bluuebunny/crossref_metadata_2025 huggingface dataset:
Contiguous and stochastic CHH methylation patterns of plant DRM2 and CMT2 revealed by single-read methylome analysis
Authors: Harris Keith D. , Zemach Assaf
Published: August 2020

Cytosine methylome data is commonly generated through next-generation sequencing, with analyses averaging methylation states of individual reads. We propose an alternative method of analysing single-read methylome data. Using this method, we identify patterns relating to the mechanism of two plant non-CG-methylating enzymes, CMT2 and DRM2. CMT2-methylated regions show higher stochasticity, while DRM2-methylated regions have higher variation among cells. Based on these patterns, we develop a classifier that predicts enzyme activity in different species and tissues. To facilitate further single-read analyses, we develop a genome browser, SRBrowse, optimised for visualising and analysing sequencing data at single-read resolution.
The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation
Authors: Kosti Adam , de Araujo Patricia Rosa , Li Wei-Qing , Guardia Gabriela D. A. , Chiou Jennifer , Yi Caihong , Ray Debashish , Meliso Fabiana , Li Yi-Ming , Delambre Talia , Qiao Mei , Burns Suzanne S. , Lorbeer Franziska K. , Georgi Fanny , Flosbach Markus , Klinnert Sarah , Jenseit Anne , Lei Xiufen , Sandoval Carolina Romero , Ha Kevin , Zheng Hong , Pandey Renu , Gruslova Aleksandra , Gupta Yogesh K. , Brenner Andrew , Kokovay Erzsebet , Hughes Timothy R. , Morris Quaid D. , Galante Pedro A. F. , Tiziani Stefano , Penalva Luiz O. F.
Published: August 2020

Background

RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in RBP expression and function are often observed in cancer and influence critical pathways implicated in tumor initiation and growth. Identification and characterization of oncogenic RBPs and their regulatory networks provide new opportunities for targeted therapy.

Results

We identify the RNA-binding protein SERBP1 as a novel regulator of glioblastoma (GBM) development. High SERBP1 expression is prevalent in GBMs and correlates with poor patient survival and poor response to chemo- and radiotherapy. SERBP1 knockdown causes delay in tumor growth and impacts cancer-relevant phenotypes in GBM and glioma stem cell lines. RNAcompete identifies a GC-rich region as SERBP1-binding motif; subsequent genomic and functional analyses establish SERBP1 regulation role in metabolic routes preferentially used by cancer cells. An important consequence of these functions is SERBP1 impact on methionine production. SERBP1 knockdown decreases methionine levels causing a subsequent reduction in histone methylation as shown for H3K27me3 and upregulation of genes associated with neurogenesis, neuronal differentiation, and function. Further analysis demonstrates that several of these genes are downregulated in GBM, potentially through epigenetic silencing as indicated by the presence of H3K27me3 sites.

Conclusions

SERBP1 is the first example of an RNA-binding protein functioning as a central regulator of cancer metabolism and indirect modulator of epigenetic regulation in GBM. By bridging these two processes, SERBP1 enhances glioma stem cell phenotypes and contributes to GBM poorly differentiated state.
Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose
Authors: Kołaczkowski Bartłomiej M. , Schaller Kay S. , Sørensen Trine Holst , Peters Günther H. J. , Jensen Kenneth , Krogh Kristian B. R. M. , Westh Peter
Published: August 2020

Background

Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation. For many years, Trichoderma reesei Cel7A (TrCel7A) has served as a model to understand structure–function relationships of processive cellobiohydrolases. The architecture of TrCel7A includes an N-glycosylated catalytic domain, which is connected to a carbohydrate-binding module through a flexible, O-glycosylated linker. Depending on the fungal expression host, glycosylation can vary not only in glycoforms, but also in site occupancy, leading to a complex pattern of glycans, which can affect the enzyme’s stability and kinetics.

Results

Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WTAo and WTTr) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glycAo and ΔN-glycTr). Also, we expressed single N-glycosylation site deficient mutants TrCel7A (N45QAo, N270QAo, N384QAo). The TrCel7A enzymes were studied by steady-state kinetics under both substrate- and enzyme-saturating conditions using different cellulosic substrates. The Michaelis constant (KM) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs’ value on some substrates. The ability of the enzyme to combine productively with sites on the cellulose surface followed a similar pattern on all tested substrates. Thus, site density (number of sites per gram cellulose) was 30–60% higher for the single deficient variants compared to the WT, and about twofold larger for the triple deficient enzyme. Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.

Conclusions

The kinetic changes of TrCel7A imposed by removal of N-linked glycans reflected modifications of substrate accessibility. The presence of N-glycans with extended structures increased KM and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation. This knowledge could be applied to modify enzyme glycosylation to engineer enzyme with higher activity on the insoluble substrates.
Contrasted transmission efficiency of Zika virus strains by mosquito species Aedes aegypti, Aedes albopictus and Culex quinquefasciatus from Reunion Island
Authors: Gomard Yann , Lebon Cyrille , Mavingui Patrick , Atyame Célestine M.
Published: August 2020

Background

Zika virus (ZIKV) is a mosquito-borne flavivirus that recently emerged in the South Pacific islands and Americas where unprecedented outbreaks were reported. Although Aedes aegypti is considered to be the main vector for ZIKV, other mosquito species have been shown to be potential vectors and differences in vector competence with respect to mosquito strain and ZIKV strain have been demonstrated. In this study we compared the vector competence of three mosquito species Aedes albopictus, Ae. aegypti and Culex quinquefasciatus from Reunion Island for three ZIKV strains.

Methods

Five mosquito strains (2 strains of Ae. albopictus, 1 of Ae. aegypti and 2 of Cx. quinquefasciatus) were exposed to three ZIKV strains: one African strain (Dak84) and two Asian strains (PaRi_2015 and MAS66). The vector competence parameters (infection rate, dissemination efficiency and transmission efficiency) and viral loads were examined at 14 and 21 days post-infection.

Results

The two Cx. quinquefasciatus strains did not become infected and were therefore unable to either disseminate or transmit any of the three ZIKV strains. Aedes albopictus and Ae. aegypti strains were poorly competent for the two Asian ZIKV strains, while both mosquito species displayed higher infection rates, dissemination and transmission efficiencies for the African ZIKV Dak84 strain. However, this African ZIKV strain was better transmitted by Ae. aegypti as compared to Ae. albopictus.

Conclusions

Our results show that both Ae. albopictus and Ae. aegypti, from Reunion Island, are more likely to be competent for ZIKV in contrast to Cx. quinquefasciatus which appeared refractory to all tested ZIKV strains. This improves our understanding of the role of mosquito species in the risk of the ZIKV emergence on Reunion Island.
COVID19 antibody detection using lateral flow assay tests in a cohort of convalescent plasma donors
Authors: Ragnesola Brett , Jin Daniel , Lamb Christopher C. , Shaz Beth H. , Hillyer Christopher D. , Luchsinger Larry L.
Published: August 2020

Objective

COVID19 has caused a global and ongoing pandemic. The need for population seroconversion data is apparent to monitor and respond to the pandemic. Using a lateral flow assay (LFA) testing platform, the seropositivity in 63 New York Blood Center (NYBC) Convelescent Plasma (CP) donor samples were evaluated for the presence of COVID19 specific IgG and IgM.

Results

CP donors showed diverse antibody result. Convalescent donor plasma contains SARS-CoV-2 specific antibodies. Weak antibody bands may identify low titer CP donors. LFA tests can identify antibody positive individuals that have recovered from COVID19. Confirming suspected cases using antibody detection could help inform the patient and the community as to the relative risk to future exposure and a better understanding of disease exposure.
Genome-wide methylation patterns predict clinical benefit of immunotherapy in lung cancer
Authors: Kim Jeong Yeon , Choi Jung Kyoon , Jung Hyunchul
Published: August 2020

Background

It is crucial to unravel molecular determinants of responses to immune checkpoint blockade (ICB) therapy because only a small subset of advanced non-small cell lung cancer (NSCLC) patients responds to ICB therapy. Previous studies were concentrated on genomic and transcriptomic markers (e.g., mutation burden and immune gene expression). However, these markers are not sufficient to accurately predict a response to ICB therapy.

Results

Here, we analyzed DNA methylomes of 141 advanced NSCLC samples subjected to ICB therapy (i.e., anti-programmed death-1) from two independent cohorts (60 and 81 patients from our and IDIBELL cohorts). Integrative analysis of patients with matched transcriptome data in our cohort (n = 28) at pathway level revealed significant overlaps between promoter hypermethylation and transcriptional repression in nonresponders relative to responders. Fifteen immune-related pathways, including interferon signaling, were identified to be enriched for both hypermethylation and repression. We built a reliable prognostic risk model based on eight genes using LASSO model and successfully validated the model in independent cohorts. Furthermore, we found 30 survival-associated molecular interaction networks, in which two or three hypermethylated genes showed significant mutual exclusion across nonresponders.

Conclusions

Our study demonstrates that methylation patterns can provide insight into molecular determinants underlying the clinical benefit of ICB therapy.
Mouse CD146+ muscle interstitial progenitor cells differ from satellite cells and present myogenic potential
Authors: Mierzejewski Bartosz , Grabowska Iwona , Jackowski Daniel , Irhashava Aliksandra , Michalska Zuzanna , Stremińska Władysława , Jańczyk-Ilach Katarzyna , Ciemerych Maria Anna , Brzoska Edyta
Published: August 2020

Background

The skeletal muscle regeneration relays on the satellite cells which are stem cells located between basal lamina and plasmalemma of muscle fiber. In the injured muscles, the satellite cells become activated, start to proliferate, and then differentiate into myoblasts, which fuse to form myotubes and finally myofibers. The satellite cells play the crucial role in the regeneration; however, other cells present in the muscle could also support this process. In the present study, we focused on one population of such cells, i.e., muscle interstitial progenitor cells.

Methods

We used the CD146 marker to identify the population of mouse muscle interstitial cells. We analyzed the expression of selected markers, as well as clonogenic, myogenic, adipogenic, and chondrogenic potential in vitro. Simultaneously, we analyzed satellite cell-derived myoblasts and bone marrow-derived mesenchymal stem/stromal cells that allowed us to pinpoint the differences between these cell populations. Moreover, we isolated CD146+ cells and performed heterotopic transplantations to follow their in vivo differentiation.

Results

Mouse muscle CD146+ interstitial progenitor cells expressed nestin and NG2 but not PAX7. These cells presented clonogenic and myogenic potential both in vitro and in vivo. CD146+ cells fused also with myoblasts in co-cultures in vitro. However, they were not able to differentiate to chondro- or adipocytes in vitro. Moreover, CD146+ cells followed myogenic differentiation in vivo after heterotopic transplantation.

Conclusion

Mouse CD146+ cells represent the population of mouse muscle interstitial progenitors that differ from satellite cell-derived myoblasts and have clonogenic and myogenic properties.
Treatment of gastrointestinal tumor (GIST) of the rectum requiring abdominoperineal resection following neoadjuvant imatinib: a cost-effectiveness analysis
Authors: Farid Mohamad , Ong Johnny , Chia Claramae , Tan Grace , Teo Melissa , Quek Richard , Teh Jonathan , Matchar David
Published: August 2020

Background

Neoadjuvant imatinib for gastrointestinal stromal tumors (GIST) of the rectum can reduce, but may not eliminate, risk of surgical morbidity from permanent bowel diversion. We sought to evaluate the cost-effectiveness of alternative strategies in rectal GIST patients requiring abdominoperineal resection following neoadjuvant imatinib.

Methods

We developed a Markov model using a healthcare payers’ perspective to estimate costs in 2017 Singapore dollars (SGD) and quality adjusted life years (QALYs) for upfront abdominoperineal resection (UAPR) versus continued imatinib until progression (CIUP) following 1 year of neoadjuvant imatinib. Transition probabilities and utilities were obtained from published data, and costs were estimated using data from the National Cancer Centre Singapore. Deterministic and probabilistic sensitivity analyses were conducted to probe model uncertainty. Incremental cost-effectiveness ratio below SGD 50,000 per QALY gained was considered cost-effective.

Results

In the base case, UAPR dominates CIUP being both more effective (8.66 QALYS vs 5.43 QALYs) and less expensive (SGD 312,627 vs SGD 339,011). These estimates were most sensitive to 2 variables, utility of abdominoperineal resection and annual recurrence probability post-abdominoperineal resection. However, simultaneously varying the values of these variables to maximally favor CIUP did not render it the more cost effective strategy at willingness to pay (WTP) of SGD 50,000. In probabilistic sensitivity analysis, UAPR had probability of being cost-effective compared with CIUP greater than 95%, reaching 100% at WTP SGD 10,000.

Conclusion

UAPR is more effective and less costly than CIUP for patients with rectal GIST requiring abdominoperineal resection following neoadjuvant imatinib, and is the strategy of choice in this setting.
Legg-Calve-Perthes disease in an 8-year old girl with Acrodysostosis type 1 on growth hormone therapy: case report
Authors: Lim Whei Ying , Germain-Lee Emily L. , Dunbar Nancy S.
Published: August 2020

Background

Acrodyostosis type 1 (ACRDYS1) is a rare skeletal dysplasia, and sometimes it can be misdiagnosed as pseudohypoparathyroidism type 1A (PHP1A), a subtype of Albright hereditary osteodystrophy (AHO), due to overlapping features. Growth hormone releasing hormone (GHRH) resistance with severe short stature is common in both ACRDYS1 and PHP1A (Emily L. Germain-Lee, et al. J Clin Endocrinol Metab, 88:4059–4069, 2003). Whereas growth hormone (GH) treatment has been studied in patients with PHP1a, the same is not true for the rarer ACRDYS1. Here in we report an adverse orthopedic outcome in a patient with ACRDYS1 with severe short stature treated with growth hormone. Our experience could have implications for the treatment of other patients with this disorder.

Case presentation

We report a case of Legg-Calve-Perthes Disease (LCPD) in an 8-year old female with ACRDYS1 treated with GH. She initially presented with marked short stature (height Z-score − 3.46) with a low normal insulin like growth factor-1 (IGF1) level, and had biochemical evidence of thyrotropin and parathyroid hormone resistance. GH therapy was initiated at 0.35 mg/kg/week leading to increased growth velocity. After 7 months on GH, she developed right knee pain. Radiographic images revealed flattening of her right femoral head consistent with LCPD. GH was discontinued. Six weeks later, radiographs revealed further collapse of the entire femoral head. Her lesion stabilized after 8 months with conservative management and she never resumed GH. Her final adult height is 4′2″ (128 cm).

Conclusion

Patients with ACRDYS1 on GH therapy may be at increased risk of LCPD. This has not been reported in patients with PHP1A treated with GH. Clinicians and families need to be aware of this potential complication when counseling about GH treatment.
A study of hepatic fibrosis staging methods using diffraction enhanced imaging
Authors: Wang Jing , Li Hui , Zhou Xiuling , Gao Xiao-Zhi , Wang Ming
Published: August 2020

The early hepatic fibrosis staging is very important for timely diagnosis, prognosis, and treatment of all chronic liver diseases. Diffraction-enhanced imaging, which can provide much more information on soft tissue morphology than conventional absorption radiography, might be a potential noninvasive technique to diagnose and stage hepatic fibrosis. This paper presents different feature extraction strategies and classification methods to automatically classify hepatic fibrosis using diffraction-enhanced imaging images. Texture features are obtained using a total of three methods including first order feature, gray level co-occurrence matrix, and grayscale gradient co-occurrence matrix. The fusion of these texture features is also studied. The principal component analysis is used to reduce the dimension of the features and redundant information among data. The features are classified using two popular classification techniques, namely, K-nearest neighbors and support vector machines. On the basis of the comparison of different feature strategies and classification methods, we can identify the suitable methods for grading hepatic fibrosis. The proposed approach efficiently classifies the hepatic fibrosis DEI images into four classes with the highest classification accuracy of 99.99%. We further demonstrate the potential of the DEI images in staging hepatic fibrosis.
On a system of fractional q-differential inclusions via sum of two multi-term functions on a time scale
Authors: Samei Mohammad Esmael , Rezapour Shahram
Published: August 2020

Nowadays most researchers have been focused on fractional calculus because it has been proved that fractional derivatives could describe most phenomena better than usual derivations. Numerical parts of fractional calculus such as q-derivations are considered by researchers. In this work, our aim is to review the existence of solution for an m-dimensional system of fractional q-differential inclusions via sum of two multi-term functions under some boundary conditions on the time scale $\mathbb{T}_{t_{0}}= \{ t : t =t_{0}q^{n}\}\cup\{0\}$

T

t
0

=
{
t
:
t
=

t
0

q
n

}
∪
{
0
}
, where $n\geq1$
n
≥
1
, $t_{0} \in\mathbb{R}$

t
0

∈
R
, and $q \in(0,1)$
q
∈
(
0
,
1
)
. By using the Banach contraction principle and some sufficient conditions, we guarantee the existence of solutions for the system of q-differential inclusions. Also, we provide an example, some algorithms, and a figure to illustrate our main result.
Mathematical modeling of hepatitis B virus infection for antiviral therapy using LHAM
Authors: Aniji M. , Kavitha N. , Balamuralitharan S.
Published: August 2020

Anti-viral therapy is comparatively very effective for patients who get affected by the hepatitis B virus. It is of prime importance to understand the different relations among the viruses, immune responses and overall health of the liver. In this paper, mathematical modeling is done to analyze and understand the effect of antiviral therapy using LHAM which describes the possible relation to HBV and target liver cells. The numerical simulations and error analysis are done up to a sixth-order approximation with the help of Matlab. This paper analyzes how the number of infected cells largely gets reduced and also how the liver damage can be controlled. Therefore, the treatment is successful for HBV infected patients.
Global behavior and the periodic character of some biological models
Authors: Moaaz Osama , Awrejcewicz Jan , Mahjoub Hamida
Published: August 2020

Biological models are usually described using difference equations. As a result, we are - in this work - interested in studying a general difference model which includes two biological models as special cases. In detail, we study the qualitative behaviors (local and global stability, boundedness and periodicity character) of a general difference model. Furthermore, we apply our general results to the population model with two age classes and the flour beetle model.
Experimental and Numerical Studies on the Mechanical Performance of a Wall-beam-strut Joint with Mechanical Couplers for Prefabricated Underground Construction
Authors: Liu Tingjin , Lu Jiandong , Liu Hongyuan
Published: August 2020

This paper investigates the nonlinear behavior of wall-beam-strut joints with mechanical couplers, which are proposed for prefabricated underground constructions, under monotonic and cyclic loading conditions using full-scale experimental tests and three-dimensional finite element modelings. The nonlinear behavior of the joint is discussed in terms of the load–displacement curves, concrete cracking distributions, and strains in the reinforcements obtained from both the experimental tests and the numerical modeling. The comparison indicates that the trends of both load–displacement curves are similar, although the cracking, yield and ultimate loads of the joints determined by the numerical modeling are 2.5% lower, 2.6% higher and 3.8% higher, respectively, than those determined by the experimental tests. The numerical simulation can capture the concrete cracking process in the joint in the early loading stage but cannot accurately model the crack distribution in later stages. Moreover, the reinforcement strains and the skeleton curve from the numerical modeling show the same tendency as those from the experimental test, but it is difficult to compare their exact values, especially after yielding. The differences are believed due to the fact that the numerical modeling idealizes the materials and fails to model the slippage between the reinforcements and concrete after the concrete cracking. On the basis of the experimental and numerical investigations, it is concluded that the proposed wall-beam-strut joint has not only an ultimate bearing capacity that is at least 3 times higher than the design load but also a good ductility. Therefore, the design of the wall-beam-strut joint satisfies the requirements for the prefabricated underground construction.
Correction to: Experimental Investigation on the Force-Crack Quantification Model for HSRC Columns with Flexure–Shear and Shear Failure Modes
Authors: Chiu Chien-Kuo , Tandri Alexander Ivan
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Do olfactory and gustatory psychophysical scores have prognostic value in COVID-19 patients? A prospective study of 106 patients
Authors: Vaira Luigi Angelo , Hopkins Claire , Petrocelli Marzia , Lechien Jerome R. , Soma Damiano , Giovanditto Federica , Rizzo Davide , Salzano Giovanni , Piombino Pasquale , Saussez Sven , De Riu Giacomo
Published: August 2020

Background

The lack of objective data makes it difficult to establish the prognostic value of chemosensitive disorders in coronavirus disease 2019 (COVID-19) patients. We aimed to prospectively monitor patients diagnosed with COVID-19 to see if the severity of olfactory and gustatory dysfunction associates with subsequent disease severity.

Methods

Multicentre prospective study that recruited 106 COVID-19 subjects at diagnosis. Chemosensitive functions were assessed with psychophysical tests within 4 days of clinical onset, at 10 and 20 days. Daily body temperature and oxygen saturation were recorded as markers of disease severity alongside need for hospitalisation. The correlation between olfactory and gustatory scores and disease severity was assessed with linear regression analysis.

Results

At T0, 71 patients (67%) presented with olfactory dysfunction while gustatory impairment was detected in 76 cases (65.6%). Chemosensitive disorders gradually improved over the observation period. No significant correlations were found between T0 chemosensitive scores and final disease severity. The correlation between olfactory scores and fever proved significant at T2 ( p = 0.05), while the relationship with gustatory scores was significant at T1 ( p = 0.01) and T2 ( p <  0.001), however neither was clinically relevant. The correlation between chemosensitive scores and oxygen saturation was significant only for taste at T2 ( p <  0.001). Logistic regression analysis found significant correlations between olfactory impairment severity and need for hospitalization at T2 (OR 3.750, p = 0.005).

Conclusions

Initial objective olfactory and gustatory scores do not seem to have a significant prognostic value in predicting the severity of the COVID-19 course; however, persistence of olfactory dysfunction at 20 days, associated with a more severe course. Unfortunately, olfactory and gustatory dysfunction do not seem to hold prognostic value at the time of initial diagnosis.
Inferring the votes in a new political landscape: the case of the 2019 Spanish Presidential elections
Authors: Grimaldi Didier , Cely Javier Diaz , Arboleda Hugo
Published: August 2020

The avalanche of personal and social data circulating in Online Social Networks over the past 10 years has attracted a great deal of interest from Scholars and Practitioners who seek to analyse not only their value, but also their limits. Predicting election results using Twitter data is an example of how data can directly influence the politic domain and it also serves an appealing research topic. This article aims to predict the results of the 2019 Spanish Presidential election and the voting share of each candidate, using Tweeter. The method combines sentiment analysis and volume information and compares the performance of five Machine learning algorithms. Several data scrutiny uncertainties arose that hindered the prediction of the outcome. Consequently, the method develops a political lexicon-based framework to measure the sentiments of online users. Indeed, an accurate understanding of the contextual content of the tweets posted was vital in this work. Our results correctly ranked the candidates and determined the winner by means of a better prediction of votes than official research institutes.
Macrophage activation syndrome and COVID-19
Authors: Otsuka Ryo , Seino Ken-ichiro
Published: August 2020

An emerging, rapidly spreading coronavirus SARS-CoV-2 is causing a devastating pandemic. As we have not developed curative medicine and effective vaccine, the end of this life-threatening infectious disease is still unclear. Severe COVID-19 is often associated with hypercytokinemia, which is typically found in macrophage activation syndrome. SARS-CoV-2 infection causes this strong inflammation within the lung and propagates to respiratory and, ultimately, systemic organ malfunction. Although we have not fully understood the physiological and pathological aspects of COVID-19, current research progress indicates the effectiveness of anti-cytokine therapy. Here, we summarize macrophage activation syndrome and its possible contribution to COVID-19, and cytokine targeted attempts in severe COVID-19 cases.
Maintaining critical infrastructure resilience to natural hazards during the COVID-19 pandemic: hurricane preparations by US energy companies
Authors: Clark-Ginsberg Aaron , Rueda Ismael Arciniegas , Monken Jonathon , Liu Jay , Chen Hong
Published: August 2020

The COVID-19 pandemic has the potential to compromise the ability of critical infrastructure utilities to respond to or mitigate natural hazards like wildfires and hurricanes. This article describes the ways that an energy organization, the regional transmission operator PJM, is preparing for hurricanes during the COVID-19 pandemic. PJM is using a combination of technological and organizational processes to prepare for hurricanes during the pandemic. Activities include the development of a third control room to increase redundancy and maintaining social distance at control center, investment in more resilient communications technology to maintain connectivity, and taking a holistic approach to identifying issues related to supply chain and fuel security. With this mix of organizational and technological processes, we argue that critical infrastructure resilience should be understood as a sociotechnical construct and identify several recommendations for improving resilience. The article has implications for policymakers working to maintain infrastructure resilience to natural hazards during the COVID-19 pandemic.
Mental health services for single homeless people
Authors: Timms Philip , Drife Jenny
Published: August 2020

Homelessness has long been associated with high rates of psychosis, alcohol and substance misuse, and personality disorder. However, psychiatric services in the UK have only recently engaged actively with homeless people. This article provides some background information about homelessness and mental illness and describes the elements of inclusion health and some of the models of service for homeless people that have been established over the past 30 years.
Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H
Authors: Salama April K. S. , Li Shuli , Macrae Erin R. , Park Jong-In , Mitchell Edith P. , Zwiebel James A. , Chen Helen X. , Gray Robert J. , McShane Lisa M. , Rubinstein Larry V. , Patton David , Williams P. Mickey , Hamilton Stanley R. , Armstrong Deborah K. , Conley Barbara A. , Arteaga Carlos L. , Harris Lyndsay N. , O’Dwyer Peter J. , Chen Alice P. , Flaherty Keith T.
Published: August 2020

PURPOSE

BRAFV600 mutations are commonly found in melanoma and thyroid cancers and to a lesser degree in other tumor types. Subprotocol H (EAY131-H) of the NCI-MATCH platform trial sought to investigate the selective BRAF inhibitor dabrafenib and the MEK1/2 inhibitor trametinib in patients with solid tumors, lymphomas, or multiple myeloma whose tumors harbored a BRAFV600 mutation.

PATIENTS AND METHODS

EAY131-H is an open-label, single-arm study. Patients with melanoma, thyroid, or colorectal cancer were excluded; patients with non–small-cell lung cancer were later excluded in an amendment. Patients received dabrafenib 150 mg twice per day and trametinib 2 mg per day continuously until disease progression or intolerable toxicity. The primary end point was centrally assessed objective response rate (ORR); secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival.

RESULTS

Thirty-five patients were enrolled, and 29 were included in the primary efficacy analysis as prespecified in the protocol. Median age was 59 years, and 45% of the patients had received ≥ 3 lines of therapy. The confirmed ORR was 38% (90% CI, 22.9% to 54.9%) with P < .0001 against a null rate of 5%, and PFS was 11.4 months (90% CI, 8.4 to 16.3 months); responses were seen in 7 distinct tumor types. Seven patients had a duration of response of > 12 months, including 4 patients with a duration of response of > 24 months. An additional 8 patients had a PFS > 6 months. The median overall survival was 28.6 months. Reported adverse events were comparable to those noted in previously reported profiles of dabrafenib and trametinib.

CONCLUSION

This study met its primary end point, with an ORR of 38% ( P < .0001) in this mixed histology, pretreated cohort. This promising activity warrants additional investigations in BRAFV600-mutated tumors outside of currently approved indications.
Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex
Authors: Constanthin Paul E. , Contestabile Alessandro , Petrenko Volodymyr , Quairiaux Charles , Salmon Patrick , Hüppi Petra S. , Kiss Jozsef Z.
Published: August 2020

Erythropoietin (EPO), the hypoxia-inducible hematopoietic hormone, has well-established neuroprotective/neurotrophic roles in the developing central nervous system and the therapeutic potential of EPO has been widely explored in clinical studies for treatment of perinatal hypoxic brain lesion as well as prematurity. Here we reveal, that both EPO and EPOR are expressed in the developing rat somatosensory cortex during radial migration and laminar positioning of granular and supragranular neurons. Experimental deregulation of EPO signaling using genetic approaches results in aberrant migration as well as permanent neuronal misplacement leading to abnormal network activity and protracted sensory behavioral deficits. We identify ERK as the downstream effector of the EPO signaling pathway for neuronal migration. These findings reveal a critical role for endogenous EPO signaling in neuronal migration and offer important insights for understanding how temporary deregulation of EPO could results in migration defects leading to abnormal behavior in the adult.
Imaging of COVID-19 pneumonia: Patterns, pathogenesis, and advances
Authors: Nagpal Prashant , Narayanasamy Sabarish , Vidholia Aditi , Guo Junfeng , Shin Kyung Min , Lee Chang Hyun , Hoffman Eric A
Published: August 2020

COVID-19 pneumonia is a newly recognized lung infection. Initially, CT imaging was demonstrated to be one of the most sensitive tests for the detection of infection. Currently, with broader availability of polymerase chain reaction for disease diagnosis, CT is mainly used for the identification of complications and other defined clinical indications in hospitalized patients. Nonetheless, radiologists are interpreting lung imaging in unsuspected patients as well as in suspected patients with imaging obtained to rule out other relevant clinical indications. The knowledge of pathological findings is also crucial for imagers to better interpret various imaging findings. Identification of the imaging findings that are commonly seen with the disease is important to diagnose and suggest confirmatory testing in unsuspected cases. Proper precautionary measures will be important in such unsuspected patients to prevent further spread. In addition to understanding the imaging findings for the diagnosis of the disease, it is important to understand the growing set of tools provided by artificial intelligence. The goal of this review is to highlight common imaging findings using illustrative examples, describe the evolution of disease over time, discuss differences in imaging appearance of adult and pediatric patients and review the available literature on quantitative CT for COVID-19. We briefly address the known pathological findings of the COVID-19 lung disease that may help better understand the imaging appearance, and we provide a demonstration of novel display methodologies and artificial intelligence applications serving to support clinical observations.
Outcome-Based Pricing for New Pharmaceuticals via Rebates
Authors: Adida Elodie
Published: August 2020

The price of new brand-name prescription drugs has been rising fast in the United States. For example, the Amgen cholesterol drug Repatha had an initial list price of $14,523 per year. Patients, even with insurance coverage, must pay out of pocket a significant portion of this price. The treatment might not be successful, and this possibility reduces risk-sensitive patients’ incentives to purchase the drug. The high price together with the chance of negative treatment outcomes may lead payers to deny coverage for the drug. Outcome-based pricing has been proposed as a way to reallocate the risks and improve both payer resource allocation and patient access to drugs. According to an outcome-based rebate contract between Amgen and Harvard Pilgrim Healthcare, if a patient on Repatha suffers a heart attack or a stroke, both patient and insurer are refunded the cost of the drug. We use a stylized model to analyze the effect of outcome-based pricing via rebates. Our model captures the interaction between heterogenous, price-sensitive, risk-sensitive patients who decide whether to purchase the drug; a payer deciding whether to provide coverage for the drug; and a price-setting pharmaceutical firm seeking to maximize expected profits. We find that, in many cases, a pharmaceutical firm and payer cannot simultaneously benefit from outcome-based pricing, and who will benefit is determined by the probability of treatment success. Outcome-based pricing thus appears unlikely to solve the issues of high drug prices and high payer expenditures. However, supplementing outcome-based pricing with a transfer payment from firm to payer can make payer and firm (but not necessarily the patients) better off than under uniform pricing when the drug has a low chance of success.

This paper was accepted by Stefan Scholtes, healthcare management.
Community nursing services during the COVID-19 pandemic: the Singapore experience
Authors: Yi Xu , Jamil Nursa'adah Binte , Gaik Irene Tan Cheng , Fee Lim Su
Published: August 2020

Community nurses in Singapore support vulnerable older persons with chronic health condition(s). In the situation of scaled-down community health and social services during the COVID-19 outbreak, the community nursing team adopted measures for pandemic preparedness. This report is to share the Singapore General Hospital community nursing experience, preparation and transforming efforts during the pandemic. Team segregation, active screening and triage before visits and other precautionary measures were executed to minimise the risk of exposure to COVID-19. There was a shift from face-to-face to teleconsultation to meet the requirement of safe social-distancing. Community nursing teams continued to play an active role in supporting older persons during the pandemic, despite the challenges. Moving to the lockdown phase (‘circuit breaker’), teleconsultation, virtual meetings and integrated partnerships were essential to ensure healthcare accessibility and continuity of care. The experience gleaned was valuable to advance future community nursing services in the evolving healthcare landscape. Structured teleconsultation and technology advancement are useful to complement the service.
Oral health in older adults
Authors: Hazara Roya
Published: August 2020

The UK population is rapidly ageing, and this is set to continue for many more years. Consequently, this projects a number of health problems and challenges that need to be addressed. Functional impairment and age-related diseases have a significant impact on oral health, leading to a poor quality of life. Dental diseases become more prevalent in older adults, partly as a result of their poor general health, medication side effects and, in some instances, due to limited access to good dental care. Healthcare staff should be aware of these problems and ensure that individuals are given the correct advice, care and treatment. This article outlines what is known about oral health among older adults and highlights some of the common health conditions that affect oral health status in this population. Community nurses are well placed to educate and empower older adults in maintaining good oral health.
The value of calprotectin in synovial fluid for the diagnosis of chronic prosthetic joint infection
Authors: Zhang Zeyu , Cai Yuanqing , Bai Guochang , Zhang Chaofan , Li Wenbo , Yang Bin , Zhang Wenming
Published: August 2020

Aims

This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) .

Methods

A total of 63 patients who were suspected of PJI were enrolled. The synovial fluid calprotectin was tested by an enzyme-linked immunosorbent assay (ELISA). Laboratory test data, such as ESR, CRP, synovial fluid white blood cells (SF-WBCs), and synovial fluid polymorphonuclear cells (SF-PMNs), were documented. Chi-squared tests were used to compare the sensitivity and specificity of calprotectin and laboratory tests. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to determine diagnostic efficacy.

Results

The median calprotectin level was 776 μg/ml (interquartile range (IQR) 536.5 to 1132) in the PJI group and 54.5 μg/ml (IQR, 38.75 to 78.25) in the aseptic failure (AF) group (p < 0.05). Using a threshold of 173 ug/ml, the sensitivity was 95.2%, with a 97.6% specificity, and the AUC was 0.993. The sensitivity of calprotectin of the antibiotic-treated PJI group was 100% versus 90.9% of the non-antibiotic-treated PJI group. Although 47.6% (ten cases) of the patients in the PJI group received antibiotics before aspiration, the diagnostic efficacy of calprotectin was not affected. The sensitivity and specificity of ESR, CRP, SF-WBCs, and SF-PMNs ranged from 76.2% to 90.5% and 64.3% to 85.7%, respectively.

Conclusion

Calprotectin in synovial fluid has great diagnostic efficacy for PJI diagnosisand outperformed ESR, CRP, SF-WBCs, and SF-PMNs. Cite this article: Bone Joint Res 2020;9(8):450–456.
The effect of drying time on the yield and the chemical composition of essential oil and dissolved oil in hydrolat from aerial parts of Moroccan Thymbra capitata (L.) Cav
Authors: Moukhles Abderrahman , Ibn Mansour Ahmed
Published: August 2020

The present research aimed to study the effect of drying time on the yield and chemical composition of essential oil (EO) and dissolved oil in hydrolat (HY) from aerial parts of Moroccan Thymbra capitata (L.) Cav. Drying of plant material was carried out naturally in the shade of a draughty place at room temperature          (25–27°C). A series of 10 plant samples were subjected to hydrodistillation using a Clevenger-type apparatus. The results indicated that the yield of EO increased with drying time to reach the highest value on the 8th drying day (2.7%), while the yield of HY has not undergone an apparent variation           (0.2% – 0.6%). Based on the GC-MS analyses, EO was composed mainly of the phenolic monoterpene carvacrol (80.10%–92.27%) along with its biogenetic precursors' monoterpene hydrocarbons in a 1.02%–4.81% range p-cymene and 0.24% -1.86 % γ-terpinene. Other essential components occurring in minor quantity were sesquiterpene hydrocarbon a-humulene (2.58% – 4.67%) and oxygenated monoterpene linalool (0.80% –2.06%). At the same time, HY was constituted mainly of carvacrol (94.67–98.42%) along with a-humulene at much lower concentrations     (0.31%–0.86%) and the oxygenated derivative acetovanillone acetate (0.2%–1.80%). On the other hand, the highest concentration of carvacrol in EO was reached on the 5th day of the drying plant process (92.27%), while the HY recovered on the 7th day has shown carvacrol in its highest concentration (98.42%).
Boys to men: the cost of ‘adultification’ in safeguarding responses to Black boys
Authors: Davis Jahnine , Marsh Nicholas
Published: August 2020

This commentary is in response to the publication of Child C’s serious case review, published in May 2020. Child C was a victim of child criminal exploitation. He was murdered on the streets of London at 14 years old. Using an intersectional lens, together with and the concept of ‘adultification’, this article reflects on professional and societal attitudes towards Black boys and notions of vulnerability. We argue that in order to provide meaningful and effective support to Black boys, both the use of an intersectional lens and an awareness of adultification is necessary.
‘Disordering’ the world: Frantz Fanon’s contribution to social work’s understanding of decolonisation
Authors: Garrett Paul Michael
Published: August 2020

Noting current postcolonial critiques and endeavours to ‘decolonise the university’ and its various disciplines, the article points to the importance of the work of Frantz Fanon and especially his Studies in a dying colonialism and The wretched of the earth. The focus is on Fanon’s interrogation of the use of the veil in Algeria and how he perceived that, subject to ongoing revolutionary turbulence, family relations were being progressively transformed. Moreover, it is suggested that his views on violence warrant further exploration than is ordinarily provided in mainstream and conventional accounts of his work. While pessimistic, Fanon’s concerns about the evolution of postcolonial societies were also timely and prescient.
Generalized spectral phase-only time-domain ptychographic phase reconstruction applied in nonlinear microscopy
Authors: Dwapanyin George , Spangenberg Dirk , Heidt Alexander , Feurer Thomas , Bosman Gurthwin , Neethling Pieter , Rohwer Erich
Published: August 2020

Nonlinear microscopy has evolved over the last few decades to become a powerful tool for imaging and spectroscopic applications in biological sciences. In this study,

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, a novel spectral phase control technique, was implemented in order to compress broad-bandwidth supercontinuum light pulses generated in an all-normal-dispersion (ANDi) photonic crystal fiber (PCF). The technique, based on time-domain ptychography, is demonstrated here in a nonlinear microscopy application for the first time, to the best of our knowledge. The first real-world application of this technique for second-harmonic generation and two-photon excitation fluorescence microscopies in biological samples is presented. We further show that in our implementation,

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leads to improved contrast and signal-to-noise ratios in the generated images, compared to conventional compression techniques used in nonlinear microscopy.
Design of simultaneous multicolor coherent light generation in a single MgO:PPLN bulk crystal
Authors: Choge Dismas K. , Waswa David W. , Muguro Kennedy M. , Liang Wan-Guo
Published: August 2020

We report on simultaneous sum-frequency mixing and doubling of C-band and

∼

980

n
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laser sources using a single segmented periodically poled lithium niobate (PPLN) crystal in a single-pass configuration. Our theoretical analysis on the spectral outputs show that a proper design of a five-segment single PPLN crystal has potential to generate violet, blue, green, and orange wavelengths by simultaneous sum-frequency and second-harmonic generation processes. Such a design has promising potential for a compact, tunable multicolored laser that can find various applications such as in biomedicine, visible light communications, laser-based color displays, and sensing.
Light guidance up to 6.5 µm in borosilicate soft glass hollow-core microstructured optical waveguides
Authors: Perevoschikov Stanislav , Kaydanov Nikita , Ermatov Timur , Bibikova Olga , Usenov Iskander , Sakharova Tatiana , Bocharnikov Alexey , Skibina Julia , Artyushenko Viacheslav , Gorin Dmitry
Published: August 2020

Limited operating bandwidth originated from strong absorption of glass materials in the infrared (IR) spectral region has hindered the potential applications of microstructured optical waveguide (MOW)-based sensors. Here, we demonstrate multimode waveguide regime up to 6.5 µm for the hollow-core (HC) MOWs drawn from borosilicate soft glass. Effective light guidance in central HC (diameter ∼240 µm) was observed from 0.4 to 6.5 µm despite high waveguide losses (0.4 and 1 dB/cm in near- and mid-IR, respectively). Additional optimization of the waveguide structure can potentially extend its operating range and decrease transmission losses, offering an attractive alternative to tellurite and chalcogenide-based fibers. Featuring the transparency in mid-IR, HC MOWs are promising candidates for the creation of MOW-based sensors for chemical and biomedical applications.