bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol‐enriched diet induces endosome/lysosome dysfunction in a rabbit model of inclusion body myositis
Authors: Chen Xuesong , Wagener John F. , Ghribi Othman , Geiger Jonathan D. 
Published: June 2021

Inclusion body myositis (IBM) is the most common myopathy in people over 50 years of age. The pathogenesis of IBM is poorly understood and no effective treatment is available. We have shown that rabbits fed a high cholesterol diet developed IBM‐like pathology, but the underlying mechanism is not clear. Recent studies indicate that vacuoles in human IBM muscle fiber are of endocytic origin and it is well known that the major source of cholesterol in skeletal muscle is via uptake through receptor‐mediated endocytosis. The present study tested the hypothesis that increased levels of cholesterol induce IBM‐like pathology by affecting endosomes/lysosomes. In rabbits fed a 2% cholesterol diet for 12 weeks we tested this hypothesis using immunostaining, immunoblotting and enzyme activity assays. We found that vacuoles induced by cholesterol‐enriched diet were enlarged endosomes/lysosomes; sites where free cholesterol accumulated. The cholesterol‐enriched diet also decreased the specific activities of three lysosomal enzymes. Moreover, the cholesterol‐enriched diet increased the accumulation of amyloid beta, phosphorylated tau and ubiquitin in endosomes/lysosomes. Our results indicate that cholesterol‐enriched diet induces IBM‐like pathology by disturbing endosome/lysosome function.(Supported by P20RR17699 from the National Center for Research Resources, a component of the NIH)
The barrier functions of crude cervical mucus plugs against HIV-1 infection in the context of cell-free and cell-to-cell transmission
Authors: Mhlekude Baxolele , Lenman Annasara , Sidoyi Phikolomzi , Joseph Jim , Kruppa Jochen , Businge Charles Bitamazire , Mdaka Mana Lungisa , Konietschke Frank , Pich Andreas , Gerold Gisa , Goffinet Christine , Mall Anwar Suleman 
Published: June 2021

Objective:
The cervical mucus plugs are enriched with proteins of known immunological functions. We aimed to characterize the anti-HIV-1 activity of the cervical mucus plugs against a panel of different HIV-1 strains in the contexts of cell-free and cell-associated virus.

Design:
A cohort of consenting HIV-1-negative and HIV-1-positive pregnant women in labour was recruited from Mthatha General Hospital in the Eastern Cape province of South Africa, from whom the cervical mucus plugs were collected in 6 M guanidinium chloride with protease inhibitors and transported to our laboratories at −80 °C.

Methods:
Samples were centrifuged to remove insoluble material and dialysed before freeze--drying and subjecting them to the cell viability assays. The antiviral activities of the samples were studied using luminometric reporter assays and flow cytometry. Time-of-addition and BlaM-Vpr virus-cell fusion assays were used to pin-point the antiviral mechanisms of the cervical mucus plugs, before proteomic profiling using liquid chromatography-tandem mass spectrometry.

Results:
The proteinaceous fraction of the cervical mucus plugs exhibited anti-HIV-1 activity with inter-individual variations and some degree of specificity among different HIV-1 strains. Cell-associated HIV-1 was less susceptible to inhibition by the potent samples whenever compared with the cell-free HIV-1. The samples with high antiviral potency exhibited a distinct proteomic profile when compared with the less potent samples.

Conclusion:
The crude cervical mucus plugs exhibit anti-HIV-1 activity, which is defined by a specific proteomic profile.
White Matter Disease—The True Source of Triphasic Waves?
Authors: Freund Brin , Kotchetkov Ivan S. , Kaplan Peter W. 
Published: June 2021

Summary:
Triphasic waves are EEG phenomena typically seen in patients with acute encephalopathy and have importance in diagnosis and prognosis in these cases. The underlying metabolic disturbances associated with their incidence have been described previously, but neuroimaging characteristics are not well delineated. There are a few small studies that define neuroimaging results in patients with triphasic waves. This review highlights the most common neuroimaging findings in these patients, including subcortical white matter disease, which itself may be a risk factor for triphasic waves.
Can We Distinguish Triphasic Waves From Other Generalized Periodic Discharges? Do We Need to?
Authors: Foreman Brandon 
Published: June 2021

Summary:
Triphasic waves are intuitively distinctive waveforms that fall under the umbrella of generalized periodic discharges. The ability to distinguish these waveforms consistently could be helpful if a specific underlying pathophysiology could be identified. However, scalp EEG and clinical observation have been limited in their ability to elucidate the underlying cortical physiology that leads to triphasic waves. Evidence from intracranial physiologic data and computational modeling suggest that these and other periodic discharges should be viewed not as strictly ictal nor non-ictal but rather on the spectrum between these two. Triphasic waves in particular appear to result from an abnormal balance between cortical excitation and synaptic transmission with input from functionally connected brain networks, such as the thalamocortical pathways involved in arousal. The practical implication of triphasic waves begins with acknowledgement of uncertainty and a rational approach should ask whether the pattern—or its treatment–might be creating harm.
Sepsis Subphenotyping Based on Organ Dysfunction Trajectory
Authors: Xu Zhenxing , Mao Chengsheng , Su Chang , Zhang Hao , Siempos Ilias , Torres Lisa K , Pan Di , Luo Yuan , Schenck Edward J , Wang Fei 
Published: June 2021

ABSTRACTBackgroundSepsis is a heterogeneous syndrome, and the identification of clinical subphenotypes is essential. Although organ dysfunction is a defining element of sepsis, subphenotypes of differential trajectory are not well studied. We sought to identify distinct Sequential Organ Failure Assessment (SOFA) score trajectory-based subphenotypes in sepsis.MethodsWe created 72-hour SOFA score trajectories in patients with sepsis from four diverse intensive care unit (ICU) cohorts. We then used Dynamic Time Warping (DTW) to compute heterogeneous SOFA trajectory similarities and hierarchical agglomerative clustering (HAC) to identify trajectory-based subphenotypes. Patient characteristics were compared between subphenotypes and a random forest model was developed to predict subphenotype membership at 6 and 24 hours after being admitted to the ICU. The model was tested on three validation cohorts. Sensitivity analyses were performed with alternative clustering methodologies.ResultsA total of 4678, 3665, 12282, and 4804 unique sepsis patients were included in development and three validation cohorts, respectively. Four subphenotypes were identified in the development cohort: Rapidly Worsening (n=612, 13.1%), Delayed Worsening (n=960, 20.5%), Rapidly Improving (n=1932, 41.3%) and Delayed Improving (n=1174, 25.1%). Baseline characteristics, including the pattern of organ dysfunction varied between subphenotypes. Rapidly Worsening was defined by a higher comorbidity burden, acidosis, and visceral organ dysfunction. Rapidly Improving was defined by vasopressor use without acidosis. Outcomes differed across the subphenotypes, Rapidly Worsening had the highest in-hospital mortality (28.3%, p-value<0.001), despite a lower SOFA (mean: 4.5) at ICU admission compared to Rapidly Improving (mortality:5.5%, mean SOFA: 5.5). An overall prediction accuracy of 0.78 (95% CI, [0.77, 0.8]) was obtained at 6 hours after ICU admission, which increased to 0.87 (95% CI, [0.86, 0.88]) at 24 hours. Similar subphenotypes were replicated in three validation cohorts. The majority of patients with sepsis have an improving phenotype with a lower mortality risk, however they make up over 20% of all deaths due to their larger numbers.ConclusionsFour novel, clinically-defined, trajectory-based sepsis subphenotypes were identified and validated. Identifying trajectory-based subphenotypes has immediate implications for the powering and predictive enrichment of clinical trials. Understanding the pathophysiology of these differential trajectories may reveal unanticipated therapeutic targets and identify more precise populations and endpoints for clinical trials.
Genetic overlap between multivariate measures of human functional brain connectivity and psychiatric disorders
Authors: Roelfs Daniel , van der Meer Dennis , Alnæs Dag , Frei Oleksandr , Shadrin Alexey A. , Loughnan Robert , Fan Chun Chieh , Dale Anders M. , Andreassen Ole A. , Westlye Lars T. , Kaufmann Tobias 
Published: June 2021

AbstractPsychiatric disorders are complex, heritable, and highly polygenic. Supported by findings of abnormalities in functional magnetic resonance imaging (fMRI) based measures of brain connectivity, current theoretical and empirical accounts have conceptualized them as disorders of brain connectivity and dysfunctional integration of brain signaling, however, the extent to which these findings reflect common genetic factors remains unclear. Here, we performed a multivariate genome-wide association analysis of fMRI-based functional brain connectivity in a sample of 30,701 individuals from the UK Biobank and investigated the shared genetic determinants with eight major psychiatric disorders. The analysis revealed significant genetic overlap between functional brain connectivity and schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, autism spectrum disorder, anxiety, and major depression, adding further genetic support for the dysconnectivity hypothesis of psychiatric disorders and identifying potential genetic and functional targets for future studies.
A polygenic risk score predicts mosaic loss of chromosome Y in circulating blood cells
Authors: Riaz Moeen , Mattisson Jonas , Polekhina Galina , Bakshi Andrew , Halvardson Jonatan , Danielsson Marcus , Ameur Adam , McNeil John , Forsberg Lars A. , Lacaze Paul 
Published: June 2021

AbstractMosaic loss of Y chromosome (LOY) in leukocytes is associated with risk for death and disease in men. We investigated a polygenic risk score (PRS) for LOY comprising 156 previously associated germline variants, in 5131 men aged ≥70 years. Levels of LOY were estimated using microarrays and validated by whole genome sequencing. After adjusting for covariates, the PRS was a significant predictor of LOY (odds ratio 1.74). Men in the highest quintile of the PRS distribution had >5-fold higher risk of LOY than the lowest. A PRS for LOY could become a useful tool for risk prediction and targeted intervention.
Forecast verifications for the real COVID-19 pandemic dynamics in Qatar
Authors: Nesteruk Igor 
Published: June 2021

ABSTRACTThe COVID-19 pandemic dynamics in Qatar in the second half of May and the first half of June 2021 was compared with the published results of SIR-simulations based on the data from the period April 25 - May 8, 2021. Forecast verification showed very good agreement with the real number of cases (which can exceed the laboratory-confirmed one more than 5 times). The positive effect of mass vaccination became visible in June 2021.
A physically plausible incidence rate for compartmental epidemiological models
Authors: Pitschel Thomas 
Published: June 2021

AbstractMotivated by the recent trajectory of SARS-Cov-2 new infection incidences in Germany and other European countries, this note reconsiders the need to use a non-linear incidence rate function in deterministic compartmental models for current SARS-Cov-2 epidemic modelling. Employing a homogenous contact model, it derives such function systematically using stochastic arguments. The presented result, which is relevant to modelling of proliferation of arbitrary infectious diseases, integrates well with previous analyses, in particular closes an analytical “gap” mentioned in London and Yorke (1973) and complements the stability related work on incidence rate functions of the form βIpSq seen for example in Liu, Hethcote and Levin (1987).
VEGF-A, PDGF-BB and HB-EGF engineered for promiscuous super affinity to the extracellular matrix improve wound healing in a model of type 1 diabetes
Authors: White Michael JV , Briquez Priscilla S , White David AV , Hubbell Jeffrey A 
Published: June 2021

AbstractChronic non-healing wounds, frequently caused by diabetes, lead to lower quality of life, infection, and amputation. These wounds have limited treatment options. We have previously engineered growth factors to bind to exposed extracellular matrix (ECM) in the wound environment using the heparin-binding domain of placental growth factor-2 (PlGF-2123-144), which binds promiscuously to ECM proteins. Here, in the type 1 diabetic (T1D) NOD mouse model, engineered growth factors improved both re-epithelialization and granulation tissue formation. Engineered growth factors were even more potent in combination, and the “triple therapy” of vascular endothelial growth factor-A (VEGF-PlGF-2123-144), platelet-derived growth factor-BB (PDGF-BB-PlGF-2123-144), and heparin-binding epidermal-growth factor (EGF-PlGF-2123-144) both improved wound healing and remained at the site of administration for significantly longer than wild-type growth factors. In addition, we also found that changes in the cellular milieu of a wound, including changing amounts of M1 macrophages, M2 macrophages and effector T cells, are most predictive of wound healing success in the NOD mouse model. These results suggest that the triple therapy of VEGF-PlGF-2123-144, PDGF-BB-PlGF-2123-144, and EGF-PlGF-2123-144may be an effective therapy for chronic non-healing wounds in that occur as a complication of diabetes.
Consumption attitudes and behaviors in Asia: a “discovery-oriented” fresh look
Authors: Batra Rajeev , Li Dongmei , Chiu Chi-Yue 
Published: June 2021

PurposeThis paper aims to identify distinct consumption patterns among Asian consumers and examine how these relate to cultural antecedents and key human values.Design/methodology/approachThis study uses a large, representative sample of almost 7,000 Asian consumers in 10 culturally varying markets, using latent profile analysis (LPA) to identify the consumption profiles.FindingsThe findings empirically demonstrate that the two profiles are “inner-directed nationalistic frugals” (IDNF) and “outer-directed self-eekers” (ODSS). IDNF consumers spend more time and money on education and prefer ethnocentric consumption. ODSS consumers emphasize individuality, self-expression, seeking novelty and impressing others. Consumers with more collective values in Schwartz's typology tend to demonstrate the IDNF pattern; those with more individualistic values demonstrate the ODSS pattern. The distribution of IDNF and ODSS profiles is influenced by demographics, religion and geographical region: IDNF is greater than ODSS in Southeast Asia; ODSS is greater than IDNF in East Asia; IDNF is roughly equal to ODSS in Northeast Asia. IDNF tends to be found among older and more religious consumers, while ODSS is the opposite. Importantly, in the more religious Southeast Asian countries, even younger consumers are more IDNF than ODSS.Research limitations/implicationsThis research uses an exploratory and discovery-oriented approach; future research can use more confirmatory approaches to systematically examine the relationship between cultural dimensions (e.g. individualism-collectivism) and consumption patterns.Practical implicationsFor their brands to grow in Asian markets, marketing practitioners are advised to use multiple brands to segment Asian consumers based on their values, demographics, geographical location and what religious/faith traditions they follow.Originality/valueThis is the first paper to identify consumption profiles in Asian markets using LPA without prior conceptual biases and relate them to cultural values and demographic variables.
Introducing a fuzzy MCDM model for financial management in multiple project environments
Authors: Afshar Mohammad Reza , Asadzadeh Zenozi Hamed 
Published: June 2021

Purpose
Statistics in the construction industry show that lack of timely injection of funds to projects by clients is one of the common problems confronted by contractors. This problem is intensified when contractors construct multiple projects simultaneously. In these situations, it is rational that contractors share their financial resources among projects according to project conditions and the firm’s vision. This study aims to propose a fuzzy multi-criteria decision making (MCDM) model for financial management in multiple project environments.

Design/methodology/approach
First, the project evaluation criteria are defined using exploratory study and interviews with experts. Second, the weights of criteria are determined based on company strategies. Then, each of the projects are evaluated in each criterion. Finally, the fuzzy weighted average approach is used to determine the proportion of each project from the financial resources.

Findings
The proposed model is prepared as an applicable model for general contractors to assign financial recourses among the multiple projects optimally.

Originality/value
As a lack of applicable model assigning the financial resources among the multiple projects, this study is one of the first research studies that proposed a fuzzy MCDM model to assign financial resources to multiple projects optimally.
Student venture creation: developing social networks within entrepreneurial ecosystems in the transition from student to entrepreneur
Authors: Longva Kjersti Kjos 
Published: June 2021

PurposeThe purpose of the paper is to provide insight into how students navigate entrepreneurial ecosystems and make use of social networks as they create their own ventures. Such ecosystems for students are an understudied phenomenon and there is a need for more profound insights into the issue in order to build better support systems for student entrepreneurs. The study aims to increase understanding on the elements that are important in students' entrepreneurial ecosystems and how these impact on students' venture creation processes, with emphasize on the role social networks play. Student entrepreneurs account for a substantial number of the startups that come into being at universities. Understanding more about how the surroundings affects this process is important for facilitating student entrepreneurship in higher education.Design/methodology/approachThe study is qualitative and makes use of in-depth interviews with student entrepreneurs, educators and support actors in the ecosystems. Multiple actors were interviewed in order to capture different perspectives on the matter, with a total of 15 interviews conducted.FindingsTwo main findings arose from the study. First, it provides insight into elements that are perceived as important for student venture creation by the student entrepreneurs themselves, by educators and by support actors in the ecosystems. Second, it describes how the elements make up the entrepreneurial ecosystems surrounding the students, which serve as platforms from which students can develop their social networks. Therefore, the study highlights how such ecosystems can serve as sources from which students can gain access to ideas, resources and identity processes.Research limitations/implicationsA limitation of the study is that the interviews took place in one country. Consequently, further investigation is necessary to establish whether the findings are valid in other contexts. The research has implications for higher educational institutions, policymakers and researchers concerned with student entrepreneurship and student venture creation.Originality/valueThe study contributes empirical findings on a topic that is currently not well understood and on which there are few empirical studies. While student ventures represent a substantial proportion of university spin-offs, the topic has received little attention compared to research on academic entrepreneurship. The study represents a step towards enhancing understanding of students' entrepreneurial ecosystems and how students gain access to resources through social network ties within these systems.
Websites' hue-context congruence as a vector of trust and behavioral intentions
Authors: Khrouf Lilia , Frikha Azza 
Published: June 2021

PurposeThis paper aims to determine the effect of the congruence between a website's background color and its context (product category) on online trust and resulting behavioral intentions in emerging markets.Design/methodology/approachAn online experiment, conducted on 240 web-surfers, compared two versions of a website (high vs low color-context congruence) in terms of online trust and resulting behavioral intentions. The authors also studied the moderating role of the online shopping experience on the color-context congruence impact on online trust.FindingsResults revealed that a website's color-context congruence enhances online trust. The authors have also demonstrated that online trust plays a mediating role in the relationship between color-context congruence and behavioral intentions. Moreover, they found out that the influence of the color-context congruence on online trust is enhanced when the web-surfer is highly experienced in online shopping.Research limitations/implicationsThis research contributes to fill in the theoretical gaps and to better understand the influence of color-context congruence on online trust and behavioral intentions in emerging markets. Indeed, past studies had focused on the color impact on online trust without taking into consideration congruence with the website context. However, this study is limited to a single category of products (tourist products) and only two colors (blue and red) were manipulated in the experiment.Practical implicationsThis study highlights the importance of selecting a background's color that matches with the sold product category to reassure web-surfers so that they trust the commercial website and express some favorable intentions like buying.Originality/valuePrior studies had focused on the website's color effect on online trust neglecting color-context congruence. Our study helps to highlight the importance of selecting background colors matching the product category.