bluuebunny/crossref_metadata_2025 huggingface dataset:
A high-affinity human PD-1/PD-L2 complex informs avenues for small-molecule immune checkpoint drug discovery
Authors: Tang Shaogeng , Kim Peter S.
Published: September 2019

Immune checkpoint blockade of programmed death-1 (PD-1) by monoclonal antibody drugs has delivered breakthroughs in the treatment of cancer. Nonetheless, small-molecule PD-1 inhibitors could lead to increases in treatment efficacy, safety, and global access. While the ligand-binding surface of apo-PD-1 is relatively flat, it harbors a striking pocket in the murine PD-1/PD-L2 structure. An analogous pocket in human PD-1 may serve as a small-molecule drug target, but the structure of the human complex is unknown. Because the CC′ and FG loops in murine PD-1 adopt new conformations upon binding PD-L2, we hypothesized that mutations in these two loops could be coupled to pocket formation and alter PD-1’s affinity for PD-L2. Here, we conducted deep mutational scanning in these loops and used yeast surface display to select for enhanced PD-L2 binding. A PD-1 variant with three substitutions binds PD-L2 with an affinity two orders of magnitude higher than that of the wild-type protein, permitting crystallization of the complex. We determined the X-ray crystal structures of the human triple-mutant PD-1/PD-L2 complex and the apo triple-mutant PD-1 variant at 2.0 Å and 1.2 Å resolution, respectively. Binding of PD-L2 is accompanied by formation of a prominent pocket in human PD-1, as well as substantial conformational changes in the CC′ and FG loops. The structure of the apo triple-mutant PD-1 shows that the CC′ loop adopts the ligand-bound conformation, providing support for allostery between the loop and pocket. This human PD-1/PD-L2 structure provide critical insights for the design and discovery of small-molecule PD-1 inhibitors.

Significance Statement

Immune checkpoint blockade of programmed death-1 (PD-1) by monoclonal antibody drugs has transformed the treatment of cancer. Small-molecule PD-1 drugs have the potential to offer increased efficacy, safety, and global access. Despite substantial efforts such small-molecule drugs have been out of reach. We identify a prominent pocket on the ligand-binding surface of human PD-1 that appears to be an attractive small-molecule drug target. The pocket forms when PD-1 is bound to one of its ligands, PD-L2. Our high-resolution crystal structure of the human PD-1/PD-L2 complex facilitates virtual drug-screening efforts and opens additional avenues for the design and discovery of small-molecule PD-1 inhibitors. Our work provides a strategy that may enable discovery of small-molecule inhibitors of other “undruggable” protein-protein interactions.
Group-Level Analysis of Induced Electric Field in Deep Brain Regions by Different TMS Coils
Authors: Gomez-Tames Jose , Hamasaka Atsushi , Hirata Akimasa , Laakso Ilkka , Lu Mai , Ueno Shoogo
Published: September 2019

Deep transcranial magnetic stimulation (dTMS) is a non-invasive technique used in treating depression. In this study, we computationally evaluate group-level dosage during dTMS with the aim of characterizing targeted deep brain regions to overcome the limitation of using individualized head models to characterize coil performance in a population.

We use an inter-subject registration method adapted to deep brain regions that enable projection of computed electric fields (EFs) from individual realistic head models (n= 18) to the average space of deep brain regions. The computational results showed consistent group-level hotspots of the EF in deep brain region with intensities between 20%-50% of the maximum EF in the cortex. Large co-activation in other brain regions was confirmed while half-value penetration depth from the cortical surface was smaller than 2 cm. The halo figure-8 assembly and halo circular assembly coils induced the highest EFs for caudate, putamen, and hippocampus.

Generalized induced EF maps of deep regions show target regions despite inter-individual difference. This is the first study that visualizes generalized target regions during dTMS and provides a method for making informed decisions during dTMS interventions in clinical practice.
Structural studies of the Tudor domain from the Bombyx homolog of Drosophila PAPI: Implication to piRNA biogenesis
Authors: Hubbard Paul A. , Pan Xinlei , McNally Randall , Kirino Yohei , Murali Ramachandran
Published: September 2019

PIWI proteins and their associated PIWI-interacting RNAs (piRNAs) play crucial roles in proper gametogenesis in animal gonads. Partner of PIWIs (PAPI) is one of the important piRNA biogenesis factors. PAPI contains a Tudor domain and tandem KH domains. The tudor domain specifically recognizes symmetrical-dimethylarginines (sDMAs) on PIWI proteins. BmPAPI, a Bombyx mori homolog of PAPI, is localized at the outer membrane of mitochondria and supports exonucleolytic trimming of piRNA precursors to form mature 3’-end of piRNAs. To understand the structural basis of piRNA processing by BmPAPI, we present crystal structures of the apo- and sDMA-liganded Tudor domain of BmPAPI.
Structural consequences of BMPR2 kinase domain mutations causing pulmonary arterial hypertension
Authors: Chaikuad Apirat , Thangaratnarajah Chancievan , von Delft Frank , Bullock Alex N
Published: September 2019

Bone morphogenetic proteins (BMPs) are secreted ligands of the transforming growth factor-β (TGF-β) family that control embryonic patterning, as well as tissue development and homeostasis. Loss of function mutations in the type II BMP receptor BMPR2 are the leading cause of pulmonary arterial hypertension (PAH), a rare disease of vascular occlusion and heart hypertrophy. To understand the structural consequences of these mutations, we determined the crystal structure of the human BMPR2 kinase domain at 2.35 Å resolution. The structure revealed an activate conformation of the catalytic domain that formed canonical interactions with the bound ligand Mg-ADP. Disease-associated missense mutations were mapped throughout the protein structure, but clustered predominantly in the larger kinase C-lobe. Modelling revealed that the mutations will destabilize the protein structure by varying extents consistent with their previously reported functional heterogeneity. The most severe mutations introduced steric clashes in the hydrophobic protein core, whereas those found on the protein surface were less destabilizing and potentially most favorable for therapeutic rescue strategies currently under clinical investigation.
Enriching human interactome with functional mutations to detect high-impact network modules underlying complex diseases
Authors: Cui Hongzhu , Srinivasan Suhas , Korkin Dmitry
Published: September 2019

Progress in high-throughput -omics technologies moves us one step closer to the datacalypse in life sciences. In spite of the already generated volumes of data, our knowledge of the molecular mechanisms underlying complex genetic diseases remains limited. Increasing evidence shows that biological networks are essential, albeit not sufficient, for the better understanding of these mechanisms. The identification of disease-specific functional modules in the human interactome can provide a more focused insight into the mechanistic nature of the disease. However, carving a disease network module from the whole interactome is a difficult task. In this paper, we propose a computational framework, DIMSUM, which enables the integration of genome-wide association studies (GWAS), functional effects of mutations, and protein-protein interaction (PPI) network to improve disease module detection. Specifically, our approach incorporates and propagates the functional impact of non-synonymous single nucleotide polymorphisms (nsSNPs) on PPIs to implicate the genes that are most likely influenced by the disruptive mutations, and to identify the module with the greatest impact. Comparison against state-of-the-art seed-based module detection methods shows that our approach could yield modules that are biologically more relevant and have stronger association with the studied disease. We expect for our method to become a part of the common toolbox for disease module analysis, facilitating discovery of new disease markers.
Genome sequence and characterisation of coliphage vB_Eco_SLUR29
Authors: Besler Ibrahim , Sazinas Pavelas , Harrison Christian , Gannon Lucy , Redgwell Tamsin , Michniewski Slawomir , Hooton Steven P. , Hobman Jon L. , Millard Andrew
Published: September 2019

Bacteriophage that infect Escherichia coli are relatively easily isolated, with greater than 600 coliphage genomes sequenced to date. Despite this there is still much to be discovered about the diversity of coliphage genomes. Within this study we isolated a coliphage from cattle slurry collected from a farm in rural England. Transmission electron microscopy identified the phage as member of the Siphoviridae family. Phylogenetic analysis and comparative genomics further placed it within the subfamily Tunavirinae and forms part of a new genus. Characterisation of the lytic properties reveals that it is rapidly able to lyse its host when infected at high multiplicity of infection, but not at low multiplicity of infection.
CO2 per se activates carbon dioxide receptors
Authors: Xu Pingxi , Wen Xiaolan , Leal Walter S.
Published: September 2019

Carbon dioxide has been used in traps for more than six decades to monitor mosquito populations and help make informed vector management decisions. CO2 is sensed by gustatory receptors (GRs) housed in neurons in the maxillary palps. CO2-sensitive GRs have been identified from the vinegar fly and mosquitoes, but it remains to be resolved whether these receptors respond to CO2 or bicarbonate. As opposed to the vinegar fly, mosquitoes have three GR subunits, but it is assumed that subunits GR1 and GR3 form functional receptors. In our attempt to identify the chemical species that bind these receptors, we discovered that GR2 and GR3 are essential for receptor function and that GR1 appears to function as a modulator. While Xenopus oocytes coexpressing Culex quinquefasciatus subunits CquiGR1/3 and CquiGR1/2 were not activated, CquiGR2/3 gave robust responses to sodium bicarbonate. Interestingly, CquiGR1/2/3- coexpressing oocytes gave significantly lower responses. That the tertiary combination is markedly less sensitive than the GR2/GR3 combination was also observed with orthologs from the yellow fever and the malaria mosquito. By comparing responses of CquiGR2/CquiGR3- coexpressing oocytes to sodium bicarbonate samples (with or without acidification) and measuring the concentration of aqueous CO2, we showed that there is a direct correlation between dissolved CO2 and receptor response. We then concluded that subunits GR2 and GR3 are essential for these carbon dioxide-sensitive receptors and that they are activated by CO2 per se, not bicarbonate.
Maximizing Dissimilarity in Resting State detects Heterogeneous Subtypes in Healthy population associated with High Substance-Use and Problems in Antisocial Personality
Authors: Kashyap Rajan , Bhattacharjee Sagarika , Thomas Yeo B.T. , Annabel Chen SH
Published: September 2019

Patterns in resting-state fMRI (rs-fMRI) are widely used to characterize the trait effects of brain function. In this aspect, multiple rs-fMRI scans from single subjects can provide interesting clues about the rs-fMRI patterns, though scan-to-scan variability pose challenges. Therefore, rs-fMRI’s are either concatenated or the functional connectivity is averaged. This leads to loss of information. Here, we use an alternative way to extract the rs-fMRI features that are common across all the scans by applying Common-and-Orthogonal-Basis-Extraction (COBE) technique. To address this, we employed rs-fMRI of 788 subjects from the human connectome project and estimated the common-COBE-component of each subject from the four rs-fMRI runs. Since the common-COBE-component are specific to a subject, the pattern was used to classify the subjects based on the similarity/dissimilarity of the features. The subset of subjects (n=107) with maximal-COBE-Dissimilarity (MCD) was extracted and the remaining subjects (n = 681) formed the COBE-similarity (CS) group. The distribution of weights of the common-COBE-component for the two groups across rs-fMRI networks and subcortical regions was evaluated. We found the weights in the default mode network to be lower in the MCD compared to the CS. We compared the scores of 69 behavioral measures and found 6 behaviors related to the use of marijuana, illicit drugs, alcohol, and tobacco; and including a measure of antisocial personality to differentiate the two groups. Gender differences were also significant. Altogether findings suggested that subtypes exist even in healthy control population and comparison studies (Case vs Control) need to be mindful of it.
Crystal structures of two charge–transfer complexes of benzo[1,2-c:3,4-c′:5,6-c′′]trithiophene (D
3h
-BTT)
Authors: Qin Qian , Mague Joel T. , Gould Haley E. , Vasquez Samuel E. , Heyer Anthony E.
Published: September 2019

Benzo[1,2-c:3,4-c′:5,6-c′′]trithiophene (D
3h
-BTT) is an easily prepared electron donor that readily forms charge–transfer complexes with organic acceptors. We report here two crystal structures of its charge–transfer complexes with 7,7,8,8-tetracyanoquinodimethane (TCNQ) and buckminsterfullerene (C60). The D
3h
-BTT·TCNQ complex, C12H6S3·C12H4N4, crystallizes with mixed layers of donors and acceptors, with an estimated degree of charge transfer at 0.09 e. In the D
3h
-BTT·C60·toluene complex, C12H6S3·C60·C7H8, the central ring of BTT is `squeezed' by the C60 molecules from both faces. However, the degree of charge transfer is low. The C60 unit is disordered over two sites in a 0.766 (3):0.234 (3) ratio and was refined as a two-component inversion twin.
Mentoring as meaningful professional development
Authors: Walters William , Robinson Daniel Bruce , Walters Jared
Published: September 2019

Purpose

Within teacher education, many experienced in-service teachers routinely mentor pre-service teachers during teaching practicums. Notwithstanding the benefits pre-service teachers are meant to experience from these mentor–protégé relationships and experiences, recent research has demonstrated that mentors, too, may experience some (oftentimes unintended) potential benefits. The purpose of this paper is to further investigate such potential benefits within a Canadian secondary school physical education (PE) context.

Design/methodology/approach

The researchers employed a qualitative case study methodology. The three primary data sources included field observations/notes, journals and interviews. More specifically, over a ten-week period, the researchers made 26 field visits, observing two mentors’ interactions with five protégés before, during, and after PE class instruction; collected the two mentors’ ten journal entries, all made in response to researcher-provided writing prompts; and interviewed the two mentors, both individually and together.

Findings

The mentor teachers viewed the mentor–protégé relationship/experience as meaningful professional development, recognizing that it approximated a professional learning community. Relatedly, the mentor teachers experienced professional growth with respect to their own teaching identity and teaching practice.

Research limitations/implications

This research could inform those who structure and/or coordinate mentoring research within teacher education programs so that they might place a more purposeful focus upon the potential and/or idealized outcomes for mentors (as well as for protégés). Given the single case study methodology, this research may lack generalizability to other educational contexts.

Originality/value

This research adds to the emerging body of research that investigates how mentoring may provide benefits to mentors. More specifically, this research suggests benefits to mentors relate, especially, to their own teaching identity and practice.
Industrial revolution 4.0: implication to libraries and librarians
Authors: Hussain Abid
Published: September 2019

Purpose

Industry 4.0 is a term for the so-called Fourth Industrial revolutions. It is the technological integration of cyber-physical systems (CPS) in the process of production. CPS enables internet-based process networking with all participants in the process of value creation. The industrial revolution is actually changing how we live, work and communicate. Many trades have highly been affected by 4IR, libraries are one of them. The libraries of twenty-first century are shifting their paradigms from traditional setup to modern information networking. As people and machines are connecting to each other at enormous speed, artificial intelligence, mobile computing, machine learning and automation of every trade have become a need of the day. Automation and artificial intelligence are change agents in 4IR that will make certain groups of employees redundant, replacing them with new workers with the needed skills or with machines that do the job cheaper. This paper aims to shed light on how the 4IR will “shape the future of education, gender, work and library services”. The purpose of this paper is to highlight the challenges being faced by the library and librarians in the age of Industrial 4.0 revolution in contemporary society. The purpose of this study is to review the past literature on Industrial Revolutions 4.0 in education and interlink them with Library services.

Design/methodology/approach

The current study performs a systematic and content-centric review of literature relevant to library services. The literature of this study is based on a six-stage approach to identify the design principles and technology trends of 4IR in education and Library services.

Findings

Industry 4.0 Revolution is the current trend of revolutionary technology, which has affected many services in this age of globalization. Similar, Library services have highly been affected by 4IR. An effort has been made to highlight the vari-ous challenges being faced by libraries and librarians in this age of information. Some solutions have been presented to the library professionals to overcome this technology to boost its services up to the entire satisfaction of the patrons.

Research limitations/implications

The strategic approach in this study can serve the academicians and practitioners in the field of librarianship as a stepping stone to develop a successful transition from traditional manufacturing into the industry 4.0.

Originality/value

The study is among the first to identify the challenges being faced by libraries and librarians in this age of Industrial revolutions.
Compound and heterozygous mutations of KCNQ1 in long QT syndrome with familial history of unexplained sudden death: Identified by analysis of whole exome sequencing and predisposing genes
Authors: Lin Yubi , Zhao Ting , He Siqi , Huang Jiana , Liu Qianru , Yang Zhe , Qin Jiading , Yu Nan , Lu Hongyun , Lin Xiufang
Published: September 2019

Introduction

Long QT syndrome (LQTS) increases the risk of life‐threatening arrhythmia in young individuals with structurally normal hearts. Sixteen genes such as the KCNQ1, KCNH2, and SCN5A have been reported for association with LQTS.

Case presentation

We identified the compound heterozygous mutations in the KCNQ1 gene at c. G527A (p.W176X) and c.G1765A (p.G589S) predicted as “damaging.” The in‐silico analysis showed that when compared to the characteristics of mRNA and protein of wild‐type KCNQ1, the mRNA of c.G527A mutation was significantly different in the centroid secondary structure. The subunit coded by W176X would lose the transmembrane domains S3–S6 and helices A‐D. The protein secondary structure of G589S was slightly shortened in helix structure; the protein physics‐chemical parameters of W176X and G589S significantly and slightly changed, respectively.

Conclusions

The compound heterozygous mutations of W176X and G589S coexisting in KCNQ1 gene of homologous chromosomes, resulting in more severe phenotype, are the likely pathogenic and genetic risks of LQTS and USD in this Chinese family.
De la alienación imitativa a la potencia mimética: Platón y Adorno, Aristóteles y Benjamin
Authors: Bartolomé Ruiz Castor M.M.
Published: September 2019

En este ensayo se sostiene la tesis de que la mímesis es una práctica humana atravesada por una condición agonística que la torna paradójica. Las visiones divergentes sobre la mímesis de Platón y Aristóteles, así como las de Adorno y Benjamin son el reflejo filosófico de la tensión agonística de la mímesis humana. Esta tensión no se resuelve en la verdad exclusiva de una de las posiciones, sino que se mantiene como potencia creadora que permite crear disyuntivas históricas.
Efficient, wide-band rigid-body and elastic scattering computations using transient equivalent sources
Authors: Fahnline John B.
Published: September 2019

A previous paper by the author has shown that transient structural-acoustic problems can be solved using time stepping procedures with the structure and fluid modeled using finite elements and equivalent sources, respectively. Here, the analysis is extended to included scattering problems. Although scattering problems have been discussed extensively in the literature, the current formulation is unique because the acoustic coupling matrix is treated as sparse. Also, most of the previous analyses have assumed the problem is time harmonic, and there is an advantage to performing the computations in the time domain because only a limited number of time steps are required to obtain wideband frequency resolution. This is especially true if the main emphasis is on the mid- to high-frequencies since the ringing response is typically dominated by the lowest frequency modes. Several examples are solved to validate the computations and to document the computation times and solution accuracy.
The inferred determination of the phase speed of a bubbly liquid of less than 2 m/s by using a transfer function technique
Authors: Cheyne Stanley A. , Thurman Hugh O. , Tiblin Cecil M.
Published: September 2019

The phase speed of a bubbly liquid has been inferred at the single bubble resonance. The difficulty in this measurement is the fact that acoustic absorption is very strong at the single bubble resonance making it impossible to measure with standard techniques, e.g., time-of-flight or the use of standing waves. Instead, the strong absorption was exploited by first measuring the change in the reflection coefficient and relating it to the acoustic impedance and the sound speed. A sound speed of less than 2 m/s was determined possibly making it one of the slowest sound speeds ever recorded.
Modeling and Simulation of Pretomanid Pharmacodynamics in Pulmonary Tuberculosis Patients
Authors: Lyons Michael A.
Published: September 2019

Pretomanid (PA-824) is a nitroimidazole in clinical testing for the treatment of tuberculosis. A population pharmacodynamic model for pretomanid was developed using a Bayesian analysis of efficacy data from two early bactericidal activity (EBA) studies, PA-824-CL-007 and PA-824-CL-010, conducted in Cape Town, South Africa.
Genetic Interaction Studies Reveal Superior Performance of Rhizobium tropici CIAT899 on a Range of Diverse East African Common Bean (Phaseolus vulgaris L.) Genotypes
Authors: Gunnabo A. H. , Geurts R. , Wolde-meskel E. , Degefu T. , Giller K. E. , van Heerwaarden J.
Published: September 2019

The existence of genotype-by-strain (G
L
× G
R
) interaction has implications for the expected stability of performance of legume inoculants and could represent both challenges and opportunities for improvement of nitrogen fixation. We find that significant genotype-by-strain interaction exists in common bean (
Phaseolus vulgaris
L.) but that the strength and direction of this interaction depends on the growing environment used to evaluate biomass. Strong genotype and strain main effects, combined with a lack of predictable patterns in G
L
× G
R
, suggests that at best individual bean genotypes and strains can be selected for superior additive performance. The observation that the screening environment may affect experimental outcome of G
L
× G
R
means that identified patterns should be corroborated under more realistic conditions.
Impact of Metazooplankton Filter Feeding on Escherichia coli under Variable Environmental Conditions
Authors: Ismail Niveen S. , Blokker Brittney M. , Feeney Tyler R. , Kohn Ruby H. , Liu Jingyi , Nelson Vivian E. , Ollive Mariah C. , Price Sarah B. L. , Underdah Emma J.
Published: September 2019

Escherichia coli
is a fecal indicator bacterial species monitored by the U.S. Environmental Protection Agency to assess microbial water quality. Due to the potential human health implications linked to high levels of
E. coli
, it is important to understand the inactivation or reduction mechanisms in surface waters. Our research examines the capacities of two types of widespread filter-feeding freshwater metazooplankton,
Daphnia magna
and
Brachionus calyciflorus
, to reduce
E. coli
concentrations. We examine the impacts of different environmentally relevant conditions on the clearance rates. Our results contribute to a better understanding of the importance of metazooplankton in controlling
E. coli
concentrations and what conditions will reduce or increase grazing. These results provide baseline data to support future efforts to develop a quantitative model relating zooplankton uptake rates to relevant environmental variables.
Changes in the Molecular and Functional Phenotype of Bovine Monocytes during
Theileria parva
Infection
Authors: Bastos Reginaldo G. , Sears Kelly , Dinkel Kelcey D. , Knowles Donald P. , Fry Lindsay M.
Published: September 2019

Theileria parva
is the causative agent of East Coast fever (ECF), a tick-borne disease that kills over a million cattle each year in sub-Saharan Africa. Immune protection against
T. parva
involves a CD8
+
cytotoxic T cell response to parasite-infected cells. However, there is currently a paucity of knowledge regarding the role played by innate immune cells in ECF pathogenesis and
T. parva
control.
Epigenetic Suppression of Interferon Lambda Receptor Expression Leads to Enhanced Human Norovirus Replication
In Vitro
Authors: Arthur Sabastine E. , Sorgeloos Frédéric , Hosmillo Myra , Goodfellow Ian G.
Published: September 2019

Noroviruses are one of the most widespread causes of gastroenteritis, yet no suitable therapeutics are available for their control. Moreover, to date, knowledge of the precise cellular processes that control the replication of the human norovirus remains ill defined. Recent work has highlighted the importance of type III interferon (IFN) responses in the restriction of viruses that infect the intestine. Here, we analyzed the adaptive changes required to support long-term replication of noroviruses in cell culture and found that the receptor for type III IFN is decreased in its expression. We confirmed that this decreased expression was driven by epigenetic modifications and that cells lacking the type III IFN receptor are more permissive for norovirus replication. This work provides new insights into key host-virus interactions required for the control of noroviruses and opens potential novel avenues for their therapeutic control.
Establishment of Chronic Typhoid Infection in a Mouse Carriage Model Involves a Type 2 Immune Shift and T and B Cell Recruitment to the Gallbladder
Authors: González Juan F. , Kurtz Jonathan , Bauer David L. , Hitt Regan , Fitch James , Wetzel Amy , La Perle Krista , White Peter , McLachlan James , Gunn John S.
Published: September 2019

The existence of chronic typhoid carriers has been in the public eye for over 100 years in part because of the publicity around Typhoid Mary. Additionally, it has been known for decades that the gallbladder is the main site of persistence and recently that gallstones play a key role. Despite this, very little is known about the physiological conditions that allow
Salmonella enterica
serovar Typhi to persist in the gallbladder. In this study, we analyze the transcriptional profile of the gallbladder in a mouse model of chronic carriage. We found a shift from an early proinflammatory immune response toward a later anti-inflammatory response, which could explain the stalemate that allows
Salmonella
persistence. Interestingly, we found a 10-fold increase in the number of
Salmonella
-specific T cells in mice with gallstones. This work moves us closer to understanding the mechanistic basis of chronic carriage, with a goal toward eradication of the disease.
Antifungals in a case of basidiobolomycosis: role and limitations
Authors: Saeed Anjum , Assiri Asaad M , Bukhari Ishfaq A , Assiri Rasha
Published: September 2019

A 10-year-old Saudi boy was diagnosed to have basidiobolomycosis after a stormy course of his ailment. Therapy was initiated with intravenous antifungal, voriconazole, which was well tolerated for 6 weeks except for local excoriation at the site of ileostomy. He developed drug-induced hepatitis on oral voriconazole, therefore, switched to oral itraconazole following which he experienced severe chest pain. Alternatively, co-trimoxazole (bactrim) an antibacterial with antifungal activity was prescribed but he had the intolerance to it as well. Unfortunately, posaconazole as an alternative antifungal was not available in our centre. We report here a Saudi boy who developed an intolerance to most common antifungals used clinically 6 weeks after the therapy was initiated.
Ureterocolic fistula detected by mercaptoacetyltriglycine (MAG-3) diuretic renography including single photon emission CT and low-dose CT (SPECT–CT)
Authors: Draaisma Jos , Janssen Marcel , Graafland Niels , Stommel Martijn
Published: September 2019

We describe the case of a 60‐year‐old man with a ureterocolic fistula following laparoscopic sigmoid resection. The fistulous tract between the left ureter and sigmoid colon was detected by mercaptoacetyltriglycine diuretic renography including single photon emission CT with low-dose CT. Ureteroneocystostomy was successfully performed.
Patient’s perspective on improving the quality of acute medical care: determining patient reported outcomes
Authors: Kremers Marjolein N T , Zaalberg Tessel , van den Ende Eva S , van Beneden Marlou , Holleman Frits , Nanayakkara Prabath W B , Haak Harm R
Published: September 2019

Rationale

There is an increasing societal demand for quality assurance and transparency of medical care. The American National Academy of Medicine has determined patient centredness as a quality domain for improvement of healthcare. While many of the current quality indicators are disease specific, most emergency department (ED) patients present with undifferentiated complaints. Therefore, there is a need for generic outcome measures. Our objective was to determine relevant patient reported outcomes (PROs) for quality measurement of acute care.

Methods

We conducted semistructured interviews in patients ≥18 years presenting at the ED for internal medicine. Patients with a cognitive impairment or language barrier were excluded. Interviews were analysed using qualitative content analysis.

Results

Thirty patients were interviewed. Patients reported outcomes as relevant in five domains: relief of symptoms, understanding the diagnosis, presence and understanding of the diagnostic and/or therapeutic plan, reassurance and patient experiences. Experiences were often mentioned as relevant to the perceived quality of care and appeared to influence the domain reassurance.

Conclusion

We determined five domains of relevant PROs in acute care. These domains will be used for developing generic patient reported measures for acute care. The patients’ perspective will be incorporated in these measures with the ultimate aim of organising truly patient-centred care at the ED.
Mechanical Characterization of 2219 Aluminum Alloy Welded Joints Under Bi-Axial Loading
Authors: Cao Guanglong , Huang Cheng , Li Tong , Zhang Yahui , Ren Mingfa
Published: September 2019

The mechanical performances of welded joints under bi-axial loading are significant to the reliability of various engineering structures. However, the protocol for the mechanical characterization of welded joints still needs to be improved to represent the mechanical performances of welded joints under complex loading conditions. In this work, an experimental design is proposed for the mechanical characterization of 2219 aluminum alloy welded joints. The target is to investigate the effects of combined tensile-shear load on the mechanical responses and failure behavior of 2219 aluminum alloy welded joints. The tensile-shear characterization was then conducted using a newly developed U-notch aluminum alloy welded joints specimen. In addition, standard tensile test and standard shear test were conducted to validate of the U-notch specimen design. This newly proposed experimental protocol is suitable to obtain mechanical properties of 2219 aluminum alloy welded joints subjected to tensile-shear load.
Computational Analysis of Linear Elastic Crack Growth in Functionally Graded Bodies Using Non-Uniform Steps Integrated in the MLPG
Authors: Memari Amin
Published: September 2019

This paper describes the estimation of mixed-mode crack growth path in functionally graded materials under mechanical and thermal loads by the meshless method. Simple and complex geometries with single and double cracks are provided to verify the merits of a recently proposed modified meshless local Petrov–Galerkin method and to show the applicability of this method in crack growth simulation. Polygon test function domains are constructed locally at every crack growth step in order to numerically calculate contour and domain integrals. The classical form of thin plate spline radial basis function without enrichment with a regular distribution of points in the vicinity of crack tips are used. In this efficient method, the total number of domain points are kept fixed during crack growth steps forever. For this end, a simple method of new crack tip determination at every growth step is proposed. The MLPG results are compared with reference solutions including experimental, finite element, boundary element and other meshless methods and the accuracy of this method is investigated in different numerical test problems.
Recent advancement of chemical imaging in pharmaceutical quality control: From final product testing to industrial utilization
Authors: Liu Luming , Qu Haibin
Published: September 2019

Chemical imaging (CI) possesses a strong ability of pharmaceutical analysis. Its great strength relies on the integration of traditional spectroscopy (one dimension) and imaging technique (two dimensions) to generate three-dimensional data hypercubes. Data pre-processing or processing methods are proposed to analyze vast data matrixes and thereby realizing different research objectives. In this review paper, various pharmaceutical applications of quality control over the past few years are summed up in two groups of final product test and industrial utilization. The scope of “quality control” here includes traditional analytical use, process understanding and manufactural control. Finally, two major challenges about undesirable sample geometry and lengthy acquisition time are discussed for prospective commercial or industrial application.
A predictor–corrector scheme for solving nonlinear fractional differential equations with uniform and nonuniform meshes
Authors: Javidi Mohammad , Heris Mahdi Saedshoar , Ahmad Bashir
Published: September 2019

In this paper, we develop two algorithms for solving linear and nonlinear fractional differential equations involving Caputo derivative. For designing new predictor–corrector (PC) schemes, we select the mesh points based on the two equal-height and equal-area distribution. Furthermore, the error bounds of PC schemes with uniform and equidistributing meshes are obtained. Finally, examples are constructed for illustrating the obtained PC schemes with uniform and equidistributing meshes. A comparative study is also presented.
Eu-doped K0.5Na0.5NbO3-(Ba,Sr)TiO3: A novel lead-free luminescent ferroelectric transparent ceramic with reversible photochromism
Authors: Lin Jinfeng , Wu Xiao , Lin Cong , Lin Tengfei , Wang Yaojin
Published: September 2019

Photochromic (PC) luminescent ferroelectric materials have aroused great interest because of their potential applications in optical information memories, optical switches and bio-imaging. However, those materials are basically opaque. In this work, we prepared a PC luminescent [Formula: see text][Formula: see text]NbO3-based ferroelectric transparent ceramic by modifying with [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text], which not only have good optical transmittances ([Formula: see text]60% at 900[Formula: see text]nm), moderate ferroelectric properties and down-conversion photoluminescence (PL) properties, but also exhibit reversible PC behavior. After the illumination by xenon lamp, the colors of the ceramics change from pale green to gray, and then reversibly recover to their initial state via thermal stimulus (200∘C for 10[Formula: see text]min). Interestingly, both the optical transmittances and PL intensities can be effectively tailored by controlling the PC reaction process. The results suggest that the ferroelectric transparent ceramics are promising for the modulation of photoenergy and the design of optoelectronic devices.
Macrophage polarization in chronic kidney disease: a balancing act between renal recovery and decline?
Authors: Engel Jason E. , Chade Alejandro R.
Published: September 2019

Macrophages are heterogenous cells of the innate immune system that can fluidly modulate their phenotype to respond to their local microenvironment. They are found throughout the renal compartments, where they contribute to homeostasis and function. However, renal injury activates molecular pathways that initially stimulate differentiation of macrophages into a proinflammatory M1 phenotype. Later in the course of healing, abundant apoptotic debris and anti-inflammatory cytokines induce the production of anti-inflammatory M2 macrophages, which contribute to tissue regeneration and repair. Thus, the dynamic balance of M1 and M2 populations may outline the burden of inflammation and process of tissue repair that define renal outcomes, which has been the impetus for therapeutic efforts targeting macrophages. This review will discuss the role of these phenotypes in the progression of chronic renal injury, potential pathogenic mechanisms, and the promise of macrophage-based therapeutic applications for chronic kidney disease.
A Prospective Six-Month Study of Chronic Pain Sufferers: A Novel OTC Neuromodulation Therapy
Authors: Staelin Richard , Koneru Sree N. , Rawe Ian M.
Published: September 2019

Objective. To assess the durability of treatment over various chronic pain conditions of an emerging, nonprescription electromagnetic neuromodulation device that uses pulsed shortwave therapy. Methods. A 6-month prospective study, involving 240 chronic pain sufferers, 94% of whom reported using pain pills and 98% reported using pain therapies prior to entering the study. Their average baseline pain was 8.2 VAS points before treatment; they had a pain duration of 6.5 years, and they were positive responders to pulsed shortwave therapy in an initial 7-day trial. Prospective assessments were obtained at intervals of 3, 4, and 6 months following a retrospective 7-day assessment. Longitudinal analyses were conducted to determine pain relief trends after the initial 7-day device use. Results. Seven days after initial treatment, the average pain was reduced to 2.9, a 65% pain reduction for the study subjects. At the 6-month measurement, the average pain was 3.3, a 60% pain reduction from baseline. Only 17% of the subjects saw their pain level increase although this new level was still lower than baseline pain. Pain relief translated into improved quality of life and reduced medication use for the majority of the subjects. There were no significant adverse side effects reported over the 6 months of use. Conclusion. Ninety-seven percent of the recruited subjects, all of whom had previously reported clinically significant pain relief using the 7-day PSWT device, sustained this relief for 6 months by using the device on an as-needed basis.
Subdural Hygroma: A Morbid Complication of Intrathecal Chemotherapy in a Patient with B-Cell Acute Lymphocytic Leukemia
Authors: Shenouda Mina , Urella Madhulika , Dotson Jennifer , Yasin Hassaan , Lebowicz Yehuda
Published: September 2019

A subdural hygroma is an accumulation of cerebrospinal fluid in the subdural space that may occur secondary to trauma and surgery, or for iatrogenic reasons, such as a lumbar puncture. Lumbar puncture is a procedure used commonly for intrathecal chemotherapy for patients with B-cell acute lymphocytic leukemia (B-ALL) though subdural hygroma is a very rare complication. We present a case of a fatal, refractory subdural hygroma in a patient with B-ALL.
An Analytic Expression for the Inverse Involute
Authors: Rosado Alberto López , Muñoz Federico Prieto , Fernández Roberto Alvarez
Published: September 2019

This article introduces new types of rational approximations of the inverse involute function, widely used in gear engineering, allowing the processing of this function with a very low error. This approximated function is appropriate for engineering applications, with a much reduced number of operations than previous formulae in the existing literature, and a very efficient computation. The proposed expressions avoid the use of iterative methods. The theoretical foundations of the approximation theory of rational functions, the Chebyshev and Jacobi polynomials that allow these approximations to be obtained, are presented in this work, and an adaptation of the Remez algorithm is also provided, which gets a null error at the origin. This way, approximations in ranges or degrees different from those presented here can be obtained. A rational approximation of the direct involute function is computed, which avoids the computation of the tangent function. Finally, the direct polar equation of the circle involute curve is approximated with some application examples.
Partial ML Detection for Frequency-Asynchronous Distributed Alamouti-Coded (FADAC) OFDM
Authors: Kim Bong-seok , Na Dongjun , Choi Kwonhue
Published: September 2019

To further enhance frequency-asynchronous distributed Alamouti-coded (FADAC) orthogonal frequency division multiplexing (OFDM), we propose a new scheme which combines the partial maximum likelihood detection (PMLD) to the residual intercarrier interference cancellation (RIC). In order to decrease the performance gap from intercarrier interference- (ICI-) free level after single time iteration of the RIC, the final stage of the proposed scheme performs the PMLD limited to the symbols of less-reliable decision variables. We show that with the practically acceptable candidate symbol set size, a single iteration for RIC is enough to achieve the ICI-free performance. Moreover, the proposed scheme substantially expands the allowable ranges of the three undesirable terms, i.e., the timing and frequency offsets between the transmit antennas and the multipath delay spreads.
Vascular Endothelial Growth Factor Is Regulated by the Canonical and Noncanonical Transforming Growth Factor-βPathway in Synovial Fibroblasts Derived from Osteoarthritis Patients
Authors: Takano Shotaro , Uchida Kentaro , Shoji Shintaro , Itakura Makoto , Iwase Dai , Aikawa Jun , Mukai Manabu , Sekiguchi Hiroyuki , Inoue Gen , Takaso Masashi
Published: September 2019

Background. Previous studies suggest the presence of an association of vascular endothelial growth factor (VEGF) with osteoarthritis (OA) severity and pain in patients with knee OA. VEGF expression in human synovial fibroblasts (SFs) is induced by transforming growth factor-beta (TGFβ). However, the signaling pathway governing TGFβ-mediated regulation of VEGF in SFs has not been identified.Methods. OA patients who underwent total knee arthroplasty had their synovial tissue (SYT) extracted and the constituent SFs cultured. The cells were stimulated with culture medium (control), human recombinant TGFβ(hrTGFβ), hrTGFβ + ALK5 inhibitor SB505124, hrTGFβ + transforming growth factor activating kinase 1 (TAK1) inhibitor (5Z)-7-oxozeaenol, or hrTGFβ + p38 inhibitor SB203580 for 6 h.VEGFmRNA expression in SFs was examined using real-time polymerase chain reaction and VEGF protein production in the cell supernatant was examined using enzyme-linked immunosorbent assay. Additionally, phosphorylated levels of SMAD2 and p38 were examined using western blotting.Results. ALK5 (SB505124) and TAK1 (5Z-oxozeaenol) inhibitors completely suppressed TGFβ-inducedVEGFmRNA expression and VEGF protein production. Both SB505124 and 5Z-oxozeaenol also suppressed SMAD2 and p38 phosphorylation. The p38 inhibitor (SB203580) partially inhibited TGFβ-mediatedVEGFmRNA and VEGF protein production.Conclusion. TGFβ-mediated regulation ofVEGFexpression and VEGF protein production in the SYT of OA patients occurs through both the canonical and noncanonical pathway.
A Study of the Change in Sodium and Potassium Ion Concentrations in Stored Donor Blood and Their Effect on Electrolyte Balance of Recipients
Authors: Antwi-Baffour Samuel , Adjei Jonathan Kofi , Tsyawo Felix , Kyeremeh Ransford , Botchway Felix Abekah , Seidu Mahmood Abdulai
Published: September 2019

Background. Preserved blood cells undergo progressive structural and functional changes that may affect their function, integrity, and viability after transfusion. The impact of transfusion of stored blood on potassium, sodium, or acid-base balance in the recipient may be complex, but information on it is inconsistent. This study therefore sought to determine the changes in the potassium and sodium levels in whole blood stored at 4°C for 28 days and clinical outcomes when such blood are transfused. Methods. Whole blood were taken into double CPDA-1 bags and 50 ml transferred into the satellite bags for the study. Electrolyte concentration determinations were made on each of the blood sample on days 0, 7, 14, 21, and 28 using the Vitalab Selectra Junior chemistry analyser. The remaining blood in the main bags was transfused after the 28-day period, and biochemical analysis carried out on the patients before and after the transfusion. One-way ANOVA was used for the analysis of variance between the weekly ion concentrations and independent sample Mann–Whitney U test for the data obtained from the patients. Results. The mean potassium level of all the samples started with a normal value of 3.45 mmol/L on the first day followed by a sharp rise to 9.40 mmol/L on day 7, 13.40 mmol/L on day 14, 14.60 mmol/L on day 21, and 15.40 mmol/L on day 28. Sodium on the other hand started with a high value of 148.4 mmol/L on day 0 and then reduced to 146.4 mmol/L on day 7, 140.8 mmol/L on day 14, 135.6 mmol/L on day 21, and a low value of 130.8 mmol/L on day 28. No adverse clinical outcomes were seen in patients after they were transfused with the blood. Conclusion. It can be deduced that potassium concentration in refrigerated blood increases, whilst sodium concentration reduces with time and when such blood is transfused, it may not result in any adverse clinical outcome.