bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural oscillatory responses to performance monitoring differ between high‐ and low‐impulsive individuals, but are unaffected by TMS
Authors: Barth Beatrix , Rohe Tim , Deppermann Saskia , Fallgatter Andreas Jochen , Ehlis Ann‐Christine
Published: February 2021

Higher impulsivity may arise from neurophysiological deficits of cognitive control in the prefrontal cortex. Cognitive control can be assessed by time‐frequency decompositions of electrophysiological data. We aimed to clarify neuroelectric mechanisms of performance monitoring in connection with impulsiveness during a modified Eriksen flanker task in high‐ (n = 24) and low‐impulsive subjects (n = 21) and whether these are modulated by double‐blind, sham‐controlled intermittent theta burst stimulation (iTBS). We found a larger error‐specific peri‐response beta power decrease over fronto‐central sites in high‐impulsive compared to low‐impulsive participants, presumably indexing less effective motor execution processes. Lower parieto‐occipital theta intertrial phase coherence (ITPC) preceding correct responses predicted higher reaction time (RT) and higher RT variability, potentially reflecting efficacy of cognitive control or general attention. Single‐trial preresponse theta phase clustering was coupled to RT in correct trials (weighted ITPC), reflecting oscillatory dynamics that predict trial‐specific behavior. iTBS did not modulate behavior or EEG time‐frequency power. Performance monitoring was associated with time‐frequency patterns reflecting cognitive control (parieto‐occipital theta ITPC, theta weighted ITPC) as well as differential action planning/execution processes linked to trait impulsivity (frontal low beta power). Beyond that, results suggest no stimulation effect related to response‐locked time‐frequency dynamics with the current stimulation protocol. Neural oscillatory responses to performance monitoring differ between high‐ and low‐impulsive individuals, but are unaffected by iTBS.
Variability and effect sizes of intracranial current source density estimations during pain: Systematic review, experimental findings, and future perspectives
Authors: Völker Juan Manuel , Arguissain Federico Gabriel , Andersen Ole Kæseler , Biurrun Manresa José
Published: February 2021

Pain arises from the integration of sensory and cognitive processes in the brain, resulting in specific patterns of neural oscillations that can be characterized by measuring electrical brain activity. Current source density (CSD) estimation from low‐resolution brain electromagnetic tomography (LORETA) and its standardized (sLORETA) and exact (eLORETA) variants, is a common approach to identify the spatiotemporal dynamics of the brain sources in physiological and pathological pain‐related conditions. However, there is no consensus on the magnitude and variability of clinically or experimentally relevant effects for CSD estimations. Here, we systematically examined reports of sample size calculations and effect size estimations in all studies that included the keywords pain, and LORETA, sLORETA, or eLORETA in Scopus and PubMed. We also assessed the reliability of LORETA CSD estimations during non‐painful and painful conditions to estimate hypothetical sample sizes for future experiments using CSD estimations. We found that none of the studies included in the systematic review reported sample size calculations, and less than 20% reported measures of central tendency and dispersion, which are necessary to estimate effect sizes. Based on these data and our experimental results, we determined that sample sizes commonly used in pain studies using CSD estimations are suitable to detect medium and large effect sizes in crossover designs and only large effects in parallel designs. These results provide a comprehensive summary of the effect sizes observed using LORETA in pain research, and this information can be used by clinicians and researchers to improve settings and designs of future pain studies.
Fiber ball white matter modeling in focal epilepsy
Authors: Bryant Lorna , McKinnon Emilie T. , Taylor James A. , Jensen Jens H. , Bonilha Leonardo , de Bezenac Christophe , Kreilkamp Barbara A. K. , Adan Guleed , Wieshmann Udo C. , Biswas Shubhabrata , Marson Anthony G. , Keller Simon S.
Published: February 2021

Multicompartment diffusion magnetic resonance imaging (MRI) approaches are increasingly being applied to estimate intra‐axonal and extra‐axonal diffusion characteristics in the human brain. Fiber ball imaging (FBI) and its extension fiber ball white matter modeling (FBWM) are such recently described multicompartment approaches. However, these particular approaches have yet to be applied in clinical cohorts. The modeling of several diffusion parameters with interpretable biological meaning may offer the development of new, noninvasive biomarkers of pharmacoresistance in epilepsy. In the present study, we used FBI and FBWM to evaluate intra‐axonal and extra‐axonal diffusion properties of white matter tracts in patients with longstanding focal epilepsy. FBI/FBWM diffusion parameters were calculated along the length of 50 white matter tract bundles and statistically compared between patients with refractory epilepsy, nonrefractory epilepsy and controls. We report that patients with chronic epilepsy had a widespread distribution of extra‐axonal diffusivity relative to controls, particularly in circumscribed regions along white matter tracts projecting to cerebral cortex from thalamic, striatal, brainstem, and peduncular regions. Patients with refractory epilepsy had significantly greater markers of extra‐axonal diffusivity compared to those with nonrefractory epilepsy. The extra‐axonal diffusivity alterations in patients with epilepsy observed in the present study could be markers of neuroinflammatory processes or a reflection of reduced axonal density, both of which have been histologically demonstrated in focal epilepsy. FBI is a clinically feasible MRI approach that provides the basis for more interpretive conclusions about the microstructural environment of the brain and may represent a unique biomarker of pharmacoresistance in epilepsy.
Nomograms for predicting survival outcomes in intensity‐modulated radiotherapy era of nasopharyngeal carcinoma: A study based on Epstein–Barr virus DNA biological responses
Authors: Yang Kaixuan , Li Mei , Zhu Jinbing , Zeng Lei , Tian Jiangfang , Xie Wenji , Shou Arthur , Li Yiping , Li Guangjun
Published: February 2021

Background

Treatment of nasopharyngeal carcinoma (NPC) is evolving toward Intensity‐modulated radiotherapy (IMRT) era, which requires patient‐specific reestimation of survival outcomes in modern health care.

Methods

A total of 488 detectable pre‐treatment Epstein–Barr virus (EBV) DNA patients (stage II‐IVa) treated with induction chemotherapy (IC) and IMRT were examined (training set, n = 325; validation set, n = 163).

Results

Concurrent chemotherapy (CC) was still an independent prognosticator for overall survival (OS) and progression‐free survival (PFS). Both nomograms included age, T classification, N classification, post‐IC EBV DNA, and CC. Predictions correlated well with observed 3‐/5‐year OS and PFS. The concordance index was 0.776 (95% confidence interval (CI) 0.69–0.86) for OS and 0.742 (95% CI 0.65–0.83) for PFS in the validation cohort. The nomograms can successfully classify patients into low‐ and high‐risk groups.

Conclusion

The validated nomograms provided useful prediction of OS and PFS for detectable pre‐treatment EBV DNA patients with NPC in IMRT era.
Microbiota‐Driven Activation of Intrahepatic B Cells Aggravates NASH Through Innate and Adaptive Signaling
Authors: Barrow Fanta , Khan Saad , Fredrickson Gavin , Wang Haiguang , Dietsche Katrina , Parthiban Preethy , Robert Sacha , Kaiser Thomas , Winer Shawn , Herman Adam , Adeyi Oyedele , Mouzaki Marialena , Khoruts Alexander , Hogquist Kristin A. , Staley Christopher , Winer Daniel A. , Revelo Xavier S.
Published: February 2021

Background and Aims

Nonalcoholic steatohepatitis is rapidly becoming the leading cause of liver failure and indication for liver transplantation. Hepatic inflammation is a key feature of NASH but the immune pathways involved in this process are poorly understood. B lymphocytes are cells of the adaptive immune system that are critical regulators of immune responses. However, the role of B cells in the pathogenesis of NASH and the potential mechanisms leading to their activation in the liver are unclear.

Approach and Results

In this study, we report that NASH livers accumulate B cells with elevated pro‐inflammatory cytokine secretion and antigen‐presentation ability. Single‐cell and bulk RNA sequencing of intrahepatic B cells from mice with NASH unveiled a transcriptional landscape that reflects their pro‐inflammatory function. Accordingly, B‐cell deficiency ameliorated NASH progression, and adoptively transferring B cells from NASH livers recapitulates the disease. Mechanistically, B‐cell activation during NASH involves signaling through the innate adaptor myeloid differentiation primary response protein 88 (MyD88) as B cell–specific deletion of MyD88 reduced hepatic T cell–mediated inflammation and fibrosis, but not steatosis. In addition, activation of intrahepatic B cells implicates B cell–receptor signaling, delineating a synergy between innate and adaptive mechanisms of antigen recognition. Furthermore, fecal microbiota transplantation of human NAFLD gut microbiotas into recipient mice promoted the progression of NASH by increasing the accumulation and activation of intrahepatic B cells, suggesting that gut microbial factors drive the pathogenic function of B cells during NASH.

Conclusion

Our findings reveal that a gut microbiota–driven activation of intrahepatic B cells leads to hepatic inflammation and fibrosis during the progression of NASH through innate and adaptive immune mechanisms.
Experimental investigation of heat transfer in a triple tube heat exchanger with coiled spring inserts
Authors: Kumar Rajan , Chandra Prakash
Published: February 2021

Experiments have been performed to investigate the effect of coiled spring inserts on heat transfer, pressure drop, and performance parameters of a triple tube heat exchanger (TTHX). Three different spring inserts having a pitch of 5, 10, and 15 mm are used and the diameter of the spring wire is taken as 1 mm. The experiments were carried out under a turbulent flow regime, with water as a working medium in parallel and counter flow configurations. The variation in different performance characteristics like heat transfer coefficient, Nusselt number, and effectiveness have been compared at various Reynolds numbers ranging between 4000 and 16,000 in the considered flow patterns. The Nusselt number of TTHX with the lowest pitch spring is found to be higher than that of the plain TTHX by 57.27% at Re = 4000 for the counter flow configuration. Both the thermal performance factor and effectiveness increased as the pitch of the spring insert was decreased. The effectiveness of TTHX with the lowest pitch spring insert is found higher than that of the plain TTHX by 43.84% in the counter flow pattern.
Fluorescent Probes for the Supramolecular Interactions responsible for Binding of Polycyclic Aromatic Hydrocarbons to Hyperbranched Polyelectrolytes in Aqueous Media
Authors: Ihde Michael H. , Steelman Ashley M. , Bonizzoni Marco
Published: February 2021

Cationic poly(amidoamine) (PAMAM) dendrimers are known as good supramolecular hosts for a variety of smaller water‐soluble guests. We expanded their binding scope to the uptake of very hydrophobic guests such as polycyclic aromatic hydrocarbons (PAH) in neutral aqueous solution. We used anthracene and pyrene as representatives of this family of hydrocarbons, and as capable fluorescent emitters to probe mode and location of interaction for these hydrocarbons with polycationic amine‐terminated PAMAM dendrimers. We used steady‐state and time‐resolved fluorescence emission spectroscopy, as well as fluorescence anisotropy measurements and selective quenching experiments, to establish the mode and location of these binding interactions, demonstrating that, although these probes may look relatively similar, their interaction with PAMAM dendrimers is nevertheless significantly different. The results presented here provide insight into the attractive forces at play in the uptake of featureless hydrophobic PAH guests by hydrophilic PAMAM dendrimer hosts, whose applications span practical challenges including chemical separations, analytical discrimination, solubility and bioavailability enhancement of hydrophobic compounds.
What are the triggers for arrears on debt over a business cycle? Evidence from panel data
Authors: Kukk Merike
Published: February 2021

The paper investigates the triggers of arrears on debt in a full recourse euro area country. An extensive individual‐level quarterly panel dataset enables quarterly arrears on debt to be tracked while controlling for individual specific heterogeneity. The estimations show that lower income and higher debt service ratios are associated with a higher probability of arrears, confirming the “ability to pay” hypothesis. The results reveal different debt repayment behaviour for housing and consumer loans over a business cycle. Newly taken housing loans exhibit a lower probability of arrears and the same applies to loans granted during the period of easy credit conditions and high real estate prices, indicating that housing credit boom has not contributed to the rise in arrears on debt. Newly taken consumer loans are related to a higher probability of arrears, suggesting that consumer loans have been used to alleviate financial difficulties.
Evaluation of water productivity with three rice genotypes under different irrigation regimes and nitrogen fertilizer treatments in Rasht, northern Iran*
Authors: Najafi Samaneh , Khaledian Mohammadreza , Rezaei Mojtaba
Published: February 2021

This study investigates the water productivity of three rice genotypes in physical, economic and virtual water terms through different irrigation and fertilizer treatments. The experiment was conducted in 2017 and 2018 in split plot designs based on a randomized complete block design with three replications. The main factors include irrigation regimes: flood irrigation of I1 and alternate irrigation treatments of I2, I3 and I4 that involve alternate irrigation with irrigation intervals of 7, 14 and 21 days, respectively. The subfactors include different rice genotypes at three levels of certified local Hashemi, M5 and M12 genotypes at three levels of nitrogen fertilizer of 60, 80 and 100 kg N/ha1. Results showed that the certified Hashemi variety with the 7‐day irrigation interval and 100 kg N/ha1; treatment showed satisfactory physical water productivity (being 1.41 and 1.01 kg/m3 in 2017 and 2018, respectively), and also the highest net benefit per drop (being 31 200 and 29 800 rials/m3 in 2017 and 2018, respectively). According to the results of this study, using alternate irrigation at the 7‐day irrigation interval would save 285 million m3 of water in the Sefidroud irrigation and drainage network.
Performing Piety and Perfection: The Affective Labor of Hijabi Fashion Videos
Authors: Peterson Kristin
Published: February 2021

This article examines the work of a popular Muslim woman on YouTube, Amena Khan, who has attracted over 310 thousand subscribers to her channel and runs a successful online boutique. While Amena's hijab tutorials and lifestyle videos might appear to be just about superficial topics like fashion or makeup, this article argues that she does actual labor to not only produce an aesthetic style but to also create an affective condition of what it means to be a Muslim woman living within a neoliberal context. Amena's videos illustrate what Michael Hardt (1999) defines as “affective labor” within this neoliberal economy. Amena might sell hijabs online, but she does not actually produce physical objects. What she does produce is an affective state–feelings around how to properly act within this neoliberal culture while still maintaining Islamic piety. The space of YouTube also allows for Amena to blend different affects and aesthetic styles, such as neoliberal elements of aspiration, creativity and individuality with Islamic ethics like piety, modesty and submission. Ultimately, the reason why Amena can attract viewers and run a successful fashion business is because she works to produce an affective state that seamlessly moves between Islamic ethics and neoliberal values.
Contextualizing Internet Studies: Beyond the Online/Offline Divide
Authors: Nordenson Jon
Published: February 2021

This essay discusses the issue of contextualization in studies of online platform usage and online material. It argues that a separation between online and offline cannot be sustained, as social media users relate to many different online and offline contexts simultaneously. Why protagonists make use of online platforms, which platforms they use, how they make use of them, who they seek to reach, and so on, is all dependent on the various geographical and social contexts within which they work. At the same time, these users are also part of and are influenced by different online contexts that may be based on topic, identity, or geography, and which may be local, national, regional or international. When we study online material – be it activism, language use, discourse, or something else - we must do so with all these relevant settings in mind. Throughout the essay, I seek to illustrate these complex relationships between different online and offline contexts through concrete examples from Egypt and Kuwait. I argue that the material shows that we cannot generalize and simply assume similar patterns of usage of online platforms producing similar outcomes across different contexts. Still, research so far has provided insights that are important both in their own right and, not least, as methodological and theoretical considerations for future studies, and I conclude by suggesting three principles that should guide our investigations of online material.
Telehealth parent coaching to improve daily living skills for children with ASD
Authors: Gerow Stephanie , Radhakrishnan Supriya , S. Akers Jessica , McGinnis Kristina , Swensson Remington
Published: February 2021

Children with autism spectrum disorder often display deficits in daily living skills. Behavior analysts can use telehealth, such as videoconferencing technology, to deliver interventions to families of these children. Given the COVID‐19 pandemic and the common barriers to accessing behavioral interventions, it is imperative to evaluate the effectiveness and practicality of delivering behavioral interventions via telehealth. This study evaluated the efficacy of a parent‐implemented intervention with coaching via telehealth to improve daily living skills. Children ranging in age from 5 to 9 years participated in the study with 1 or 2 of their parents serving as the primary implementer(s). Parents implemented the intervention with fidelity and the intervention yielded increases in independent daily living skill completion for all 4 participants.
Increased oxidative stress and mitochondrial impairments associated with increased expression of TNF‐α and caspase‐3 in palmitic acid‐induced lipotoxicity in myoblasts
Authors: Mansuri Mohammad Lukman , Sharma Garima , Parihar Priyanka , Dube Kirti Tiwari , Sharma Tejasweta , Parihar Arti , Parihar Mordhwaj Singh
Published: February 2021

Saturated fatty acids, whose circulating levels are markedly increased in the body, significantly affect the growth and functions of skeletal muscle. These fatty acids may exert a detrimental effect on the undifferentiated skeletal myoblasts that may adversely affect their differentiation. In the present study, the exposure of myoblasts to excess palmitic acid caused an elevation of tumor necrosis factor‐α expression and an increase in reactive oxygen species levels consistent with the enhanced inflammation and oxidative stress. Various concentrations of palmitic acid significantly decreased the mitochondrial membrane potential, induced the programmed cell death by an increase in the caspase‐3 expression, and DNA fragmentation in the myoblasts. These findings suggest that the increased concentrations of saturated fatty acid in the myoblasts increase lipotoxicity by increasing inflammation and oxidative stress, decreasing the mitochondrial function, and inducing apoptosis.
To control or to compromise? The prominence of chief compliance officer and foreign corrupt practices act violation
Authors: Liu Chenyong , Xu Chunhao , Liu Zhenfeng
Published: February 2021

We investigate the influence of chief compliance office (CCO) prominence in the corporate management team on FCPA violation and audit fees. Based on the compliance function leader's position seniority, we find that a CCO's position rank is positively associated with the propensity of FCPA violation. It indicates that promoting CCO in the firm can facilitate more aggressive compliance policies—it is a “compromise” instead of a “control.” We also find that CCO prominence is positively associated with audit fees even without an FCPA violation happening, which implies that auditors could fully perceive the potential risks embedded in the compliance chief's promotion. The results of this study can be of interest to audit practitioners as well as regulators to better monitor the firms with higher FCPA violation risks.
Surface charging‐dependent deposition of silver on gold nanorods
Authors: Chang Sheng‐Te , Dong Wen‐Yi , Chen Kai‐Cheng , He Yan , Yen Yi‐An , Kao Chih‐Wei , Deng Jin‐Pei
Published: February 2021

The surface of gold nanorods is chemically charged by ascorbic acid; the charging effect results in not only the blue shift on their surface plasmon bands, but also the change of the deposition rate of silver on their surfaces. The rate was prominently accelerated at room temperature, but slightly slowed down at higher temperature. The shape of gold‐silver core‐shell nanoparticles could not be obviously affected. The Fermi level of gold nanorods begins to increase under the action of charging and alters the electrical double‐layer structure of gold nanorods, resulting in the different deposition rate of silver on gold.
One‐step ultrasonic production of the chitosan/lactose/g‐C3N4 nanocomposites with lactose as a biological capping agent: Photocatalytic activity study
Authors: Karimi Mohammad Ali , Ranjbar Mehdi , Mohadesi Alireza
Published: February 2021

In this work, the basic and applied purpose was to synthesize and modify chitosan/lactose nanocomposites with g‐C3N4 structures using the ultrasonic‐assisted electrospinning method. We evaluated effective photocatalytic of chitosan/lactose/g‐C3N4 nanocomposites to photodegrade methyl red, methyl orange, and methyl blue in different nanophotocatalyst concentration such as 0.1–1%g/L in pH 6.5. According to the experimental results, it was found that nanocomposites in different concentrations of g‐C3N4 had high potential in degradation of organic compounds. The lactose structures as a green capping agent and stabilizer modified chitosan surfaces to produce uniform particle size distribution. Different lactose concentrations like 0.1–0.5%wt/vol indicate a particle size range between 270 and 422 nm. The obtained as‐synthesized nanomaterials were characterized by scanning electron microscope, energy‐dispersive X‐ray spectroscopy, transmission electron microscopy, X‐ray diffraction (XRD), Fourier‐transform infrared spectroscopy, and UV–Vis spectroscopy. The crystalline size and diameter (Dc) of the nanostructures can be determined through XRD data with ∼90–110 nm. Results show that photocatalytic activity in low pH is more increased than other values due to more electron–hole pairs formed on the surface.
Molecular Structure, Molecular Docking and Absorption, Distribution, Metabolism, Excretion and Toxicity study of cellulose II
Authors: Celik Sefa , Demirag Aliye Demet , E. Ozel Aysen , Akyuz Sevim
Published: February 2021

Cellulose is a renewable biopolymer which is the most abundant in nature, formed by binding of glucose units with β‐1,4 glycosidic bonds. Cellulose is divided into two groups as bacterial cellulose (BC) and vegetable cellulose. This study reports the interaction mechanism of Cellulose II, which is a BC, with the cellulase enzymes, determined by molecular docking method based on key‐lock theory. The most stable molecular geometry of the Cellulose II molecule was determined by density functional theory using Gaussian 09 program. The scaled vibration frequencies of optimized geometry were calculated by using Molvib program. Molecular electrostatic potential and frontier molecular orbital analyses were performed. Molecular interactions between cellulose II and endoglucanase, exogluconase and β‐glucosidase II have been determined. Moreover, the drug likeness and ADMET properties of cellulose II were analyzed for the prediction of pharmacokinetic profiles.
Multi‐compartment metabolomics and metagenomics reveal major hepatic and intestinal disturbances in cancer cachectic mice
Authors: Pötgens Sarah A. , Thibaut Morgane M. , Joudiou Nicolas , Sboarina Martina , Neyrinck Audrey M. , Cani Patrice D. , Claus Sandrine P. , Delzenne Nathalie M. , Bindels Laure B.
Published: February 2021

Background

Cancer cachexia is a multifactorial syndrome characterized by multiple metabolic dysfunctions. Besides the muscle, other organs such as the liver and the gut microbiota may also contribute to this syndrome. Indeed, the gut microbiota, an important regulator of the host metabolism, is altered in the C26 preclinical model of cancer cachexia. Interventions targeting the gut microbiota have shown benefits, but mechanisms underlying the host–microbiota crosstalk in this context are still poorly understood.

Methods

To explore this crosstalk, we combined proton nuclear magnetic resonance (1H‐NMR) metabolomics in multiple compartments with 16S rDNA sequencing. These analyses were complemented by molecular and biochemical analyses, as well as hepatic transcriptomics.

Results

1H‐NMR revealed major changes between control (CT) and cachectic (C26) mice in the four analysed compartments (i.e. caecal content, portal vein, liver, and vena cava). More specifically, glucose metabolism pathways in the C26 model were altered with a reduction in glycolysis and gluconeogenesis and an activation of the hexosamine pathway, arguing against the existence of a Cori cycle in this model. In parallel, amino acid uptake by the liver, with an up to four‐fold accumulation of nine amino acids (q‐value <0.05), was mainly used for acute phase response proteins synthesis rather than to fuel the tricarboxylic acid cycle and gluconeogenesis. We also identified a 35% reduction in hepatic carnitine levels (q‐value <0.05) and a lower activation of the phosphatidylcholine pathway as potential contributors to the hepatic steatosis present in this model. Our work also reveals a reduction of different beneficial intestinal bacterial activities in cancer cachexia. We found decreased levels of two short‐chain fatty acids, acetate and butyrate (72% and 88% reduction in C26 caecal content; q‐value <0.001), and a reduction in aromatic amino acid metabolites, which may contribute to the altered intestinal homeostasis in these mice. A member of the Ruminococcaceae family (ASV 2) was identified as the main bacterium responsible for the drop in butyrate. Finally, we report a two‐fold intestinal transit acceleration (P‐value <0.001) as a key factor shaping the gut microbiota composition and activity in cancer cachexia, which together lead to a faecal loss of proteins and amino acids.

Conclusions

Our work highlights new metabolic pathways potentially involved in cancer cachexia and further supports the interest of exploring the gut microbiota composition and activity, as well as intestinal transit, in cancer patients with and without cachexia.
Scanning electron microscopy of Sophora alopecuroides L. seeds and their cytotoxic, antimicrobial, antioxidant, and enzyme inhibition potentials
Authors: Zahra Syeda Anber , Iqbal Javed , Abbasi Banzeer Ahsan , Yaseen Tabassum , Hameed Ayesha , Shahbaz Amir , Kanwal Sobia , Mahmood Tariq , Ahmad Parvaiz
Published: February 2021

Sophora alopecuroides L. is a highly medicinal plant. The aim of the current study was to determine the phytochemical screening, pharmacological potentials and application of scanning electron microscope (SEM) of S. alopecuroides (SA) seeds. To achieve this purpose, six different solvents were used to prepare SA seed extracts. Phytochemical and antioxidant activities were determined calorimetrically. To investigate the antidiabetic activity, α‐amylase inhibition assay was determined. Brine shrimp assay was used to determine cytotoxicity potential. Anti‐leishmanial potential was confirmed using MTT assay. Disc‐diffusion method was used to detect protein kinase inhibitory, antibacterial and antifungal activities and showed significant results. SEM analysis was used as an identification tool. Considerable amount of phenolic and flavonoid contents were identified in methanol extract (SASM) (93.76 ± 2.71 GAE/mg) and (77 ± 3.60 QE/mg). Highest DPPH scavenging potential (82%) was reported for SASM. Significant total antioxidant capacity (90.60 ± 1.55 alpha amylase enzyme [AAE]/mg) and total reducing power (94.44 ± 1.38 AAE/mg) were determined for LOSM. Highest α‐amylase inhibition was reported in SASM (78.20 ± 1.58%). Highest LD50 of brine shrimp was found for n‐hexane extract (SASH) 13.03 μg/ml. All extracts showed strong anti‐leishmanial activity except SASH. The seeds of SA were seen to be oblong to obovate, projections, wavy slightly straight, anticlinal wall was raised with apex acuminate. In conclusion, our experimental findings highly support the ethnomedicinal and biological potentials of the SA seeds. Moreover, SA seeds need to be explored for identification and isolation of bioactive compounds. In future, we recommend further in vivo toxicity assays and clinical efficacies to further evaluate its different biomedical properties.
Isolation methodology is essential to the evaluation of the extracellular vesicle component of the senescence‐associated secretory phenotype
Authors: Wallis Ryan , Josipovic Natasa , Mizen Hannah , Robles‐Tenorio Arturo , Tyler Eleanor J. , Papantonis Argyris , Bishop Cleo L.
Published: February 2021

A hallmark of senescence is the acquisition of an enhanced secretome comprising inflammatory mediators and tissue remodelling agents – the senescence‐associated secretory phenotype (SASP). Through the SASP, senescent cells are hypothesised to contribute to both ageing and pathologies associated with age. Whilst soluble factors have been the most widely investigated components of the SASP, there is growing evidence that small extracellular vesicles (EVs) comprise functionally important constituents. Thus, dissecting the contribution of the soluble SASP from the vesicular component is crucial to elucidating the functional significance of senescent cell derived EVs. Here, we take advantage of a systematic proteomics based approach to determine that soluble SASP factors co‐isolate with EVs following differential ultracentrifugation (dUC). We present size‐exclusion chromatography (SEC) as a method for separation of the soluble and vesicular components of the senescent secretome and thus EV purification. Furthermore, we demonstrate that SEC EVs isolated from senescent cells contribute to non‐cell autonomous paracrine senescence. Therefore, this work emphasises the requirement for methodological rigor due to the propensity of SASP components to co‐isolate during dUC and provides a framework for future investigations of the vesicular component of the SASP.
Dynamical systems approach to evolution–development congruence: Revisiting Haeckel's recapitulation theory
Authors: Kohsokabe Takahiro , Kaneko Kunihiko
Published: February 2021

It is acknowledged that embryonic development has a tendency to proceed from common toward specific. Ernst Haeckel raised the question of why that tendency prevailed through evolution, and the question remains unsolved. Here, we revisit Haeckel's recapitulation theory, that is, the parallelism between evolution and development through numerical evolution and dynamical systems theory. By using intracellular gene expression dynamics with cell‐to‐cell interaction over spatially aligned cells to represent the developmental process, gene regulation networks (GRN) that govern these dynamics evolve under the selection pressure to achieve a prescribed spatial gene expression pattern. For most numerical evolutionary experiments, the evolutionary pattern changes over generations, as well as the developmental pattern changes governed by the evolved GRN exhibit remarkable similarity. Changes in both patterns consisted of several epochs where stripes are formed in a short time, whereas for other temporal regimes, the pattern hardly changes. In evolution, these quasi‐stationary generations are needed to achieve relevant mutations, whereas, in development, they are due to some gene expressions that vary slowly and control the pattern change. These successive epochal changes in development and evolution are represented as common bifurcations in dynamical systems theory, regulating working network structure from feedforward subnetwork to those containing feedback loops. The congruence is the correspondence between successive acquisitions of subnetworks through evolution and changes in working subnetworks in development. Consistency of the theory with the segmentation gene‐expression dynamics is discussed. Novel outlook on recapitulation and heterochrony are provided, testable experimentally by the transcriptome and network analysis.
Genetic counselors' experiences with transgender individuals in prenatal and preconception settings
Authors: Ruderman Maggie , Berro Tala , Torrey Sosa Lillian , Zayhowski Kimberly
Published: February 2021

Many transgender individuals want to have children and are pursuing reproductive care. Limited research has described the experiences of transgender individuals during pregnancy, and no known studies have examined reproductive genetic counseling sessions with this patient population. To understand what topics and considerations are explored within this sector of reproductive care, prenatal and preconception genetic counselors that have seen a transgender patient and/or transgender partner of a patient were recruited through an email blast to members of the National Society of Genetic Counselors. Nine genetic counselors completed phone interviews. Content analysis was used to identify, quantify, and examine the concepts within the transcripts. Six major themes emerged: (1) Trans individuals were referred for common genetic counseling indications, (2) genetic counselors were driven to think of more inclusive language, (3) genetic counselors considered ways to make written materials more inclusive, (4) trans individuals expressed discomforts in the prenatal/preconception setting, (5) genetic counselors observed challenges with the care team, and (6) genetic counselors felt underprepared. This study identifies areas within reproductive spaces of genetic counseling that could be more inclusive, particularly relating to commonly used gendered language and written materials, and provides training recommendations for genetic counselors. Additionally, we outline the reported areas of discrimination for these patients and partners, and discuss ways that genetic counselors can be advocates for respectful and equitable care within their clinics.
Mortality, morbidity, and failure to rescue in hepatopancreatoduodenectomy: An analysis of patients registered in the National Clinical Database in Japan
Authors: Endo Itaru , Hirahara Norimichi , Miyata Hiroaki , Yamamoto Hiroyuki , Matsuyama Ryusei , Kumamoto Takafumi , Homma Yuki , Mori Masaki , Seto Yasuyuki , Wakabayashi Go , Kitagawa Yuko , Miura Fumihiko , Kokudo Norihiro , Kosuge Tomoo , Nagino Masato , Horiguchi Akihiko , Hirano Satoshi , Yamaue Hiroki , Yamamoto Masakazu , Miyazaki Masaru
Published: February 2021

Background

The high operative mortality rate after hepatopancreatoduodenectomy (HPD) is still a major issue. The present study explored why operative mortality differs significantly due to hospital volume.

Method

Surgical case data were extracted from the National Clinical Database (NCD) in Japan from 2011 to 2014. Surgical procedures were categorized as major (≥2 sections) and minor (<2 sections) hepatectomy. Hospitals were categorized according to the certification system by the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery (JSHBPS) based on the number of major hepato‐biliary‐pancreatic surgeries performed per year. The FTR rate was defined as death in a patient with at least one postoperative complication.

Results

A total of 422 patients who underwent HPD were analyzed. The operative mortality rates in board‐certified A training institutions, board‐certified B training institutions, and non‐certified institution were 7.2%, 11.6%, and 21.4%, respectively. Multiple logistic regression showed that certified A institutions, major hepatectomy, and blood transfusion were the predictors of operative mortality. Failure to rescue rates were lowest in certified A institutions (9.3%, 17.0%, and 33.3% in certified A, certified B, and non‐certified, respectively).

Conclusions

To reduce operative mortality after HPD, further centralization of this procedure is desirable. Future studies should clarify specific ways to improve the failure‐to‐rescue rates in certified institutions.
Proposal of a novel H category‐based classification of colorectal liver metastases based on a Japanese nationwide survey
Authors: Beppu Toru , Imai Katsunori , Honda Goro , Sakamoto Katsunori , Kobayashi Shin , Endo Itaru , Hasegawa Kiyoshi , Kotake Kenjiro , Itabashi Michio , Hashiguchi Yojiro , Kotera Yoshihito , Yamaguchi Tatsuro , Tabuchi Ken , Kobayashi Hirotoshi , Yamaguchi Kensei , Morita Satoshi , Kikuchi Ken , Miyazaki Masaru , Sugihara Kenichi , Yamamoto Masakazu , Takahashi Keiichi ,   Joint Committee for Nationwide Survey on Colorectal Liver Metastasis
Published: February 2021

Background

The conventional H category‐based classification for colorectal liver metastases (CRLM) was created by equal weighting of tumor number and tumor size; however, our previous nomogram to predict postoperative disease‐free survival demonstrated that CRLM ≥5 as a parameter provided 4.5 times greater impact compared with a largest CRLM size >5 cm.

Methods

A total of 3815 patients newly diagnosed with CRLM between 2005 and 2007, including 2220 resectable cases, were investigated. Six groups were created based on largest lesion size (≤ 5 vs >5 cm) and lesion number (1, 2‐4, and ≥5).

Results

The novel (n) H1, nH2, and nH3 categories were defined as solitary lesions with a size ≤5 cm; lesions other than nH1 or nH3; and ≥5 lesions with any lesion size, respectively. In the resectable cohort, the 5‐year cumulative overall survival rates were 64.0%, 53.5%, and 42.6% in the nH1, nH2, and nH3 groups, respectively (P < .001), and no significant differences were observed between the conventional H2 and H3 categories. In the overall cohort, the discrimination ability of the two classifications were comparable.

Conclusion

The novel H category‐based classification might be beneficial in predicting overall survival in patients with CRLM independent of their resectability.
Synthesis of 4H‐chromene‐isoxazole hybrids via ortho‐hydroxy directing cyclization of isoxazole‐styrenes and Michael addition of imino‐chromenes in aqueous medium
Authors: Nagaraju Sakkani , Sathish Kota , Kashinath Dhurke
Published: February 2021

A green, efficient, and one‐pot method synthesis of functionalized 4H‐chromene‐isoxazole hybrids is reported via o‐hydroxy group directing cyclization of isoxazole‐styrenes and Michael addition of 3,5‐dimethyl‐4‐nitroisoxazole on 2‐imino‐2H‐chromene‐3‐carbonitrile (independent methods). The developed methodology was further extended for nitromethane, malononitrile, and alkylcyanoacetates as Michael donors.
Attrition in HIV care following HIV diagnosis: a comparison of the pre‐UTT and UTT eras in South Africa
Authors: Onoya Dorina , Hendrickson Cheryl , Sineke Tembeka , Maskew Mhairi , Long Lawrence , Bor Jacob , Fox Matthew P.
Published: February 2021

Abstract

Introduction

Policies for Universal Test & Treat (UTT) and same‐day initiation (SDI) of antiretroviral therapy (ART) were instituted in South Africa in September 2016 and 2017 respectively. However, there is limited evidence on whether these changes have improved patient retention after HIV diagnosis.

Methods

We enrolled three cohorts of newly diagnosed HIV‐infected adults from two primary health clinics in Johannesburg from April to November 2015 (Pre‐UTT, N = 144), May‐September 2017 (UTT, N = 178) and October‐December 2017 (SDI, N = 88). A baseline survey was administered immediately after HIV diagnosis after which follow‐up using clinical records (paper charts, electronic health records and laboratory data) ensued for 12 months. The primary outcome was patient loss to follow‐up (being >90 days late for the last scheduled appointment) at 12 months post‐HIV diagnosis. We modelled attrition across HIV policy periods with Cox proportional hazard regression.

Results

Overall, 410 of 580 screened HIV‐positive patients were enrolled. Overall, attrition at 12 months was 30% lower in the UTT guideline period (38.2%) compared to pre‐UTT (47.2%, aHR 0.7, 95% CI: 0.5 to 1.0). However, the total attrition was similar between the SDI (47.7%) and pre‐UTT cohorts (aHR 1.0, 95% CI: 0.7 to 1.5). Older age at HIV diagnosis (aHR 0.5 for ≥40 vs. 25 to 29 years, 95% CI: 0.3 to 0.8) and being in a non‐marital relationship (aHR 0.5 vs. being single, 95% CI: 0.3 to 0.8) protected against LTFU at 12 months, whereas LTFU rates increased with longer travel time to the diagnosing clinic (aHR 1.8 for ≥30 minutes vs. ≤15 minutes, 95% CI: 1.1 to 3.1). In analyses adjusted for the time‐varying ART initiation status, compared to the pre‐ART period of care, the hazard of on‐ART LTFU was 90% higher among participants diagnosed under the SDI policy compared to pre‐UTT (aHR 1.9, 95% CI: 1.1 to 2.9).

Conclusions

Overall, nearly two‐fifths of HIV positive patients are likely to disengage from care by 12 months after HIV diagnosis under the new SDI policy. Furthermore, the increase in on‐ART patient attrition after the introduction of the SDI policy is cause for concern. Further research is needed to determine the best way for rapidly initiating patients on ART and also reducing long‐term attrition from care.
Improved Quantification of Myocardium Scar in Late Gadolinium Enhancement Images: Deep Learning Based Image Fusion Approach
Authors: Fahmy Ahmed S. , Rowin Ethan J. , Chan Raymond H. , Manning Warren J. , Maron Martin S. , Nezafat Reza
Published: February 2021

Background

Quantification of myocardium scarring in late gadolinium enhanced (LGE) cardiac magnetic resonance imaging can be challenging due to low scar‐to‐background contrast and low image quality. To resolve ambiguous LGE regions, experienced readers often use conventional cine sequences to accurately identify the myocardium borders.

Purpose

To develop a deep learning model for combining LGE and cine images to improve the robustness and accuracy of LGE scar quantification.

Study Type

Retrospective.

Population

A total of 191 hypertrophic cardiomyopathy patients: 1) 162 patients from two sites randomly split into training (50%; 81 patients), validation (25%, 40 patients), and testing (25%; 41 patients); and 2) an external testing dataset (29 patients) from a third site.

Field Strength/Sequence

1.5T, inversion‐recovery segmented gradient‐echo LGE and balanced steady‐state free‐precession cine sequences

Assessment

Two convolutional neural networks (CNN) were trained for myocardium and scar segmentation, one with and one without LGE‐Cine fusion. For CNN with fusion, the input was two aligned LGE and cine images at matched cardiac phase and anatomical location. For CNN without fusion, only LGE images were used as input. Manual segmentation of the datasets was used as reference standard.

Statistical Tests

Manual and CNN‐based quantifications of LGE scar burden and of myocardial volume were assessed using Pearson linear correlation coefficients (r) and Bland–Altman analysis.

Results

Both CNN models showed strong agreement with manual quantification of LGE scar burden and myocardium volume. CNN with LGE‐Cine fusion was more robust than CNN without LGE‐Cine fusion, allowing for successful segmentation of significantly more slices (603 [95%] vs. 562 (89%) of 635 slices; P < 0.001). Also, CNN with LGE‐Cine fusion showed better agreement with manual quantification of LGE scar burden than CNN without LGE‐Cine fusion (%ScarLGE‐cine = 0.82 × %Scarmanual, r = 0.84 vs. %ScarLGE = 0.47 × %Scarmanual, r = 0.81) and myocardium volume (VolumeLGE‐cine = 1.03 × Volumemanual, r = 0.96 vs. VolumeLGE = 0.91 × Volumemanual, r = 0.91).

Data Conclusion

CNN based LGE‐Cine fusion can improve the robustness and accuracy of automated scar quantification.

Level of Evidence

3

Technical Efficacy

1
Assessment of Repeatability, Reproducibility, and Performances of T2 Mapping‐Based Radiomics Features: A Comparative Study
Authors: Crombé Amandine , Buy Xavier , Han Fei , Toupin Solenn , Kind Michèle
Published: February 2021

Background

Magnetic resonance imaging (MRI)‐based radiomics features (RFs) quantify tumors radiological phenotypes but are sensitive to postprocessing parameters, including the intensity harmonization technique (IHT), while mappings enable objective quantitative assessment.

Purpose

To investigate whether T2 mapping could improve repeatability, reproducibility, and performances of radiomics compared to conventional T2‐weighted imaging (T2WI).

Study Type

Prospective.

Subjects

Twenty‐six healthy adults.

Field Strength/Sequence

Respiratory‐trigged radial turbo spin echo (TSE) multiecho T2 mapping (prototype) and conventional TSE T2WI of the abdomen were acquired twice at 1.5 T.

Assessment

T2 maps were reconstructed using a two‐parameter exponential fitting model. Volumes‐of‐interest (VOIs) were manually drawn in six tissues: liver, kidney, pancreas, muscle, bone, and spleen. After co‐registration, conventional T2WIs were processed with two IHTs (standardization [std] and histogram‐matching [HM]) resulting in four paired input image types: initial T2WI, T2WIstd, T2WIHM, and T2‐map. VOIs were propagated to extract 45 RFs from MRI‐1 and MRI‐2 of each image type (LIFEx, v5.10).

Statistical Tests

Influence of the input data type on RF values was evaluated with analysis of variance. RFs test–retest repeatability and reproducibility over multiple segmentations were evaluated with intra‐class correlation coefficient (ICC). Correlations between k‐means clusters and the six tissues depending on the RFs dataset were investigated with adjusted‐Rand‐index (ARI).

Results

About 41 of 45 (91.1%) RFs were significantly influenced by the input image type (P values < 0.05), which was the most influential factor on repeatability of RFs (P‐value < 0.05). Repeatability ICCs from T2‐map displayed intermediate values between the initial T2WI (range: 0.407–0.736) and the T2WIHM (range: 0.724–0.817). The number of RFs with interobserver and intraobserver reproducibility ICCs ≥ 0.90 was 37/45 (82.2%) for T2WIHM, 33/45 (73.3%) for T2WIstd, 31/45 (68.9%) for T2 map, and 25/45 (55.6%) for the initial T2WI. T2 map provided the best tissue discrimination (ARI = 0.414 vs. 0.157 with T2WIHM).

Data Conclusion

T2 mapping provided RFs with moderate to substantial repeatability and reproducibility ICCs, along with the most preserved discriminative information.

Level of Evidence

1

Technical Efficacy

1