bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in DNA methylation profiles of myalgic encephalomyelitis/chronic fatigue syndrome patients reflect systemic dysfunctions
Authors: Helliwell A. M. , Sweetman E. C. , Stockwell P. A. , Edgar C. D. , Chatterjee A. , Tate W. P.
Published: November 2020

Background

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a lifelong debilitating disease with a complex pathology not yet clearly defined. Susceptibility to ME/CFS involves genetic predisposition and exposure to environmental factors, suggesting an epigenetic association. Epigenetic studies with other ME/CFS cohorts have used array-based technology to identify differentially methylated individual sites. Changes in RNA quantities and protein abundance have been documented in our previous investigations with the same ME/CFS cohort used for this study.

Results

DNA from a well-characterised New Zealand cohort of 10 ME/CFS patients and 10 age-/sex-matched healthy controls was isolated from peripheral blood mononuclear (PBMC) cells, and used to generate reduced genome-scale DNA methylation maps using reduced representation bisulphite sequencing (RRBS). The sequencing data were analysed utilising the DMAP analysis pipeline to identify differentially methylated fragments, and the MethylKit pipeline was used to quantify methylation differences at individual CpG sites. DMAP identified 76 differentially methylated fragments and Methylkit identified 394 differentially methylated cytosines that included both hyper- and hypo-methylation. Four clusters were identified where differentially methylated DNA fragments overlapped with or were within close proximity to multiple differentially methylated individual cytosines. These clusters identified regulatory regions for 17 protein encoding genes related to metabolic and immune activity. Analysis of differentially methylated gene bodies (exons/introns) identified 122 unique genes. Comparison with other studies on PBMCs from ME/CFS patients and controls with array technology showed 59% of the genes identified in this study were also found in one or more of these studies. Functional pathway enrichment analysis identified 30 associated pathways. These included immune, metabolic and neurological-related functions differentially regulated in ME/CFS patients compared to the matched healthy controls.

Conclusions

Major differences were identified in the DNA methylation patterns of ME/CFS patients that clearly distinguished them from the healthy controls. Over half found in gene bodies with RRBS in this study had been identified in other ME/CFS studies using the same cells but with array technology. Within the enriched functional immune, metabolic and neurological pathways, a number of enriched neurotransmitter and neuropeptide reactome pathways highlighted a disturbed neurological pathophysiology within the patient group.
APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer’s disease: a systematic review
Authors: Emrani Sheina , Arain Hirra A. , DeMarshall Cassandra , Nuriel Tal
Published: November 2020

Possession of the ε4 allele of apolipoprotein E (APOE) is the primary genetic risk factor for the sporadic form of Alzheimer’s disease (AD). While researchers have extensively characterized the impact that APOE ε4 (APOE4) has on the susceptibility of AD, far fewer studies have investigated the phenotypic differences of patients with AD who are APOE4 carriers vs. those who are non-carriers. In order to understand these differences, we performed a qualitative systematic literature review of the reported cognitive and pathological differences between APOE4-positive (APOE4+) vs. APOE4-negative (APOE4−) AD patients. The studies performed on this topic to date suggest that APOE4 is not only an important mediator of AD susceptibility, but that it likely confers specific phenotypic heterogeneity in AD presentation, as well. Specifically, APOE4+ AD patients appear to possess more tau accumulation and brain atrophy in the medial temporal lobe, resulting in greater memory impairment, compared to APOE4− AD patients. On the other hand, APOE4− AD patients appear to possess more tau accumulation and brain atrophy in the frontal and parietal lobes, resulting in greater impairment in executive function, visuospatial abilities, and language, compared to APOE4+ AD patients. Although more work is necessary to validate and interrogate these findings, these initial observations of pathological and cognitive heterogeneity between APOE4+ vs. APOE4− AD patients suggest that there is a fundamental divergence in AD manifestation related to APOE genotype, which may have important implications in regard to the therapeutic treatment of these two patient populations.
Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells
Authors: Hong Taeui , Kim Moon Young , Da Ly Dat , Park Su Jung , Eom Young Woo , Park Kyu-Sang , Baik Soon Koo
Published: November 2020

Although mitochondrial functions are essential for cell survival, their critical roles in stem cell fate, including proliferation, differentiation, and senescence, remain elusive. Ginsenoside Rg3 exhibits various biological activities and reportedly increases mitochondrial biogenesis and respiration. Herein, we observed that Rg3 increased proliferation and suppressed senescence of human bone marrow-derived mesenchymal stem cells. Osteogenic, but not adipogenic, differentiation was facilitated by Rg3 treatment. Rg3 suppressed reactive oxygen species production and upregulated mitochondrial biogenesis and antioxidant enzymes, including superoxide dismutase. Consistently, Rg3 strongly augmented basal and ATP synthesis-linked respiration with high spare respiratory capacity. Rg3 treatment elevated cytosolic Ca2+ concentration contributing to mitochondrial activation. Reduction of intracellular or extracellular Ca2+ levels strongly inhibited Rg3-induced activation of mitochondrial respiration and biogenesis. Taken together, Rg3 enhances capabilities of mitochondrial and antioxidant functions mainly through a Ca2+-dependent pathway, which improves the proliferation and differentiation potentials and prevents the senescence of human mesenchymal stem cells.
The in vitro efficacy of eye drops containing a bacteriophage solution specific for Staphylococcus spp. isolated from dogs with bacterial conjunctivitis
Authors: Urban-Chmiel Renata , Balicki Ireneusz , Świąder Katarzyna , Nowaczek Anna , Pyzik Ewelina , Stępień-Pyśniak Dagmara , Marek Agnieszka , Puchalski Andrzej , Wernicki Andrzej , Poleszak Ewa , Dec Marta
Published: November 2020

Background

The purpose of the study was to evaluate the in vitro antibacterial effect of experimental eye drops with bacteriophages in elimination of Staphylococcus spp. isolated from dogs with bacterial conjunctivitis.. The bacterial material was collected from dogs with independent clinical signs of bacterial conjunctivitis. Staphylococcus spp. were identified by phenotypic and genotypic methods (MALDI-TOF MS mass spectrometry). Antibiotic resistance was determined by the disc-diffusion method. Phage activity (Plaque forming units, PFU) was determined on double-layer agar plates. Phages with lytic titres > 108 PFU were used to prepare eye drops. The stability of the antibacterial titre was evaluated for preparations stored in sealed bottles as well as after opening and reclosing.

Results

The tests confirmed the occurrence of Staphylococcus spp. strains as etiological agents of bacterial conjunctivitis in dogs. A high percentage of strains were resistant to more than three antibiotics. The experimental phage eye drops used in the study exhibited 100% efficacy in vitro against the tested Staphylococcus isolates. Particularly noteworthy is the long duration of activity and constant antibacterial lytic titre of ≥108 PFU/mL of two eye drop solutions, nos. 7 and 12, after the bottle had been opened (21 days) and after hermetically sealed packaging (28 days) at 4–8 °C.

Conclusions

The results represent the first stage of research and require continuation in vivo. If positive effects are obtained in animals, the results can be used in applied research in humans and animals.
A note on Nakano generalized difference sequence space
Authors: Bakery Awad A. , Elmatty Afaf R. Abou
Published: November 2020

In this paper, we investigate the necessary conditions on any s-type sequence space to form an operator ideal. As a result, we show that the s-type Nakano generalized difference sequence space X fails to generate an operator ideal. We investigate the sufficient conditions on X to be premodular Banach special space of sequences and the constructed prequasi-operator ideal becomes a small, simple, and closed Banach space and has eigenvalues identical with its s-numbers. Finally, we introduce necessary and sufficient conditions on X explaining some topological and geometrical structures of the multiplication operator defined on X.
A decade of antimicrobial resistance research in social science fields: a scientometric review
Authors: Lu Jiahui , Sheldenkar Anita , Lwin May Oo
Published: November 2020

Background

Though social sciences are expectedly instrumental in combating antimicrobial resistance (AMR), their research on AMR has been historically lacking.

Objectives

This study aims to understand the current academic literature on AMR within the social science field by investigating international contributions, emerging topics, influential articles, and prominent outlets, to identify research gaps and future directions.

Methods

Bibliometric data of 787 peer-reviewed journal articles published in the period of 2010 to 2019 were extracted from the Social Science Citation Index in the Web of Science database. Bibliographic networks of the extracted articles were examined.

Results

Social science research on AMR has grown rapidly in the past 5 years. While western developed countries contributed the most to the field in the past decade, research within developing regions such as Asia and Africa have increased in the last 2 years. Social sciences have been contributing to AMR research in several different domains from surveillance and risk assessment of AMR, to promotions of appropriate use of antimicrobials in primary care and clinical settings. Though the idea of one health has been incorporated into research on AMR within the medical and microbial science fields, it has not been well recognized by social sciences.

Conclusion

Social science research on AMR is a new, while rapidly developing, research area that requires continued and intense global efforts from an interdisciplinary and one health approach. Research on social issues surrounding AMR transmissions between human, animal, and environments should be emphasized in the future.
Assessment of geographical origin and production period of royal jelly by NMR metabolomics
Authors: Mazzei Pierluigi , Piccolo Alessandro , Brescia Marianna , Caprio Emilio
Published: November 2020

Background

Royal jelly (RJ) represents the most valuable product of beekeeping activities. The illegal introduction of RJ of uncertain quality/origin in European agrofood markets is not controlled, since the conventional analytical methods cannot unambiguously distinguish foreign from autochthonous RJ products. Here, we applied liquid-state NMR spectroscopy combined with chemometry to characterize the metabolic profile of representative Italian high-quality RJ products and evaluate the discrimination capacity of this analytical technique.

Materials and methods

RJ samples were supplied by an Italian consortium of royal jellies producers and developed in the period May–July 2016. Samples were dissolved in a deuterated water solution brought at pH 7.3 and analysed through high resolution liquid-state NMR spectroscopy. 1D and 2D homo- and heteronuclear experiments were acquired to identify the RJ metabolomics profile. Proton NMR spectra were elaborated to conduct an NMR-based metabolomic approach based on PCA and DA chemometric analyses.

Results

The NMR-based metabolomics precisely and significantly (pvalue < 0.05, according to Benjamini-Hochberg’s test) authenticated the RJ products, by reliably tracing both their geographical and botanical origin, as well as their production period. In particular, Chinese RJ products exhibited a larger amount of citrate and lysine, accompanied by a lower content of 10-HDA. Our results showed that NMR spectroscopy can recognize low-quality fraudulent products and become an useful analytical tool to certify and trace the RJ molecular composition.

Conclusions

The application of NMR spectroscopy promises to enable the efficient protection of both the producers and consumers of high-quality royal jelly. In addition, the proposed method may be used in combination with the conventional melissopalynological methods for recognizing frauds.
Correction to: A full sequence of the Matuyama–Brunhes geomagnetic reversal in the Chiba composite section, Central Japan
Authors: Haneda Yuki , Okada Makoto , Suganuma Yusuke , Kitamura Takahiro
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
Prevalence and factors associated with neonatal hypoglycemia in Northern Uganda: a community-based cross-sectional study
Authors: Mukunya David , Odongkara Beatrice , Piloya Thereza , Nankabirwa Victoria , Achora Vincentina , Batte Charles , Ditai James , Tylleskar Thorkild , Ndeezi Grace , Kiguli Sarah , Tumwine James K.
Published: November 2020

Background

Neonatal hypoglycemia is the most common endocrine abnormality in children, which is associated with increased morbidity and mortality. The burden and risk factors of neonatal hypoglycemia in rural communities in sub-Saharan Africa are unknown.

Objective

To determine the prevalence and risk factors for neonatal hypoglycemia in Lira District, Northern Uganda.

Methods

This was a community-based cross-sectional study, nested in a cluster randomized controlled trial designed to promote health facility births and newborn care practices in Lira District, Northern Uganda. This study recruited neonates born to mothers in the parent study. Random blood glucose was measured using an On Call® Plus glucometer (ACON Laboratories, Inc., 10125 Mesa Road, San Diego, CA, USA). We defined hypoglycemia as a blood glucose of < 47 mg/dl. To determine the factors associated with neonatal hypoglycemia, a multivariable linear regression mixed-effects model was used.

Results

We examined 1416 participants of mean age 3.1 days (standard deviation (SD) 2.1) and mean weight of 3.2 kg (SD 0.5). The mean neonatal blood glucose level was 81.6 mg/dl (SD 16.8). The prevalence of a blood glucose concentration of < 47 mg/dl was 2.2% (31/1416): 95% CI 1.2%, 3.9%. The risk factors for neonatal hypoglycemia were delayed breastfeeding initiation [adjusted mean difference, − 2.6; 95% CI, − 4.4, − 0.79] and child age of 3 days or less [adjusted mean, − 12.2; 95% CI, − 14.0, − 10.4].

Conclusion

The incidence of neonatal hypoglycemia was low in this community and was predicted by delay in initiating breastfeeding and a child age of 3 days or less. We therefore suggest targeted screening and management of neonatal hypoglycemia among neonates before 3 days of age and those who are delayed in the onset of breastfeeding.
Performance evaluation of the novel portable PIMA point-of-care CD4 analyzer in comparison with conventional flow cytometer instruments in Cameroon
Authors: Sagnia Bertrand , Kamgaing Rachel , Kouanfack Charles , Kamdem Georgette , Sosso Samuel , Temgoua Edith , Tsomo Zéphyrin , Mabouli Zoa Lucille , Tangimpundu Charlotte , Nchinda Godwin , Ndjolo Alexis
Published: November 2020

Background

Absolute CD4+ T-lymphocyte counts are used in the initiation and monitoring of antiretroviral therapy in HIV-infected patients: with the increase number of HIV infected patient and the reduce number of heath care system in rural zones, HIV monitoring in resource-constrained settings demands affordable and reliable CD4+ T lymphocytes enumeration methods. We evaluated a simple PIMA POC which is a dedicated system for enumeration that uses immunomagnetic and immunofluorescent technologies. The instrument was designed to be a low-cost, yet reliable and robust one. In this study, we assessed the correlation between most representative flow cytometry instruments present in Cameroon instead of CyFlow from PARTEC, FACSCount, and FACSCalibur both from Becton Dickinson.

Methods

CD4 surface markers on lymphocytes was measured on samples collected in EDTA tubes from 268 patients aged from 1 to 65 years old in three different health care structures. HIV infected patients are coming from CIRCB, Day Hospital of Hopital Central de Yaounde (HCY) and Hopital General de Yaounde (HGY). After inform consent, samples were collected and 101 samples were tested with the FACSCalibur, 60 samples were tested with the CyFlow and 107 samples were tested with the FACSCount flow cytometers. All these samples were tested by different technician with PIMA POC present in all these health care structures and the correlation and agreement were analyzed using linear regression and Bland–Altman analysis.

Results

The PIMA POC system has excellent precision, accuracy and linearity for CD4+ T lymphocytes enumeration. Good correlations were obtained between the PIMA POC system and other single platform methods. Bland–Altman plots showed interchangeability between the three machines. Absolute CD4+ T-lymphocyte values obtained from the PIMA system correlated well with Cyflow, FACSCount, and FACSCalibur method (r2 varies from 0.88 to 0.968, P < 0.0001). The comparison between values obtained from PIMA with CYFLOW, FACSCount, and FACSCalibur give P = 0.17, P = 0.5 and P = 0.6 respectively meaning that there is not significant differences between values obtained with PIMA and other flow machines.

Conclusion

This POC PIMA system is a simple and reliable system for enumeration of absolute CD4+ T-lymphocytes. Having one PIMA system easy to use, should reduce the cost and thus increase access to CD4 testing for HIV infected patients in resource-constrained countries. POC CD4 may also alleviate testing burdens at traditional central CD4 laboratories, hence improving test access in both rural and urban environments. This will reduce also the loss of follow up.
Outcome predictors of intravenous thrombolytic therapy in acute ischemic stroke patients: an Egyptian center experiences
Authors: Tork Mohamed A. , Aref Hany M. , El-Khawas Hala M. , Khalil Mohamed F. , ElSadek Ahmed
Published: November 2020

Background

Intravenous thrombolytic therapy remains the guideline-recommended treatment to improve outcomes after acute ischemic stroke. However, the functional outcome among patients with acute ischemic stroke after receiving intravenous thrombolytic therapy is influenced by huge variety of factors, and this was the aim of our study to evaluate the outcome predictors of intravenous thrombolytic therapy in a sample of Egyptian patients with acute ischemic stroke.

Methods

We enrolled 183 acute ischemic stroke patients who were treated with intravenous recombinant tissue plasminogen activator (IV rtPA) according to the last updated guidelines of American Heart Association and American Stroke Association (AHA/ASA) from February 2018 to February 2020; however, only 150 patients of them completed our study plan till the end. Data of study variables were collected, analyzed statistically and correlated with the functional outcome 3 months after receiving IV rtPA using the modified Rankin Scale (mRS).

Results

Good functional outcome was seen in 98 (65.3%) patients and poor functional outcome was seen in 52 (34.7%) patients. Multivariate analysis of the study variables was done to detect the significant independent predictors of the functional outcome. Atrial fibrillation (AF) (Pvalue < 0.001*OR 6.28*(95% C.I)), hypertension (Pvalue 0.001*OR 3.65*(95% C.I)), diabetes mellitus (DM) (Pvalue 0.009*OR 2.805*(95% C.I)), increased National Institute of Health Stroke Scale (NIHSS) score 24 h after receiving IV rtPA (Pvalue 0.003*OR 8.039*(95% C.I)), increased pulsatility index (PI) value in cerebral vessels at the same side of stroke lesion (Pvalue 0.038*OR 42.48*(95% C.I)) were the significant independent predictors of poor functional outcome. On the other hand decreased NIHSS score 24 h after receiving IV rtPA (Pvalue 0.003*OR 0.124*(95% C.I)), Normal value of PI in cerebral vessels at the same side of stroke lesion (Pvalue 0.038*OR 42.48*(95% C.I)) were the significant independent predictors of good functional outcome.

Conclusion

Intravenous thrombolytic therapy improves the functional outcome of acute ischemic stroke patients. Also, AF, hypertension, DM, NIHSS 24 h after receiving IV rtPA and PI could be used as independent predictors of the functional outcome.
Pain related viral infections: a literature review
Authors: Widyadharma I. Putu Eka , Dewi Putri Rossyana , Wijayanti Ida Ayu Sri , Utami Desak Ketut Indrasari
Published: November 2020

Pain is a common health problem all around the world. The pain symptoms are various depending on the underlying disease or the direct cause of pain itself. Viral infection could cause arthralgia or acute-onset arthritis, moreover in pandemic era of SARS-CoV-2 infection. The patients might experience arthritis, arthralgia, joint pain, or musculoskeletal pain. Viral infection including parvovirus B19, hepatitis virus, human immunodeficiency virus, arthropod-borne virus, and coronavirus could cause various types of pain. The pathogenesis of these symptoms is similar to each other despite of different causative organism. This review will discuss about pain caused by various causative organisms.
Exploration of nature-based biomimetic approach in landscape architectural design: parametric study of candelabra model design
Authors: Jović Biljana S. , Mitić Anđela D.
Published: November 2020

This research provides an exploration of a biomimetic approach in the process of designing a candelabra model using linear shaped leaves of a Bell flower. The design process described in this research contains two steps: biological and geometrical. In the first biological step, a proper model for the creation of an urban element was found from nature in a Bell flower (Campanula persicifolia L.). The upper leaves of the selected plant, which are small with a linear spear and sharpening at the top, were chosen for the modeling process. The second step included applying two geometrical methods, i.e., Voronoi diagrams and Delaunay triangulation. A geometrical leaf form of the selected plant species and the modeling process were obtained using aparametric modeling software, Blender. Using different Blender plug-ins and modifiers, Delaunay triangulation and Voronoi diagram were implemented by marking the starting points on the leaf form in the image data source, adjusting the Delaunay triangulation parameters, and creating Voronoi diagrams in which the Voronoi points were located at the shortest distance from the edges of the Voronoi polygon. Consequently, a three dimensional model of a candelabra was developed through this study.
Introducing an interactional approach to exploring facilitation as an implementation intervention: examining the utility of Conversation Analysis
Authors: Hunter Sarah C. , Young Jessica A. , Lawless Michael T. , Kitson Alison L. , Feo Rebecca
Published: November 2020

Background

The widely adopted integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework identifies facilitation as a ‘core ingredient’ for successful implementation. Indeed, most implementation scientists agree that a certain degree of facilitation is required to translate research into clinical practice; that is, there must be some intentional effort to assist the implementation of evidence-based approaches and practices into healthcare. Yet understandings of what constitutes facilitation and how to facilitate effectively remain largely theoretical and, therefore, provide scant practical guidance to ensure facilitator success. Implementation Science theories and frameworks often describe facilitation as an activity accomplished in, and through, formal and informal communication amongst facilitators and those involved in the implementation process (i.e. ‘recipients’). However, the specific communication practices that constitute and enable effective facilitation are currently inadequately understood.

Aim

In this debate article, we argue that without effective facilitation—a practice requiring significant interactional and interpersonal skills—many implementation projects encounter difficulties. Therefore, we explore whether and how the application of Conversation Analysis, a rigorous research methodology for researching patterns of interaction, could expand existing understandings of facilitation within the Implementation Science field. First, we illustrate how Conversation Analysis methods can be applied to identifying what facilitation looks like in interaction. Second, we draw from existing conversation analytic research into facilitation outside of Implementation Science to expand current understandings of how facilitation might be achieved within implementation.

Conclusion

In this paper, we argue that conversation analytic methods show potential to understand and refine facilitation as a critical, and inherently interactional, component of implementation efforts. Conversation analytic investigations of facilitation as it occurs in real-time between participants could inform mechanisms to (1) improve understandings of how to achieve successful implementation through facilitation, (2) overcome difficulties and challenges in implementation related to interpersonal communication and interaction, (3) inform future facilitator training and (4) inform refinement of existing facilitation theories and frameworks (e.g. i-PARIHS) currently used in implementation interventions.
TRIM65 Promotes Invasion of Endometrial Stromal Cells by Activating ERK1/2/C-myc Signaling via Ubiquitination of DUSP6
Authors: Wu Ying-Ting , Ma Si-Yu , Sun Wen-Qin , Shen Wei-Wei , Zhu Hui-Ting , Zhang Qin , Chen Hui-Fen
Published: November 2020

Background

Endometriosis (EM) is a benign gynecological disease that shares some characteristics with malignancy, such as proliferation and invasion. So far, the pathogenesis of EM is still unclear. In this study, we investigated whether TRIM65 can play a role in the development of EM.

Methods

TRIM65 expression levels in eutopic, ectopic, and normal endometrium were detected by quantitative real-time PCR and Western blot. Cell proliferation and invasion of primary endometrial stromal (EMS) cells were detected by CCK-8 and Transwell analysis. The interaction between TRIM65 and DUSP6 or C-myc was measured by coimmunoprecipitation, ubiquitylation, dual luciferase, and chromatin immunoprecipitation analysis.

Results

We found that TRIM65 was identified as an up-regulated gene in ectopic endometrial tissues and EMS cells compared with control groups without EM. TRIM65 expression was positively correlated with the levels of p-ERK1/2, C-myc, matrix metalloproteinase-2, and integrin β1 in ectopic endometrial tissues in patients and mice. TRIM65 promoted the cell proliferation and invasion of EMS cells via the ERK1/2/C-myc pathway through ubiquitination of DUSP6. C-myc promoted TRIM65 expression through inducing TRIM65 promoter activity. Additionally, the increased expression of TRIM65, C-myc, matrix metalloproteinase-2, integrin β1, and p-ERK1/2 and the decreased expression of DUSP6 in ectopic endometrial tissues were significantly suppressed by inhibition of ERK1/2 signaling pathway in ectopic endometrial tissues in experimental mice model.

Conclusion

In conclusion, TRIM65 promotes invasion of ectopic EMS cells by activating a feedback loop with the ERK1/2/C-myc signaling pathway and may be a potential therapeutic target for EM.
Progressive tracking: a novel procedure to facilitate manual digitization of videos
Authors: Mielke Maja , Aerts Peter , Van Ginneken Chris , Van Wassenbergh Sam , Mielke Falk
Published: November 2020

Digitization of video recordings often requires the laborious procedure of manually clicking points of interest on individual video frames. Here, we present progressive tracking, a procedure that facilitates manual digitization of markerless videos. In contrast to existing software, it allows the user to follow points of interest with a cursor in the progressing video, without the need to click. To compare the performance of progressive tracking with the conventional frame-wise tracking, we quantified speed and accuracy of both methods, testing two different input devices (mouse and stylus pen). We show that progressive tracking can be twice as fast as frame-wise tracking while maintaining accuracy, given that playback speed is controlled. Using a stylus pen can increase frame-wise tracking speed. The complementary application of the progressive and frame-wise mode is exemplified on a realistic video recording. This study reveals that progressive tracking can vastly facilitate video analysis in experimental research.
E2A regulates neural ectoderm fate specification in human embryonic stem cells
Authors: Yi Siqi , Huang Xiaotian , Zhou Shixin , Zhou Yuan , Anderson Michele K. , Zúñiga-Pflücker Juan Carlos , Luan Qingxian , Li Yang
Published: November 2020

E proteins transcription factors are critical for many cell fate decisions. However, the roles of E proteins in the germ-layer specification of human embryonic stem cells (hESC) are poorly understood. We disrupted the TCF3 gene locus to delete the E protein E2A in hESCs. E2A KO hESCs retained key features of pluripotency, but displayed decreased neural ectoderm coupled with enhanced mesoendoderm outcomes. Genome-wide analyses showed that E2A directly regulates neural ectoderm and Nodal pathway genes. Accordingly, inhibition of Nodal or E2A overexpression partially rescued the neural ectoderm defect in E2A KO hESCs. Loss of E2A had little impact on the epigenetic landscape of hESCs, whereas E2A KO neural precursors displayed increased accessibility of the gene locus encoding the Nodal agonist CRIPTO. Double-deletion of both E2A and HEB (TCF12) resulted in a more severe neural ectoderm defect. Therefore, this study reveals critical context-dependent functions for E2A in human neural ectoderm fate-specification.
Molecular mechanisms underlying simplification of venation patterns in holometabolous insects
Authors: Banerjee Tirtha Das , Monteiro Antónia
Published: November 2020

How mechanisms of pattern formation evolve has remained a central research theme in the field of evolutionary and developmental biology. The mechanism of wing vein differentiation in Drosophila is a classic text-book example of pattern formation using a system of positional-information, yet very little is known about how species with a different number of veins pattern their wings, and how insect venation patterns evolved. Here, we examine the expression pattern of genes previously implicated in vein differentiation in Drosophila in two butterfly species with more complex venation Bicyclus anynana and Pieris canidia. We also test the function of some of these genes in B. anynana. We identify both conserved as well as new domains of decapentaplegic, engrailed, invected, spalt, optix, wingless, armadillo, blistered, and rhomboid gene expression in butterflies, and propose how the simplified venation in Drosophila might have evolved via loss of decapentaplegic, spalt and optix gene expression domains, silencing of vein inducing programs at Spalt-expression boundaries, and changes in gene expression of vein maintenance genes.
AGS3-dependent trans-Golgi network membrane trafficking is essential for compaction in mouse embryos
Authors: Nie Zheng-Wen , Niu Ying-Jie , Zhou Wenjun , Zhou Dong-Jie , Kim Ju-Yeon , Cui Xiang-Shun
Published: November 2020

Activator of G-protein signaling 3 (AGS3, also known as GPSM1) regulates the trans-Golgi network. The AGS3 GoLoco motif binds to Gαi and thereby regulates the transport of proteins to the plasma membrane. Compaction of early embryos is based on the accumulation of E-cadherin (Cdh1) at cell-contacted membranes. However, how AGS3 regulates the transport of Cdh1 to the plasma membrane remains undetermined. To investigate this, AGS3 was knocked out using the Cas9-sgRNA system. Both trans-Golgi network protein 46 (TGN46, also known as TGOLN2) and transmembrane p24-trafficking protein 7 (TMED7) were tracked in early mouse embryos by tagging these proteins with a fluorescent protein label. We observed that the majority of the AGS3-edited embryos were developmentally arrested and were fragmented after the four-cell stage, exhibiting decreased accumulation of Cdh1 at the membrane. The trans-Golgi network and TMED7-positive vesicles were also dispersed and were not polarized near the membrane. Additionally, increased Gαi1 (encoded by GNAI1) expression could rescue AGS3-overexpressed embryos. In conclusion, AGS3 reinforces the dynamics of the trans-Golgi network and the transport of TMED7-positive cargo containing Cdh1 to the cell-contact surface during early mouse embryo development.
BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages
Authors: Ko Jeong-Hun , Olona Antoni , Papathanassiu Adonia E. , Buang Norzawani , Park Kwon-Sik , Costa Ana S. H. , Mauro Claudio , Frezza Christian , Behmoaras Jacques
Published: November 2020

In response to environmental stimuli, macrophages change their nutrient consumption and undergo an early metabolic adaptation that progressively shapes their polarization state. During the transient, early phase of pro-inflammatory macrophage activation, an increase in tricarboxylic acid (TCA) cycle activity has been reported, but the relative contribution of branched-chain amino acid (BCAA) leucine remains to be determined. Here, we show that glucose but not glutamine is a major contributor of the increase in TCA cycle metabolites during early macrophage activation in humans. We then show that, although uptake of BCAAs is not altered, their transamination by BCAT1 is increased following 8 h lipopolysaccharide (LPS) stimulation. Of note, leucine is not metabolized to integrate into the TCA cycle in basal or stimulated human macrophages. Surprisingly, the pharmacological inhibition of BCAT1 reduced glucose-derived itaconate, α-ketoglutarate and 2-hydroxyglutarate levels without affecting succinate and citrate levels, indicating a partial inhibition of the TCA cycle. This indirect effect is associated with NRF2 (also known as NFE2L2) activation and anti-oxidant responses. These results suggest a moonlighting role of BCAT1 through redox-mediated control of mitochondrial function during early macrophage activation.
Development of Organosilicon Peroxides as Practical Alkyl Radical Precursors and Their Applications to Transition Metal Catalysis
Authors: Matsumoto Akira , Maruoka Keiji
Published: November 2020

This account highlights the development of efficient methods for generation of alkyl radicals from organosilicon peroxides and their applications in selective alkylation reactions. Compared with commonly used organic peroxides, a more diverse range of organosilicon peroxides can be prepared as bench-stable alkyl radical precursors, and their use in combination with transition metal catalysts allows for generation of alkyl radicals under mild conditions. Consequently, these methods have opened up a new way for the formation of various carbon–carbon and carbon–heteroatom bonds, affording highly functionalized carbon skeletons in chemoselective or asymmetric manners.
Obese Patients Decrease Work Rate in Order to Keep a Constant Target Heart Rate
Authors: ZUCCARELLI LUCREZIA , SARTORIO ALESSANDRO , DE MICHELI ROBERTA , TRINGALI GABRIELLA , GRASSI BRUNO
Published: November 2020

Purpose

“Slow components” of heart rate (HR) kinetics, occurring also during moderate-intensity constant work rate exercise, represent a problem for exercise prescription at fixed HR values. This problem, described in young healthy subjects, could be more pronounced in obese patients.

Methods

Sixteen male obese patients (age, 22 ± 7 yr; body mass, 127 ± 19 kg; body mass index, 41.6 ± 3.9 kg·m−2) were tested before (PRE) and after (POST) a 3-wk multidisciplinary body mass reduction program, entailing moderate-intensity exercise. They performed on a cycle ergometer an incremental exercise to voluntary exhaustion (to determine peak pulmonary oxygen uptake (V˙O2peak) and gas exchange threshold (GET)) and constant work rate exercises: moderate-intensity (MODERATE; 80% of GET determined in PRE), heavy-intensity (HEAVY; 120% of GET determined in PRE), and “HRCLAMPED” exercise, in which work rate was continuously adjusted to maintain a constant HR corresponding to that at 120% of GET. Breath-by-breath V˙O2 and HR were determined.

Results

V˙O2peak and GET (expressed as a percent of V˙O2peak) were not significantly different in PRE versus POST. In POST versus PRE, the HR slow component disappeared (MODERATE) or was reduced (HEAVY). In PRE, work rate had to decrease by ~20% over a 15-min task in order to keep HR constant; this decrease was significantly smaller (~5%) in POST.

Conclusions

In obese patients, a 3-wk multidisciplinary body mass reduction intervention i) increased exercise tolerance by eliminating (during MODERATE) or by reducing (during HEAVY) the slow component of HR kinetics, and ii) facilitated exercise prescription by allowing to translate a fixed submaximal HR value into a work rate slightly above GET.
Lower Extremity Kinematic and Kinetic Asymmetries during Running
Authors: STIFFLER-JOACHIM MIKEL RENEE , LUKES DREW HENRY , KLIETHERMES STEPHANIE A. , HEIDERSCHEIT BRYAN C.
Published: November 2020

Between-limb asymmetries during running are often evaluated to assess injury risk or recovery. Asymmetries less than 10% are generally considered normal, but it is unknown if asymmetries vary depending on the metric of interest, the athlete’s sex, or running speed.

Purpose

The primary aims of this investigation were to describe the magnitude of asymmetries of common variables during running among healthy athletes and to determine if sex and speed influence magnitudes of asymmetry.

Methods

This study analyzed routinely collected running gait data on healthy Division I collegiate athletes. All athletes had no history of lower extremity surgery, no lower extremity injuries for 3 months before testing, and running data available at 2.68, 2.95, 3.35, 3.80, and 4.47 m·s−1. Asymmetries were calculated for ground reaction forces, spatiotemporal metrics, joint kinematics, and joint kinetics. Separate linear mixed-effects models assessed the influence of sex, speed, and the interaction on asymmetries of interest. z Scores were calculated for significant effects to further assess the magnitude of differences.

Results

Results from 204 athletes were included. The magnitude of asymmetry varied depending on the variable of interest, with asymmetries ≤3° observed for joint kinematics and greater asymmetries observed among joint work asymmetries ranging from 10% to 40%. No significant interactions between sex and speed were observed. Differences in sex and speed were noted; however, the effect sizes were very small based on z score comparison (−0.17 ≤ z ≤ 0.36) and were unlikely to be meaningful.

Conclusions

The magnitude of asymmetry varies considerably depending on the running gait variable. Interpretation of between-limb asymmetry in running mechanics needs to be specific to the variable of interest, whereas sex or running speed seem to be minor factors.
Kinetics of Muscle Carnosine Decay after β-Alanine Supplementation: A 16-wk Washout Study
Authors: YAMAGUCHI GUILHERME CARVALHO , NEMEZIO KLEINER , SCHULZ MARIANE LEICHSENRING , NATALI JOSÉ , CESAR JONATAS EDUARDO , RIANI LUIZ AUGUSTO , GONÇALVES LÍVIA DE SOUZA , MÖLLER GABRIELLA BERWIG , SALE CRAIG , DE MEDEIROS MARISA HELENA GENNARI , GUALANO BRUNO , ARTIOLI GUILHERME GIANNINI
Published: November 2020

Purpose

This study aimed to describe the kinetics of carnosine washout in human skeletal muscle over 16 wk.

Methods

Carnosine washout kinetics were studied in 15 young, physically active omnivorous men randomly assigned to take 6.4 g·d−1 of β-alanine (n = 11) or placebo (n = 4) for 8 wk. Muscle carnosine content (M-Carn) was determined before (PRE), immediately after (POST), and 4, 8, 12, and 16 wk after supplementation. High-intensity exercise tests were performed at these same time points. Linear and exponential models were fitted to the washout data, and the leave-one-out method was used to select the model with the best fit for M-Carn decay data. Repeated-measures correlation analysis was used to assess the association between changes in M-Carn and changes in performance.

Results

M-Carn increased from PRE to POST in the β-alanine group only (+91.1% ± 29.1%; placebo, +0.04% ± 10.1%; P < 0.0001). M-Carn started to decrease after cessation of β-alanine supplementation and continued to decrease until week 16 (POST4, +59% ± 40%; POST8, +35% ± 39%; POST12, +18% ± 32%; POST16, −3% ± 24% of PRE M-Carn). From week 12 onward, M-Carn was no longer statistically different from PRE. Both linear and exponential models displayed very similar fit and could be used to describe carnosine washout, although the linear model presented a slightly better fit. The decay in M-Carn was mirrored by a similar decay in high-intensity exercise tolerance; M-Carn was moderately and significantly correlated with total mechanical work done (r = 0.505; P = 0.032) and time to exhaustion (r = 0.72; P < 0.001).

Conclusions

Carnosine washout takes 12–16 wk to complete, and it can be described either by linear or exponential curves. Changes in M-Carn seem to be mirrored by changes in high-intensity exercise tolerance. This information can be used to optimize β-alanine supplementation strategies.
Early childhood bilingualism: effects on brain structure and function
Authors: Goksan Sezgi , Argyri Froso , Clayden Jonathan D. , Liegeois Frederique , Wei Li
Published: November 2020

Growing up in a bilingual environment is becoming increasingly common. Yet, we know little about how this enriched language environment influences the connectivity of children’s brains. Behavioural research in children and adults has shown that bilingualism experience may boost executive control (EC) skills, such as inhibitory control and attention. Moreover, increased structural and functional (resting-state) connectivity in language-related and EC-related brain networks is associated with increased executive control in bilingual adults. However, how bilingualism factors alter brain connectivity early in brain development remains poorly understood.

We will combine standardised tests of attention with structural and resting-state functional magnetic resonance imaging (MRI) in bilingual children. This study will allow us to address an important field of inquiry within linguistics and developmental cognitive neuroscience by examining the following questions: Does bilingual experience modulate connectivity in language-related and EC-related networks in children? Do differences in resting-state brain connectivity correlate with differences in EC skills (specifically attention skills)? How do bilingualism-related factors, such as age of exposure to two languages, language usage and proficiency, modulate brain connectivity?

We will collect structural and functional MRI, and quantitative measures of EC and language skills from two groups of English-Greek bilingual children - 20 simultaneous bilinguals (exposure to both languages from birth) and 20 successive bilinguals (exposure to English between the ages of 3 and 5 years) - and 20 English monolingual children, 8-10 years old. We will compare connectivity measures and attention skills between monolinguals and bilinguals to examine the effects of bilingual exposure. We will also examine to what extent bilingualism factors predict brain connectivity in EC and language networks.

Overall, we hypothesize that connectivity and EC will be enhanced in bilingual children compared to monolingual children, and each outcome will be modulated by age of exposure to two languages and by bilingual language usage.
Synthesis and characterization of chitosan nanoparticles of Achillea millefolium L. and their activities
Authors: Kain Dolly , Kumar Suresh
Published: November 2020

Background: Achillea millefolium L. is an herbal aromatic plant of family Asteraceae reported to have various medicinal activities in the literature. The current study evaluated the potential of chitosan nanoparticles of A. millefolium as an effective strategy for targeted treatment of bacterial diseases and urolithiasis.

Methods: A. millefolium was collected from Poonch, Jammu and Kashmir, and its inflorescence extracted in water by maceration. Chitosan nanoparticles of A. millefolium (AMCSNPs) were prepared by ionic gelation method using 0.1% chitosan, different concentrations of the cross-linking agent sodium tripolyphosphate (STPP; 0.5%, 1%, 1.5%, 2%) and different concentrations of A. millefolium extract (0.5%, 1%, 1.5%, 2%). Characterization of AMCSNPs was done using UV-Vis spectroscopy, Fourier transform-infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Antibacterial screening of AMCSNPs was performed by well-diffusion method. Antiurolithiatic screening of AMCSNPs was done by nucleation and aggregation assay.

Results: The best chitosan nanoparticles of A. millefolium (AMCSNPs) were obtained with 0.1% chitosan, 1% STPP and 20% A. millefolium. These AMCSNPs showed maximum zone of inhibition of 30±0.5 mm using the well-diffusion method against both Bacillus subtilis (Gram-positive) and Pseudomonas aeruginosa (Gram-negative) and maximum antiurolithiatic activity with 68% inhibition shown at aggregation stage.

Conclusions: The current study suggests that AMCSNPs are an excellent strategy for targeted drug delivery for treatment of bacterial diseases and urolithiasis.
Effect of Parental Adverse Childhood Experiences and Resilience on a Child's Healthcare Reutilization
Authors: Shah Anita N , Auger Katherine A , Sucharew Heidi J , Mangeot Colleen , Childress Kelsey , Haney Julianne , Shah Samir S , Simmons Jeffrey M , Beck Andrew F , Group on behalf of the Hospital‐to‐Homes Outcomes Trial Study
Published: November 2020

BACKGROUND

Adverse childhood experiences (ACEs) are associated with poor health outcomes in adults. Resilience may mitigate this effect. There is limited evidence regarding how parents' ACEs and resilience may be associated with their children's health outcomes.

OBJECTIVE

To determine the association of parental ACEs and resilience with their child's risk of unanticipated healthcare reutilization.

DESIGN, SETTING, AND PARTICIPANTS

We conducted a prospective cohort study (August 2015 to October 2016) at a tertiary, freestanding pediatric medical center in Cincinnati, Ohio. Eligible participants were English‐speaking parents of children hospitalized on a Hospital Medicine or Complex Services team. A total of 1,320 parents of hospitalized children completed both the ACE questionnaire and the Brief Resilience Scale Survey.

EXPOSURE

Number of ACEs and Brief Resilience Scale Score among parents.

MAIN OUTCOMES

Unanticipated reutilization by children, defined as returning to the emergency room, urgent care, or being readmitted to the hospital within 30 days of hospital discharge.

RESULTS

In adjusted analyses, children of parents with 4 or more ACEs had 1.69‐times higher odds (95% CI, 1.11‐2.60) of unanticipated reutilization after an index hospitalization, compared with children of parents with no ACEs. Resilience was not significantly associated with reutilization.

CONCLUSION

Parental history of ACEs is strongly associated with higher odds of their child having unanticipated healthcare reutilization after a hospital discharge, highlighting an intergenerational effect. Screening may be an important tool for outcome prediction and intervention guidance following pediatric hospitalization.