bluuebunny/crossref_metadata_2025 huggingface dataset:
ANALISIS HOTS PADA SOAL PENILAIAN TENGAH SEMESTER DALAM MATA PELAJARAN ILMU PENGETAHUAN SOSIAL DI KELAS IV
Authors: Dikdas Hastuti
Published: July 2021

ABSTRAKAlasan dilakukannya penelitian ini, dikarenakan masih kurangnya kemampuan guru dalam menyusun soal Hots dan  adanya faktor yang menjadi penghambat guru didalam menyusun soal PTS. Metode penelitian yang digunakan adalah metode penelitian deskriptif dengan pendekatan kualitatif. Berdasarkan hasil analisis, diperoleh temuan, yakni ditemukan 31 butir soal yang tidak memenuhi kriteria pengembangan Hots (High Order Thinking Skills), dimana dari hasil analisis level kognitif untuk menentukan Keterampilan berpikir kritis murid namun 31 butir soal tersebut terdapat 0% (Hots) dan 100% (Lots) dimana soal tersebut tidak dapat mengukur kemampuan berpikir kritis murid yang menyebabkan kemampuan guru dalam menyusun soal Hots (High Order Thinking Skills) masuk pada kategori sangat kurang dan perlu bimbingan.
Bureaucracy across Borders: Administering Cosmopolitan Hospitality at the English P.E.N., 1930–1945
Authors: Ridge Emily
Published: July 2021

From its inception, hospitality was inscribed in the vision of the English P.E.N., one of its stipulated aims being to provide a ‘vehicle for friendliness and hospitality’. Yet several writers who took leading administrative and representational roles during the 1930s and 1940s – Storm Jameson, E. M. Forster and J. B. Priestley, for example – were uncomfortable with the kinds of hospitality the P.E.N. sometimes purported to offer. They were concerned about the wartime propriety of elaborate lunches, dinners and parties. At the same time, this was an organisation that also tirelessly advocated for more substantial forms of refuge for displaced writers. Drawing on extensive archival material, this essay will examine some of the ambiguities embedded in the P.E.N.’s conception of hospitality during this period: the perceived clash between a social etiquette of hospitality (expressed through P.E.N. social gatherings) and a wider politics of hospitality (expressed in its drive to facilitate refugee reception in Britain).
Beckett's Molloy, the Promise of Youth, and the Postwar
Authors: Ross Stephen
Published: July 2021

This paper argues that Samuel Beckett's Molloy charts the historical transition of the postwar moment in generational terms – terms that themselves had real historical significance in the years immediately following the Allied victory in World War II – ultimately, and uncharacteristically, advancing a youthful figure of promise in young Jacques Moran, Jr. Though Beckett is much more commonly read as an allegorist of existential ambivalence – if not despair – I contend that his first postwar novel must properly be understood as staging history in its confused, agonistic, and frustrating family dynamics. Beckett's rendering of authority, history, and hierarchy in terms of perversion, queerness, and sterility ultimately preserves a futurity centred not precisely on the child per se, but on the emergent figure of the adolescent – the teenager, even, I will venture to claim –  avant la lettre: Jacques Moran, Jr.
Politics of rule of law: A human and state security perspective in the case of Zuma
Authors: Matthew Mare
Published: July 2021

This research is a desktop research on politics of rule of law, human security and state security perspectives in the case of Zuma. The study looked at various framing and diverging interpretations of Zuma’s case by the various sections. Some sections of the society especially the Zulu and Malema believed that, Zuma’s case is a continuation of apartheid politics. From the perspective of the principle of the rule of law the law was applied without fear or favour. Former president Thabo Mbeki was concerned about timing as he believed that there was no urgency in handing inn the arrest warrant. Mbeki believed that, Ramaphosa should not pride himself in succeeding to jail Zuma but should look beyond the act. From a security perspective the study noted that, the Bantustan revolution is not far from being imminent. The study in light of the foregoing proposed case scenarios of the likelihood outcomes.
Recent Advances in Strategies for the Cloning of Natural Product Biosynthetic Gene Clusters
Authors: Wang Wenfang , Zheng Guosong , Lu Yinhua
Published: July 2021

Microbial natural products (NPs) are a major source of pharmacological agents. Most NPs are synthesized from specific biosynthetic gene clusters (BGCs). With the rapid increase of sequenced microbial genomes, large numbers of NP BGCs have been discovered, regarded as a treasure trove of novel bioactive compounds. However, many NP BGCs are silent in native hosts under laboratory conditions. In order to explore their therapeutic potential, a main route is to activate these silent NP BGCs in heterologous hosts. To this end, the first step is to accurately and efficiently capture these BGCs. In the past decades, a large number of effective technologies for cloning NP BGCs have been established, which has greatly promoted drug discovery research. Herein, we describe recent advances in strategies for BGC cloning, with a focus on the preparation of high-molecular-weight DNA fragment, selection and optimization of vectors used for carrying large-size DNA, and methods for assembling targeted DNA fragment and appropriate vector. The future direction into novel, universal, and high-efficiency methods for cloning NP BGCs is also prospected.
Mutual Preservation: A Review of Interactions Between Cervicovaginal Mucus and Microbiota
Authors: Vagios Stylianos , Mitchell Caroline M.
Published: July 2021

At mucosal surfaces throughout the body mucus and mucins regulate interactions between epithelia and both commensal and pathogenic bacteria. Although the microbes in the female genital tract have been linked to multiple reproductive health outcomes, the role of cervicovaginal mucus in regulating genital tract microbes is largely unexplored. Mucus-microbe interactions could support the predominance of specific bacterial species and, conversely, commensal bacteria can influence mucus properties and its influence on reproductive health. Herein, we discuss the current evidence for both synergistic and antagonistic interactions between cervicovaginal mucus and the female genital tract microbiome, and how an improved understanding of these relationships could significantly improve women’s health.
Uncovering Transcriptional Regulators and Targets of sRNAs Using an Integrative Data-Mining Approach: H-NS-Regulated RseX as a Case Study
Authors: Mihailovic Mia K. , Ekdahl Alyssa M. , Chen Angela , Leistra Abigail N. , Li Bridget , González Martínez Javier , Law Matthew , Ejindu Cindy , Massé Éric , Freddolino Peter L. , Contreras Lydia M.
Published: July 2021

Bacterial small RNAs (sRNAs) play a vital role in pathogenesis by enabling rapid, efficient networks of gene attenuation during infection. In recent decades, there has been a surge in the number of proposed and biochemically-confirmed sRNAs in both Gram-positive and Gram-negative pathogens. However, limited homology, network complexity, and condition specificity of sRNA has stunted complete characterization of the activity and regulation of these RNA regulators. To streamline the discovery of the expression of sRNAs, and their post-transcriptional activities, we propose an integrative in vivo data-mining approach that couples DNA protein occupancy, RNA-seq, and RNA accessibility data with motif identification and target prediction algorithms. We benchmark the approach against a subset of well-characterized E. coli sRNAs for which a degree of in vivo transcriptional regulation and post-transcriptional activity has been previously reported, finding support for known regulation in a large proportion of this sRNA set. We showcase the abilities of our method to expand understanding of sRNA RseX, a known envelope stress-linked sRNA for which a cellular role has been elusive due to a lack of native expression detection. Using the presented approach, we identify a small set of putative RseX regulators and targets for experimental investigation. These findings have allowed us to confirm native RseX expression under conditions that eliminate H-NS repression as well as uncover a post-transcriptional role of RseX in fimbrial regulation. Beyond RseX, we uncover 163 putative regulatory DNA-binding protein sites, corresponding to regulation of 62 sRNAs, that could lead to new understanding of sRNA transcription regulation. For 32 sRNAs, we also propose a subset of top targets filtered by engagement of regions that exhibit binding site accessibility behavior in vivo. We broadly anticipate that the proposed approach will be useful for sRNA-reliant network characterization in bacteria. Such investigations under pathogenesis-relevant environmental conditions will enable us to deduce complex rapid-regulation schemes that support infection.
The Effect of Lockdown and Physical Activity on Glycemic Control in Italian Children and Young Patients With Type 1 Diabetes
Authors: Minuto Nicola , Bassi Marta , Montobbio Carolina , Vinci Francesco , Mercuri Claudia , Perri Francesca Nastasia , Cabri Mara , Calevo Maria Grazia , d’Annunzio Giuseppe , Maghnie Mohamad
Published: July 2021

Aims

The purpose of the study was to evaluate the impact of the lockdown established by the Italian government to limit the spread of Coronavirus disease (COVID-19) on glycemic control in a large sample of patients with type 1 diabetes (T1D) based on age, type of insulin therapy, number of telemedicine visits and physical activity.

Material and Methods

We retrospectively evaluated glycemic control in young T1D patients using the DexcomG6® system before the Italian lockdown (February 10–23, 2020—Time 0) and during lockdown (April 17–30, 2020—Time 1). Data on age, type of insulin therapy, number of telemedicine visits and physical activity of 202 patients with T1D and a median age of 18.2 years (range: 6–39) were collected.

Results

Data showed a significant improvement of TIR from 54.58% at T0 to 59.09% at T1 (p ≤0.0001). Glycemic control improved significantly in patients ≥14 years old, showing the best outcome in the “university students and young adults” group (55.40% at T0 and 61.37% at T1, p ≤0.001). All patients reduced physical activity during lockdown; in the 56 patients of “intense physical activity” group both at T0 and T1 TIR increased from ±56.91 to 64.11% (p ≤0.0001).

Conclusions

Overall, the lockdown led to an unexpected improvement in glycemic control of young patients with T1D. A healthier and stressless lifestyle changes in association with the maintenance of physical activity resulted in a significant age-proportional improvement in glycemic control.
Short-Term Temporal Dynamics of VOC Emissions by Soil Systems in Different Biotopes
Authors: Monard Cécile , Caudal Jean-Pierre , Cluzeau Daniel , Le Garrec Jean-Luc , Hellequin Eve , Hoeffner Kevin , Humbert Guillaume , Jung Vincent , Le Lann Cécile , Nicolai Annegret
Published: July 2021

Volatile organic compounds (VOCs) are emitted by plants and microorganisms and have significant impacts on atmospheric chemistry. Soil systems are sources of VOCs driven by abiotic and biotic factors. We investigated the emissions of VOCs by soils and their plant cover from three contrasted biotopes: meadow, heathland and oak forest, during 24-h in summer. We hypothesized that the spatial and temporal dynamics of VOC fluxes are reflected in soil properties, soil microbial communities, vegetation covers, and litter composition that differed in the three biotopes VOC fluxes were measured after direct on-field sampling at four sampling times (two at night and two at day) using a proton transfer reaction mass spectrometer, and results were linked to some climatic, edaphic and biotic parameters simultaneously monitored in each biotope. While differences in the composition of the soil bacterial communities, in the richness of the plant cover and in some soil physicochemical properties between the three biotopes were observed, the total VOC fluxes from the soil to the atmosphere did not present spatial patterns. However, differences in the mass composition of the VOC spectra were detected; for example, the soil from the forest that was covered with oak leaf litter had specific bacterial communities and emitted distinct VOC spectra than the two other biotopes. The total VOC fluxes responded to rainfall and were significantly driven by soil temperature. While we observed changes in the structure of soil bacterial communities between day and night in all biotopes using fingerprinting analysis, a diurnal dynamic of VOC fluxes was only observed in the forest biotope where the soil was protected from rainfall due to the canopy. This soil presented higher fluxes in day time up to 10.8 µg VOCs h−1 m−2 and lower fluxes in night time down to 3.8 µg VOCs h−1 m−2. Overall, the present study supplies data regarding VOC emissions by soils which are scare compared to plant sources. The results highlighted the complex interconnections existing between abiotic and biotic parameters that could directly or indirectly drive VOC emissions by soil systems.
Co-Design of a Trustworthy AI System in Healthcare: Deep Learning Based Skin Lesion Classifier
Authors: Zicari Roberto V. , Ahmed Sheraz , Amann Julia , Braun Stephan Alexander , Brodersen John , Bruneault Frédérick , Brusseau James , Campano Erik , Coffee Megan , Dengel Andreas , Düdder Boris , Gallucci Alessio , Gilbert Thomas Krendl , Gottfrois Philippe , Goffi Emmanuel , Haase Christoffer Bjerre , Hagendorff Thilo , Hickman Eleanore , Hildt Elisabeth , Holm Sune , Kringen Pedro , Kühne Ulrich , Lucieri Adriano , Madai Vince I. , Moreno-Sánchez Pedro A. , Medlicott Oriana , Ozols Matiss , Schnebel Eberhard , Spezzatti Andy , Tithi Jesmin Jahan , Umbrello Steven , Vetter Dennis , Volland Holger , Westerlund Magnus , Wurth Renee
Published: July 2021

This paper documents how an ethically aligned co-design methodology ensures trustworthiness in the early design phase of an artificial intelligence (AI) system component for healthcare. The system explains decisions made by deep learning networks analyzing images of skin lesions. The co-design of trustworthy AI developed here used a holistic approach rather than a static ethical checklist and required a multidisciplinary team of experts working with the AI designers and their managers. Ethical, legal, and technical issues potentially arising from the future use of the AI system were investigated. This paper is a first report on co-designing in the early design phase. Our results can also serve as guidance for other early-phase AI-similar tool developments.
Human Newborn Monocytes Demonstrate Distinct BCG-Induced Primary and Trained Innate Cytokine Production and Metabolic Activation In Vitro
Authors: Angelidou Asimenia , Diray-Arce Joann , Conti Maria-Giulia , Netea Mihai G. , Blok Bastiaan A. , Liu Mark , Sanchez-Schmitz Guzman , Ozonoff Al , van Haren Simon D. , Levy Ofer
Published: July 2021

Background

Newborns exhibit distinct immune responses and are at high risk of infection. Neonatal immunization with BCG, the live attenuated vaccine against tuberculosis (TB), is associated with broad protection against a range of unrelated pathogens, possibly reflecting vaccine-induced training of innate immune cells (“innate memory”). However, little is known regarding the impact of age on BCG-induced innate responses.

Objective

Establish an age-specific human monocyte in vitro training platform to characterize and compare BCG-induced primary and memory cytokine responses and immunometabolic shifts.

Design/Methods

Human neonatal and adult CD33-selected monocytes were stimulated for 24h with RPMI (control) or BCG (Danish strain) in 10% autologous serum, washed and cultured for 5 additional days, prior to re-stimulation with the TLR4 agonist LPS for another 24h. Supernatants were collected at Day 1 (D1) to measure primary innate responses and at Day 7 (D7) to assess memory innate responses by ELISA and multiplex cytokine and chemokine assays. Lactate, a signature metabolite increased during trained immunity, was measured by colorimetric assay.

Results

Cytokine production by human monocytes differed significantly by age at D1 (primary, BCG 1:750 and 1:100 vol/vol, p<0.0001) and D7 (innate memory response, BCG 1:100 vol/vol, p<0.05). Compared to RPMI control, newborn monocytes demonstrated greater TNF (1:100, 1:10 vol/vol, p<0.01) and IL-12p40 (1:100 vol/vol, p<0.05) production than adult monocytes (1:100, p<0.05). At D7, while BCG-trained adult monocytes, as previously reported, demonstrated enhanced LPS-induced TNF production, BCG-trained newborn monocytes demonstrated tolerization, as evidenced by significantly diminished subsequent LPS-induced TNF (RPMI vs. BCG 1:10, p <0.01), IL-10 and CCL5 production (p<0.05). With the exception of IL-1RA production by newborn monocytes, BCG-induced monocyte production of D1 cytokines/chemokines was inversely correlated with D7 LPS-induced TNF in both age groups (p<0.0001). Compared to BCG-trained adult monocytes, newborn monocytes demonstrated markedly impaired BCG-induced production of lactate, a metabolite implicated in immune training in adults.

Conclusions

BCG-induced human monocyte primary- and memory-innate cytokine responses were age-dependent and accompanied by distinct immunometabolic shifts that impact both glycolysis and training. Our results suggest that immune ontogeny may shape innate responses to live attenuated vaccines, suggesting age-specific approaches to leverage innate training for broad protection against infection.
Macrophages, as a Promising Strategy to Targeted Treatment for Colorectal Cancer Metastasis in Tumor Immune Microenvironment
Authors: Zhang Yingru , Zhao Yiyang , Li Qi , Wang Yan
Published: July 2021

The tumor immune microenvironment plays a vital role in the metastasis of colorectal cancer. As one of the most important immune cells, macrophages act as phagocytes, patrol the surroundings of tissues, and remove invading pathogens and cell debris to maintain tissue homeostasis. Significantly, macrophages have a characteristic of high plasticity and can be classified into different subtypes according to the different functions, which can undergo reciprocal phenotypic switching induced by different types of molecules and signaling pathways. Macrophages regulate the development and metastatic potential of colorectal cancer by changing the tumor immune microenvironment. In tumor tissues, the tumor-associated macrophages usually play a tumor-promoting role in the tumor immune microenvironment, and they are also associated with poor prognosis. This paper reviews the mechanisms and stimulating factors of macrophages in the process of colorectal cancer metastasis and intends to indicate that targeting macrophages may be a promising strategy in colorectal cancer treatment.
Predictive Value of High ICAM-1 Level for Poor Treatment Response to Low-Dose Decitabine in Adult Corticosteroid Resistant ITP Patients
Authors: Li Chaoyang , Li Lizhen , Sun Meng , Sun Jianzhi , Shao Linlin , Xu Miao , Hou Yu , Peng Jun , Wang Lin , Hou Ming
Published: July 2021

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. Endothelial cell activation/injury has been found in some autoimmune diseases including SLE, systemic sclerosis, and rheumatoid arthritis, but its role in ITP pathogenesis remains unclear. This study attempted to elucidate the correlation between endothelial dysfunction and disease severity of ITP and find related markers to predict response to low-dose decitabine treatment. Compared with healthy volunteers, higher plasma levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and Angiopoietin-2 were found in adult corticosteroid resistant ITP patients. Notably, ICAM-1 levels were negatively correlated with the platelet count, and positively associated with the bleeding score. Recently, we have reported the efficacy and safety of low-dose decitabine in adult patients with ITP who failed for the first line therapies. Here, we evaluated the correlation of plasma ICAM-1 level with the efficacy of low-dose decitabine therapy for corticosteroid resistant ITP. A total of 29 adult corticosteroid resistant ITP patients who received consecutive treatments of low-dose decitabine were enrolled in this study. Fourteen patients showed response (nine showed complete response and five showed partial response). The levels of ICAM-1 before and after treatment were significantly higher in the non-responsive ITP patients than in the responsive patients. As shown in the multivariable logistic regression model, the odds of developing no-response to low-dose decitabine increased by 36.8% for per 5 ng/ml increase in plasma ICAM-1 level [odds ratio (OR) 1.368, 95% confidence interval (CI): 1.060 to 1.764]. In summary, this was the first study to elucidate the relationship between endothelial dysfunction and corticosteroid resistant ITP and identify the potential predictive value of ICAM-1 level for response to low-dose decitabine.
Impaired Priming of SARS-CoV-2-Specific Naive CD8+ T Cells in Older Subjects
Authors: Gallerani Eleonora , Proietto Davide , Dallan Beatrice , Campagnaro Marco , Pacifico Salvatore , Albanese Valentina , Marzola Erika , Marconi Peggy , Caputo Antonella , Appay Victor , Gavioli Riccardo , Nicoli Francesco
Published: July 2021

Advanced age is associated with severe symptoms and death upon SARS-CoV-2 infection. Virus-specific CD8+ T-cell responses have shown to be protective toward critical COVID-19 manifestations, suggesting that suboptimal cellular immunity may contribute to the age-pattern of the disease. The induction of a CD8+ T-cell response against an emerging pathogen like SARS-CoV-2 relies on the activation of naive T cells. To investigate whether the primary CD8+ T-cell response against this virus is defective in advanced age, we used an in vitro approach to prime SARS-CoV-2-specific naive CD8+ T cells from healthy, unexposed donors of different age groups. Compared to younger adults, older individuals display a poor SARS-CoV-2-specific T-cell priming capacity in terms of both magnitude and quality of the response. In addition, older subjects recognize a lower number of epitopes. Our results implicate that immune aging is associated with altered primary SARS-CoV-2-specific CD8+ T-cell responses.
Effects of Microplastics Exposure on the Acropora sp. Antioxidant, Immunization and Energy Metabolism Enzyme Activities
Authors: Xiao Baohua , Li Dongdong , Liao Baolin , Zheng Huina , Yang Xiaodong , Xie Yongqi , Xie Ziqiang , Li Chengyong
Published: July 2021

Graphical Abstract

The experiment flow chart of anti-inflammatory and analgesic effects of P. orientale extracts.
Translational GTPase BipA Is Involved in the Maturation of a Large Subunit of Bacterial Ribosome at Suboptimal Temperature
Authors: Goh Kwok Jian , Ero Rya , Yan Xin-Fu , Park Jung-Eun , Kundukad Binu , Zheng Jun , Sze Siu Kwan , Gao Yong-Gui
Published: July 2021

BPI-inducible protein A (BipA), a highly conserved paralog of the well-known translational GTPases LepA and EF-G, has been implicated in bacterial motility, cold shock, stress response, biofilm formation, and virulence. BipA binds to the aminoacyl-(A) site of the bacterial ribosome and establishes contacts with the functionally important regions of both subunits, implying a specific role relevant to the ribosome, such as functioning in ribosome biogenesis and/or conditional protein translation. When cultured at suboptimal temperatures, the Escherichia coli bipA genomic deletion strain (ΔbipA) exhibits defects in growth, swimming motility, and ribosome assembly, which can be complemented by a plasmid-borne bipA supplementation or suppressed by the genomic rluC deletion. Based on the growth curve, soft agar swimming assay, and sucrose gradient sedimentation analysis, mutation of the catalytic residue His78 rendered plasmid-borne bipA unable to complement its deletion phenotypes. Interestingly, truncation of the C-terminal loop of BipA exacerbates the aforementioned phenotypes, demonstrating the involvement of BipA in ribosome assembly or its function. Furthermore, tandem mass tag-mass spectrometry analysis of the ΔbipA strain proteome revealed upregulations of a number of proteins (e.g., DeaD, RNase R, CspA, RpoS, and ObgE) implicated in ribosome biogenesis and RNA metabolism, and these proteins were restored to wild-type levels by plasmid-borne bipA supplementation or the genomic rluC deletion, implying BipA involvement in RNA metabolism and ribosome biogenesis. We have also determined that BipA interacts with ribosome 50S precursor (pre-50S), suggesting its role in 50S maturation and ribosome biogenesis. Taken together, BipA demonstrates the characteristics of a bona fide 50S assembly factor in ribosome biogenesis.
Genomic Analysis and Stability Evaluation of the Phenol-Degrading Bacterium Acinetobacter sp. DW-1 During Water Treatment
Authors: Gu Qihui , Chen Moutong , Zhang Jumei , Guo Weipeng , Wu Huiqing , Sun Ming , Wei Lei , Wang Juan , Wei Xianhu , Zhang Youxiong , Ye Qinghua , Xue Liang , Pang Rui , Ding Yu , Wu Qingping
Published: July 2021

Phenol is a toxic organic molecule that is widely detected in the natural environment, even in drinking water sources. Biological methods were considered to be a good tool for phenol removal, especially microbial immobilized technology. However, research on the “seed” bacteria along with microbial community analysis in oligotrophic environment such as drinking water system has not been addressed. In this study, Acinetobacter sp. DW-1 with high phenol degradation ability had been isolated from a drinking water biofilter was used as seeded bacteria to treat phenol micro-polluted drinking water source. Meanwhile, the whole genome of strain DW-1 was sequenced using nanopore technology. The genomic analysis suggests that Acinetobacter sp. DW-1 could utilize phenol via the β-ketoadipate pathway, including the catechol and protocatechuate branches. Subsequently, a bio-enhanced polyhedral hollow polypropylene sphere (BEPHPS) filter was constructed to investigate the stability of the seeded bacteria during the water treatment process. The denatured gradient gel electrophoresis (DGGE) profile and the quantification of phenol hydroxylase gene results indicate that when the BEPHPS filter was operated for 56 days, Acinetobacter sp. was still a persistent and competitive bacterium in the treatment group. In addition, 16S rRNA gene amplicon sequencing results indicate that Acinetobacter sp., as well as Pseudomonas sp., Nitrospira sp., Rubrivivax sp. were the predominant bacteria in the treatment group, which were different from that in the CK group. This study provides a better understanding of the mechanisms of phenol degradation by Acinetobacter sp. DW-1 at the gene level, and provides new insights into the stability of seeded bacteria and its effects on microbial ecology during drinking water treatment.
Core Genome MLST for Source Attribution of Campylobacter coli
Authors: Harrison Lucas , Mukherjee Sampa , Hsu Chih-Hao , Young Shenia , Strain Errol , Zhang Qijing , Tillman Glenn E. , Morales Cesar , Haro Jovita , Zhao Shaohua
Published: July 2021

Campylobacter species are among the leading foodborne bacterial agents of human diarrheal illness. The majority of campylobacteriosis has been attributed to Campylobacter jejuni (85% or more), followed by Campylobacter coli (5–10%). The distribution of C. jejuni and C. coli varies by host organism, indicating that the contribution to human infection may differ between isolation sources. To address the relative contribution of each source to C. coli infections in humans, core genome multilocus sequence type with a 200-allele difference scheme (cgMLST200) was used to determine cgMLST type for 3,432 C. coli isolated from food animals (n = 2,613), retail poultry meats (n = 389), human clinical settings (n = 285), and environmental sources (n = 145). Source attribution was determined by analyzing the core genome with a minimal multilocus distance methodology (MMD). Using MMD, a higher proportion of the clinical C. coli population was attributed to poultry (49.6%) and environmental (20.9%) sources than from cattle (9.8%) and swine (3.2%). Within the population of C. coli clinical isolates, 70% of the isolates that were attributed to non-cecal retail poultry, dairy cattle, beef cattle and environmental waters came from two cgMLST200 groups from each source. The most common antibiotic resistance genes among all C. coli were tetO (65.6%), blaOXA–193 (54.2%), aph(3′)-IIIa (23.5%), and aadE-Cc (20.1%). Of the antibiotic resistance determinants, only one gene was isolated from a single source: blaOXA–61 was only isolated from retail poultry. Within cgMLST200 groups, 17/17 cgMLST200-435 and 89/92 cgMLST200-707 isolates encoded for aph(3’)-VIIa and 16/16 cgMLST200-319 harbored aph(2’)-If genes. Distribution of blaOXA alleles showed 49/50 cgMLST200-5 isolates contained blaOXA–498 while blaOXA–460 was present in 37/38 cgMLST200-650 isolates. The cgMLST200-514 group revealed both ant(6)-Ia and sat4 resistance genes in 23/23 and 22/23 isolates, respectively. Also, cgMLST200-266 and cgMLST200-84 had GyrAT86I mutation with 16/16 (100%) and 14/15 (93.3%), respectively. These findings illustrate how cgMLST and MMD methods can be used to evaluate the relative contribution of known sources of C. coli to the human burden of campylobacteriosis and how cgMLST typing can be used as an indicator of antimicrobial resistance in C. coli.
Decoding EEG Brain Activity for Multi-Modal Natural Language Processing
Authors: Hollenstein Nora , Renggli Cedric , Glaus Benjamin , Barrett Maria , Troendle Marius , Langer Nicolas , Zhang Ce
Published: July 2021

Until recently, human behavioral data from reading has mainly been of interest to researchers to understand human cognition. However, these human language processing signals can also be beneficial in machine learning-based natural language processing tasks. Using EEG brain activity for this purpose is largely unexplored as of yet. In this paper, we present the first large-scale study of systematically analyzing the potential of EEG brain activity data for improving natural language processing tasks, with a special focus on which features of the signal are most beneficial. We present a multi-modal machine learning architecture that learns jointly from textual input as well as from EEG features. We find that filtering the EEG signals into frequency bands is more beneficial than using the broadband signal. Moreover, for a range of word embedding types, EEG data improves binary and ternary sentiment classification and outperforms multiple baselines. For more complex tasks such as relation detection, only the contextualized BERT embeddings outperform the baselines in our experiments, which raises the need for further research. Finally, EEG data shows to be particularly promising when limited training data is available.
A Review of Parameter Settings for Invasive and Non-invasive Vagus Nerve Stimulation (VNS) Applied in Neurological and Psychiatric Disorders
Authors: Thompson Sean L. , O’Leary Georgia H. , Austelle Christopher W. , Gruber Elise , Kahn Alex T. , Manett Andrew J. , Short Baron , Badran Bashar W.
Published: July 2021

Vagus nerve stimulation (VNS) is an established form of neuromodulation with a long history of promising applications. Earliest reports of VNS in the literature date to the late 1800’s in experiments conducted by Dr. James Corning. Over the past century, both invasive and non-invasive VNS have demonstrated promise in treating a variety of disorders, including epilepsy, depression, and post-stroke motor rehabilitation. As VNS continues to rapidly grow in popularity and application, the field generally lacks a consensus on optimum stimulation parameters. Stimulation parameters have a significant impact on the efficacy of neuromodulation, and here we will describe the longitudinal evolution of VNS parameters in the following categorical progression: (1) animal models, (2) epilepsy, (3) treatment resistant depression, (4) neuroplasticity and rehabilitation, and (5) transcutaneous auricular VNS (taVNS). We additionally offer a historical perspective of the various applications and summarize the range and most commonly used parameters in over 130 implanted and non-invasive VNS studies over five applications.
NU9056, a KAT 5 Inhibitor, Treatment Alleviates Brain Dysfunction by Inhibiting NLRP3 Inflammasome Activation, Affecting Gut Microbiota, and Derived Metabolites in LPS-Treated Mice
Authors: Chen Lu , Qing Wenxiang , Yi Zexiong , Lin Guoxin , Peng Qianyi , Zhou Fan
Published: July 2021

Background: The pathogenesis of sepsis-associated encephalopathy (SAE) is complicated, while the efficacy of current treatment technologies is poor. Therefore, the discovery of related targets and the development of new drugs are essential.

Methods: A mouse model of SAE was constructed by intraperitoneal injection of lipopolysaccharide (LPS). LPS treatment of microglia was used to build an in vitro model of inflammation. Nine-day survival rates, behavioral testing, transmission electron microscopy (TEM), immunohistochemical (IHC), immunofluorescence (IF), and ELISA were performed. The expression levels of Occludin, Claudin 5, NLRP3, caspase-1, and ASC genes and proteins were detected by RT-qPCR or Western blot. Caspase-1 P10 (Casp-1 P10) protein expression was detected. 16S rDNA sequencing and gas chromatography-mass spectrometer (GC-MS) were used to analyze the gut microbiota and metabolism. Flow cytometric experiment and Cell Counting Kit-8 (CCK8) assay were performed.

Results: NU9056 improved the survival rate of mice and alleviated LPS-induced cognitive impairment, anxiety, and depression in vivo. The tight junctions were thickened via NU9056 treatment. Further, the mRNAs and proteins expression levels of Occludin and Claudin 5 were up-regulated by NU9056. NU9056 increased the expression level of DCX. The expression levels of Iba-1, NLRP3, IL-1β, ASC, and Casp-1 P10 were down-regulated by NU9056. The composition of the gut microbiota changed. Kyoto Encyclopedia of Genes and Genomes data predicted that the effects of NU9056 might be related to apoptosis and tight junction pathways. NU9056 up-regulated the concentration of acetate, propionate, and butyrate. NU9056 significantly reduced LPS-induced apoptosis of microglia, the average fluorescence intensity of ROS, and the release of IL-1β and IL-18, while improving cell viability in vitro.

Conclusions: NU9056 might effectively alleviate LPS-induced cognitive impairment and emotional disorder in experimental mice by inhibiting the NLRP3 inflammasome. The therapeutic effects may be related to gut microbiota and derived metabolites. NU9056 might be a potential drug of SAE prevention.
Magnetic Resonance Imaging Evaluation of the Accuracy of Various Lymph Node Staging Criteria in Rectal Cancer: A Systematic Review and Meta-Analysis
Authors: Zhuang Zixuan , Zhang Yang , Wei Mingtian , Yang Xuyang , Wang Ziqiang
Published: July 2021

Background

Magnetic resonance imaging (MRI)-based lymph node staging remains a significant challenge in the treatment of rectal cancer. Pretreatment evaluation of lymph node metastasis guides the formulation of treatment plans. This systematic review aimed to evaluate the diagnostic performance of MRI in lymph node staging using various morphological criteria.

Methods

A systematic search of the EMBASE, Medline, and Cochrane databases was performed. Original articles published between 2000 and January 2021 that used MRI for lymph node staging in rectal cancer were eligible. The included studies were assessed using the QUADAS-2 tool. A bivariate random-effects model was used to conduct a meta-analysis of diagnostic test accuracy.

Results

Thirty-seven studies were eligible for this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of preoperative MRI for the lymph node stage were 0.73 (95% confidence interval [CI], 0.68–0.77), 0.74 (95% CI, 0.68–0.80), and 7.85 (95% CI, 5.78–10.66), respectively. Criteria for positive mesorectal lymph node metastasis included (A) a short-axis diameter of 5 mm, (B) morphological standard, including an irregular border and mixed-signal intensity within the lymph node, (C) a short-axis diameter of 5 mm with the morphological standard, (D) a short-axis diameter of 8 mm with the morphological standard, and (E) a short-axis diameter of 10 mm with the morphological standard. The pooled sensitivity/specificity for these criteria were 75%/64%, 81%/67%, 74%/79%, 72%/66%, and 62%/91%, respectively. There was no significant difference among the criteria in sensitivity/specificity. The area under the receiver operating characteristic (ROC) curve values of the fitted summary ROC indicated a diagnostic accuracy rate of 0.75–0.81.

Conclusion

MRI scans have minimal accuracy as a reference index for pretreatment staging of various lymph node staging criteria in rectal cancer. Multiple types of evidence should be used in clinical decision-making.
Population Pharmacokinetics of High-Dose Methotrexate in Chinese Pediatric Patients With Acute Lymphoblastic Leukemia
Authors: Gao Xuan , Qian Xiao-Wen , Zhu Xiao-Hua , Yu Yi , Miao Hui , Meng Jian-Hua , Jiang Jun-Ye , Wang Hong-Sheng , Zhai Xiao-Wen
Published: July 2021

High-dose methotrexate (HD-MTX) is widely used in pediatric acute lymphoblastic leukemia (ALL) treatment regimens. In this study, we aimed to develop a population pharmacokinetic (PK) model of HD-MTX in Chinese pediatric patients with ALL for designing personalized dosage regimens. In total, 4,517 MTX serum concentration data for 311 pediatric patients with ALL, aged 0.75–15.2 years and under HD-MTX treatment, were retrospectively collected at a tertiary Children’s Hospital in China. The non-linear mixed-effect model was used to establish the population PK model, using NONMEM software. The potential covariate effects of age, body weight, and biochemical measurements (renal and liver function) on MTX PK disposition were investigated. The model was then evaluated using goodness-of-fit, visual predictive check. MTX PK disposition was described using a three-compartment model reasonable well. Body weight, implemented as a fixed allometric function on all clearance and volume of distribution parameters, showed a substantial improvement in model fit. The final population model demonstrated that the MTX clearance estimate in a typical child with body weight of 19 kg was 6.9 L/h and the central distribution of volume estimate was 20.7 L. The serum creatinine significantly affected the MTX clearance, with a 0.97% decrease in clearance per 1 μmol/L of serum creatinine. Other covariates (e.g., age, sex, bilirubin, albumin, aspartate transaminase, concomitant medication) did not significantly affect PK properties of MTX. The proposed population PK model could describe the MTX concentration data in Chinese pediatric patients with ALL. This population PK model combined with a maximum a posteriori Bayesian approach could be used to estimate individual PK parameters, and optimize personalized MTX therapy in target patients, thus aiming to reduce toxicity and improve treatment outcomes.
Random Walks of a Cell With Correlated Speed and Persistence Influenced by the Extracellular Topography
Authors: Chen Kejie , Qin Kai-Rong
Published: July 2021

Cell migration through extracellular matrices is critical to many physiological processes, such as tissue development, immunological response and cancer metastasis. Previous models including persistent random walk (PRW) and Lévy walk only explain the migratory dynamics of some cell types in a homogeneous environment. Recently, it was discovered that the intracellular actin flow can robustly ensure a universal coupling between cell migratory speed and persistence for a variety of cell types migrating in the in vitro assays and live tissues. However, effects of the correlation between speed and persistence on the macroscopic cell migration dynamics and patterns in complex environments are largely unknown. In this study, we developed a Monte Carlo random walk simulation to investigate the motility, the search ability and the search efficiency of a cell moving in both homogeneous and porous environments. The cell is simplified as a dimensionless particle, moving according to PRW, Lévy walk, random walk with linear speed-persistence correlation (linear RWSP) and random walk with nonlinear speed-persistence correlation (nonlinear RWSP). The coarse-grained analysis showed that the nonlinear RWSP achieved the largest motility in both homogeneous and porous environments. When a particle searches for targets, the nonlinear coupling of speed and persistence improves the search ability (i.e. find more targets in a fixed time period), but sacrifices the search efficiency (i.e. find less targets per unit distance). Moreover, both the convex and concave pores restrict particle motion, especially for the nonlinear RWSP and Lévy walk. Overall, our results demonstrate that the nonlinear correlation of speed and persistence has the potential to enhance the motility and searching properties in complex environments, and could serve as a starting point for more detailed studies of active particles in biological, engineering and social science fields.
Elevated Levels of Soluble Axl (sAxl) Regulates Key Angiogenic Molecules to Induce Placental Endothelial Dysfunction and a Preeclampsia-Like Phenotype
Authors: Gui Shunping , Zhou Shengping , Liu Min , Zhang Yanping , Gao Linbo , Wang Tao , Zhou Rong
Published: July 2021

Preeclampsia (PE), a severe pregnancy-specific syndrome, is characterized by impaired placental angiogenesis. Although the pathogenesis of this condition remains largely unclear, vascular systemic endothelial injury is thought to be the common contributing factor. Soluble Axl (sAxl), a biomarker of endothelial dysfunction, is known to be abnormally increased in a variety of diseases associated with vascular injury. In a previous study, we found that the plasma levels of sAxl were significantly higher in PE with severe features (sPE) than in pregnant women who did not have PE. The current study aimed to further explore the potential role of sAxl in vascular injury in patients with sPE. We found that the upregulation of sAxl in maternal plasma was positively correlated with the plasma levels of sFlt-1 and negatively correlated with placental NO synthase (eNOS) in women with sPE. Furthermore, elevated levels of sAxl suppressed proliferation and endothelial tube formation and promoted cytotoxicity in human umbilical vein endothelial cells (HUVECs) through the downregulation of p-Akt, p-p70S6K, p-mTOR, and Grb2. Subsequently, we established a pregnant rat model with PE-like characteristics by injecting pregnant rats with an adenovirus expressing sAxl. These rats exhibited a typical PE-like phenotype, including increased blood pressure, proteinuria, and fetal growth restriction, along with abnormal placental and fetal renal morphology. In conclusion, our study demonstrated the role of sAxl in systemic vascular injury through the regulation of the expression of key molecules of angiogenesis and described its potential contribution to the development of sPE.
“No Way Out Except From External Intervention”: First-Hand Accounts of Autistic Inertia
Authors: Buckle Karen Leneh , Leadbitter Kathy , Poliakoff Ellen , Gowen Emma
Published: July 2021

This study, called for by autistic people and led by an autistic researcher, is the first to explore ‘autistic inertia,’ a widespread and often debilitating difficulty acting on their intentions. Previous research has considered initiation only in the context of social interaction or experimental conditions. This study is unique in considering difficulty initiating tasks of any type in real life settings, and by gathering qualitative data directly from autistic people. Four face-to-face and 2 online (text) focus groups were conducted with 32 autistic adults (19 female, 8 male, and 5 other), aged 23–64 who were able to express their internal experiences in words. They articulate in detail the actions they have difficulty with, what makes it easier or harder to act, and the impact on their lives. Thematic analysis of the transcripts found four overarching themes: descriptions of inertia, scaffolding to support action, the influence of wellbeing, and the impact on day-to-day activities. Participants described difficulty starting, stopping and changing activities that was not within their conscious control. While difficulty with planning was common, a subset of participants described a profound impairment in initiating even simple actions more suggestive of a movement disorder. Prompting and compatible activity in the environment promoted action, while mental health difficulties and stress exacerbated difficulties. Inertia had pervasive effects on participants’ day-to-day activities and wellbeing. This overdue research opens the door to many areas of further investigation to better understand autistic inertia and effective support strategies.
Emotional Regulation as a Remedy for Teacher Burnout in Special Schools: Evaluating School Climate, Teacher’s Work-Life Balance and Children Behavior
Authors: Mulyani Sri , Salameh Anas A. , Komariah Aan , Timoshin Anton , Hashim Nik Alif Amri Nik , Fauziah R. Siti Pupu , Mulyaningsih Mulyaningsih , Ahmad Israr , Ul din Sajid Mohy
Published: July 2021

This research aimed to identify whether improvement in working conditions, children’s classroom behavior and work-life balance can lower teacher burnout ratio in Pakistan’s special schools by using techniques such as emotions regulation. The researcher employed a quantitative research methodology to fulfill the research’s purpose. The data for this research was collected using a questionnaire-based instrument. The confirmatory factor analysis and structural equation modeling techniques were used to test the construct validity and underlying structural relationships. The findings demonstrated that the impacts of all three variables are significant in reducing job burnout in teachers. Emotional regulation helps decrease the impact of working conditions and the children’s behavior. Nevertheless, it does not aid work-life balance as it requires other techniques of emotional regulation. The research is significant as it highlights the importance of overall working conditions’ improvement for teachers working with special needs children. The improvements are essential because the teachers must take extra effort and emotions into their job compared to a typical teacher. The researcher has highlighted the key finding, implications and limitations of this research besides suggesting directions for future research to facilitate peer researchers.