bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating effect of metallic ions on aggregation behavior of β-amyloid peptides by atomic force microscope and surface-enhanced Raman Scattering
Authors: Xie Yang , Yu Lin , Fu Yuna , Sun Heng , Wang Jianhua 
Published: December 2021

Abstract
Background
Excessive aggregation of β-amyloid peptides (Aβ) is regarded as the hallmark of Alzheimer’s disease. Exploring the underlying mechanism regulating Aβ aggregation remains challenging and investigating aggregation events of Aβ in the presence and absence of metallic ions at molecular level would be meaningful in elucidating the role of metal cations on interactions between Aβ molecules. In this study, chemical self-assembled monolayer (SAM) method was employed to fabricate monolayer of β-amyloid peptides Aβ42 on gold substrate with a bolaamphiphile named 16-Mercaptohexadecanoic acid (MHA). Firstly, the samples of gold substrate (blank control), the MHA-modified substrate, and the Aβ42-modified substrate were detected by X-ray photoelectron spectroscopy (XPS) to track the self-assembly process. Aggregation behaviors of Aβ42 before and after metallic ions (Zn2+, Ca2+, Al3+) treatment were monitored by atomic force microscopy (AFM) and the interaction between Aβ42 and metallic ions (Zn2+, Ca2+, Al3+) was investigated by surface-enhanced Raman Scattering (SERS).

Results
The XPS spectra of binding energy of gold substrate (blank control), the MHA-modified substrate, and the Aβ42-modified substrate are well fitted with the corresponding monolayer’s composition, which indicates that Aβ42 monolayer is well formed. The recorded surface morphology of different experimental groups obtained by AFM showed markedly different nanostructures, indicating occurrence of aggregation events between Aβ42 molecules after adding metal ions to the solution. Compared to the control group, the presence of metallic ions resulted in the increased size of surface structures on the observed 3D topography. Besides, the intermolecular rupture force of Aβ42 increased with the addition of metallic ions. Further study by SERS showed that the Raman strength of Aβ42 changes significantly after the metal cation treatment. A considerable part of the amide bonds interacts with metal cations, leading to a structural change, which is characterized by the weakened β-fold Raman peak.

Conclusion
The AFM imaging results suggest that aggregation events occurred between Aβ42 molecules with the addition of metal cations. In addition, the results of force tests indicate that the presence of metallic ions could promote adhesion between Aβ42 molecules, which is likely to be the trigger for aggregation behavior of Aβ42. Furthermore, the effect of metallic cations on the conformational change of Aβ42 studied by SERS supported the results obtained by AFM. Taken together, the results showed that the presence of substoichiometric metal cations promotes aggregation behavior between Aβ42 molecules on the substrate at pH 7.4.
A systematic review on the modifications of extracellular vesicles: a revolutionized tool of nano-biotechnology
Authors: Raghav Alok , Jeong Goo-Bo 
Published: December 2021

Abstract
Background
Tailoring extracellular vesicles (EVs) can bequeath them with diverse functions and efficient performance in nano-biotechnology. Engineering and modification of EVs improves the targeted drug delivery efficiency. Here, we performed systematic review of various methods for EVs modifications.

Methods
PubMed, Scopus, ISI Web of Science, EMBASE, and Google Scholar were searched for available articles on EVs modifications (up to March 2021). In total, 1208 articles were identified and assessed, and then only 36 articles were found eligible and included.

Results
Six studies demonstrate the application of click chemistry, seven studies used co-incubation, two studies used chemical transfection, four studies implicated electroporation and sonication approach for modification of EVs. Moreover, two studies utilized microfluidics as suitable approach for loading cargo into EVs, while eight studies showed freeze–thaw method as feasible for these biological nanoparticles.

Conclusion
Freeze–thaw approach is found to be convenient and popular among researchers for performing modifications in EVs for the purpose of targeted drug delivery loading. Clinical-grade EVs production with good clinical practices (GCPs) is challenging in the current scenario. More studies are needed to determine the best suitable approach for cargo loading of EVs that may be exploited for research and therapeutic use.

Graphical Abstract
Deletion of PTP1B From Brain Neurons Partly Protects Mice From Diet-Induced Obesity and Minimally Improves Fertility
Authors: Ancel Caroline M , Evans Maggie C , Kerbus Romy I , Wallace Elliot G , Anderson Greg M 
Published: December 2021

AbstractReproductive dysfunction in women has been linked to high caloric diet (HCD)-feeding and obesity. Central resistance to leptin and insulin have been shown to accompany diet-induced infertility in rodent studies, and we have previously shown that deleting suppressor of cytokine signaling 3, which is a negative regulator of leptin signaling, from all forebrain neurons partially protects mice from HCD-induced infertility. In this study, we were interested in exploring the role of protein tyrosine phosphatase 1B (PTP1B), which is a negative regulator of both leptin and insulin signaling, in the pathophysiology of HCD-induced obesity and infertility. To this end, we generated male and female neuron-specific PTP1B knockout mice and compared their body weight gain, food intake, glucose tolerance, and fertility relative to control littermates under both normal calorie diet and HCD feeding conditions. Both male and female mice with neuronal PTP1B deletion exhibited slower body weight gain in response to HCD feeding, yet only male knockout mice exhibited improved glucose tolerance compared with controls. Neuronal PTP1B deletion improved the time to first litter in HCD-fed mice but did not protect female mice from eventual HCD-induced infertility. While the mice fed a normal caloric diet remained fertile throughout the 150-day period of assessment, HCD-fed females became infertile after producing only a single litter, regardless of their genotype. These data show that neuronal PTP1B deletion is able to partially protect mice from HCD-induced obesity but is not a critical mediator of HCD-induced infertility.
Growth Hormone-induced STAT5B RegulatesStarGene Expression Through a Cooperation With cJUN in Mouse MA-10 Leydig Cells
Authors: Hébert-Mercier Pierre-Olivier , Bergeron Francis , Robert Nicholas M , Mehanovic Samir , Pierre Kenley Joule , Mendoza-Villarroel Raifish E , de Mattos Karine , Brousseau Catherine , Tremblay Jacques J 
Published: December 2021

AbstractLeydig cells produce androgens that are essential for male sex differentiation and reproductive function. Leydig cell function is regulated by several hormones and signaling molecules, including growth hormone (GH). Although GH is known to upregulate Star gene expression in Leydig cells, its molecular mechanism of action remains unknown. The STAT5B transcription factor is a downstream effector of GH signaling in other systems. While STAT5B is present in both primary and Leydig cell lines, its function in these cells has yet to be ascertained. Here we report that treatment of MA-10 Leydig cells with GH or overexpression of STAT5B induces Star messenger RNA levels and increases steroid hormone output. The mouse Star promoter contains a consensus STAT5B element (TTCnnnGAA) at −756 bp to which STAT5B binds in vitro (electrophoretic mobility shift assay and supershift) and in vivo (chromatin immunoprecipitation) in a GH-induced manner. In functional promoter assays, STAT5B was found to activate a −980 bp mouse Star reporter. Mutating the −756 bp element prevented STAT5B binding but did not abrogate STAT5B-responsiveness. STAT5B was found to functionally cooperate with DNA-bound cJUN. The STAT5B/cJUN cooperation was only observed in Leydig cells and not in Sertoli or fibroblast cells, indicating that additional Leydig cell–enriched transcription factors are required. The STAT5B/cJUN cooperation was lost only when both STAT5B and cJUN elements were mutated. In addition to identifying the Star gene as a novel target for STAT5B in Leydig cells, our data provide important new insights into the mechanism of GH and STAT5B action in the regulation of Leydig cell function.
Stem Cells and Organs-on-chips: New Promising Technologies for Human Infertility Treatment
Authors: Tahmasbpour Marzouni Eisa , Stern Catharyn , Henrik Sinclair Andrew , Tucker Elena Jane 
Published: December 2021

Abstract
Having biological children remains an unattainable dream for most couples with reproductive failure or gonadal dysgenesis. The combination of stem cells with gene editing technology and organ-on-a-chip models provides a unique opportunity for infertile patients with impaired gametogenesis caused by congenital disorders in sex development or cancer survivors. But how will these technologies overcome human infertility? This review discusses the regenerative mechanisms, applications, and advantages of different types of stem cells for restoring gametogenesis in infertile patients, as well as major challenges that must be overcome before clinical application. The importance and limitations of in vitro generation of gametes from patient-specific human-induced pluripotent stem cells (hiPSCs) will be discussed in the context of human reproduction. The potential role of organ-on-a-chip models that can direct differentiation of hiPSC-derived primordial germ cell-like cells to gametes and other reproductive organoids is also explored. These rapidly evolving technologies provide prospects for improving fertility to individuals and couples who experience reproductive failure.
Physical Activity, Coronary Artery Calcium, and Cardiovascular Outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: GERMAN CHARLES A. , FANNING JASON , SINGLETON MATTHEW J. , SHAPIRO MICHAEL D. , BRUBAKER PETER H. , BERTONI ALAIN G. , YEBOAH JOSEPH 
Published: December 2021

ABSTRACT

Introduction
Although the inverse relationship between physical activity (PA) and cardiovascular disease (CVD) is well established, observational studies suggest that very high levels of PA may be harmful. This study sought to understand the relationship between PA, coronary artery calcium (CAC), and cardiovascular outcomes among individuals at different levels of risk.

Methods
PA and CAC were assessed in 6777 baseline participants of the Multi-Ethnic Study of Atherosclerosis. Total PA in MET-minutes per week was categorized into quartiles, and CAC was categorized as “low risk” (<100 Agatston units; n = 5180) and “high risk” (≥100 Agatston units; n = 1597). Cox proportional hazard regression analyses and Kaplan–Meier curves were generated to understand relationships between PA and CAC with CVD and all-cause mortality.

Results
In low-risk participants in the highest PA quartile, there was a decrease in the adjusted hazard ratio (HR) for CVD (HR, 0.72; 95% confidence interval (CI), 0.56–0.94) and all-cause mortality (HR, 0.69; 95% CI, 0.57–0.84) compared with those in the lowest PA quartile. In high-risk participants in the highest PA quartile, there was a decrease in the adjusted HR for all-cause mortality (HR, 0.59; 95% CI, 0.47–0.74) compared with those in the lowest PA quartile. High PA was not associated with an increased risk of either outcome, regardless of CAC category, sex, or race/ethnicity.

Conclusions
Our research suggests that there is no increased risk associated with high levels of PA, even among individuals at high risk of CVD.
Is the Chinese Anticorruption Campaign Authentic? Evidence from Corporate Investigations
Authors: Griffin John M. , Liu Clark , Shu Tao 
Published: December 2021

This paper examines whether the massive Chinese anticorruption campaign ensnares corrupt firms, contains a political component, and reduces corporate corruption. Consistent with the campaign’s stated objectives, investigated executives are more likely to come from Chinese firms with characteristics commonly associated with measures of poor governance, self-dealing, and inefficiencies. However, affiliations with prominent investigated political leaders increase investigation likelihood, while university affiliations with current central leadership decrease investigation likelihood, possibly indicating political partiality. Except for reported entertainment expenditures and chief executive officer pay, there has been little evidence of a substantial overall decrease in measures of potential corporate corruption. This paper was accepted by Tomasz Piskorski, finance.
False Discovery in A/B Testing
Authors: Berman Ron , Van den Bulte Christophe 
Published: December 2021

We investigate what fraction of all significant results in website A/B testing is actually null effects (i.e., the false discovery rate (FDR)). Our data consist of 4,964 effects from 2,766 experiments conducted on a commercial A/B testing platform. Using three different methods, we find that the FDR ranges between 28% and 37% for tests conducted at 10% significance and between 18% and 25% for tests at 5% significance (two sided). These high FDRs stem mostly from the high fraction of true null effects, about 70%, rather than from low power. Using our estimates, we also assess the potential of various A/B test designs to reduce the FDR. The two main implications are that decision makers should expect one in five interventions achieving significance at 5% confidence to be ineffective when deployed in the field and that analysts should consider using two-stage designs with multiple variations rather than basic A/B tests.This paper was accepted by Eric Anderson, marketing.
Victorious and Hierarchical: Past Performance as a Determinant of Team Hierarchical Differentiation
Authors: To Christopher , Yan Thomas Taiyi , Sherf Elad N. 
Published: December 2021

Hierarchies emerge as collectives attempt to organize themselves toward successful performance. Consequently, research has focused on how team hierarchies affect performance. We extend existing models of the hierarchy-performance relationship by adopting an alternative: Performance is not only an output of hierarchy but also a critical input, as teams’ hierarchical differentiation may vary based on whether they are succeeding. Integrating research on exploitation and exploration with work on group attributions, we argue that teams engage in exploitation by committing to what they attribute as the cause of their performance success. Specifically, collectives tend to attribute their success to individuals who wielded greater influence within the team; these individuals are consequently granted relatively higher levels of influence, leading to a higher degree of hierarchy. We additionally suggest that the tendency to attribute, and therefore grant more influence, to members believed to be the cause of success is stronger for teams previously higher (versus lower) in hierarchy, as a higher degree of hierarchical differentiation provides clarity as to which members had a greater impact on the team outcome. We test our hypotheses experimentally with teams engaging in an online judgement task and observationally with teams from the National Basketball Association. Our work makes two primary contributions: (a) altering existing hierarchy-performance models by highlighting performance as both an input and output to hierarchy and (b) extending research on the dynamics of hierarchy beyond individual rank changes toward examining what factors increase or decrease hierarchical differentiation of the team as a whole.Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2021.1528 .
Assessment and examination of the respiratory system
Authors: Squires Eleanor 
Published: December 2021

Respiratory complaints are seen regularly in general practice. Eleanor Squires looks at the importance of advanced practitioners carrying out a systematic assessment and examination of a patient with respiratory symptoms The aim of this article is to explore the importance of carrying out a systematic assessment and examination of a patient with respiratory complaints. History taking using recommended acronyms will be discussed, along with a focus on the most common presentations. Finally, it will discuss a systematic examination of the patient.
The effect of different levels of pre-damage loading on the strength and structural behavior of CFRP strengthened R.C. beams: Experimental and analytical investigation
Authors: Hamah-Ali Brwa Hamah Saeed , Qadir Mohamed Raouf Abdul 
Published: December 2021

In order to investigate the effect of pre-loading damage on the structural performance of Carbon Fiber Reinforced Polymer (CFRP) strengthened Reinforced Concrete (R.C.) beams, experimental and Finite Element Modelling (FEM) investigation was carried out on six R.C. beams. Five of the R.C. beams were damaged up to different levels of strain in the main steel bars before Flexure CFRP strengthening. One of the R.C. beams loaded up to failure and was kept as a control beam for comparison. The experimental results showed that the failure mode of the CFRP strengthened specimen was controlled by CFRP debonding followed by concrete crushing; however, the control beam failed in concrete crushing after yielding the steel bars, which is a ductile failure. The CFRP sheet increases the strength and initial stiffness of the R.C. beams and reduces ductility and toughness. Also, CFRP application increases the first crack and yielding steel bars load by 87.4% and 34.4%, respectively. Furthermore, the pre-damage level does not influence the strength and ductility of the strengthened R.C. beams except for the highest damage levels, which experienced a slight decrease in load capacity and ductility. However, the initial stiffness decreases with increasing pre-damage levels by 40%.Design guideline ACI 440.2R (2004) predicts the ultimate load capacity marvelously for externally bonded Fiber-Reinforced Polymer (FRP) beams compared to the experimental maximum load capacity. The excellent agreement between experimental and FEM results indicates that the constitutive models used for concrete and reinforcement and the cohesive interface model can well capture fracture behavior. However, The FEM analysis predicts the beam to be slightly stiffer and more robust, probably because of the assumed perfect bond between concrete and reinforcement. The developed FEM can be used for further parametric study.
A 2-year longitudinal follow-up of quantitative assessment neck tics in Tourette’s syndrome
Authors: Eriguchi Yosuke , Gu Xiaoxue , Aoki Naoto , Nonaka Maiko , Goto Ryunosuke , Kuwabara Hitoshi , Kano Yukiko , Kasai Kiyoto 
Published: December 2021

BackgroundNeck motor tics in Tourette’s syndrome can cause severe neck complications. Although addressed in a few longitudinal studies, the clinical course of Tourette’s syndrome has not been quantitatively assessed. We had previously developed a method for quantifying the angular movements of neck tics using a compact gyroscope. Here, we present a follow-up study aimed at elucidating the clinical course of neck tics at both the group and individual levels.MethodsEleven patients with Tourette’s syndrome from our previous study participated in the present study, and their neck tics were recorded during a 5-min observation period. The severity of neck symptoms was assessed using the Yale Global Tic Severity Scale. The peak angular velocities and accelerations, tic counts, and severity scores in our previous study (baseline) and the present study (2-year follow-up) were compared at the group and individual levels. The individual level consistency between baseline and follow-up were calculated using intra-class correlation coefficients (ICCs, one-way random, single measure).ResultsAt the group level, no significant change was observed between baseline and follow-up. At the individual level, angular velocity (ICC 0.73) and YGTSS scores (ICC 0.75) had substantial consistency over the two time points, and angular acceleration (ICC 0.59) and tic counts (ICC 0.69) had moderate consistency.ConclusionsThe intensity and frequency of neck tics did not change over time. Therefore, quantification of angular neck motor tics will aid in identifying patients with neck tics at high risk for severe neck complications.
VALUE AT RISK (VAR) METODE DELTA-NORMAL BERDASARKAN DURASI UNTUK UKURAN RISIKO OBLIGASI PEMERINTAH
Authors: Setiani Setiani , Maruddani Di Asih I , Ispriyanti Dwi 
Published: December 2021

A bond is one of invesment instrument that is basically a debt instrument. In investing, beside getting profit there is also the risk of loss. The risk of loss is unavoidable but it can be manageable. The concept of a portfolio in investing is to minimize risk. Value at Risk (VaR) is a method used to measure risk where VaR states the estimated amount of the maximum loss that will be obtained at a certain level of confidence during a certain period in normal market conditions. In this article the risk of bonds FR0053, FR0056, FR0059, FR0061 and portfolio combinations calculated with VaR value of the Delta-Normal method are calculated based on the duration of the bonds. Normality test of the bond market price return is required before calculating VaR. The results obtained if it is assumed that the bonds are purchased at a price of 100 and with a confidence level of 95%, then the portfolio that has the smallest risk is the Bond portfolio of FR0059 and FR0061 with a VaR value Rp 21,436 (Trillions).
SIT1 transporter as a potential novel target in treatment of COVID-19
Authors: Semiz Sabina 
Published: December 2021

Abstract
Studies published earlier this year demonstrated the association of the solute carrier SLC6A20 gene with the risk and severity of COVID-19. The SLC6A20 protein product (Sodium-dependent Imino Transporter 1 (SIT1)) is involved in the transport of amino acids, including glycine. Here we summarized the results of recent studies demonstrating the interaction of SIT1 with the ACE2 receptor for SARS-CoV-2 as well as an observed association of SLC6A20 with the risk and traits of Type 2 diabetes (T2D). Recently, it was also proposed that SLC6A20 represents the novel regulator of glycine levels and that glycine has beneficial effects against the proinflammatory cytokine secretion induced by SARS-CoV-2 infection. Ivermectin, as a partial agonist of glycine-gated chloride channels, was also recently suggested to interfere with the COVID-19 cytokine storm by inducing the activation of glycine receptors. Furthermore, plasma glycine levels are found to be decreased in diabetic patients. Thus, further clinical trials are warranted to confirm the potential favorable effects of targeting the SIT1 transporter and glycine levels in the treatment of COVID-19, particularly for the severe case of disease associated with hyperglycemia, inflammation, and T2D. These findings suggest that SIT1 may potentially represent one of the missing pieces in the complex puzzle observed between these two pandemic diseases and the potential novel target for their efficient treatment.