conclusions
Taken together, our results demonstrated that the Target-AID base editor provided a powerful tool for targeted in situ mutagenesis in S. cerevisiae and more potential targets of Spt15 residues for enhancing yeast stress tolerance.
Nomogram-Based Prediction of the Risk of Macrosomia: A Prospective Cohort Study in a Chinese Population
Authors: Du Jing , Chai Sanbao , Zhao Xin , Sun Jianbin , Yuan Ning , Yu Xiaofeng , Zhang Qiaoling , Zhang Xiaomei
Published: March 2021

Objective: This study aimed to establish a nomogram for predicting the risk of macrosomia in early pregnancy.Methods: We performed a prospective cohort study involving 1,549 pregnant women. According to the birth weight of newborn, the subjects were divided into two groups: macrosomia group and non-macrosomia group. Multivariate logistic regression was used to analyze the risk factors for macrosomia.Results: The prevalence of macrosomia was 6.13% (95/1549) in our hospital. Multivariate logistic regression analysis showed the risk factors of macrosomia were prepregnancy overweight (OR: 2.126, 95% CI: 1.181-3.826)/obesity (OR: 3.536, 95% CI: 1.555-8.036), multiparity (OR:1.877, 95% CI: 1.160-3.039), the history of macrosomia (OR: 36.971, 95% CI: 19.903-68.674), the history of GDM/DM (OR: 2.285, 95% CI: 1.314-3.976), the higher levels of HbA1c (OR: 1.763, 95% CI: 1.004-3.097) and TC (OR: 1.360, 95% CI: 1.004-1.842). A nomogram was developed for predicting macrosomia based on maternal factors related to the risk of macrosomia in early pregnancy. The area under the receiver operating characteristic (ROC) curve of the nomogram was 0.807 (95% CI: 0.755–0.859), the sensitivity and specificity of the model were 0.716 and 0.777, respectively.Conclusion: The nomogram model provides an accurate mothed for clinicians to early predict macrosomia.