bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurophysiology of Juvenile and Progressive Myoclonic Epilepsy
Authors: Acharya Jayant N. , Acharya Vinita J. 
Published: July 2022

Summary:
Myoclonus can be epileptic or nonepileptic. Epileptic myoclonus has been defined in clinical, neurophysiological, and neuroanatomical terms. Juvenile myoclonic epilepsy (JME) is typically considered to be an adolescent-onset idiopathic generalized epilepsy with a combination of myoclonic, generalized tonic–clonic, and absence seizures and normal cognitive status that responds well to anti-seizure medications but requires lifelong treatment. EEG shows generalized epileptiform discharges and photosensitivity. Recent observations indicate that the clinical picture of JME is heterogeneous and a number of neuropsychological and imaging studies have shown structural and functional abnormalities in the frontal lobes and thalamus. Advances in neurophysiology and imaging suggest that JME may not be a truly generalized epilepsy, in that restricted cortical and subcortical networks appear to be involved rather than the entire brain. Some patients with JME may be refractory to anti-seizure medications and attempts have been made to identify neurophysiological biomarkers predicting resistance. Progressive myoclonic epilepsy is a syndrome with multiple specific causes. It is distinct from JME because of the occurrence of progressive neurologic dysfunction in addition to myoclonus and generalized tonic–clonic seizures but may sometimes be difficult to distinguish from JME or misdiagnosed as drug-resistant JME. This article provides an overview of progressive myoclonic epilepsy and focuses on the clinical and neurophysiological findings in the two most commonly recognized forms of progressive myoclonic epilepsy—Unverricht–Lundborg disease (EPM1) and Lafora disease (EPM2). A variety of neurophysiological tests can be used to distinguish between JME and progressive myoclonic epilepsy and between EPM1 and EPM2.
Hexokinase 1b is a novel target for Non–small-cell lung cancer
Authors: Yozgat Yasemin , Karakoc Emre , Sahin Ozgur , Cimen Seyma , Rabeh Wael M. , Aydin Mehmet Serif , Mardinoglu Adil , Gursel Ihsan , Cakir Asli , Sensoy Ozge , Ozdemir Ekrem M. , Bayrak Yusuf , Gunluoglu Mehmet Z. , Saatci Ozge , Jabbar Javaid , Ferreira Juliana C. , Aslan Melike Dinccelik , Yildirim Muzaffer , Mansoor Samman , Kerman Bilal E. , Aladag Zeynep , Kim Woonghee , Arif Muhammad , Vatandaslar Emre , Tok Olgu E. , Dogru Zeynep , Demir Aslı G. O. , Yildirim Tugce Canavar , Yozgat İhsan , Senturk Serif , Ozturk Gurkan , Cevher Murat Alper 
Published: July 2022

SUMMARYDeregulation of glycolysis is common in non-small cell lung cancer (NSCLC). Hexokinase (HK) enzymes catalyze the phosphoryl-group-transfer in glucose metabolism. There are a very few studies that have begun to reveal the connections between glucose metabolism and splicing programs. Unlike HK2 gene, which is expressed as a single transcript, there are several transcripts of the HK1 gene due to alternative splicing. However, the functional differential roles of HK1 isoforms in glucose metabolism and tumor progression are still elusive. Here, we show that primary NSCLC patient tumor cells metabolically differ from the normal lung epithelium where they display predominant expression of one of the HK1 transcripts, hexokinase1b (HK1b). We utilized CRISPR-Cas9 system to selectively target specific HK1b isoform in NSCLC and show that silencing HK1b in NSCLC cells inhibits tumorigenesis through diminishing glycolysis and proliferation. Our findings constitute the first demonstration of the first biochemical distinction between the HK1 splice variants. Finally, HK1b deletion sensitizes NSCLC cells to standard-of-care, cisplatin treatment, and the combination therapy synergistically increases both apoptotic cell death by cisplatin and autophagic cell death by increased formation of LC3-II associated autophagic vesicles and myelinoid bodies. Notably, loss of HK1b leads to cellular DNA damage, further combination with cisplatin therapy showed significantly increased levels of DNA damage. Importantly, we showed that glycolysis and cisplatin resistance can be restored by adding-back HK1b in HK1b knock-out cells. Our findings reveal that targeting HK1b isoform alone or in combination with cisplatin may represent a novel strategy for NSCLC patients.
High Variability Periods in the EEG: A New Temporal Metric that Reflects Brain States
Authors: Parameshwaran Dhanya , Thiagarajan Tara 
Published: July 2022

AbstractHere we define a new metric to characterize temporal patterns of amplitude variability in the EEG signal and demonstrate that this feature of the signal varies significantly with brain state. The metric uses the standard deviation of waveform amplitude in a short moving time window of 3-20 seconds with 50% overlap. We define “High Variability Periods” or “HVPs” as segments when the moving standard deviation of the waveform amplitude is continuously higher than a cutoff defined as the 25th percentile of variability. HVPs typically last on the order of tens of seconds and are punctuated by low variability periods or “LVPs” of shorter duration. We further show that the HVP characteristics differ between various conditions. HVPs in the resting state eyes closed condition are substantially and significantly shorter in duration and smaller in area relative to eyes open. In addition, in recordings from monkeys, HVPs disappear under anesthesia and do not reappear in early periods of recovery from anesthesia suggesting long term changes to the signal. Altogether this demonstrates that HVP metrics have discriminatory power and may therefore be important in predicting brain states and outcomes. Finally, they are fast to estimate and can be tracked in time, and therefore suited for near real-time monitoring in low-electrode configuration systems.
PTEN and BRCA1 tumor suppressor loss associated tumor immune microenvironment exhibits differential response to therapeutic STING pathway activation in a murine model of ovarian cancer
Authors: Shakfa Noor , Li Deyang , Conseil Gwenaëlle , Lightbody Elizabeth , Wilson-Sanchez Juliette , Hamade Ali , Chenard Stephen , Laight Brian , Afriyie-Asante Afrakoma , Tyryshkin Kathrin , Köbel Martin , Koti Madhuri 
Published: July 2022

ABSTRACTBackgroundHigh grade serous ovarian carcinoma (HGSC) is the most lethal gynecologic malignancy characterized by chemoresistance and high rates of recurrence. HGSC tumors display a high prevalence of tumor suppressor gene loss. Loss of BRCA1 and PTEN function due to mutations or epigenetic influence have been widely associated with variable clinical outcomes, where tumors with BRCA1 mutations exhibit increased chemosensitivity and those with PTEN mutations have been reported to exhibit chemoresistance. Given the established type 1 interferon regulatory function of BRCA1 and PTEN genes and associated contrasting T cell infiltrated and non-infiltrated tumor immune microenvironment (TIME) states, in this study we investigated the potential of Stimulator of Interferon Genes (STING) pathway activation in improving overall survival via enhancing chemotherapy response, specifically in tumors with PTEN deficiency.MethodsExpression of PTEN protein was evaluated in tissue microarrays generated using pre-treatment tumors collected from a cohort of 110 patients with HGSC. Multiplex immunofluorescence staining was performed to determine spatial profiles and density of selected lymphoid and myeloid cells. In vivo studies using the syngeneic murine HGSC cell lines, ID8-Trp53-/-; Pten-/-and ID8-Trp53-/-; Brca1-/-, were conducted to characterize the TIME and response to carboplatin chemotherapy in combination with exogenous STING activation therapy.ResultsTumors with absence of PTEN protein exhibited a significantly decreased disease specific survival and intra-epithelial CD68+ macrophage infiltration as compared to intact PTEN expression. In vivo studies demonstrated that Pten deficient ovarian cancer cells establish an immunosuppressed TIME characterized by increased proportions of M2-like macrophages, GR1+ MDSCs in the ascites, and reduced effector CD8+ cytotoxic T cell function compared to Brca1 deficient cells; further, tumors from mice injected with Pten deficient ID8 cells exhibited an aggressive behavior due to suppressive macrophage dominance in the malignant ascites. In combination with chemotherapy, exogenous STING activation resulted in longer overall survival in mice injected with Pten deficient ID8 cells, reprogrammed intraperitoneal M2-like macrophages derived from Pten deficient ascites to a M1-like phenotype and rescued CD8+ cytotoxic T cell activation.ConclusionsThis study reveals the importance of considering the influence of cancer cell intrinsic genetic alterations on the TIME for therapeutic selection. We establish the rationale for the optimal incorporation of interferon activating therapies as a novel combination strategy in PTEN deficient HGSC.
The role of wingbeat frequency and amplitude in flight power
Authors: Krishnan Krishnamoorthy , Garde Baptiste , Bennison Ashley , Cole Nik C. , Cole Emma-L. , Darby Jamie , Elliott Kyle H. , Fell Adam , Gómez-Laich Agustina , de Grissac Sophie , Jessopp Mark , Lempidakis Emmanouil , Mizutani Yuichi , Prudor Aurélien , Quetting Michael , Quintana Flavio , Robotka Hermina , Roulin Alexandre , Ryan Peter G. , Schalcher Kim , Schoombie Stefan , Tatayah Vikash , Tremblay Fred , Weimerskirch Henri , Whelan Shannon , Wikelski Martin , Yoda Ken , Hedenström Anders , Shepard Emily L.C. 
Published: July 2022

AbstractBody-mounted accelerometers provide a new prospect for estimating power use in flying birds, as the signal varies with the two major kinematic determinants of aerodynamic power: wingbeat frequency and amplitude. Yet wingbeat frequency is sometimes used as a proxy for power output in isolation. There is therefore a need to understand which kinematic parameter birds vary and whether this is predicted by flight mode (e.g., accelerating, ascending/descending flight), speed or morphology. We investigate this using high-frequency acceleration data from (i) 14 species flying in the wild, (ii) two species flying in controlled conditions in a wind tunnel and (iii) a review of experimental and field studies. While wingbeat frequency and amplitude were positively correlated, R2 values were generally low, supporting the idea that parameters can vary independently. Indeed, birds were more likely to modulate wingbeat amplitude for more energy-demanding flight modes, including climbing and take-off. Nonetheless, the striking variability even within species and flight types, highlights the complexity of describing the kinematic relationships, which appear sensitive to both the biological and physical context. Notwithstanding this acceleration metrics that incorporate both kinematic parameters should be more robust proxies for power than wingbeat frequency alone.
Genome assembly and association tests identify interacting loci associated with vigor, precocity, and sex in interspecific pistachio rootstocks
Authors: Palmer William , Jacygrad Ewelina , Sagayaradj Sagayamary , Cavanaugh Keri , Han Rongkui , Bertier Lien , Beede Bob , Kafkas Salih , Golino Deborah , Preece John , Michelmore Richard 
Published: July 2022

AbstractUnderstanding the basis of hybrid vigor remains a key question in crop breeding and improvement, especially for rootstock development where F1hybrids are extensively utilized. Full-sibling UCB-1 F1seedling rootstocks are widely planted in commercial pistachio orchards that are generated by crossing two highly heterozygous outbreeding parental trees ofPistacia atlantica(female) andP. integerrima(male). This results in extensive phenotypic variability, prompting costly removal of low-yielding small trees. To identify the genetic basis of this variability, we assembled chromosome-scale genome assemblies of the parental trees of UCB-1. We genotyped 960 UCB-1 trees in an experimental orchard for which we also collected multi-year phenotypes. We genotyped an additional 1,358 rootstocks in six commercial pistachio orchards and collected single-year tree size data. Genome-wide single marker association tests identified loci associated with tree size and shape, sex, and precocity. In the experimental orchard, we identified multiple trait-associated loci and a strong candidate for ZZ/ZW sex chromosomes. We found significant marker associations unique to different traits and to early vs. late phenotypic measures of the same trait. We detected two loci strongly associated with rootstock size in commercial orchards. Pseudo-testcross classification of markers demonstrated that the trait-associated alleles for each locus were segregating in the gametes of opposite parents. These two loci interact epistatically to generate the bimodal distribution of tree size with undesirable small trees observed by growers. We identified candidate genes within these regions. These findings provide a foundational resource for marker development and genetic selection of vigorous pistachio UCB-1 rootstock.
Nuclear architecture protein Distal antenna balances genome-binding and phase-separation properties to regulate neuroblast competence
Authors: Benchorin Gillie , Li Maggie Jiaqi , Cho Richard Jangwon , Hu Yuxin , Kohwi Minoree 
Published: July 2022

AbstractNeural progenitors transit through multiple competence states that restrict production of each neural cell type. In Drosophila neuroblasts, a timed genome reorganization relocates the cell fate gene, hunchback, to the nuclear periphery, terminating competence to produce early-born neurons. Distal antenna (Dan), a pipsqueak (Psq) superfamily protein, is transiently downregulated at mid-embryogenesis, which is required for this relocation. Here we find that Dan is a highly intrinsically disordered protein, and when its Psq DNA-binding domain is increasingly disrupted, Dan coalesces into steadily larger, interconnected hubs of rapid protein exchange. Consistent with these phase-separation properties, Dan has a predicted LARKS domain, a structural motif that forms reversible interactions associated with phase-separation. In the embryo, loss of either the Psq motif or the LARKS domain abrogates Dan’s ability to maintain neuroblast early competence upon misexpression, suggesting that Dan requires both DNA-binding and phase-separation to regulate neuroblast competence. Finally, we found that Dan strongly interacts with proteins of the nuclear pore complex (NPC), and Elys, a core NPC scaffold protein known to regulate genome architecture, binds the hb intron and is required for competence termination. Together, the results support a model for how Dan’s phase-separation properties can mediate dynamic restructuring by balancing genome-binding, self-association, and interaction among nuclear architecture regulators.
Implicit prices of attributes of fine German Riesling: magnitude and heterogeneity
Authors: Fedoseev Vladimir , Fedoseeva Svetlana , Herrmann Roland 
Published: July 2022

PurposeThis study aims to analyse how wine attributes affect prices of fine German Riesling wines, provide estimates of the magnitude and heterogeneity of the attributes' implicit prices and draw conclusions on the pricing of fine wine and the research methodology.Design/methodology/approachImplicit prices of attributes of fine German Rieslings are estimated with fixed-effects regressions and their heterogeneity across quantiles of the conditional price distribution is tested with quantile-regression techniques. The analysis is based on a unique online data set for prices and characteristics of collectible wines.FindingsQuality levels according to the German Prädikat system, additional quality awards for exceptional quality, the wine region, age or vintage as well as ullage and the bottle condition are relevant when explaining the price of cellarable wine. Additionally, the influence of the firm's individual reputation is very strong. Relative price premiums for some major attributes of fine German Riesling change significantly across quantiles of the conditional price distribution. Other attributes are characterised by a rather stable relative (but not absolute) price premium.Originality/valueThis is, to the best of our knowledge, the first hedonic price analysis which concentrates exclusively on fine German Riesling wine. By applying both classical and quantile regressions, the authors are able to derive new insights on quality-price linkages in this growing segment of collectible wine and on the research methodology.
Resilience assessment of health-care facilities within urban context: learning from a non-profit hospital in Tehran, Iran
Authors: Rahmani Mehrdad , Lotfata Aynaz , Khoshnevis Sarasadat , Javanmardi Komar , Akdogan Mehmet Emin 
Published: July 2022

Purpose
Tehran’s health-care system is growing, yet it lacks emergency planning procedures. The premise of this study is that the urban environment around a hospital is just as robust as the hospital itself. This study aims to look at hospital resilience in an urban setting to see where it may be improved to keep the hospital operational during a disaster.

Design/methodology/approach
The urban resilience (UR) of Amir-Alam Hospital was analyzed in this study using a customized version of the United Nations Office for Disaster Risk Reduction’s City Resilience Profiling Tool. The 34 indications were broken down into five categories.

Findings
The result revealed that the hospital’s UR score was 51.75 out of 100, indicating medium resilience. The results of this study enable the decision-makers to determine what measures they may take to improve the hospital’s resilience in terms of its surrounding urban context.

Originality/value
The originality of this research is based on the surrounding urban environment’s resilience as an integral part of hospital resilience.
The impact of advanced manufacturing technology (AMT) application on product innovation performance: a model of mediated moderated effect
Authors: Wang Guilian , Zhang Liyan , Guo Jing 
Published: July 2022

Purpose
Drawing on the integration of the knowledge-based theory and the resource orchestration theory, this study aims to develop a moderated mediation model on how design/manufacturing/administrative advanced manufacturing technology (AMT) influences product innovation performance. The authors hypothesized that the absorption capacity could mediate the AMT-innovation performance link and that design–manufacturing integration (DMI) could positively moderate the mediating effect of the absorption capacity.

Design/methodology/approach
To test the hypothesis, the authors conducted a mail survey of equipment manufacturing firms and obtained 302 valid responses for data analysis. Both hierarchical regression and bootstrapping analysis were conducted to empirically test the research model.

Findings
It is revealed that the absorption capacity partially mediated the effect of AMT on innovation and that DMI enhanced the mediated effect. Specifically, the mediating effect of the absorption capacity was more substantial and significant when DMI was high. However, the mediating effect of the absorption capacity was weaker and insignificant when DMI was low.

Originality/value
Overall, this study contributes to the AMT theory on innovation by identifying the absorption capacity and DMI as two key factors that elucidate why and under what conditions AMT affects innovation. Moreover, this study advises managers that besides developing AMT, firms should cultivate a strong DMI, which directs the absorption capacity toward converting the valuable knowledge in firms’ capital equipment into increased innovation performance.
Family firm competitiveness and owner involvement
Authors: Buchanan Bonnie , Martikainen Minna , Nikkinen Jussi 
Published: July 2022

PurposeIn many countries, small and medium-sizes enterprises (SMEs) are primarily responsible for wealth, economic growth, innovation and research and development. In this paper, the authors examine the impact of family ownership and owner involvement on the financial performance of unlisted Finnish SMEs.Design/methodology/approachThis is an empirical paper using a random sample of 1,137 non-listed Finnish SMEs. Through regression analyses and robustness tests, the authors examine the effects of family management, family and employee ownership and involvement.FindingsUsing profitability measures, the authors find family-owned and controlled SMEs perform significantly better than non-family firms. The number of family members actively involved in daily business operations bears a significant negative relation to firm performance. In contrast, non-family firms in which owners are actively involved, provide comparable returns to family firms, suggesting that in non-family firms active involvement contributes to performance. The authors find that employee ownership in SMEs does not provide an efficient way to compensate employees since more dispersed ownership does not lead to higher performance.Research limitations/implicationsSME employee ownership does not provide an efficient way to compensate employees since more dispersed ownership does not lead to higher performance.Practical implicationsIn the case of Finland, family ownership is an effective organisational structure. As the depth of the COVID pandemic remains uncertain, firms with committed ownership are key to the economic recovery.Originality/valueThe authors approach the family ownership and involvement issue from a different angle. Unlike earlier studies, the authors examine the impact of both family ownership and involvement on the financial performance of privately owned SMEs. This paper helps shed light on the role of family ownership and involvement as a possible explanatory factor of overall economic performance.
Integrating circular economy strategies and business models: a systematic literature review
Authors: Foroozanfar Mohammad Hossein , Imanipour Narges , Sajadi Seyed Mojtaba 
Published: July 2022

Purpose
This study aims to undertake a review of the circular economy (CE) and business model (BM) literature by conducting a thematic analysis and developing a framework.

Design/methodology/approach
To address the research questions, a systematic literature review was conducted. Finally, 106 publications were chosen based on two main criteria.

Findings
The authors performed an athematic analysis of CE drivers. This analysis identifies five key areas: environmental, economic, social, regulatory and institutional factors, as well as emerging approaches for addressing CE drivers. A framework for the circular economy business model (CEBM) has been developed by integrating BM value dimensions and three primary CE strategies, including closing, slowing and narrowing resource loops. Additionally, the authors’ framework considers the CEBM’s sustainability impact in emerging economies.

Research limitations/implications
This study is limited in two ways: one is inherent in the concept of CE, particularly CEBM, and the other is methodological.

Originality/value
This study contributes to the body of knowledge about CE and BM in three ways. First, this research includes a thematic analysis of CE drivers, as well as themes and subthemes. Additionally, the authors discuss an emerging approach for CE drivers. Second, the authors make a contribution by proposing a framework for CEBM that takes value dimensions and CE strategies into account for the emerging economy context. Third, the authors shed light on potential avenues for further research.