bluuebunny/crossref_metadata_2025 huggingface dataset:
The structural and functional connectivity neural underpinnings of body image
Authors: Moayedi Massieh , Noroozbahari Nasim , Hadjis Georgia , Themelis Kristy , Salomons Tim V. , Newport Roger , Lewis Jennifer
Published: August 2020

How we perceive our bodies is fundamental to our self-consciousness and our experience in the world. There are two types interrelated internal body representations—a subjective experience of the position of a limb in space (body schema) and the subjective experience of the shape and size of the limb (body image). Body schema has been extensively studied, but there is no evidence of the brain structure and network dynamics underpinning body image. Here, we provide the first evidence for the extrastriate body area (EBA), a multisensory brain area, as the structural and functional neural substrate for body shape and size. We performed a multisensory finger-stretch illusion that elongated the index finger. EBA volume and functional connectivity to the posterior parietal cortex are both related to the participants’ susceptibility to the illusion. Taken together, these data suggest that EBA structure and connectivity encode body representation and body perception disturbances.
Genotype & Phenotype in Lowe Syndrome: SpecificOCRL1patient mutations differentially impact cellular phenotypes
Authors: Ramadesikan Swetha , Skiba Lisette , Lee Jennifer , Madhivanan Kayalvizhi , Sarkar Daipayan , De La Fuente Agustina , Hanna Claudia B. , Terashi Genki , Hazbun Tony , Kihara Daisuke , Aguilar R. Claudio
Published: August 2020

Lowe Syndrome (LS) is a lethal genetic disorder caused by mutations in theOCRL1gene which encodes the lipid 5’ phosphatase Ocrl1. Patients exhibit a characteristic triad of symptoms including eyes, brain and kidneys abnormalities with renal failure as the most common cause of premature death. Over 200OCRL1mutations have been identified in LS, but their specific impact on cellular processes is unknown. Despite observations of heterogeneity in patient symptom severity, there is little understanding of the correlation between genotype and its impact on phenotype.

Here, we show that different mutations had diverse effects on protein localization and on triggering LS cellular phenotypes. In addition, some mutations affecting specific domains imparted unique characteristics to the resulting mutated protein. We also propose that certain mutations conformationally affect the 5’-phosphatase domain of the protein, resulting in loss of enzymatic activity and causing common and specific phenotypes.

This study is the first to show the differential effect of patient 5’-phosphatase mutations on cellular phenotypes and introduces a conformational disease component in LS. This work provides a framework that can help stratify patients as well as to produce a more accurate prognosis depending on the nature and location of the mutation within theOCRL1gene.
Genome-wide Prediction of Small Molecule Binding to Remote Orphan Proteins Using Distilled Sequence Alignment Embedding
Authors: Cai Tian , Lim Hansaim , Abbu Kyra Alyssa , Qiu Yue , Nussinov Ruth , Xie Lei
Published: August 2020

Endogenous or surrogate ligands of a vast number of proteins remain unknown. Identification of small molecules that bind to these orphan proteins will not only shed new light into their biological functions but also provide new opportunities for drug discovery. Deep learning plays an increasing role in the prediction of chemical-protein interactions, but it faces several challenges in protein deorphanization. Bioassay data are highly biased to certain proteins, making it difficult to train a generalizable machine learning model for the proteins that are dissimilar from the ones in the training data set. Pre-training offers a general solution to improving the model generalization, but needs incorporation of domain knowledge and customization of task-specific supervised learning. To address these challenges, we develop a novel protein pre-training method, DIstilled Sequence Alignment Embedding (DISAE), and a module-based fine-tuning strategy for the protein deorphanization. In the benchmark studies, DISAE significantly improves the generalizability and outperforms the state-of-the-art methods with a large margin. The interpretability analysis of pre-trained model suggests that it learns biologically meaningful information. We further use DISAE to assign ligands to 649 human orphan G-Protein Coupled Receptors (GPCRs) and to cluster the human GPCRome by integrating their phylogenetic and ligand relationships. The promising results of DISAE open an avenue for exploring the chemical landscape of entire sequenced genomes.
Small molecule FGF23 inhibitors increase serum phosphate and improve skeletal abnormalities inHypmice
Authors: Xiao Zhousheng , Liu Jiawang , Liu Shih-Hsien , Petridis Loukas , Cai Chun , Cao Li , Wang Guangwei , Chin Ai Lin , Cleveland Jacob W. , Ikedionwu Munachi O. , Carrick Jesse D. , Smith Jeremy C. , Quarles L. Darryl
Published: August 2020

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that binds to binary FGFR/α-Klotho receptor complexes in the kidney tubules to inhibit phosphate reabsorption and 1,25(OH)2D production. Excess FGF23 causes X-linked hypophosphatemia (XLH) and tumor induced osteomalacia (TIO). Recently, Burosumab, an FGF23 blocking antibody, was approved for treating these hypophosphatemic disorders. A small molecule inhibitor that specifically binds to FGF23 to prevent activation of FGFR/α-Klotho complexes has potential advantages over a systemically administered FGF23 blocking antibody. We previously identified the small molecule ZINC13407541 (N-[[2-(2-phenylethenyl)cyclopenten-1-yl]methylidene]hydroxylamine) as a therapeutic lead FGF23 antagonist. Additional structure-activity studies developed a series of ZINC13407541 analogues with enhanced drug-like properties. In this study, we tested in a pre-clinicalHypmouse homologue of XLH a direct connect analogue (8n) [(E)-2-(4-(tert-butyl)phenyl)cyclopent-1-ene-1-carbaldehyde oxime] that exhibited the greatest stability in microsomal assays, and13a[(E)-2-((E)-4-methylstyryl)benzaldehyde oxime] that exhibited increasedin vitropotency. We found that pharmacological inhibition of FGF23 with either of these compounds blocked FGF23 signaling and significantly increased serum phosphate and 1,25(OH)2D concentrations inHypmice. Long-term parenteral treatment with8nor13aalso enhanced linear bone growth, increased mineralization of bone, and narrowed the growth plate inHypmice. The more potent13acompound showed greater therapeutic efficacy inHypmice. Further optimization of these FGF23 inhibitors may lead to versatile drugs to treat FGF23-mediated disorders.
Development of mass spectrometry-based targeted assay for direct detection of novel SARS-CoV-2 coronavirus from clinical specimens
Authors: Renuse Santosh , Vanderboom Patrick M. , Maus Anthony D. , Kemp Jennifer V. , Gurtner Kari M. , Madugundu Anil K. , Chavan Sandip , Peterson Jane A. , Madden Benjamin J. , Mangalaparthi Kiran K. , Mun Dong-Gi , Singh Smrita , Kipp Benjamin R. , Dasari Surendra , Singh Ravinder J. , Grebe Stefan K. , Pandey Akhilesh
Published: August 2020

The COVID-19 pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has overwhelmed health systems worldwide and highlighted limitations of diagnostic testing. Several types of diagnostics including RT-PCR-based assays, antigen detection by lateral flow assays and antibody-based assays have been developed and deployed in a short time. However, many of these assays are lacking in sensitivity and/or specificity. Here, we describe an immunoaffinity purification followed by high resolution mass spectrometry-based targeted assay capable of detecting viral antigen in nasopharyngeal swab samples of SARS-CoV-2 infected individuals. Based on our discovery experiments using purified virus, recombinant viral protein and nasopharyngeal swab samples from COVID-19 positive patients, nucleocapsid protein was selected as a target antigen. We then developed an automated antibody capture-based workflow coupled to targeted high-field asymmetric ion mobility spectrometry (FAIMS) - parallel reaction monitoring (PRM) assays on an Orbitrap Exploris 480 mass spectrometer. An ensemble machine learning-based model for determining COVID-19 positive samples was created using fragment ion intensities in the PRM data. This resulted in 97.8% sensitivity and 100% specificity with RT-PCR-based molecular testing as the gold standard. Our results demonstrate that direct detection of infectious agents from clinical samples by mass spectrometry-based assays have potential to be deployed as diagnostic assays in clinical laboratories.
Threshold concentration and random collision determine the growth of the phase-separated huntingtin inclusion from a stable core
Authors: Pei Sen , Swayne Theresa C. , Morris Jeffrey F. , Emtage Lesley
Published: August 2020

The processes underlying formation and growth of unfolded protein inclusions are relevant to neurodegenerative diseases. InS. cerevisiae, inclusion bodies formed by mutant huntingtin have characteristics of phase-separated compartments: they are mobile, ovoid, and the contents are diffusible. We have used molecular genetics and quantitative confocal microscopy to probe the relationship between concentration and inclusion growth in vivo. Our analysis and modeling of the growth of mutant huntingtin inclusion bodies (mHtt IBs) suggests that there is a cytoplasmic threshold concentration that triggers the formation of an IB, regardless of proteasome capacity, and that reduction in cytoplasmic mHtt causes IBs to shrink. These findings confirm that the IB is a phase-separated compartment that continuously exchanges material with the cytoplasm. The growth rate of the IB is most consistent with a model in which material is incorporated through collision with the IB. A small remnant of the IB is relatively long-lasting, suggesting that the IB contains a core that is structurally distinct, and which may serve to nucleate it.
Plumbagin and oridonin reveal new CRM1 binding sites and NES-binding groove features
Authors: Lei Yuqin , Li Yuling , Tan Yuping , Jia Da , Sun Qingxiang
Published: August 2020

CRM1 is an important drug target in diseases such as cancer and viral infection. Plumbagin and oridonin, the herbal ingredients with known anti-cancer activities, were reported to inhibit CRM1-mediated nuclear export. However, their modes of CRM1 inhibition are unclear. Here, a multi-mutant of yeast CRM1 was engineered to enable the crystallization of these two small molecules in CRM1’s NES-binding groove. Each structure showed three inhibitor-binding sites, among which two are conserved in humans. Besides the known binding site, another site also participated in oridonin and plumbagin’s CRM1 inhibition. While the plumbagin-bound NES groove resembled the NES-bound groove state, the oridonin-bound groove revealed for the first time a more open NES groove, which may potentially improve cargo-loading through a capture-and-tighten mechanism. Our work thus provides a tool for CRM1 inhibitor crystallization, new insights of CRM1-cargo interaction, and a structural basis for further development of these or other CRM1 inhibitors.
Dynamic brain-to-brain concordance and behavioral mirroring as a mechanism of the patient-clinician interaction
Authors: Ellingsen Dan-Mikael , Isenburg Kylie , Jung Changjin , Lee Jeungchan , Gerber Jessica , Mawla Ishtiaq , Sclocco Roberta , Jensen Karin B , Edwards Robert Randolph , Kelley John M. , Kirsch Irving , Kaptchuk Ted J. , Napadow Vitaly
Published: August 2020

The patient-clinician interaction can powerfully shape treatment outcomes such as pain, but is often considered an intangible “art-of-medicine”, and has largely eluded scientific inquiry. Although brain correlates of social processes such as empathy and theory-of-mind have been studied using single-subject designs, the specific behavioral and neural mechanisms underpinning the patient-clinician interaction are unknown. Using a two-person interactive design, we simultaneously recorded functional MRI (i.e. hyperscanning) in patient-clinician dyads, who interacted via live video while clinicians treated evoked pain in chronic pain patients. Our results show that patient analgesia is mediated by patient-clinician nonverbal behavioral mirroring and brain-to-brain concordance in circuitry implicated in theory-of-mind and social mirroring. Dyad-based analyses showed extensive dynamic coupling of these brain nodes with the partners’ brain activity, yet only in dyads where clinical rapport had been established prior to the interaction. These findings point to a putatively key brain-behavioral mechanism for therapeutic alliance and psychosocial analgesia.
Does plant root architecture respond to potassium nutrition under water stress? A case from rice seedling root responses
Authors: Patel Dipika S. , Kirti Bardhan , Patel Dhiraji P , Vipulkumar Parekh , Suchismita Jena , Narwade Ajay V. , Chhatrola Harshadkumar N
Published: August 2020

The root is the sensing organ for potassium (K) and water availability. We evaluated whether K availability influences root architecture and contributes to drought tolerance under moisture stress. Rice seedling growth was severely affected by low K availability under water stress, and the substantial reductions in root projected area, maximum width, and width to depth ratio were observed. High K availability helps maintain root top and bottom angles and reduces root steepness under mild water stress, but over K nutrition does not ensure higher seedling growth. Under severe water stress, the steepness was more regulated by water than K availability.
Enhancing employee advocacy on social media: the value of internal relationship management approach
Authors: Lee Yeunjae , Kim Katie Haejung
Published: August 2020

Purpose

To advance the theoretical understanding of employees' advocacy on social media, this study aims to propose and test an integrative model that incorporates individual and organizational antecedents. Drawing from the relationship management theory in public relations and online behavior literature, the model specifically examines the collective impacts of the social media-related behavioral motivations of individuals and the quality of employee–organization relationship (EOR) on their positive information-sharing intentions about their company on personal social media.

Design/methodology/approach

An online survey was conducted with 419 full-time employees in the USA who use social media.

Findings

The results of an online survey with full-time employees in the USA showed that the EOR influenced by symmetrical internal communication significantly increases employees' advocacy intentions and social media-related motivations. Considerable and distinct effects of individuals' positive behavioral motivations on social media (i.e. self-enhancement, altruism, enjoyment) on advocacy intentions are also found.

Originality/value

This study is among the first attempts to test the value of strategic internal communication and relationship management approach in enhancing employee advocacy on the digital environment, social media and their motives of using such channel for benefiting their company.
Current trends analysis and prioritization of success factors: a systematic literature review of ICT projects
Authors: Ayat Muhammad , Imran Muhammad , Ullah Azmat , Kang Chang Wook
Published: August 2020

Purpose

The purpose of this study is to investigate the current literature that has explored project success in the information and communication technology (ICT) sector.

Design/methodology/approach

The literature search was carried out for related articles in three databases: the Web of Science, Scopus and Ebscohost. Using a systematic literature review (SLR) methodology, 75 related articles were sorted out. Furthermore, the methods of frequency and content analysis were used to identify, categorize and arrange critical success factors (CSF) of ICT projects based on their importance, interrelation and cultural regions.

Findings

The findings in this study revealed that interest in researching success in ICT projects has increased significantly during the last five years. Through reviewing the selected articles, 25 CSF were identified. User participation, stakeholder relationship, project manager emotional intelligence, communication skills, and leadership skills, and top management support in the project emerged as the most important factors for ICT projects. Furthermore, we found that each regional group gives different level of importance to different CSF.

Practical implications

This study gives the opportunity to practitioners to control the highest value CSF to increase the success rate of ICT projects carried out in different cultural regions.

Originality/value

As the first study of its type, CSF were divided for different cultural regional groups. This paper further explained that certain CSF have different levels of importance in different culture regions. This study suggests that regional culture needs consideration during the evaluation of CSF.
Government transition in the time of the COVID-19 crisis: Slovak case
Authors: Nemec Juraj
Published: August 2020

Purpose

Most media evaluate Slovakia as the most successful European country in the fight against the spread of coronavirus disease 2019 (COVID-19). Such excellent results have been achieved in a really specific period – the change of the government overlapped the initial days of the outbreak of the pandemic in the country. The goal of this viewpoint paper is to investigate how individual public leaders (Prime Ministers) shaped the governance response, how these key political leaders have helped to make the transition to a new government so seamless in times of crisis.

Design/methodology/approach

Qualitative approach is used to map the situation and to show how key political leaders shaped the governance response to the crisis. The official government COVID-19 web page and core national media were investigated to collect the necessary information for our research.

Findings

The most positive finding of this article is the fact that the departing Prime Minister Pellegrini did not decide to wait till the end of office in a passive or moderate way, but managed during last days of office of “his” government to realize a set of really comprehensive measures to prevent the spread of COVID-19 in Slovakia. Politics has been set a bit aside; coalition and opposition parties prioritized the need to fight COVID-19 instead of the need for permanent political fights.

Originality/value

The article introduces the example of the political “takeover” during the crisis, which has been realized in such positive ways, especially thanks to the fact that Pellegrini behaved as a real national leader just a few days before leaving office.
Robot posture generation method for laser melting deposition
Authors: Zheng Huadong , Wang Caidong , Fei Zhigen , Chen Lumin , Cheng Yan
Published: August 2020

Purpose

This paper aims to provide a posture generation method of robot deposition paths based on intersection topology, which is helpful to contribute to improving the flexibility and deposition capability of the deposition system.

Design/methodology/approach

Via the geometry information and normal vector information of the stereolithography (STL) model, the intersecting edge information is generated and the topological relationship of the model is established. Through the removal of redundant points for the STL model and the sort of robot path points, the position information of robot path points is obtained. According to the geometric relationship between the normal vector information of the STL model and the robot deposition path points, combining with the robot posture representation method of roll-pitch-yaw angles, the posture information of path points is achieved. Then, the generation from CAD model of parts to robot paths for laser melting is realized, and the experimental verification is carried out.

Findings

For simple parts, the laser melting process can be completed without the posture information of deposition paths. However, in the melting process of a turbine blade, there are some accumulated burls on the sidewall. The posture generation method of robot deposition paths based on the intersection topology can solve this problem. The light spot of deposition points irradiates on the surface of the forming part, and the forming process can proceed smoothly.

Practical implications

As a motion platform in laser melting deposition (LMD), the application of the multi-joint robot can improve the flexibility and deposition capability of the deposition system, as well as promote the LMD application for individuation manufacturing, parts repair and green remanufacturing.

Originality/value

The posture is essential for robot deposition paths. This paper first proposes a posture generation method of deposition paths for LMD to improve the flexibility and deposition capability of LMD systems.
Factors affecting pre-visit destination image: application on the Grand Egyptian Museum (GEM)
Authors: El Sheikh Samia Adly Hanna
Published: August 2020

Purpose

The purpose of this study is to investigate through an empirical research the factors that would attract visitors to heritage and cultural sites as museums applied on the Grand Egyptian Museum (GEM). The paper aims to study the impact of the proposed attraction features learning/knowledge, museum facilities, fun/entertainment and socializing and accessibility/location on pre-visit destination image.

Design/methodology/approach

The author started by a thorough literature review to arrive to the suggested conceptual model, which is tested by adopting a quantitative approach where data were collected using a self-administered questionnaire from a convenient sample of 300 respondents with 90% response rate and used partial least squares – structure equation modelling using Smart PLS v.3.2.8.

Findings

The results show that three of the tested factors were accepted and one was rejected.

Practical implications

Management of GEM, which will be one of the biggest museums world-wide, can make use of the empirical results of this research to enhance their understanding of the factors that impact pre-visit destination image, and thus, most attract visitors to justify the budget set in this huge project and achieve highest visitation and revenue

Originality/value

This research deals with a new museum that has not opened its doors yet and will start functioning in late 2020, and thus, the pre-visit image of the museum is not based on previous experience of visitors but rather on secondary sources as messages sent to visitors based on attraction features, while most previous studies dealt with post-visit image of museums
Employees’ perceptions of organizational learning: the role of knowledge and trust
Authors: Kim Eunjee , Park Sunyoung
Published: August 2020

Purpose

This paper aims to investigate the roles of employees’ perceived knowledge sharing and trust on organizational learning.

Design/methodology/approach

The authors examined the proposed hypotheses by using survey data from 228 responses collected from an IT services company.

Findings

The authors found that a knowledge sharing culture was positively related to interpersonal trust, knowledge sharing behavior and organizational learning. Employees’ perceived trust among people had a positive effect on knowledge sharing behavior and organizational learning. Knowledge sharing behavior was also positively related to organizational learning. In addition, interpersonal trust and knowledge sharing behavior played mediating roles in linking knowledge sharing culture and organizational learning.

Originality/value

This study provides empirical support for the mediating role of interpersonal trust and knowledge sharing behavior on the link between knowledge sharing culture and organizational learning.
Exon splicing analysis of intronic variants in multigene cancer panel testing for hereditary breast/ovarian cancer
Authors: Ryu Jin‐Sun , Lee Hye‐Young , Cho Eun Hae , Yoon Kyong‐Ah , Kim Min‐Kyeong , Joo Jungnam , Lee Eun‐Sook , Kang Han‐Sung , Lee Seeyoun , Lee Dong Ock , Lim Myong Cheol , Kong Sun‐Young
Published: August 2020

The use of multigene panel testing for patients with a predisposition to breast/ovarian cancer is increasing as the identification of variants is useful for diagnosis and disease management. We identified pathogenic and likely pathogenic (P/LP) variants of high‐and moderate‐risk genes using a 23‐gene germline cancer panel in 518 patients with hereditary breast and ovarian cancers (HBOC). The frequency of P/LP variants was 12.4% (64/518) for high‐ and moderate‐penetrant genes, namely, BRCA2 (5.6%), BRCA1 (3.3%), CHEK2 (1.2%), MUTYH (0.8%), PALB2 (0.8%), MLH1 (0.4%), ATM (0.4%), BRIP1 (0.4%), TP53 (0.2%), and PMS2 (0.2%). Five patients possessed two P/LP variants in BRCA1/2 and other genes. We also compared the results from in silico splicing predictive tools and exon splicing patterns from patient samples by analyzing RT‐PCR product sequences in six P/LP intronic variants and two intronic variants of unknown significance (VUS). Altered transcriptional fragments were detected for P/LP intronic variants in BRCA1, BRIP1, CHEK2, PARB2, and PMS2. Notably, we identified an in‐frame deletion of the BRCA1 C‐terminal (BRCT) domain by exon skipping in BRCA1 c.5152+6T>C—as known VUS—indicating a risk for HBOC. Thus, exon splicing analysis can improve the identification of veiled intronic variants that would aid decision making and determination of hereditary cancer risk.
Impact of HEC72702 chirality on the selective inhibition of hepatitis B virus capsid dimer: A dynamics–structure–energetics perspective
Authors: Farrokhzadeh Abdolkarim , Badichi Akher Farideh , Olotu Fisayo A. , Van Heerden Fanie R.
Published: August 2020

Chirality in drug design has been attracting wide interests and attention over the years based on its innate potentials of enhancing the selectivity and prowess of therapeutic molecules. This approach was fundamental to the recent design of two inhibitors, where (R,R)‐HEC72702 exhibited higher potency inhibition against hepatitis B virus capsid (HBVC) than (R,S)‐HEC72702. Nevertheless, the detailed molecular mechanism has remained unresolved. Here, we apply multiple computational approaches to explore, validate, and differentiate the binding modes of (R,R) and (R,S)‐HEC72702 and to explain the systematic roles mediated by chirality on the distinctive inhibition of HBVC dimer (HBVCd). Our findings revealed that chirality change from R,S to R,R engenders variations in the position of the propanoic acid group of HEC72702 toward the α5′ and C‐TER′ region of HBVCd chain B which could explain the higher inhibitory affinity of (R,R)‐HEC72702. Estimated binding free energies revealed a good correlation with bioactivity data. Moreover, analysis of energy decomposition revealed the prominent effects of van der Waals interactions in the binding process of both compounds to HBVCd. Furthermore, hierarchical clustering of residue‐based energetic contributions suggested two hot‐spot residues W125´ and F156´ play crucial roles in the systematic motions of the propanoic acid group toward chain B.
2017 KLEIN LECTURE: THE SCIENCE OF USING SCIENCE: TOWARD AN UNDERSTANDING OF THE THREATS TO SCALABILITY
Authors: Al‐Ubaydli Omar , List John A. , Suskind Dana
Published: August 2020

Policymakers are increasingly facing the challenge of scaling empirical insights. This study provides a theoretical lens into the science of how to use science. Through a simple model, we highlight three elements of the scale‐up problem: (1) when does evidence become actionable; (2) properties of the population; and (3) properties of the situation. Until these three areas are fully understood, the threats to scalability will render any scaling exercise as particularly vulnerable. Accordingly, our work represents a call for more policy‐based evidence, whereby the nature and extent of the various threats to scalability are explored in the original research program.
Complex roles of Rabs and SNAREs in the secretory pathway and plant development: a never‐ending story
Authors: MARTINIÈRE A. , MOREAU P.
Published: August 2020

Membrane trafficking is critical for cell compartmentation which allows the maintenance of specialised environments required for specific cellular activities. To achieve this goal, cells need to tightly regulate vesicle transport between donor and acceptor compartments. Several different protein families are involved: among them the SNAREs (65 genes) and the small GTPases Rabs (57 genes) show the highest number of isoforms and will be in the spotlight. We will focus on the roles of these proteins in the ER–Golgi–plasma membrane pathway to illustrate how Rabs and SNAREs are involved to achieve specific set of functions.

Lay Description

Protein and lipid transport between the different compartments inside cells are critical for many physiological functions of organisms. To achieve this goal, cells have developed several vesicular transport systems between these compartments. Numerous different protein families are involved in these processes among which two protein families are the focus of the review in plant cells: the SNAREs and the small GTPases Rabs. These proteins are essentially controlling the different steps of the transport processes to warrant that proteins and lipids will reach the right compartments. The SNAREs are encoded by 65 genes meaning that plant cells synthesise 65 different SNARE proteins, and the small GTPases Rabs are encoded by 57 genes meaning that plant cells synthesise 57 different GTPases Rabs proteins. This high number of proteins illustrates the complexity of the vesicular transport systems existing between plant cell compartments. The review discusses the different roles of these proteins in these processes and particularly in the functioning of the secretory pathway which contributes to transport proteins and lipids to the cell surface. The review describes how the Rabs and SNAREs proteins are involved to achieve their respective set of functions in the different transport pathways of plant cells, and illustrates the tremendous complexity of these mechanisms.
Primary vulvar Ewing sarcoma/peripheral primitive neuroectodermal tumor with pelvic lymph nodes metastasis: A case report and review of literature
Authors: El Housheimi Alaa , Khalil Ali , Khalifeh Dalia , Berjawi Ghina , Seoud Muhieddine , Tabbarah Abir , Khaled Chirine , Mahfouz Rami , Abdallah Reem
Published: August 2020

Ewing sarcoma (ES) and peripheral primitive neuroectodermal tumors (pPNET) are soft tissue tumors that generally affect the bones. Extraosseous ES/pPNET has been rarely reported. Our patient presented with a 6 × 4 cm right subcutaneous solid vulvar lesion causing pain and discomfort. Pathology and immunohistochemistry staining showed strong positivity for CD99 and vimentin, favoring the diagnosis of ES/pPNET. Magnetic resonance imaging showed a 6‐cm lesion in the right vulvar region with enlarged bilateral inguinal and right iliac lymph nodes. Fluorescence in situ hybridization test for translocation t(11;22)(q24;q12) was positive, confirming the diagnosis. The patient received three cycles of neoadjuvant chemotherapy with vincristine, adriamycin, cyclophosphamide alternating with ifosfamide and etoposide with complete response. The patient underwent vulvar radical local excision. Residual tumor measured 1.6 cm with free margins. She received four additional cycles of adjuvant chemotherapy and 30 sessions radiotherapy. She is currently disease free after 37 months. No ES/pPNET cases with pelvic lymph nodes metastasis were ever reported.
Immunomodulatory and antitumour bioactive labdane diterpenoids from Leonurus japonicus
Authors: Yue Grace Gar-Lee , Liang Xin-Xin , Li Xiao-Li , Lee Julia Kin-Ming , Gao Si , Kwok Hin-Fai , Lau Clara Bik-San , Xiao Wei-Lie
Published: August 2020

Objectives

Two labdane diterpenoids, leojapone B and heteronone B, were isolated from Leonurus japonicus Houtt., and their biological activity were evaluated in this study.

Methods

Human and mouse cancer cells, human peripheral blood mononuclear cells (PBMCs) and mouse macrophages (RAW264.7 cells) were used to evaluate the activity of leojapone B and heteronone B, while the in vivo effects of leojapone B were further examined in Lewis Lung Cancer tumour-bearing mice.

Key findings

In vitro studies showed that leojapone B selectively inhibited the proliferation of lung cancer cells, and both leojapone B and heteronone B inhibited the production of pro-inflammatory cytokines in activated PBMCs. In tumour-bearing mice model, lung tumours were reduced in size in mice treated with intraperitoneal injections of leojapone B at 20 and 30 mg/kg for 14 days. The population ratio of CD4+/CD8+ T cells in mouse spleens was found to be increased, while regulatory T cells were decreased after leojapone B treatment.

Conclusions

The inhibitory effects of leojapone B in mouse lung tumours were demonstrated for the first time in this study. The immunomodulatory activity of heteronone B were also demonstrated. Our findings indicated that both leojapone B and heteronone B may act as active components in L. japonicus.
Efficacy of gastric electrical stimulation in intractable nausea and vomiting at 10 years: A retrospective analysis of prospectively collected data
Authors: Hedjoudje Abdellah , Huet Emmanuel , Leroi Anne‐marie , Desprez Charlotte , Melchior Chloé , Gourcerol Guillaume
Published: August 2020

Background

Gastric electrical simulation has been shown to relieve nausea and vomiting in medically refractory patients. Efficacy of gastric electrical stimulation has been reported mostly in short‐term studies, but none has evaluated its efficacy beyond 10 years after implantation.

Methods

Patients implanted at our center for medically refractory severe and chronic nausea and/or vomiting were evaluated before and over 10 years after implantation using symptomatic scale and quality of life (GIQLI) score. Improvement was defined as a reduction of more than 50% in vomiting frequency.

Key Results

A total of 50 patients were implanted from January 1998 to December 2009. Among them, 7 were explanted due to a lack of efficacy and/or side effects, 2 died, and 4 were lost to follow‐up. Mean follow‐up was 10.5 ± 3.7 years. In intention‐to‐treat analysis, 27/50 (54%) patients reported an improvement. Beyond 10 years, an improvement in early satiety (3.05 vs 1.76, <0.001), bloating (2.51 vs 1.70, P = .012), nausea (2.46 vs 1.35, P = .001), and vomiting (3.35 vs 1.49 P < .001) scores were observed. Quality of life improved over 10 years (GIQLI score: 69.7 vs. 86.4, P = .005) and body mass index (BMI: 23.4 vs. 26.2 kg/m2; P = .048).

Conclusions and Inferences

Gastric electrical simulation is effective in the long‐term in patients with medically refractory nausea and vomiting, with an efficacy of 54% at 10 years on an intention‐to‐treat analysis. Other long‐term observational studies are warranted to confirm these results.
Do preliterate children spontaneously employ spatial coding for serial order in working memory?
Authors: van Dijck Jean‐Philippe , Abrahamse Elger , Fias Wim
Published: August 2020

The ability to memorize arbitrary sequences contributes to cognitive faculties like language and mathematics. Research suggests that in literate adults, serial order in verbal working memory (WM) is grounded in spatial attention and is mentally organized according to our reading habits, that is, from left‐to‐right in Western cultures. Currently, it is unknown whether spatialization is a consequence of literacy, or whether the ability already exists early in life but is shaped by literacy in “calibrating” the initial individual differences in the orientation of spatial coding. Here, we investigated the spatial coding of serial order in WM in 5‐year‐old children who did not yet enter formal literacy education. At the group level, no systematic spatial coding was observed. To investigate whether this absence was due to subjects with reliable but opposing effects, we determined the prevalence of spatial coding at the individual level. This analysis revealed that 36% of the children systematically associated serial order to space, with approximately half of them coding from left‐to‐right and the rest from right‐to‐left. These results indicate that a subgroup of preliterate children associate serial order with space and suggest that reading and writing experience calibrates the orientation of spatial coding with reading habits.
SCEPTICAL DELIBERATIONS
Authors: Chevarie‐Cossette Simon‐Pierre
Published: August 2020

Suppose I am a leeway sceptic: I think that, whenever I face a choice between two courses of action, I lack true alternatives. Can my practical deliberation be rational? Call this the Deliberation Question. This paper has three aims in tackling it. Its constructive aim is to provide a unified account of practical deliberation. Its corrective aim is to amend the way that philosophers have recently framed the Deliberation Question. Finally, its disputative aim is to argue that leeway sceptics cannot deliberate entirely rationally about what to do because of the connection between deliberating and deciding.
A Florida public health‐based endocrine clinic for low‐income pregnant women with diabetes
Authors: LaManna Jacqueline B. , Quelly Susan B. , Stahl Maria , Giurgescu Carmen
Published: August 2020

Objectives

To evaluate pregnancy outcomes of low‐income women with diabetes‐complicated pregnancies who received care from an embedded, public health‐based endocrine specialty clinic (ESC) in Florida.

Design

This program evaluation used retrospective chart data to analyze client characteristics, pre‐program and during‐program glycemic control, and pregnancy outcomes of women enrolled in a prenatal ESC.

Sample

Ninety‐two low‐income, pregnant women with type 1/type 2 diabetes or gestational diabetes (GDM) comprised this racially/ethnically diverse sample.

Variables/Analysis

Neonatal outcomes included frequencies of prematurity, hypoglycemia, hyperbilirubinemia, and birth weight‐for‐gestational‐age categories. Differences in maternal HbA1C at program entry and mean HbA1C during ESC care were determined by a Wilcoxon and paired sample t test.

Results

HbA1C levels during ESC care (6.9 ± 1.4) were less than program entry HbA1C levels (7.9 ± 1.8) for women with pregestational diabetes (Z = −3.364, p = .001). Among women with GDM, mean HbA1C values during ESC care (5.5 ± 0.4) did not significantly differ (t(51) = −0.532, p > .05) from program entry HbA1C levels (5.5 ± 0.5), suggestive of glycemic goal achievement. No neonatal hypoglycemia or hyperbilirubinemia cases were observed in both groups. Approximately 11% of births were preterm, and 16% of neonates were large‐for‐gestational‐age.

Conclusions

A public health‐based ESC for low‐income pregnant women with diabetes may positively affect pregnancy outcomes.
Colitis nucleomigrans: The third type of microscopic colitis (part 2). An ultrastructural study
Authors: Tachibana Mitsuhiro , Tsutsumi Yutaka
Published: August 2020

In the preceding article (part 1), we proposed the third type of microscopic colitis: colitis nucleomigrans (CN). Microscopically, the nuclei of surface‐lining columnar cells were migrated in chain to the middle part of the cells, and apoptotic nuclear debris was scattered in the cytoplasm beneath the nuclei. For ultrastructural analysis, buffered formalin‐fixed biopsy tissue of CN (n = 2) was dug out of paraffin blocks. After deparaffinization, tissue blocks were prepared with conventional sequences. Ultrathin sections were stained with uranyl acetate and lead citrate. Fine morphological preservation was satisfactory even after paraffin embedding. Apoptotic nuclear debris was localized within the cytoplasm beneath the migrated nuclei of the surface‐lining columnar cells. Abnormality of cytoskeletal filaments (actin, cytokeratin and tubulin) was scarcely recognized in the epithelial cytoplasm. Macrophages located in the uppermost part of the lamina propria phagocytized electron‐dense globular materials. Intraepithelial lymphocytes with scattered dense bodies were observed among the columnar cells. We suppose that altered apoptotic processes in the colorectal surface‐lining epithelial cells may be involved in the pathogenesis of CN. Mechanisms of nuclear migration to the unusual position or impairment of nuclear anchoring to the basal situation in the surface‐lining epithelial cells remain unsettled, because cytoskeletal components showed little ultrastructural abnormality.
Colitis nucleomigrans: The third type of microscopic colitis (part 1)
Authors: Tachibana Mitsuhiro , Hanaoka Tomohiko , Watanabe Shinya , Matsushita Masahiro , Isono Tadahiro , Tsutsumi Yutaka
Published: August 2020

Microscopic colitis (MC), encompassing collagenous colitis and lymphocytic colitis, is featured by chronic diarrhea, normal‐looking endoscopic findings and unique microscopic appearance. After reviewing biopsied nonspecific colitis, we propose the third type of MC: colitis nucleomigrans (CN). Histopathological criteria of CN included: (i) chained nuclear migration to the middle part of the surface‐lining columnar epithelium; (ii) apoptotic nuclear debris scattered below the nuclei; and (iii) mild/moderate chronic inflammation in the lamina propria. Thirty‐three patients (M:F = 20:13; median age 63 years, range 17–88) fulfilled our criteria. Seven cases demonstrated MC‐like clinical/endoscopic features. Mucosal reddening with or without erosion/aphtha was endoscopically observed in the remaining 26 cases with inflammatory bowel disease (IBD)‐like features: occult/gross hematochezia seen in 19, abdominal pain in two and mucin secretion in two. Cleaved caspase‐3‐immunoreactive apoptotic debris appeared more frequently in IBD‐like CN than in MC‐like CN, while CD8‐positive intraepithelial lymphocytes comparably appeared in both. Proton pump inhibitors (PPIs) were administered in five (71%) cases with MC‐like features, and in three diarrhea improved after drug cessation. In IBD‐like CN cases, eight (31%) received PPIs. Four patients received chemotherapy against malignancies. Four patients associated immune‐related disorders. Microscopic appearance of CN also appeared in a remission state of ulcerative colitis (12/20 lesions).
Investigation on Simultaneous Charging and Discharging Process of Water Thermocline Storage Tank Employed in Combined Heat and Power Units
Authors: ELSihy ELSaeed Saad , Wang Xiaohui , Xu Chao , Du Xiaoze
Published: August 2020

Thermal energy storage (TES) has become a key component in combined heat and power (CHP) generation, which enhances the load regulation capability and overall thermal performance. In line with that concept, the present work addresses a numerical study that aims at investigating and predicting the transient thermal behavior of a water thermocline storage tank that integrates into a CHP plant. Investigations are carried out on two distinct two-dimensional models. The first model studies thermocline characteristics of the heat storage system through a single-charge/discharge operation. The influences of various operating parameters such as the inlet flowrate and the inlet temperature of HTF are investigated. Results indicate that the thermocline thickness increases as the inlet flowrate increases, and consequently, the heat storage/release period decreases. The second modified model discusses the technique of simultaneous charging and discharging operation applied in the CHP unit. Two types of operations are analyzing with (a) stable charging with steady discharging and (b) periodic charging with steady discharging. The results ravel out that the mixing ratio of charging and discharging flowrate (Qc/Qd) has a strong influence on the operation performance. When the ratio of Qc/Qd >1, the thermocline forms, and its thickness increases with time. The thermocline thickness remains constant as this ratio declines to 0.625. In the case of periodic charging, both larger charging flowrate and shorter non-charging periods result in maintaining the discharge outlet temperature of HTF stable for the heat-supply net, and discharge performance improved.
Productivity Enhancement in Multilayered Unconventional Rocks Using Thermochemicals
Authors: Tariq Zeeshan , Mahmoud Mohamed , Alade Olalekan , Abdulraheem Abdulazeez , Mustafa Ayyaz , Mokheimer Esmail M. A. , Al-Jawad Murtada , Al-Nakhli Ayman
Published: August 2020

Elastic moduli contrast between the adjacent layers in a layered formation can lead to various problems in a conventional hydraulic fracturing job such as improper fracture height growth, limited penetration in a weaker layer only, and nonconductive fractures. In this study, the results of thermochemical fracturing experiment are presented. The hydraulic fracturing experiments presented in this study were carried out on four-layered very tight cement block samples. The results revealed that the novel fracturing technique can reduce the required breakdown pressure in a layered rock by 26%, from 1495 psi (reference breakdown pressure recorded in the conventional hydraulic fracturing technique) to 1107 psi (breakdown pressure recorded in the thermochemical fracturing). The posttreatment experimental analysis showed that the thermochemical fracturing approach resulted in deep and long fractures, passing through majority of the layers, while conventional hydraulic fracturing resulted in a thin fracture that affected only the top layer. A productivity analysis was also carried out which suggested that the fracturing with thermochemical fluids can raise the oil flowrate up to 76% when compared to a conventional hydraulic fracturing technique. Thermochemical fluids injection caused the creation of microfractures and reduces the linear elastic parameters of the rocks. The new technique is cost effective, nontoxic, and sustainable in terms of no environmental hazards.
Upgrading Refuse-Derived Fuel Properties From Reclaimed Landfill Using Torrefaction
Authors: Kerdsuwan S. , Laohalidanond K. , Gupta Ashwani K.
Published: August 2020

Landfill resource reclamation or landfill mining offers an attractive option to harvest the primary materials remaining behind in landfills or open dump sites. After reclamation, the major fractions left after removing soil-like material are paper and plastic fractions, which can be used transformed to refuse-derived fuel (RDF) as a fuel. However, the variation of constituents in RDF causes to low-quality fuel derived from the reclaimed landfill. The torrefaction process is proposed here to upgrade the fuel properties in terms of heating value, energy density ratio, and hydrophobicity. A torrefaction oven was used to torrefy RDF from reclaimed landfill at a controlled temperature of 250, 300, and 300 °C and a residence time of approximately 30 min in an inert environment using Nitrogen gas. The experiment results showed an optimum torrefaction temperature of 250 °C, which resulted in the improved heating value of RDF by up to 14.12%, an increased energy yield of 107.78%, and an energy density ratio of 1.14. These results demonstrated greater energy yield from the torrefied RDF compared with raw RDF. The hydrophobic property of torrefied RDF was also improved with the torrefaction process due to low water adsorption capability of torrefied RDF that was evaluated to be only one-half of that of raw RDF. The fuel upgrading of RDF from reclaimed landfill achieved via the torrefaction process improved the fuel properties that offers its direct use or, in conjunction with other coal fuels, for power generation.