bluuebunny/crossref_metadata_2025 huggingface dataset:
Off-The-Grid Variational Sparse Spike Recovery: Methods and Algorithms
Authors: Laville Bastien , Blanc-Féraud Laure , Aubert Gilles
Published: December 2021

Gridless sparse spike reconstruction is a rather new research field with significant results for the super-resolution problem, where we want to retrieve fine-scale details from a noisy and filtered acquisition. To tackle this problem, we are interested in optimisation under some prior, typically the sparsity i.e., the source is composed of spikes. Following the seminal work on the generalised LASSO for measures called the Beurling-Lasso (BLASSO), we will give a review on the chief theoretical and numerical breakthrough of the off-the-grid inverse problem, as we illustrate its usefulness to the super-resolution problem in Single Molecule Localisation Microscopy (SMLM) through new reconstruction metrics and tests on synthetic and real SMLM data we performed for this review.
Simulation of VVER-1000 Guillotine Large Break Loss of Coolant Accident Using RELAP5/SCDAPSIM/MOD3.5
Authors: Thulu Fabiano Gibson Daud , Elshahat Ayah , H. M. Hassan Mohamed
Published: December 2021

The safety performance of nuclear power plants (NPPs) is a very important factor in evaluating nuclear energy sustainability. Safety analysis of passive and active safety systems have a positive influence on reactor transient mitigation. One of the common transients is primary coolant leg rupture. This study focused on guillotine large break loss of coolant (LB-LOCA) in one of the reactor vessels, in which cold leg rupture occurred, after establishment of a steady-state condition for the VVER-1000. The reactor responses and performance of emergence core cooling systems (ECCSs) were investigated. The main safety margin considered during this simulation was to check the maximum value of the clad surface temperature, and it was then compared with the design licensing limit of 1474 K. The calculations of event progression used the engineering-level RELAP5/SCDAPSIM/MOD3.5 thermal-hydraulic program, which also provide a more detailed treatment of coolant system thermal hydraulics and core behavior. The obtained results show that actuation of ECCSs at their actuation set points provided core cooling by injecting water into the reactor pressure vessel, as expected. The peak cladding temperature did not overpass the licensing limit during this LB-LOCA transient. The primary pressure above the core decreased rapidly from 15.7 MPa to 1 MPa in less than 10 s, then stabilizes up to the end of transient. The fuel temperature decreased from 847 K to 378 K during the first 30 s of the transient time. The coolant leakage reduced from 9945 kg/s to approximately 461 kg/s during the first 190 s in the transient. Overall, the study shows that, within the design of the VVER-1000, safety systems of the have inherent robustness of containing guillotine LB-LOCA.
The Nanotheranostic Researcher’s Guide for Use of Animal Models of Traumatic Brain Injury
Authors: McDonald Brandon Z. , Gee Connor C. , Kievit Forrest M.
Published: December 2021

Traumatic brain injury (TBI) is currently the leading cause of injury-related morbidity and mortality worldwide, with an estimated global cost of USD 400 billion annually. Both clinical and preclinical behavioral outcomes associated with TBI are heterogeneous in nature and influenced by the mechanism and frequency of injury. Previous literature has investigated this relationship through the development of animal models and behavioral tasks. However, recent advancements in these methods may provide insight into the translation of therapeutics into a clinical setting. In this review, we characterize various animal models and behavioral tasks to provide guidelines for evaluating the therapeutic efficacy of treatment options in TBI. We provide a brief review into the systems utilized in TBI classification and provide comparisons to the animal models that have been developed. In addition, we discuss the role of behavioral tasks in evaluating outcomes associated with TBI. Our goal is to provide those in the nanotheranostic field a guide for selecting an adequate TBI animal model and behavioral task for assessment of outcomes to increase research in this field.
Association of Thyroid Function with Blood Pressure and Cardiovascular Disease: A Mendelian Randomization
Authors: Giontella Alice , Lotta Luca A. , Overton John D. , Baras Aris ,   on behalf of Regeneron Genetics Center, Sartorio Andrea , Minuz Pietro , Gill Dipender , Melander Olle , Fava Cristiano
Published: December 2021

Thyroid function has a widespread effect on the cardiometabolic system. However, the causal association between either subclinical hyper- or hypothyroidism and the thyroid hormones with blood pressure (BP) and cardiovascular diseases (CVD) is not clear. We aim to investigate this in a two-sample Mendelian randomization (MR) study. Single nucleotide polymorphisms (SNPs) associated with thyroid-stimulating hormone (TSH), free tetraiodothyronine (FT4), hyper- and hypothyroidism, and anti-thyroid peroxidase antibodies (TPOAb), from genome-wide association studies (GWAS), were selected as MR instrumental variables. SNPs–outcome (BP, CVD) associations were evaluated in a large-scale cohort, the Malmö Diet and Cancer Study (n = 29,298). Causal estimates were computed by inverse-variance weighted (IVW), weighted median, and MR-Egger approaches. Genetically increased levels of TSH were associated with decreased systolic BP and with a lower risk of atrial fibrillation. Hyperthyroidism and TPOAb were associated with a lower risk of atrial fibrillation. Our data support a causal association between genetically decreased levels of TSH and both atrial fibrillation and systolic BP. The lack of significance after Bonferroni correction and the sensitivity analyses suggesting pleiotropy, should prompt us to be cautious in their interpretation. Nevertheless, these findings offer mechanistic insight into the etiology of CVD. Further work into the genes involved in thyroid functions and their relation to cardiovascular outcomes may highlight pathways for targeted intervention.
Transdermal Electrical Neuromodulation for Anxiety and Sleep Problems in High-Functioning Autism Spectrum Disorder: Feasibility and Preliminary Findings
Authors: Foldes Stephen T. , Jensen Amanda R. , Jacobson Austin , Vassall Sarah , Foldes Emily , Guthery Ann , Brown Danni , Levine Todd , Tyler William James , Frye Richard E.
Published: December 2021

Background: Autism spectrum disorder (ASD) is associated with anxiety and sleep problems. We investigated transdermal electrical neuromodulation (TEN) of the cervical nerves in the neck as a safe, effective, comfortable and non-pharmacological therapy for decreasing anxiety and enhancing sleep quality in ASD. Methods: In this blinded, sham-controlled study, seven adolescents and young adults with high-functioning ASD underwent five consecutive treatment days, one day of the sham followed by four days of subthreshold TEN for 20 min. Anxiety-provoking cognitive tasks were performed after the sham/TEN. Measures of autonomic nervous system activity, including saliva α-amylase and cortisol, electrodermal activity, and heart rate variability, were collected from six participants. Results: Self-rated and caretaker-rated measures of anxiety were significantly improved with TEN treatment as compared to the sham, with effect sizes ranging from medium to large depending on the rating scale. Sleep scores from caretaker questionnaires also improved, but not significantly. Performance on two of the three anxiety-provoking cognitive tasks and heart rate variability significantly improved with TEN stimulation as compared to the sham. Four of the seven (57%) participants were responders, defined as a ≥ 30% improvement in self-reported anxiety. Salivary α-amylase decreased with more TEN sessions and decreased from the beginning to the end of the session on TEN days for responders. TEN was well-tolerated without significant adverse events. Conclusions: This study provides preliminary evidence that TEN is well-tolerated in individuals with ASD and can improve anxiety.
Influence of Deep Neuromuscular Blockade on Perioperative Stress Response in Patients Undergoing Robot-Assisted Gastrectomy: A Prospective Double-Blinded Randomized-Controlled Trial
Authors: Kim Myoung Hwa , Kim Na Young , Yoo Young Chul , Kong Hee Jung , Lee Hye Sun , Jo Arim , Bai Sun Joon
Published: December 2021

Attenuating the intraoperative stress response is crucial; however, the effect of neuromuscular blockade (NMB) on surgical stress is not completely understood. We aimed to investigate the effects of NMB on the perioperative stress response during robot-assisted gastrectomy. Patients were assigned to the deep or moderate NMB group. Serum cortisol, prolactin, and interleukin-6 (IL-6) levels and natural killer (NK) cell percentage were measured before anesthesia induction, 90 min after pneumoperitoneum, operation end (OPEnd), and postoperative day 1. Additionally, C-reactive protein (CRP) and albumin levels were estimated. Additionally, intraoperative heart rate variability was evaluated. The deep NMB group showed significantly lower levels of low-frequency/high-frequency (HF) ratio at OPEnd compared to the moderate NMB group (1.4 ± 0.2 vs. 2.2 ± 0.3, respectively; Bonferroni corrected p = 0.039). Furthermore, HF power in the deep NMB group was significantly higher at OPEnd than that in the moderate NMB group (45.2 ± 3.6 vs. 33.8 ± 4.0, respectively; Bonferroni corrected p = 0.044). However, no significant differences in cortisol, prolactin, IL-6, CRP, and albumin levels and NK cell percentage were found between the two groups. The degree of NMB may have similar effects on stress-related biological markers in patients undergoing robot-assisted gastrectomy.
Ultra-Hypofractionated Proton Therapy in Localized Prostate Cancer: Passive Scattering versus Intensity-Modulated Proton Therapy
Authors: Borowicz Dorota Maria , Shipulin Konstantin N. , Mytsin Gennady V. , Skrobała Agnieszka , Milecki Piotr , Gayevsky Victor N. , Vondráček Vladimir , Malicki Julian
Published: December 2021

Few studies have directly compared passive scattering (PS) to intensity-modulated proton therapy (IMPT) in the delivery of ultra-hypofractionated proton beams to the localized prostate cancer (PCa). In this preliminary study involving five patients previously treated with CyberKnife, treatment plans were created for PS and IMPT (36.25 CGE in five fractions with two opposing fields) to compare the dosimetric parameters to the planning target volume (PTV) and organs-at-risk (OAR: rectum, bladder, femoral heads). Both plans met the acceptance criteria. Significant differences were observed in the minimum and maximum doses to the PTV. The mean dose to the PTV was lower for PS (35.62 ± 0.26 vs. 37.18 ± 0.14; p = 0.002). Target coverage (D98%) was better for IMPT (96.79% vs. 99.10%; p = 0.004). IMPT resulted in significantly lower mean doses to the rectum (16.75 CGE vs. 6.88 CGE; p = 0.004) and bladder (17.69 CGE vs. 5.98 CGE p = 0.002). High dose to the rectum (V36.25 CGE) were lower with PS, but not significantly opposite to high dose to the bladder. No significant differences were observed in mean conformity index values, with a non-significant trend towards higher mean homogeneity index values for PS. Non-significant differences in the gamma index for both fields were observed. These findings suggest that both PS and IMPT ultra-hypofractionated proton therapy for PCa are highly precise, offering good target coverage and sparing of normal tissues and OARs.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 7: PD-L1 Expression in Liquid Biopsy
Authors: Palicelli Andrea , Bonacini Martina , Croci Stefania , Bisagni Alessandra , Zanetti Eleonora , De Biase Dario , Sanguedolce Francesca , Ragazzi Moira , Zanelli Magda , Chaux Alcides , Cañete-Portillo Sofia , Bonasoni Maria Paola , Ascani Stefano , De Leo Antonio , Gandhi Jatin , Tafuni Alessandro , Melli Beatrice
Published: December 2021

Liquid biopsy is an accessible, non-invasive diagnostic tool for advanced prostate cancer (PC) patients, potentially representing a real-time monitoring test for tumor evolution and response to treatment through the analysis of circulating tumor cells (CTCs) and exosomes. We performed a systematic literature review (PRISMA guidelines) to describe the current knowledge about PD-L1 expression in liquid biopsies of PC patients: 101/159 (64%) cases revealed a variable number of PD-L1+ CTCs. Outcome correlations should be investigated in larger series. Nuclear PD-L1 expression by CTCs was occasionally associated with worse prognosis. Treatment (abiraterone, enzalutamide, radiotherapy, checkpoint-inhibitors) influenced PD-L1+ CTC levels. Discordance in PD-L1 status was detected between primary vs. metastatic PC tissue biopsies and CTCs vs. corresponding tumor tissues. PD-L1 is also released by PC cells through soluble exosomes, which could inhibit the T cell function, causing immune evasion. PD-L1+ PC-CTC monitoring and genomic profiling may better characterize the ongoing aggressive PC forms compared to PD-L1 evaluation on primary tumor biopsies/prostatectomy specimens (sometimes sampled a long time before recurrence/progression). Myeloid-derived suppressor cells and dendritic cells (DCs), which may have immune-suppressive effects in tumor microenvironment, have been found in PC patients circulation, sometimes expressing PD-L1. Occasionally, their levels correlated to clinical outcome. Enzalutamide-progressing castration-resistant PC patients revealed increased PD-1+ T cells and circulating PD-L1/2+ DCs.
Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research
Authors: Filby Caitlin E. , Wyatt Katherine A. , Mortlock Sally , Cousins Fiona L. , McKinnon Brett , Tyson Kate E. , Montgomery Grant W. , Gargett Caroline E.
Published: December 2021

Endometrial organoids (EMO) are an important tool for gynecological research but have been limited by generation from (1) invasively acquired tissues and thus advanced disease states and (2) from women who are not taking hormones, thus excluding 50% of the female reproductive-aged population. We sought to overcome these limitations by generating organoids from (1) menstrual fluid (MF; MFO) using a method that enables the concurrent isolation of menstrual fluid supernatant, stromal cells, and leukocytes and (2) from biopsies and hysterectomy samples from women taking hormonal medication (EMO-H). MF was collected in a menstrual cup for 4–6 h on day 2 of menstruation. Biopsies and hysterectomies were obtained during laparoscopic surgery. Organoids were generated from all sample types, with MFO and EMO-H showing similar cell proliferation rates, proportion and localization of the endometrial basalis epithelial marker, Stage Specific Embryonic Antigen-1 (SSEA-1), and gene expression profiles. Organoids from different disease states showed the moderate clustering of epithelial secretory and androgen receptor signaling genes. Thus, MFO and EMO-H are novel organoids that share similar features to EMO but with the advantage of (1) MFO being obtained non-invasively and (2) EMO-H being obtained from 50% of the women who are not currently being studied through standard methods. Thus, MFO and EMO-H are likely to prove to be invaluable tools for gynecological research, enabling the population-wide assessment of endometrial health and personalized medicine.
Correlation between Post-Acute Electroconvulsive Therapy Alpha-Band Spectrum Power Increase and Improvement of Psychiatric Symptoms
Authors: Iwanaga Hideyuki , Ueno Takefumi , Oribe Naoya , Hashimoto Manabu , Nishimura Jun , Nakayama Naho , Haraguchi Nami , Tateishi Hiroshi , Kunitake Yutaka , Mizoguchi Yoshito , Monji Akira
Published: December 2021

The results of quantitative electroencephalography (qEEG) studies on electroconvulsive therapy (ECT) have been inconsistent, and indicators of the efficacy of ECT have not been clearly identified. In this study, we examined whether qEEG could be used as an indicator of the effect of ECT by measuring it during the course of treatment. We analyzed qEEG data before and after acute-phase ECT in 18 patients with schizophrenia, mood disorders, and other psychiatric disorders. We processed the qEEG data and compared the spectral power between the data acquired before and after ECT. The spectral power increased significantly after ECT in the delta, theta, and alpha bands. There was a strong significant correlation between the increase in the spectral power of the alpha band after acute ECT and improvement in the Brief Psychiatric Rating Scale score. Our results suggest that an increase in the alpha-band spectral power may be useful as an objective indicator of the treatment effect of acute ECT.
Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study
Authors: de Rojas Itziar , Hernández Isabel , Montrreal Laura , Quintela Inés , Calero Miguel , Royo Jose Luís , Huerto Vilas Raquel , González-Pérez Antonio , Franco-Macías Emilio , Macías Juan , Menéndez-González Manuel , Frank-García Ana , Diez-Fairen Mónica , Lage Carmen , García-Madrona Sebastián , Aguilera Nuria , García-González Pablo , Puerta Raquel , Sotolongo-Grau Oscar , Alonso-Lana Silvia , Rábano Alberto , Arias Pastor Alfonso , Pastor Ana Belén , Corma-Gómez Anaïs , Martín Montes Angel , Martínez Rodríguez Carmen , Buiza-Rueda Dolores , Periñán Maria Teresa , Rodriguez-Rodriguez Eloy , Alvarez Ignacio , Rosas Allende Irene , Pineda Juan A. , Bernal Sánchez-Arjona María , Fernández-Fuertes Marta , Mendoza Silvia , del Ser Teodoro ,   GR@ACE/DEGESCO Consortium, Garcia-Ribas Guillermo , Sánchez-Juan Pascual , Pastor Pau , Bullido María J. , Álvarez Victoria , Real Luis M. , Mir Pablo , Piñol-Ripoll Gerard , García-Alberca Jose María , Medina Miguel , Orellana Adelina , Butler Chris R. , Marquié Marta , Sáez María Eugenia , Carracedo Ángel , Tárraga Lluís , Boada Mercè , Ruiz Agustín
Published: December 2021

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis.
Restoration of Normal NF1 Function with Antisense Morpholino Treatment of Recurrent Pathogenic Patient-Specific Variant c.1466A>G; p.Y489C
Authors: Awad Elias K. , Moore Marc , Liu Hui , Ciszewski Lukasz , Lambert Laura , Korf Bruce R. , Popplewell Linda , Kesterson Robert A. , Wallis Deeann
Published: December 2021

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with almost 3000 different disease-causing variants within the NF1 gene identified. Up to 44% of these variants cause splicing errors to occur within pre-mRNA. A recurrent variant in exon 13, c.1466A>G; p.Y489C (Y489C) results in the creation of an intragenic cryptic splice site, aberrant splicing, a 62 base pair deletion from the mRNA, and subsequent frameshift. We investigated the ability of phosphorodiamidate morpholino oligomers (PMOs) to mask this variant on the RNA level, thus restoring normal splicing. To model this variant, we have developed a human iPS cell line homozygous for the variant using CRISPR/Cas9. PMOs were designed to be 25 base pairs long, and to cover the mutation site so it could not be read by splicing machinery. Results from our in vitro testing showed restoration of normal splicing in the RNA and restoration of full length neurofibromin protein. In addition, we observe the restoration of neurofibromin functionality through GTP-Ras and pERK/ERK testing. The results from this study demonstrate the ability of a PMO to correct splicing errors in NF1 variants at the RNA level, which could open the door for splicing corrections for other variants in this and a variety of diseases.
Genetic Markers as Risk Factors for the Development of Impulsive-Compulsive Behaviors in Patients with Parkinson’s Disease Receiving Dopaminergic Therapy
Authors: Fedosova Anna , Titova Nataliya , Kokaeva Zarema , Shipilova Natalia , Katunina Elena , Klimov Eugene
Published: December 2021

Impulsive–compulsive and related behavioral disorders (ICD) are drug-induced non-motor symptoms of Parkinson’s disease (PD). Recently research has focused on evaluating whether ICD could be predicted and managed using a pharmacogenetic approach based on dopaminergic therapies, which are the main risk factors. The aim of our study was to evaluate the role of candidate genes such as DBH, DRD2, MAOA, BDNF, COMT, SLC6A4, SLC6A3, ACE, DRD1 gene polymorphisms in the pathogenesis of ICD in PD. We compared patients with PD and ICD (n = 49), patients with PD without ICD (n = 36) and a healthy control group (n = 365). ICD was diagnosed using the QUIP questionnaires and specific diagnostic criteria for subtypes of ICD. Genotyping was conducted using a number of PCR techniques and SNaPshot. Statistical analysis was performed using WinPepi and APSampler v3.6 software. PCA testing was conducted using RStudio software v1.4.1106-5. The following substitutions showed statistically significant correlations with PD and ICD: DBH (rs2097629, rs1611115), DRD2 (rs6275, rs12364283, rs1076560), ACE (rs4646994), DRD1 (rs686), BDNF (rs6265), these associations are novel in Russian PD patients. Our findings suggest that polymorphisms in DBH, BDNF, DRD2, ACE genes in Russian subjects are associated with an increased risk of ICD development.
Escalation Time to Open Triple Combination Therapy from the Initiation of LAMA versus ICS/LABA in COPD Management: Findings from Comparing the Incidence of Tiotropium and ICS/LABA in Real-World Use in South Korea (CITRUS) Study
Authors: Lee Ye Jin , Rhee Chin Kook , Hwang Yong Il , Yoo Kwang Ha , Lee So Eun , Lee Doik , Park Yong Bum , Kim Youlim
Published: December 2021

Background: bronchodilators are the key treatment for chronic obstructive pulmonary disease (COPD), however, inhaled corticosteroids (ICSs)/long-acting β2-agonists (LABA) are widely prescribed. We compared the escalation time to open triple combination therapy between long-acting muscarinic receptor antagonists (LAMA) and ICS/LABA in COPD management. Methods: this retrospective study included COPD patients selected from the National Health Insurance Service of South Korea from January 2005 to April 2015. The primary outcome was the escalation time to triple therapy in patients who initially received LAMA or ICS/LABA. Other outcomes included risk factors predisposing escalation to triple combination therapy. Results: a total of 2444 patients were assigned to the LAMA or ICS/LABA groups. The incidences of triple combination therapy in the LAMA and ICS/LABA groups were 81.0 and 139.8 per 1000 person-years, respectively (p < 0.001); the median times to triple therapy escalation were 281 and 207 days, respectively (p = 0.03). Treatment with ICS/LABA showed a higher risk of triple therapy escalation compared to LAMA (hazard ratio (HR), 1.601; 95% confidence interval (CI), 1.402–1.829). The associated risk factor was male sex. (HR, 1.564; 95% CI, 1.352–1.809). Conclusions: the initiation of COPD treatment with LAMA is associated with a reduced escalation time to triple therapy compared with ICS/LABA.
Digitalization of Institutions of Corporate Law: Current Trends and Future Prospects
Authors: Laptev Vasiliy Andreevich , Feyzrakhmanova Daria Rinatovna
Published: December 2021

Digital technologies have been integrated into all aspects of public life, including politics, law, finance, business, education, science, and society. As a result of the use of digital technologies by various subjects, a transformation has occurred of the economic relations existing in society, including corporate relations. This study analyzes the impact of digitalization on individual institutions of corporate law. The authors investigate the following aspects of the digitalization of corporate law: (1) digital legal personality of the corporation (online registration (e-residency) of corporations and the digital footprint that companies leave in public registers); (2) digital corporate governance; and (3) digital (network or decentralized) autonomous organizations. The purpose of this research is to identify trends and directions of transformation of individual institutions of corporate law in a digital society. The authors conclude that the digitalization of institutions of corporate law will result in: (1) the reinterpretation of certain concepts of corporate law, such as corporation and corporate governance; (2) the improvement of the legal mechanisms of corporate governance following the introduction of AI into the collegial executive bodies of corporations; (3) the digitalization of corporate assets; and (4) the emergence of new subjects of corporate and other relevant relations.
The Role of Pediatric Nutrition as a Modifiable Risk Factor for Precocious Puberty
Authors: Calcaterra Valeria , Verduci Elvira , Magenes Vittoria Carlotta , Pascuzzi Martina Chiara , Rossi Virginia , Sangiorgio Arianna , Bosetti Alessandra , Zuccotti Gianvincenzo , Mameli Chiara
Published: December 2021

Puberty is a critical phase of growth and development characterized by a complex process regulated by the neuroendocrine system. Precocious puberty (PP) is defined as the appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal. The timing of puberty has important public health, clinical, and social implications. In fact, it is crucial in psychological and physical development and can impact future health. Nutritional status is considered as one of the most important factors modulating pubertal development. This narrative review presents an overview on the role of nutritional factors as determinants of the timing of sexual maturation, focusing on early-life and childhood nutrition. As reported, breast milk seems to have an important protective role against early puberty onset, mainly due to its positive influence on infant growth rate and childhood overweight prevention. The energy imbalance, macro/micronutrient food content, and dietary patterns may modulate the premature activation of the hypothalamic–pituitary–gonadal axis, inducing precocious activation of puberty. An increase in knowledge on the mechanism whereby nutrients may influence puberty will be useful in providing adequate nutritional recommendations to prevent PP and related complications.
Antibacterial Polymers Based on Poly(2-hydroxyethyl methacrylate) and Thiazolium Groups with Hydrolytically Labile Linkages Leading to Inactive and Low Cytotoxic Compounds
Authors: Cuervo-Rodríguez Rocío , López-Fabal Fátima , Muñoz-Bonilla Alexandra , Fernández-García Marta
Published: December 2021

Herein, we develop a well-defined antibacterial polymer based on poly(2-hydroxyethyl methacrylate) (PHEMA) and a derivative of vitamin B1, easily degradable into inactive and biocompatible compounds. Hence, thiazole moiety was attached to HEMA monomer through a carbonate pH-sensitive linkage and the resulting monomer was polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. N-alkylation reaction of the thiazole groups leads to cationic polymer with thiazolium groups. This polymer exhibits excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with an MIC value of 78 µg mL−1, whereas its degradation product, thiazolium small molecule, was found to be inactive. Hemotoxicity studies confirm the negligible cytotoxicity of the degradation product in comparison with the original antibacterial polymer. The degradation of the polymer at physiological pH was found to be progressive and slow, thus the cationic polymer is expected to maintain its antibacterial characteristics at physiological conditions for a relative long period of time before its degradation. This degradation minimizes antimicrobial pollution in the environment and side effects in the body after eradicating bacterial infection.
Effects of Steel Fibers (SF) and Ground Granulated Blast Furnace Slag (GGBS) on Recycled Aggregate Concrete
Authors: Ahmad Jawad , Martínez-García Rebeca , Szelag Maciej , de-Prado-Gil Jesús , Marzouki Riadh , Alqurashi Muwaffaq , Hussein Enas E.
Published: December 2021

Recycled aggregate is a good option to be used in concrete production as a coarse aggregate that results in environmental benefits as well as sustainable development. However, recycled aggregate causes a reduction in the mechanical and durability performance of concrete. On the other hand, the removal of industrial waste would be considerably decreased if it could be incorporated into concrete production. One of these possibilities is the substitution of the cement by slag, which enhances the concrete poor properties of recycled aggregate concrete as well as provides a decrease in cement consumption, reducing carbon dioxide production, while resolving a waste management challenge. Furthermore, steel fiber was also added to enhance the tensile capacity of recycled aggregate concrete. The main goal of this study was to investigate the characteristics of concrete using ground granulated blast-furnace slag (GGBS) as a binding material on recycled aggregate fibers reinforced concrete (RAFRC). Mechanical performance was assessed through compressive strength and split tensile strength, while durability aspects were studied through water absorption, acid resistance, and dry shrinkage. The results detected from the different experiments depict that, at an optimum dose (40% RCA, 20%GGBS, and 2.0%), compressive and split tensile strength were 39% and 120% more than the reference concrete, respectively. Furthermore, acid resistance at the optimum dose was 36% more than the reference concrete. Furthermore, decreased water absorption and dry shrinkage cracks were observed with the substitution of GGBS into RAFRC.
Methods of Ensuring Invariance with Respect to External Disturbances: Overview and New Advances
Authors: Antipov Aleksey , Krasnova Svetlana , Utkin Victor
Published: December 2021

In this paper, we carry out a demonstration and comparative analysis of known methods of the synthesis of various control laws ensuring the invariance of the output (controlled) variable with respect to external disturbances under various assumptions about their type and channels of acting on the control plant. Methods of the synthesis are presented on the example of a third-order nonlinear system with single input and single output (SISO-systems), dynamic feedback synthesis is presented at a descriptive level and the focus is on procedures of static feedback synthesis. For the systems in which the matching conditions are not satisfied, it is concluded that it is expedient to introduce smooth and bounded nonlinear local feedbacks. Within the framework of the block control principle, we developed an iterative procedure of synthesis of S-shaped sigmoid feedbacks for such systems. Nonlinear local feedbacks ensure stabilization of the output variable with the given accuracy and settling time as in a system with traditionally used linear local feedbacks with high gains. However, in contrast to it, sigmoid functions do not lead to a large overshoot of state variables and control actions.
BRAF, MEK, and EGFR Triplet Inhibitors as Salvage Therapy in BRAF-Mutated Metastatic Colorectal Cancer—A Case Series Study Target Therapy of BRAF-Mutated mCRC
Authors: Yeh Jen-Hao , Tsai Hsiang-Lin , Chen Yen-Cheng , Li Ching-Chun , Huang Ching-Wen , Chang Tsung-Kun , Su Wei-Chih , Chen Po-Jung , Liu Yu-Peng , Wang Jaw-Yuan
Published: December 2021

Backgroundand objectives: Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. The real-world effects of triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in Asia have not been well-reported. Materials and Methods: This single-center case series included patients with BRAF-mutated metastatic colorectal cancer undergoing triplet therapy after failure of prior systemic treatment from 2016 to 2020. The primary outcome was progression-free survival, and secondary outcomes were overall survival, response rate, disease control rate, and adverse events. Results: Nine eligible patients with BRAF-mutated metastatic colorectal cancer receiving triplet therapy were enrolled, with a median follow-up time of 14.5 months (range, 1–26). Most patients (88.8%) had two or more prior systemic treatments, and the triplet regimen was mainly dabrafenib, trametinib, and panitumumab. The overall response rate and disease control rate were 11.1% and 33.3%, respectively. Median progression-free survival and overall survival were 2.9 and 7.4 months, respectively, and a trend toward better overall survival was found with left-sided metastatic colorectal cancer compared with right-sided disease (9.2 vs. 6.9 months, p = 0.093). Adverse events were mostly Grade 1–2, including nausea, hypertension, gastrointestinal symptoms, and skin disorders. Conclusions: In this single-center case series, triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in BRAF-mutated metastatic colorectal cancer had an acceptable safety profile and reasonable efficacy.
Geometrical Influence on Particle Transport in Cross-Flow Ultrafiltration: Cylindrical and Flat Sheet Membranes
Authors: Park Gun Woo , Nägele Gerhard
Published: December 2021

Cross-flow membrane ultrafiltration (UF) is used for the enrichment and purification of small colloidal particles and proteins. We explore the influence of different membrane geometries on the particle transport in, and the efficiency of, inside-out cross-flow UF. For this purpose, we generalize the accurate and numerically efficient modified boundary layer approximation (mBLA) method, developed in recent work by us for a hollow cylindrical membrane, to parallel flat sheet geometries with one or two solvent-permeable membrane sheets. Considering a reference dispersion of Brownian hard spheres where accurate expressions for its transport properties are available, the generalized mBLA method is used to analyze how particle transport and global UF process indicators are affected by varying operating parameters and the membrane geometry. We show that global process indicators including the mean permeate flux, the solvent recovery indicator, and the concentration factor are strongly dependent on the membrane geometry. A key finding is that irrespective of the many input parameters characterizing an UF experiment and its membrane geometry, the process indicators are determined by three independent dimensionless variables only. This finding can be very useful in the design, optimization, and scale-up of UF processes.
Effect of Nanopatterning on Concentration Polarization during Nanofiltration
Authors: Ward Lauren M. , Fickling Barbara G. , Weinman Steven T.
Published: December 2021

Membranes used for desalination still face challenges during operation. One of these challenges is the buildup of salt ions at the membrane surface. This is known as concentration polarization, and it has a negative effect on membrane water permeance and salt rejection. In an attempt to decrease concentration polarization, a line-and-groove nanopattern was applied to a nanofiltration (NF) membrane. Aqueous sodium sulfate (Na2SO4) solutions were used to test the rejection and permeance of both pristine and patterned membranes. It was found that the nanopatterns did not reduce but increased the concentration polarization at the membrane surface. Based on these studies, different pattern shapes and sizes should be investigated to gain a fundamental understanding of the influence of pattern size and shape on concentration polarization.
Kinetic and Thermodynamic Studies of Lysozyme Adsorption on Cibacron Blue F3GA Dye-Ligand Immobilized on Aminated Nanofiber Membrane
Authors: Hsin Ai , How Su-Chun , Wang Steven , Ooi Chien , Chiu Chen-Yaw , Chang Yu-Kaung
Published: December 2021

The polyacrylonitrile (PAN) nanofiber membrane was prepared by the electrospinning technique. The nitrile group on the PAN nanofiber surface was oxidized to carboxyl group by alkaline hydrolysis. The carboxylic group on the membrane surface was then converted to dye affinity membrane through reaction with ethylenediamine (EDA) and Cibacron Blue F3GA, sequentially. The adsorption characteristics of lysozyme onto the dye ligand affinity nanofiber membrane (namely P-EDA-Dye) were investigated under various conditions (e.g., adsorption pH, EDA coupling concentration, lysozyme concentration, ionic strength, and temperature). Optimum experimental parameters were determined to be pH 7.5, a coupling concentration of EDA 40 μmol/mL, and an immobilization density of dye 267.19 mg/g membrane. To understand the mechanism of adsorption and possible rate controlling steps, a pseudo first-order, a pseudo second-order, and the Elovich models were first used to describe the experimental kinetic data. Equilibrium isotherms for the adsorption of lysozyme onto P-EDA-Dye nanofiber membrane were determined experimentally in this work. Our kinetic analysis on the adsorption of lysozyme onto P-EDA-Dye nanofiber membranes revealed that the pseudo second-order rate equation was favorable. The experimental data were satisfactorily fitted by the Langmuir isotherm model, and the thermodynamic parameters including the free energy change, enthalpy change, and entropy change of adsorption were also determined accordingly. Our results indicated that the free energy change had a negative value, suggesting that the adsorption process occurred spontaneously. Moreover, after five cycles of reuse, P-EDA-Dye nanofiber membranes still showed promising efficiency of lysozyme adsorption.
The Corrosion and Wear Behaviors of a Medium-Carbon Bainitic Steel Treated by Boro-Austempering Process
Authors: Liu Man , Wang Wei , Hu Haijiang , Cai Feng , Liu Sheng , Xu Guang
Published: December 2021

The effects of boro-austempering treatment on growth kinetics of borided layers, microstructure, and properties in a medium-carbon bainitic steel were investigated. The microstructure, distribution in coatings, corrosion, and wear properties of boro-austempered steels were characterized by a microscope, field-emission electron probe micro analyzer, scanning vibrating electrode technique system and wear resistance machine. The results show that the corrosion resistance of steels in different corrosive mediums was significantly enhanced by boro-austempering treatment. In addition, the wear performance of borided layers was improved by more than two times compared to bainitic substrates, proving a better wear property of samples treated through the boro-austempering route. The solubility of carbon and silicon in borides is very little. In addition, the dual-phase coating of FeB and Fe2B was observed, and the internal stress induced during the growth of Fe2B and FeB was almost eliminated. The preferential crystallographic growth directions of Fe2B and FeB are [001] and [010], respectively, which belongs to the (100) plane. Finally, the kinetics equation d2 = 0.125·t of the borided layers at 1223 K was established.
Practical Approbation of Thermodynamic Criteria for the Consolidation of Bimetallic and Functionally Gradient Materials
Authors: Khaimovich Alexander , Erisov Yaroslav , Agapovichev Anton , Shishkovsky Igor , Smelov Vitaliy , Razzhivin Vasilii
Published: December 2021

This study concerns the key problem of determining the conditions for the consolidation or fracture of bimetallic compounds and high-gradient materials with different coefficients of thermal expansion. The well-known approach to determining the strength is based on the assessment of the critical energy release rates during fracture, depending on the conditions of loading (the portion of shear loading). Unfortunately, most of the experimental results cannot be used directly to select suitable fracture toughness criteria before such a connection is made. This especially applies to the region of interphase interaction, when it is required to estimate the internal energy of destruction accumulated during the preparation of the joint in the adhesion layer within the range of 20–50 μm. Hence, criteria for the adhesive consolidation of bimetallic compound layers were obtained on the basis of the thermodynamics of nonequilibrium processes. The analysis of the quality of the joint using the obtained criteria was carried out on the basis of the calculation of isochoric and isobaric heat capacities and coefficients of thermal expansion of multiphase layers. The applicability of the criteria for the qualitative assessment of the adhesion of layers is demonstrated in the example of bimetallic joints of steel 316L—aluminum alloy AlSi10Mg obtained by the SLM method at various fusion modes.
Influence of LPBF-Surface Characteristics on Fatigue Properties of Scalmalloy®
Authors: Musekamp Jens , Reiber Thorsten , Hoche Holger Claus , Oechsner Matthias , Weigold Matthias , Abele Eberhard
Published: December 2021

Laser powder bed fusion (LPBF) has indisputable advantages when designing new components with complex geometries due to toolless manufacturing and the ability to manufacture components with undercuts. However, fatigue properties rely heavily on the surface condition. In this work, in-process surface parameters (three differing contour parameter sets) and post-process surface treatments, namely turning and shot peening, are varied to investigate the influence of each treatment on the resulting fatigue properties of LPBF-manufactured specimens of the aluminium–magnesium–scandium alloy Scalmalloy®. Therefore, metallographic analysis and surface roughness measurements, as well as residual stress measurements, computer tomography measurements, SEM-analyses, tensile and fatigue tests, along with fracture surface analysis, were performed. Despite the fact that newly developed in-process contour parameters are able to reduce the surface roughness significantly, only a minor improvement in fatigue properties could be observed: Crack initiation is caused by sharp, microscopic notches at the surface in combination with high tensile residual stresses at the surface, which are present on all in-process contour parameter specimens. Specimens using contour parameters with high line energy show keyhole pores localized in the subsurface area, which have no effect on crack initiation. Contours with low line energy have a slightly positive effect on fatigue strength because less pores can be found at the surface and subsurface area, which even more greatly promotes an early crack initiation. The post-process parameter sets, turning and shot peening, both improve fatigue behaviour significantly: Turned specimens show lowest surface roughness, while, for shot peened specimens, the tensile residual stresses of the surface radially shifted from the surface towards the centre of the specimens, which counteracts the crack initiation at the surface.
An Investigation of Atomic Interaction between Ag and Ti2AlC under the Processing Temperature of 1080 °C
Authors: Wang Guochao , Li Yafei , Chen Weijian , Yang Jianguo , Zhang Jie , He Yanming
Published: December 2021

Ti2AlC is a typical MAX (M: early transition metal, A: main group element, and X: carbon and/or nitrogen) phase with ceramic and metallic properties due to its unique nano-layered structure. In order to investigate the interaction behavior between Ag and Ti2AlC, a sessile drop experiment was conducted at 1080 °C for 5 min. The atomic rearrangement occurred at the Ag–Ti2AlC interface was revealed using high-angle annular dark-field scanning transmission electron microscopy coupled with high-resolution transmission electron microscopy analysis. The results show that Ag nanoclusters generally appeared in most of the Ag–Ti2AlC interaction regions thermally processed at 1080 °C. In addition, Ag can also substitute for Al and Ti atoms in the Ti2AlC, promoting local structural decomposition of the Ti2AlC and producing 4H–Ag with a hexagonal close-packed (hcp) structure. Additionally, Al atoms released from the Ti2AlC lattices can dissolve locally into the liquid Ag, particularly at the grain boundaries. When the loss concentration of Al exceeded the critical level, the Ti2AlC started to decompose and the residual Ti6C octahedrons and Al atoms recombined, giving rise to the production of anti-perovskite Ti3AlC with a cubic structure. Lastly, the discrepancy in substitution behavior of Ag in the Ti2AlC was compared when thermally processed at different temperatures (1030 °C and 1080 °C). This work contributes to the understanding of the intrinsic stability of Ti2AlC MAX ceramics under high-temperature treatment.
Researching a Moving Target Detection Method Based on Magnetic Flux Induction Technology
Authors: Xu Chaoqun , Yang Li , Huang Kui , Gao Yang , Zhang Shaohua , Gao Yuting , Meng Lifei , Xiao Qi , Liu Chaobo , Wang Bin , Yi Zhong
Published: December 2021

The ocean is a very important arena in modern warfare where all marine powers deploy their military forces. Due to the complex environment of the ocean, underwater equipment has become a very threatening means of surprise attack in modern warfare. Therefore, the timely and effective detection of underwater moving targets is the key to obtaining warfare advantages and has important strategic significance for national security. In this paper, magnetic flux induction technology was studied with regard to the difficulty of detecting underwater concealed moving targets. Firstly, the characteristics of a magnetic target were analyzed and an equivalent magnetic dipole model was established. Secondly, the structure of the rectangular induction coil was designed according to the model, and the relationship between the target’s magnetism and the detection signal was deduced. The variation curves of the magnetic flux and the electromotive force induced in the coil were calculated by using the numerical simulation method, and the effects of the different motion parameters of the magnetic dipole and the size parameters of the coil on the induced electromotive force were analyzed. Finally, combined with the wavelet threshold filter, a series of field tests were carried out using ships of different materials in shallow water in order to verify the moving target detection method based on magnetic flux induction technology. The results showed that this method has an obvious response to moving targets and can effectively capture target signals, which verifies the feasibility of the magnetic flux induction detection technology.