bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroinflammation in Epilepsy—Diagnostics and Therapeutic Perspectives
Authors: Lach Piotr , Klus Wiktoria , Zajdel Krystian , Szeleszczuk Adam , Komorowska Ewelina , Burda Klaudia , Kurowski Przemysław 
Published: December 2021

Abstract
Epilepsy is a neurological disease that affects approximately 1% of the world’s population. Epilepsy is characterized by the occurrence of repeated epileptic seizures due to abnormal neuronal activity. Although this disorder is currently incurable, it can be controlled for years with the appropriate therapy and patient adherence. Inflammation is an organism’s natural response to a pathological stimulus, aimed at eliminating the triggering factor. Multiple studies point out a significant correlation between an increased level of inflammatory mediators and the frequency of epileptic seizures. Increased levels of IL-1β, IL-2, IL-4, IL-6, IFN-γ, and TNF-α were found in the serum of patients with epilepsy. Additionally, pro-inflammatory cytokines were found to be upregulated during epileptic activity in rodents: CCL2 and CCR2 receptor expression was shown to be upregulated during inflammation induced by lipopolysaccharide administration, and CXCR5 was found to be primarily upregulated in brain cells. Early detection of the described factors may serve as a biomarker for epilepsy but also hold potential in developing novel immunomodulating therapies. Thus, a better understanding of the immune system’s involvement is necessary for the development of new therapeutic perspectives in epilepsy.
Nonlinear pentagonal intuitionistic fuzzy number and its application in EPQ model under learning and forgetting
Authors: Chakraborty Avishek , Pal Shilpi , Mondal Sankar Prasad , Alam Shariful 
Published: December 2021

AbstractIn this current era, the concept of nonlinearity plays an important and essential role in intuitionistic fuzzy arena. This article portrays an impression of different representation of nonlinear pentagonal intuitionistic fuzzy number (PIFN) and its classification under different scenarios. A new de-intuitification technique of non-linear PIFN is addressed in this article along with its various graphical representations. Additionally, in this paper, we have observed this by applying it in an economic production quantity model where the production is not perfect and defective items are produced which are reworked. The model is considered under learning and forgetting, where learning is considered as linear, nonlinear PIFN and crisps arena. It is observed from the numerical study that high learning effects in rework lead to decrease in production of defective item, which, besides an economic advantage, may have a positive effect on the environment. Even though forgetting has an adverse effect, the average total cost is much less than that of the basic model which ignores worker learning and forgetting. Finally, comparative and sensitivity analysis result shows the utility of this noble work.
Do Guarantees of Non-Recurrence Actually Help to Prevent Systemic Violations? Reflections on Measures Taken to Prevent Domestic Violence
Authors: Ferstman Carla 
Published: December 2021

AbstractThis article assesses the effectiveness of guarantees of non-recurrence to prevent the recurring, systemic violation of domestic violence. I consider whether there is any evidence to demonstrate that the measures ordered in response to state due diligence failings concerning domestic violence produced a change that that can be understood as effectively contributing to prevention. This is done principally by reviewing reports on the implementation of domestic violence judgments and decisions issued by the Inter-American and European regional human rights systems and by the UN CEDAW Committee. However, as is shown, for the most part these bodies have carried out only superficial scrutiny of the effectiveness in practice of measures undertaken by states to guarantee non-recurrence. Thus, I identify a number of areas which merit further cross-disciplinary study.
Molecular epidemiology of an extended multiple-species OXA-48 CPE outbreak in a hospital ward in Ireland, 2018–2019
Authors: Brehony Carina , Domegan Lisa , Foley Margaret , Fitzpatrick Margaret , Cafferkey Jacqueline P. , O’Connell Karina , Dinesh Binu , McNamara Eleanor , Duffy Fionnuala , Fitzpatrick Fidelma , Burns Karen 
Published: December 2021

Abstract

Objectives:
Molecular epidemiological description of an OXA-48 CPE outbreak affecting a tertiary-care hospital ward in Ireland over an extended period (2018–2019).

Methods:
Microbiological testing and whole-genome sequencing (WGS) were performed on all 56 positive OXA-48 outbreak case isolates.

Results:
In total, 7 different species were identified: Enterobacter hormaechei (n = 35, 62.5%), Escherichia coli (n = 12, 21.4%), Klebsiella pneumoniae (n = 5, 8.9%), Klebsiella oxytoca (n = 1, 1.8%), Klebsiella michiganensis (n = 1, 1.8%), Citrobacter freundii (n = 1, 1.8%), and Serratia marcesens (n = 1, 1.8%). E. hormaechei ST78 was the most common genotype (n = 14, 25%). Two major pOXA-48 plasmid types were identified throughout the outbreak, ‘types’ 1 and 2, and 5 major E. hormaechei clonal groupings were identified: ST78, ST108, ST1126, ST135, and ST66. Within each of the ST108, ST1126, ST135 and ST66 groups, the pOXA-48 harbored within each isolate were the same. Within ST78, 9 isolates contained the pOXA48 ‘type 2’ plasmid and 5 contained the ‘type 1’ plasmid. Environmental specimens were taken from different outbreak ward locations: handwash basins, sink and shower drains, and taps. Of 394 environmental specimens, OXA-48 CPE was isolated from 26 (6.6%).

Conclusions:
This prolonged outbreak of OXA-48 CPE was confined to one ward, but it exemplifies the complexity and difficulty in the control of these organisms. With multiple species and genotypes involved, they may be better described as ‘plasmid outbreaks.’ WGS provided insights into this diversity and potential transmission among cases, though its usefulness would be enhanced by analysis as close as possible to real time so that interventions can be implemented as soon as data are available.
Distribution of Gymnodinium catenatum Graham cysts and its relation to harmful algae blooms in the northern Gulf of California
Authors: Castañeda-Quezada Rigel , García-Mendoza Ernesto , Ramírez-Mendoza Rafael , Helenes Javier , Rivas David , Romo-Curiel Alfonsina E. , Lago-Lestón Asunción 
Published: December 2021

AbstractGermination of cysts serves as inoculum for the proliferation of some dinoflagellates, and cyst abundance in sediments represents crucial information to understand and possibly predict Harmful Algae Blooms (HABs). Cyst distribution is related to the physical characteristics of the sediments and the hydrodynamics (circulation) of a particular region. In the northern Gulf of California (nGC) several Gymnodinium catenatum HABs have been recorded. However, the presence of resting cysts and the effect of hydrodynamics on their distribution in the nGC have not been investigated. This study evaluated cyst abundance, distribution and their relation to local circulation in surface sediments during two periods that coincided with a non-bloom year condition (July 2016) and after a major HAB registered in the nGC that occurred in January 2017. Also, a numerical ocean model was implemented to characterize the transport and relocation of cysts and sediments in the region. Gymnodinium catenatum cysts were heterogeneously distributed with some areas of high accumulation (as high as 158 cyst g−1, and 27% of total cyst registered). Cysts seemed to be transported in an eastward direction after deposition and accumulated in an extensive area that probably is the seedbed responsible for the initiation of HABs in the region. The nGC is a retention area of cysts (and sediments) that permit the formation of seedbeds that could be important for G. catenatum HAB development. Our results provide key information to understand G. catenatum ecology and specifically, to understand the geographic and temporal appearance of HABs in the nGC.
Reverse Research Design: Research Design in the Undergraduate Classroom
Authors: Ayoub Phillip M. 
Published: December 2021

ABSTRACTTeaching research design is a core component of a political science curriculum. In our pedagogy, we often do two things separately: expecting students to (1) read and digest the work of established scholars, and (2) explore their own interests in the form of a research design or research paper. In a reverse research design, I bridge these two components with a pedagogical tool. I use a published book or article relevant to the course and students retrace the published author’s process, placing themselves in the author’s shoes. Rewinding some years, students imagine that they are this author writing a grant proposal to conduct the (now-completed) study. This helps students to work through the steps of research design, putting aside until later the more intimidating hurdle of articulating their own research question and project. This article explains reverse research design and describes the teaching resources and methods for implementation.
Unraveling the Controls on Snow Disappearance in Montane Conifer Forests Using Multi‐Site Lidar
Authors: Safa H. , Krogh S. A. , Greenberg J. , Kostadinov T. S. , Harpold A. A. 
Published: December 2021

AbstractSnow disappearance date (SDD) affects the ecohydrological dynamics of montane forests, by altering water availability, forest fire regime, and the land surface energy budget. The forest canopy modulates SDD through competing processes; dense canopy intercepts snowfall and enhances longwave radiation while shading snowpack from shortwave radiation and sheltering it from the wind. Limited ground‐based observations of snow presence and absence have restricted our ability to unravel the dominant processes affecting SDD in montane forests. We apply a lidar‐derived method to estimate fractional snow cover area (fSCA) at two relatively warm sites in the Sierra Nevada and two colder sites in the Rocky Mountains, which we link to SDD. With the exception of late season snowpack and low fSCA, snow retention is longer under low vegetation density than under high vegetation density in both warm and cold sites. Warm forests consistently have longer snow retention in open areas compared to dense under canopy areas, particularly on south‐facing slopes. Cold forests tend to have longer snow retention under lower density canopy compared to open areas, particularly on north‐facing slopes. We use this empirical analysis to make process inferences and develop an initial framework to predict SDD that incorporates the role of topography and vegetation structure. Building on our framework will be necessary to provide better forest management recommendations for snowpack retention across complex terrain and heterogenous canopy structure.
A Novel Network‐Based Approach to Determining Measurement Representation Error for Model Evaluation of Aerosol Microphysical Properties
Authors: Asher Elizabeth , Thornberry Troy , Fahey David W. , McComiskey Allison , Carslaw Kenneth , Grunau Sophie , Chang Kai‐Lan , Telg Hagen , Chen Ping , Gao Ru‐Shan 
Published: December 2021

AbstractAtmospheric aerosol size and abundance influence radiative effects and climate change. To date, efforts to constrain global climate models' radiative forcing with in situ aerosol observations have been hamstrung by uncertainty. One source of error, the regional “representation error,” arises when accurate but sparse single‐point measurements of atmospheric aerosol distributions are compared with a model value, assuming that the single‐point measurement is representative of the model domain. The Portable Optical Particle Spectrometer network in the Southern Great Plains (POPSnet‐SGP) campaign has demonstrated that a network of nearly autonomous aerosol instruments operating at ambient temperature and relative humidity (with low measurement error) may be used to quantify measurement representation error and investigate the factors introducing heterogeneity in aerosol distributions across a rural, continental background region. Measurements were made using Portable Optical Particle Spectrometer (POPS) instruments at several sites for five months across the Department of Energy's Aerosol Radiation Measurement Southern Great Plains (ARM‐SGP) User Facility in the central USA. Measurement representation error decreased with longer averaging periods (20%–40% between 1 s and 1 day), varied between sites by 10%–20% for aerosol concentration 140–2,500 nm in diameter (N_140), and was higher for aerosols >400 nm in diameter (N_400). Our measurements also show the influence of local meteorology on aerosol surface area (A_140) and size distributions: A_140 is positively correlated with wind speed and relative humidity, negatively correlated with precipitation, and lower given westerly winds. We conclude that the POPSnet approach provides considerably more insight into the spatial variability in the aerosol population that can be used to constrain climate models than would be available from similar networks of PM 2.5 monitors.
Ionospheric Disturbances Observed From a Single GPS Station in Hong Kong During the Passage of Super Typhoon Hato in 2017
Authors: Yu Shiwei , Liu Zhizhao , Lee Tsz Cheung 
Published: December 2021

AbstractThe powerful convection in the lower atmosphere, for example, tropical cyclones (TCs), has a high probability of causing ionospheric disturbances. We observed evident ionospheric disturbances during the passage of Super Typhoon Hato in 2017 by analyzing the highest elevation vertical total electron content (HeVTEC) time series, that is, the VTEC from the Global Positioning System (GPS) satellite with the highest elevation at each epoch, retrieved from a single GPS station in Hong Kong. The results demonstrate that the daily maximum of HeVTEC time series on each day during the TC period experienced a large fluctuation ranging from 33.5 TEC unit (TECU) to the peak value 62.0 TECU. The peak value 62.0 TECU occurred on the TC landfall day 23 August 2017, approximately twice as high as that of non‐TC‐impacted days. We also found that the TEC spatial gradients above the landfall area increased by around 50% and 200% in the north‐to‐south and west‐to‐east directions, respectively. We also examined the daily mean bias (MB) of VTEC above Hong Kong with respect to the mean VTEC during the past 27 days from 20 July to 15 August in 2017. The largest VTEC MB was observed in the west of the landfall area along the TC moving direction, on the TC landfall day. Our findings provided the evidence that the Hato's landfall over the coast near Hong Kong caused the apparent ionospheric disturbances above the landfall area.
Identification of Characteristic Spatial Scales to Improve the Performance of Analytical Spectral Solutions to the Groundwater Flow Equation
Authors: Perez Gabriel , Gomez‐Velez Jesus D. , Chen Xingyuan , Scheibe T. , Chen Yunxiang , Bao Jie 
Published: December 2021

AbstractAnalytical solutions for the three‐dimensional groundwater flow equation have been widely used to gain insight about subsurface flow structure and as an alternative to computationally expensive numerical models. Of particular interest are solutions that decompose prescribed hydraulic head boundaries (e.g., Dirichlet boundary condition) into a collection of harmonic functions. Previous studies estimate the frequencies and amplitudes of these harmonics with a least‐square approach where the amplitudes are fitted given a pre‐assigned set of frequencies. In these studies, an ad hoc and structured discretization of the frequency domain is typically used, excluding dominant frequencies while assigning importance to spurious frequencies, with significant consequences for estimating the fluxes and residence times. This study demonstrates the advantages of using a pre‐assigned frequency spectrum that targets the dominant frequencies based on rigorous statistical analysis with predefined significance levels. The new approach is tested for three hydrologic conceptualizations: (a) a synthetic periodic basin, (b) synthetic bedforms, and (c) a natural mountainous watershed. The performance of the frequency spectrum selection is compared with exact analytical or approximate numerical solutions. We found that the new approach better describes the fluxes and residence times for Dirichlet boundaries with well‐defined characteristics spatial scales (e.g., periodic basins and bedforms). For more complex scenarios, such as natural mountainous watersheds, both pre‐assigned frequency spectrums present similar performance. The spectral solutions presented here can play a central role in developing reduced‐complexity models for assessing regional water and solute fluxes within mountain watersheds and hyporheic zones.
Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease
Authors: Xiong Liu-Lin , Xue Lu-Lu , Du Ruo-Lan , Niu Rui-Ze , Chen Li , Chen Jie , Hu Qiao , Tan Ya-Xin , Shang Hui-Fang , Liu Jia , Yu Chang-Yin , Wang Ting-Hua 
Published: December 2021

AbstractIn recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.
Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system
Authors: Barbu Miruna C. , Huider Floris , Campbell Archie , Amador Carmen , Adams Mark J. , Lynall Mary-Ellen , Howard David M. , Walker Rosie M. , Morris Stewart W. , Van Dongen Jenny , Porteous David J. , Evans Kathryn L. , Bullmore Edward , Willemsen Gonneke , Boomsma Dorret I. , Whalley Heather C. , McIntosh Andrew M. 
Published: December 2021

AbstractAntidepressants are an effective treatment for major depressive disorder (MDD), although individual response is unpredictable and highly variable. Whilst the mode of action of antidepressants is incompletely understood, many medications are associated with changes in DNA methylation in genes that are plausibly linked to their mechanisms. Studies of DNA methylation may therefore reveal the biological processes underpinning the efficacy and side effects of antidepressants. We performed a methylome-wide association study (MWAS) of self-reported antidepressant use accounting for lifestyle factors and MDD in Generation Scotland (GS:SFHS,N = 6428, EPIC array) and the Netherlands Twin Register (NTR,N = 2449, 450 K array) and ran a meta-analysis of antidepressant use across these two cohorts. We found ten CpG sites significantly associated with self-reported antidepressant use in GS:SFHS, with the top CpG located within a gene previously associated with mental health disorders,ATP6V1B2(β = −0.055,pcorrected = 0.005). Other top loci were annotated to genes includingCASP10, TMBIM1, MAPKAPK3, andHEBP2, which have previously been implicated in the innate immune response. Next, using penalised regression, we trained a methylation-based score of self-reported antidepressant use in a subset of 3799 GS:SFHS individuals that predicted antidepressant use in a second subset of GS:SFHS (N = 3360,β = 0.377,p = 3.12 × 10−11,R2 = 2.12%). In an MWAS analysis of prescribed selective serotonin reuptake inhibitors, we showed convergent findings with those based on self-report. In NTR, we did not find any CpGs significantly associated with antidepressant use. The meta-analysis identified the two CpGs of the ten above that were common to the two arrays used as being significantly associated with antidepressant use, although the effect was in the opposite direction for one of them. Antidepressants were associated with epigenetic alterations in loci previously associated with mental health disorders and the innate immune system. These changes predicted self-reported antidepressant use in a subset of GS:SFHS and identified processes that may be relevant to our mechanistic understanding of clinically relevant antidepressant drug actions and side effects.
Nucleolar stress controls mutant Huntington toxicity and monitors Huntington’s disease progression
Authors: Sönmez Aynur , Mustafa Rasem , Ryll Salome T. , Tuorto Francesca , Wacheul Ludivine , Ponti Donatella , Litke Christian , Hering Tanja , Kojer Kerstin , Koch Jenniver , Pitzer Claudia , Kirsch Joachim , Neueder Andreas , Kreiner Grzegorz , Lafontaine Denis L. J. , Orth Michael , Liss Birgit , Parlato Rosanna 
Published: December 2021

AbstractTranscriptional and cellular-stress surveillance deficits are hallmarks of Huntington’s disease (HD), a fatal autosomal-dominant neurodegenerative disorder caused by a pathological expansion of CAG repeats in the Huntingtin (HTT) gene. The nucleolus, a dynamic nuclear biomolecular condensate and the site of ribosomal RNA (rRNA) transcription, is implicated in the cellular stress response and in protein quality control. While the exact pathomechanisms of HD are still unclear, the impact of nucleolar dysfunction on HD pathophysiology in vivo remains elusive. Here we identified aberrant maturation of rRNA and decreased translational rate in association with human mutant Huntingtin (mHTT) expression. The protein nucleophosmin 1 (NPM1), important for nucleolar integrity and rRNA maturation, loses its prominent nucleolar localization. Genetic disruption of nucleolar integrity in vulnerable striatal neurons of the R6/2 HD mouse model decreases the distribution of mHTT in a disperse state in the nucleus, exacerbating motor deficits. We confirmed NPM1 delocalization in the gradually progressing zQ175 knock-in HD mouse model: in the striatum at a presymptomatic stage and in the skeletal muscle at an early symptomatic stage. In Huntington’s patient skeletal muscle biopsies, we found a selective redistribution of NPM1, similar to that in the zQ175 model. Taken together, our study demonstrates that nucleolar integrity regulates the formation of mHTT inclusions in vivo, and identifies NPM1 as a novel, readily detectable peripheral histopathological marker of HD progression.