bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of autophagy in human cytomegalovirus IE2 expression
Authors: Zhang Xinyan , Xi Ting , Zhang Linlin , Bi Yidan , Huang Yuan , Lu Yuanyuan , Liu Xinglou , Fang Feng
Published: July 2020

The purpose of this study was to determine whether autophagy regulates the expression of human cytomegalovirus (HCMV) immediately early two viral protein (IE2). Rapamycin and 3‐methyladenine (3‐MA) were used to stimulate or suppress autophagy during HCMV infection. UL122 recombinant plasmid was transfected to overexpress IE2 and small interference RNA against autophagy‐related protein 3 (ATG3) was used to knockdown ATG3. Western blot was performed to measure the expression of viral proteins and autophagy levels. Immunofluorescence was used to detect the immediately early 1 viral protein (IE1) expression. In human embryonic lung fibroblasts, infection of HCMV promotes the lipidation of light chain 3 (LC3) at 6 and 24 hours post infection (hpi), which was accompanied by the increased expression of viral protein IE2. When only IE2 was overexpressed via UL122 recombinant plasmid transfection without HCMV infection, the autophagy hallmarks LC3II and ATG3 were upregulated. Furthermore, viral protein IE2 expression was reduced at 24 and 48 hpi either by the treatment of autophagy inducer rapamycin or by the inhibitor 3‐MA before HCMV infection. At the same time, small interference ATG3 transient transfection, used to suppress autophagy, significantly inhibited IE2 expression. However, when 3‐MA was used to regulate autophagy levels after HCMV infection, expression of IE2 and IE1 were both decreased, while autophagy inducer rapamycin treatment after HCMV infection increased IE2 expression slightly. IE2 was involved in autophagy induced by HCMV infection and blocking autophagy could inhibit the expression of HCMV viral protein IE2, which might be one way for autophagy to restrict HCMV replication.
Climatic yield potential of Japonica‐type rice in the Korean Peninsula under RCP scenarios using the ensemble of multi‐GCM and multi‐RCM chains
Authors: Ahn Joong‐Bae , Kim Young‐Hyun , Shim Kyo‐Moon , Suh Myoung‐Seok , Cha Dong‐Hyun , Lee Dong‐Kyou , Hong Song‐You , Min Seung‐Ki , Park Seong‐Chan , Kang Hyun‐Suk
Published: July 2020

Rice production in the Korean Peninsula (KP) in the near future (2021–2050) is analysed in terms of the climatic yield potential (CYP) index for Japonica‐type rice. Data obtained from the dynamically downscaled daily temperature and sunshine duration for the Historical period (1981–2010) and near future under two Representative Concentration Pathway (RCP4.5 and RCP8.5) scenarios are utilized. To reduce uncertainties that might be induced by using a Coupled General Circulation Model (CGCM)—a Regional Climate Model (RCM) chain in dynamical downscaling, two CGCM—three RCM chains are used to estimate the CYP index. The results show that the mean rice production decreases, mainly due to the increase of the temperature during the grain‐filling period (40 days after the heading date). According to multi model ensemble, the optimum heading date in the near future will be approximately 12 days later and the maximum CYP will be even higher than in the Historical. This implies that the rice production is projected to decrease if the heading date is selected based on the optimum heading date of Historical, but to increase if based on that of near future. The mean rice production during the period of ripening is projected to decrease (to about 95% (RCP4.5) and 93% (RCP8.5) of the Historical) in the western and southern regions of the KP, but to increase (to about 104% (RCP4.5) and 106% (RCP8.5) of the Historical) in the northeastern coastal regions of the KP. However, if the optimum heading date is selected in the near future climate, the peak rice production is projected to increase (to about 105% (RCP4.5) and 104% (RCP8.5) of the Historical) in the western, southern and northeastern coastal regions of the KP, but to decrease (to about 98% (RCP4.5) and 96% (RCP8.5) of the Historical) in the southeastern coastal regions of the KP.
Comparative proteomic characterization of bovine milk containing β‐casein variants A1A1 and A2A2, and their heterozygote A1A2
Authors: Wang Xiaxia , Yu Zhongna , Zhao Xiaowei , Han Rongwei , Huang Dongwei , Yang Yongxin , Cheng Guanglong
Published: July 2020

BACKGROUND

Genetic variants of β‐casein are cosnidered to affect the components of milk. However, limited data are available on the bovine protein components correlated with β‐casein variants at the proteome level. In the present study, cows producing milk containing β‐casein variants (A1A1 and A2A2) and their heterozygote (A1A2) were identified using a high‐resolution melting method, and milk samples were collected and tested. Comparative analyses of casein micelles, whey and milk fat globule membrane fractions in each milk variant were performed using a label‐free proteomics approach.

RESULTS

The results obtained showed that ceruloplasmin and cathelicidin‐2 were the most abundant proteins in milk containing variant A1A1; lactoferrin and CD5 molecule‐like were the most abundant proteins in milk containing variant A2A2; and selenoprotein P and osteopontin were the most abundant proteins in milk containing heterozygote A1A2. Differences in protein components in milk containing the different β‐casein variants were visualized using hierarchical clustering, and profiles were separated using principal components analysis. The differentially expressed proteins in milk containing A1A1, A2A2 or A1A2 were predominantly involved in response to stress and defense response according to their Gene Ontology annotations.

CONCLUSION

Our findings provide new insights into differentially expressed milk proteins corresponding to the presence of different β‐casein variants. This knowledge will help determine their potential biological functions in dairy products and the effects on human health. © 2020 Society of Chemical Industry
Evaluating Open Source Software for 3D Imaging and Morphing in Cosmetic and Reconstructive Surgery
Authors: Hong Ellen M. , Hakimi Amir A. , Ho David , Torkian Behrooz A. , Wong Brian J.F.
Published: July 2020

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Chicago community task force seeks to address trauma's role in violence
Authors: Enos Gary
Published: July 2020

In a year when gun‐related violence and fatalities in Chicago are running close to 50% ahead of 2019 numbers, one incident in particular has galvanized response on the city's West Side. The killing of a three‐year‐old child over Father's Day weekend has inspired the formation of a task force that will seek to shed light on the link between a community's trauma and acts of violence.
JED evaluation finds colleges improving policies, programs
Authors: Canady Valerie A.
Published: July 2020

An evaluation of colleges and universities affiliated with the Jed Foundation (JED), a nonprofit that protects emotional health and prevents suicide in teens and young adults in colleges and universities in this country, reveals evidence of improvement across programs, policies and systems change indicators that support and protect student mental health.
Mental health advocates laud contributions of MH pioneer
Authors: Canady Valerie A.
Published: July 2020

The mental health community is mourning the loss of one of its pioneers in the field. William (Bill) Anthony, founder of the psychiatric rehabilitation movement, passed away July 15 at the age of 77 after a long battle with multiple sclerosis. Anthony was a pioneer in the field of mental illness, The Reading Post reported July 16. In 1979, he established the Center for Psychiatric Rehabilitation at Boston University and served as the executive director until his retirement in 2011. He received the Distinguished Service Award in 1992 from the president of the United States for his efforts “in promoting the dignity, equality, independence and employment of people with disabilities.”
Deblurring for spiral real‐time MRI using convolutional neural networks
Authors: Lim Yongwan , Bliesener Yannick , Narayanan Shrikanth , Nayak Krishna S.
Published: July 2020

Purpose

To develop and evaluate a fast and effective method for deblurring spiral real‐time MRI (RT‐MRI) using convolutional neural networks.

Methods

We demonstrate a 3‐layer residual convolutional neural networks to correct image domain off‐resonance artifacts in speech production spiral RT‐MRI without the knowledge of field maps. The architecture is motivated by the traditional deblurring approaches. Spatially varying off‐resonance blur is synthetically generated by using discrete object approximation and field maps with data augmentation from a large database of 2D human speech production RT‐MRI. The effect of off‐resonance range, shift‐invariance of blur, and readout durations on deblurring performance are investigated. The proposed method is validated using synthetic and real data with longer readouts, quantitatively using image quality metrics and qualitatively via visual inspection, and with a comparison to conventional deblurring methods.

Results

Deblurring performance was found superior to a current autocalibrated method for in vivo data and only slightly worse than an ideal reconstruction with perfect knowledge of the field map for synthetic test data. Convolutional neural networks deblurring made it possible to visualize articulator boundaries with readouts up to 8 ms at 1.5 T, which is 3‐fold longer than the current standard practice. The computation time was 12.3 ± 2.2 ms per frame, enabling low‐latency processing for RT‐MRI applications.

Conclusion

Convolutional neural networks deblurring is a practical, efficient, and field map‐free approach for the deblurring of spiral RT‐MRI. In the context of speech production imaging, this can enable 1.7‐fold improvement in scan efficiency and the use of spiral readouts at higher field strengths such as 3 T.
Physiological system analysis of the kidney by high‐temporal‐resolution monitoring of an oxygenation step response
Authors: Zhao Kaixuan , Pohlmann Andreas , Feng Qijian , Mei Yingjie , Yang Guixiang , Yi Peiwei , Feng Qianjin , Chen Wufang , Zhou Lili , Wu Ed X. , Seeliger Erdmann , Niendorf Thoralf , Feng Yanqiu
Published: July 2020

Purpose

Examine the feasibility of characterizing the regulation of renal oxygenation using high‐temporal‐resolution monitoring of the response to a step‐like oxygenation stimulus.

Methods

For mapping, multi‐echo gradient‐echo imaging was used (temporal resolution = 9 seconds). A step‐like renal oxygenation challenge was applied involving sequential exposure to hyperoxia (100% O2), hypoxia (10% O2 + 90% N2), and hyperoxia (100% O2). In vivo experiments were performed in healthy rats (N = 10) and in rats with bilateral ischemia‐reperfusion injury (N = 4). To assess the step response of renal oxygenation, a second‐order exponential model was used (model parameters: amplitude [A], time delay [Δt], damping constant [D], and period of the oscillation [T]) for renal cortex, outer stripe of the outer medulla, inner stripe of the outer medulla, and inner medulla.

Results

The second‐order exponential model permitted us to model the exponential recovery and the superimposed oscillation following renal oxygenation stimulus. The in vivo experiments revealed a difference in Douter medulla between healthy controls (D < 1, indicating oscillatory recovery) and ischemia‐reperfusion injury (D > 1, reflecting aperiodic recovery). The increase in Douter medulla by a factor of 3.7 (outer stripe of the outer medulla) and 10.0 (inner stripe of the outer medulla) suggests that this parameter might be rather sensitive to (patho)physiological oxygenation changes.

Conclusion

This study demonstrates the feasibility of monitoring the dynamic oxygenation response of renal tissues to a step‐like oxygenation challenge using high‐temporal‐resolution mapping. Our results suggest that the implemented system analysis approach may help to unlock questions regarding regulation of renal oxygenation, with the ultimate goal of providing imaging means for diagnostics and therapy of renal diseases.
Enhanced POCS reconstruction for partial Fourier imaging in multi‐echo and time‐series acquisitions
Authors: Koopmans Peter J. , Pfaffenrot Viktor
Published: July 2020

Purpose

To improve partial Fourier (PF) imaging reconstruction in time‐series or multi‐echo acquisitions.

Methods

Many PF methods use a phase estimate to restore Hermitian symmetry before filling missing k‐space entries with measured data from the opposite half. This estimate is obtained from the symmetrically sampled, central part of k‐space and its low‐resolution results in artifacts near high‐frequency phase effects (eg, tissue boundaries, vessels), limiting PF undersampling. Enhanced projection onto convex sets (POCS) uses full‐resolution phase estimates and relies on alternating the half of k‐space that is acquired in time series or multi‐echo acquisitions. This enables full‐resolution phase estimates to be calculated for each volume/echo, which are fed into the POCS framework. We apply enhanced POCS to high‐resolution multi‐echo FLASH and 3D‐EPI functional MRI time‐series data.

Results

Reconstruction errors and their bias dramatically reduce compared with existing methods, without leading to temporal blurring in time‐series acquisitions. This allows for higher PF acceleration factors at virtually no cost.

Conclusion

Enhanced POCS results in superior PF reconstructions. Furthermore, as the resolution of the phase estimate used for symmetry correction no longer depends on the PF factor, enhanced POCS is more robust against larger PF omission.
Cervical spine radiculopathy epidemiology: A systematic review
Authors: Mansfield Michael , Smith Toby , Spahr Nicolas , Thacker Mick
Published: July 2020

Background and objective

Cervical spine radiculopathy (CSR) is a disabling condition that has significant negative impacts on a person's mental health, physical functioning and social participation. Research has reported variable CSR incidence and prevalence among different populations. To date, no systematic review has been completed investigating the prevalence or incidence of CSR; therefore, our objective was to determine the incidence and/or prevalence of CSR in adults.

Design and method

A systematic review was conducted including searches of PubMed (MEDLINE), EMBASE and CINAHL from inception to February 25, 2020. Studies including data on incidence and/or prevalence of CSR were included. Methodological quality was assessed using a modified Hayden, Cote and Bombardier appraisal checklist. Data were analysed narratively.

Results

Nine low‐ to high‐quality studies were included in the final review. Incidence ranged between 0.832 and 1.79 per 1,000 person‐years from two high‐quality and one low‐quality study. Prevalence values ranged from 1.21 to 5.8 per 1,000 from four medium‐ to high‐quality studies. Prevalence values of 1.14% [95% confidence interval (CI): 0.45–1.82] and 1.31% (95% CI: 0.66–1.96) for males and females, respectively, were reported from one medium‐quality study. One medium‐quality study reported an unadjusted prevalence value of 6.3% for males and females.

Conclusions

This is the first systematic review investigating the epidemiology of CSR in an adult population. This review reports a variable incidence rate and prevalence of CSR among specific populations; however, this was based on nine studies. There is a priority to investigate CSR epidemiology across other populations globally and standardising CSR diagnostic criteria.
Combination molecular therapies for type 1 spinal muscular atrophy
Authors: Harada Yohei , Rao Vamshi K. , Arya Kapil , Kuntz Nancy L. , DiDonato Christine J. , Napchan‐Pomerantz Galia , Agarwal Amit , Stefans Vikki , Katsuno Masahisa , Veerapandiyan Aravindhan
Published: July 2020

Background

Data on combining molecular therapies that increase survival motor neuron protein for spinal muscular atrophy type 1 (SMA1) is lacking.

Methods

This was a retrospective study describing our centers' experiences in treating SMA1 patients with combination therapy.

Results

Five children received nusinersen and onasemnogene abeparvovec‐xioi (onasemnogene). Four were receiving nusinersen prior to onasemnogene. Nusinersen was continued in three. Marked liver enzyme elevations resulted in prolonged corticosteroid treatment in two patients with hospitalization and liver biopsy in one; milder liver enzyme elevations were noted in the other two. One patient received onasemnogene first, and then nusinersen. No adverse effects were noted. All patients improved.

Conclusions

Combination molecular therapy is tolerated in SMA1 patients. Further studies are needed to determine whether there are circumstances in which combination therapy would be more efficacious than either monotherapy. Prolonged corticosteroid use and liver toxicity monitoring may be necessary with onasemnogene therapy.
Application of muscle ultrasound for the evaluation of patients with amyotrophic lateral sclerosis: An observational cross‐sectional study
Authors: Rajabkhah Sahebeh , Moradi Kamyar , Okhovat Ali A. , Van Alfen Nens , Fathi Davood , Aghaghazvini Leila , Ashraf‐Ganjouei Amir , Attarian Shahram , Nafissi Shahriar , Fatehi Farzad
Published: July 2020

Introduction

We evaluated the association between muscle ultrasound, number of motor units, and clinical parameters, and assessed their utility for distinguishing amyotrophic lateral scleorisis (ALS) patients from healthy individuals.

Methods

Three muscle pairs (abductor pollicis brevis, abductor digiti minimi, and tibialis anterior) of 18 ALS patients and 18 controls underwent muscle ultrasound (echointensity and thickness) and assessment of motor unit number index (MUNIX). The clinical and functional status of participants were also assessed.

Results

Mean age of the patients was 53.8 ± 12.1 years, and score on the ALS Functional Rating Scale—Revised was 38.9 ± 4.1. Echointensity of all tested muscles of ALS participants was significantly higher than that of controls, but there was no significant difference in muscle thickness. Muscle echointensity correlated significantly with clinical and electrophysiological parameters.

Conclusion

Echointensity of muscles was highly associated with clinical scales and MUNIX, confirming its relevance as an ancillary diagnostic test in ALS patients.
Chronic immune polyradiculopathies: Three clinical variants of one disease?
Authors: Khadilkar Satish V. , Patel Riddhi , Shah Neha , Deshmukh Narayan D. , Patel Bhagyadhan A. , Mansukhani Khushnuma A.
Published: July 2020

Introduction

Chronic immune polyradiculopathies (sensory, motor, and mixed) are uncommon.

Methods

In this single‐center, retrospective study, the inclusion criteria for participants were progressive sensory ataxia and/or areflexic limb weakness; tibial somatosensory evoked potential (SSEP) abnormalities of the N22 and P40 potentials with normal sensory and motor nerve conduction studies or root involvement, according to magnetic resonance imaging (MRI); and albuminocytological dissociation.

Results

Eight patients were included in our study. Two had weakness, two had sensory ataxia, and four had both weakness and ataxia. Patients with weakness had abnormal SSEPs and patients with sensory ataxia also had absent F waves. Electromyography showed chronic denervation. MRI scans confirmed thickening and enhancement of roots. The patients responded to corticosteroid treatment.

Discussion

The overlapping clinicoelectrophysiological findings and similarities in radiological and therapeutic responses suggest that these entities are clinical variants of the same disease. The terms CIS(m)P, CI(s)MP, and CISMP (for chronic immune sensory motor polyradiculopathy) could be used to denote the predominant clinical involvement.
Fatigue in chronic inflammatory demyelinating polyneuropathy
Authors: Gable Karissa L. , Attarian Hrayr , Allen Jeffrey A.
Published: July 2020

Introduction

In this study we aimed to better understand fatigue in chronic inflammatory demyelinating polyneuropathy (CIDP) as it relates to disease activity status.

Methods

Patients with probable or definite CIDP were stratified into active CIDP or CIDP in remission. Assessments of fatigue, physical impairment, disability, sleepiness, sleep quality, and depression were collected.

Results

Of the 85 patients included in the study, 46 (54%) had active disease, whereas 39 (46%) were in remission. Fatigue was substantial in both groups, but was more severe in the active group. Use of sedating medications was a major contributor to fatigue. Sleep quality was poor in both groups, whereas depression more commonly affected those with active CIDP. Inflammatory Neuropathy Cause and Treatment disability, poor sleep quality, and higher level of depression had the greatest effect on fatigue severity.

Discussion

Fatigue is common in CIDP regardless of the disease activity state. Minimizing sedating medications, improving sleep quality, and managing depression may improve CIDP‐associated fatigue.
Enhancement of photovoltaic efficiency through fine adjustment of indacene‐based non‐fullerene acceptor by minimal chlorination for polymer solar cells
Authors: Keshtov Mukhamed L. , Kuklin Sergei A. , Dou Chuandong , Koukaras Emmanuel N. , Singhal Rahul , Malhotra Prateek , Sharma Ganesh D.
Published: July 2020

Two non‐fullerene small molecule acceptors (NFSMAs, BThIND‐Cl and BThIND) with an A–D–A configuration containing indacenedithiophene donor core unit and terminal unit with IC (BThIND) and chlorinated IND were synthesized for their application as an acceptor in polymer solar cells (PSCs). Compared to BThIND, the chlorinated molecule BThIND‐Cl exhibits lower energy levels and red‐shifted absorption spectrum but also exhibits improved crystallinity and molecular packing. These two NFSMAs are used as acceptors along with a well‐known conjugated polymer PM6, that exhibits complementary absorption to both NFSMAs, and has suitable frontier energy levels (highest occupied molecular orbital at –5.47 eV and lowest unoccupied molecular orbital at 3.61 eV) as a donor, in fabricating PSCs. Having optimized the active layers, the PSC based on PM6: BThIND‐Cl showed higher power conversion efficiency (PCE) of 12.36% and a fill factor (FF) of 0.71 than that of PM6: BThIND counterpart (PCE = 8.04% with a FF of 0.66). Moreover, for the PM6: BThIND‐Cl based PSC a quite high open‐circuit voltage of 0.96 V was achieved in addition to a low energy loss of 0.53. Notably higher short circuit current and FF value were found for the BThIND‐Cl based PSCs that are attributed to originate from the measured high values of charge carrier mobilities (and more balanced), to an advantageous nanoscale morphology, and finally to increased efficiency of exciton dissociation as compared to BThIND counterparts. These results demonstrate that substitution of the single chlorine atom in the IC terminal unit of A–D–A NFSMA is sufficient to enhance the PCE of PSCs
Fundamentals and applications of nanoparticles for ultrasound‐based imaging and therapy
Authors: Li Lujing , Guan Yupeng , Xiong Haiyun , Deng Tian , Ji Qiao , Xu Zuofeng , Kang Yang , Pang Jun
Published: July 2020

Ultrasonography (US) is frequently applied in clinical imaging because of its inherent merits compared with those of other imaging methods. Nanoparticle (NP)‐based imaging and therapeutic modalities have been widely used because of their unique functionalities and high performance. The report is mainly about the classifications and applications of NPs for US‐based theranostic biomedicine. The US‐based applications include single‐modality US imaging, multimodality US imaging, high‐intensity focused US, US‐triggered drug release, US‐enhanced gene transfection, and US‐irradiated sonodynamic therapy. In addition, current challenges, including the biological effects and biosafety, are discussed in this interview. NPs have tremendous potential as a US‐based theranostic tool and have revealed a new direction in cancer therapy.
Clinical Outcomes of Enteral Feeding Protocol Via Percutaneous Endoscopic Gastrostomy: A Single‐Center, Retrospective Study
Authors: Noh Jin Hee , Na Hee Kyong , Ahn Ji Yong , Hong Suk‐Kyung , Kim Jiyoun , Yang Jina , Jung Hwoon‐Yong
Published: July 2020

Background

The development of the endoscopic technique has resulted in an increasing number of patients undergoing percutaneous endoscopic gastrostomy (PEG) insertion; however, the protocols for increasing the volume of feeding formula after PEG insertion have not been established. Therefore, we compared the clinical outcomes of patients receiving low‐ and high‐volume increase in enteral feeding formula.

Methods

A total of 215 patients who underwent PEG insertion between January 2016 and March 2019 were included. They were divided into 2 groups according to the increase in volume of feeding formula: the low‐volume group (n = 135) received ≤150 mL/d, and the high‐volume group (n = 80) received ≥300 mL/d. Patient characteristics, procedure, and feeding‐related clinical outcomes were retrospectively reviewed using medical records.

Results

The adverse events of the feeding protocol did not significantly differ between the 2 groups. The number of days needed to attain the calorie targets was significantly lower in the high‐volume group than in the low‐volume group (5.4 ± 3.0 vs 2.4 ± 1.5; P < .001). The duration of supplemental parenteral nutrition and the length of hospitalization were also significantly lower in the high‐volume group (3.9 ± 3.3 vs 1.2 ± 2.2; P < .001 and 5.8 ± 2.7 vs 4.6 ± 2.6; P = .007, respectively).

Conclusion

To rapidly attain the calorie targets in appropriately selected patients with PEG insertion, a high‐volume increase in daily feeding can safely be recommended given the favorable outcomes.
Optimizing the investments in mobile networks and subscriber migrations for a telecommunication operator
Authors: Cambier Adrien , Chardy Matthieu , Figueiredo Rosa , Ouorou Adam , Poss Michael
Published: July 2020

We consider the context of a telecommunication company that is at the same time an infrastructure operator and a service provider. When planning its network expansion, the company can leverage over its knowledge of the subscriber dynamic to better optimize the network dimensioning, therefore avoiding unnecessary costs. In this work, the network expansion represents the deployment and/or reinforcement of several technologies (e.g., 2G, 3G, 4G), assuming that subscribers to a given technology can be served by this technology or older ones. The operator can influence subscriber dynamic by subsidies. The planning is made over a discretized time horizon while some strategic guideline requirements are required at the end of the time horizon. Following classical models, we consider that the willingness of customers for shifting to a new technology follows an S‐shape piecewise constant function. We propose a mixed‐integer linear programming formulation, improved through several valid inequalities and a heuristic algorithm. We assess the formulation numerically on real instances.
miRNA profiling of biliary intraepithelial neoplasia reveals stepwise tumorigenesis in distal cholangiocarcinoma via the miR‐451a/ATF2 axis
Authors: Loeffler Moritz A , Hu Jun , Kirchner Martina , Wei Xiyang , Xiao Yi , Albrecht Thomas , De La Torre Carolina , Sticht Carsten , Banales Jesus M , Vogel Monika N , Pathil‐Warth Anita , Mehrabi Arianeb , Hoffmann Katrin , Rupp Christian , Köhler Bruno , Springfeld Christoph , Schirmacher Peter , Ji Junfang , Roessler Stephanie , Goeppert Benjamin
Published: July 2020

Distal cholangiocarcinoma (dCCA) is a biliary tract cancer with a dismal prognosis and is often preceded by biliary intraepithelial neoplasia (BilIN), representing the most common biliary non‐invasive precursor lesion. BilIN are histologically well defined but have not so far been characterised systematically at the molecular level. The aim of this study was to determine miRNA‐regulated genes in cholangiocarcinogenesis via BilIN. We used a clinicopathologically well‐characterised cohort of 12 dCCA patients. Matched samples of non‐neoplastic biliary epithelia, BilIN and invasive tumour epithelia of each patient were isolated from formalin‐fixed paraffin‐embedded tissue sections by laser microdissection. The resulting 36 samples were subjected to total RNA extraction and the expression of 798 miRNAs was assessed using the Nanostring® technology. Candidate miRNAs were validated by RT‐qPCR and functionally investigated following lentiviral overexpression in dCCA‐derived cell lines. Potential direct miRNA target genes were identified by microarray and prediction algorithms and were confirmed by luciferase assay. We identified 49 deregulated miRNAs comparing non‐neoplastic and tumour tissue. Clustering of these miRNAs corresponded to the three stages of cholangiocarcinogenesis, supporting the concept of BilIN as a tumour precursor. Two downregulated miRNAs, i.e. miR‐451a (−10.9‐fold down) and miR‐144‐3p (−6.3‐fold down), stood out by relative decrease. Functional analyses of these candidates revealed a migration inhibitory effect in dCCA cell lines. Activating transcription factor 2 (ATF2) and A disintegrin and metalloproteinase domain‐containing protein 10 (ADAM10) were identified as direct miR‐451a target genes. Specific ATF2 inhibition by pooled siRNAs reproduced the inhibitory impact of miR‐451a on cancer cell migration. Thus, our data support the concept of BilIN as a direct precursor of invasive dCCA at the molecular level. In addition, we identified miR‐451a and miR‐144‐3p as putative tumour suppressors attenuating cell migration by inhibiting ATF2 in the process of dCCA tumorigenesis. © The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Thrombolytic therapy in preterm infants: Fifteen‐year experience
Authors: Grizante‐Lopes Priscila , Garanito Marlene Pereira , Celeste Daniele Martins , Krebs Vera Lucia Jornada , Carneiro Jorge David Aivazoglou
Published: July 2020

Objective

To report a single‐center experience with thrombolytic therapy using recombinant tissue plasminogen activator (rt‐PA) in preterm neonates with severe thrombotic events, in terms of thrombus resolution and bleeding complications.

Study design

This retrospective study included 21 preterm neonates with severe venous thrombotic events admitted to the neonatal intensive care unit, identified in our pharmacy database from January 2001 to December 2016, and treated with rt‐PA until complete or partial clot lysis, no‐response or bleeding complications. Our primary outcome was thrombus resolution.

Results

Twenty‐one preterm neonates were treated with rt‐PA for an average of 2.9 cycles. Seventeen patients (80.9%) had superior vena cava thrombosis and superior vena cava syndrome. All patients had a central venous catheter, parenteral nutrition, mechanical ventilation, and sepsis. Fifteen patients (71.4%) were extremely preterm, 11 (52.4%) were extremely low birth weight, and seven (33.3%) were very low birth weight. The patency rate was 85.7%, complete lysis occurred in 11 (52.4%) patients, and partial lysis in seven (33.3%). Minor bleeding occurred in five (23.8%) patients, three patients (14.2%) had clinically relevant nonmajor bleeding events, and major bleeding occurred in six (28%) patients.

Conclusion

In this study, the rate of thrombus resolution in preterm neonates treated with rt‐PA were similar to the percentages reported in children and adolescents, with a high rate of bleeding. Therefore, rt‐PA thrombolytic therapy should only be considered as a treatment option for severe life‐threatening thrombosis in premature neonates for whom the benefits of the thrombolytic treatment outweigh the risks of bleeding.
Phase II study of reduced‐dose craniospinal irradiation and combination chemotherapy for children with newly diagnosed medulloblastoma: A report from the Japanese Pediatric Brain Tumor Consortium
Authors: Okada Keiko , Soejima Toshinori , Sakamoto Hiroaki , Hirato Junko , Hara Junichi
Published: July 2020

Background

Standard doses of craniospinal irradiation (CSI) are 23.4 Gy for patients with average‐risk and 36 Gy for those with high‐risk medulloblastoma (MB). We investigated whether intensified chemotherapy including intrathecal chemotherapy with simultaneous irradiation is able to reduce CSI dose to 18 Gy.

Methods

Newly diagnosed average‐risk patients aged 3‐11 years and high‐risk patients aged 3‐18 years were eligible. Patients with Stage M1‐4 disease were classified as high‐risk MB and the others, including M0 patients with >1.5 cm2 postoperative residual tumor, were classified as average‐risk MB. Patients received chemotherapy consisting of cyclophosphamide, etoposide, cisplatin, and vincristine. Radiotherapy was started concomitantly with the second course of chemotherapy. Radiation doses were 50 Gy to the primary site and 18 Gy to the craniospinal axis. Average‐risk patients received five courses of chemotherapy. High‐risk patients received high‐dose chemotherapy consisting of thiotepa and melphalan following four courses of chemotherapy. All patients received intrathecal methotrexate.

Results

From 2006 to 2014, 48 patients (35 average and 13 high risk) who met the eligibility/exclusion criteria were enrolled. The 3‐year progression‐free survival (PFS) and 3‐year overall survival (OS) were 90.5% (standard error 5.2%) and 93.9% (4.2%), respectively, for average‐risk patients, and 100% and 100%, respectively, for high‐risk patients. There was no leukoencephalopathy or treatment‐related deaths. Two patients experienced secondary cancer.

Conclusions

These results suggest that CSI 18 Gy is adequate at least in a proportion of patients with MB treated with intensified chemotherapy including intrathecal methotrexate and simultaneous irradiation, though the results in high‐risk patients were only exploratory.
Do students notice stress in teachers? Associations between classroom teacher burnout and students' perceptions of teacher social–emotional competence
Authors: Oberle Eva , Gist Alexander , Cooray Muthutantrige S. , Pinto Joana B. R.
Published: July 2020

The goal of the present study was to investigate the link between elementary school teacher burnout and students' perceptions of teacher social–emotional competence (SEC). A total of 676 Grades 4–7 students in 35 classrooms rated their classroom teachers' SEC. In addition, teachers self‐reported their current level of experienced burnout at work (i.e., depersonalization and emotional exhaustion). Multilevel analyses revealed significant classroom‐level variability (i.e., 34%) in student‐ratings of teacher SEC. Teacher burnout significantly predicted student‐rated teacher SEC, over and above significant student‐level variables (school self‐concept, sense of autonomy in the classroom) and contextual variables (teacher age, school neighborhood income). Specifically, higher levels of teacher burnout were related to receiving lower SEC ratings by students. Teacher burnout explained a significant portion of the classroom‐level variability in student‐rated teacher SEC. The present study emphasizes the link between teacher burnout and the SEC. Furthermore, given that teacher reports (burnout) were linked to student reports (teacher SEC), these findings also suggest that students notice stress in their classroom teacher.
The Impact of a Comorbid Spinal Cord Injury on Cognitive Outcomes of Male and Female Patients with Traumatic Brain Injury
Authors: Mollayeva Tatyana , Sutton Mitchel , Escobar Michael , Hurst Mackenzie , Colantonio Angela
Published: July 2020

Introduction

Evidence of the effect of comorbid spinal cord injury (SCI) on cognitive outcomes in persons undergoing rehabilitation following newly diagnosed traumatic brain injury (TBI) is limited. We conducted a population‐based study to investigate this effect.

Objective

To compare cognitive outcomes in patients with TBI with and without a comorbid SCI.

Setting/Participants

Adult patients diagnosed with TBI were identified and followed for 1 year through provincial health administrative data; those who entered inpatient rehabilitation were studied.

Design

A retrospective matched cohort study using the National Rehabilitation Reporting System data of all acute care and freestanding rehabilitation hospitals in Ontario, Canada.

Main Measures

The exposure was a comorbid SCI in patients with diagnosed TBI. Exposed patients were matched to unexposed (TBI‐only) on sex, age, injury severity, and income, in a ratio of one to two. Gain differences in the cognitive subscale of the Functional Independence Measure were compared between exposed and unexposed patients using multivariable mixed linear model, controlling for comorbidity propensity score, gains in motor function, and rehabilitation care indicators.

Results

Over the first year post injury, 12 750 (0.84%) of all TBI patients entered inpatient rehabilitation, of whom 1359 (10.66%) had a comorbid SCI. A total of 1195 exposed patients (65.4% male, mean age 50.9 ± 20.6 for male and 61.8 ± 21.8 for female patients) were matched to 2390 unexposed patients. Controlling for confounding, exposed patients had lower cognitive gain (beta −0.43; 95% CI −0.72, −0.15), for both male (beta −0.39; 95% CI −0.75, −0.03) and female (beta −0.51; 95% CI −0.97, −0.05) patients. The adverse effects of comorbid SCI were driven largely by lower gains in problem solving and comprehension.

Conclusions

Adult patients with TBI and comorbid SCI showed a lower cognitive domain response to inpatient rehabilitation than patients with TBI alone. Identifying patients at risk for worse cognitive outcomes may facilitate the development of targeted strategies that improve cognitive outcomes.
Children and COVID‐19: Microbiological and immunological insights
Authors: Buonsenso Danilo , Sali Michela , Pata Davide , De Rose Cristina , Sanguinetti Maurizio , Valentini Piero , Delogu Giovanni
Published: July 2020

Since its first description in China, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has spread worldwide being declared a pandemic by the World Health Organization. More than 10.3 million people have been infected and more than 506 000 people died. However, SARS‐CoV‐2 had a lower impact on the pediatric population. Only about 1% to 2% of infected people are children and few deaths under the age of 14 are described so far. In this article, we discuss microbiological and immunological characteristics of SARS‐CoV‐2 infection in children highlighting the main differences from adult SARS‐CoV‐2 infection.
Insight into the pediatric and adult dichotomy of COVID‐19: Age‐related differences in the immune response to SARS‐CoV‐2 infection
Authors: Fialkowski Allison , Gernez Yael , Arya Puneeta , Weinacht Katja G. , Kinane T. Bernard , Yonker Lael M.
Published: July 2020

The difference in morbidity and mortality between adult and pediatric coronavirus disease 2019 infections is dramatic. Understanding pediatric‐specific acute and delayed immune responses to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is critical for the development of vaccination strategies, immune‐targeted therapies, and treatment and prevention of multisystem inflammatory syndrome in children. The goal of this review is to highlight research developments in the understanding of the immune responses to SARS‐CoV‐2 infections, with a specific focus on age‐related immune responses.
Value of Urine Peptides in Assessing Kidney and Cardiovascular Disease
Authors: Latosinska Agnieszka , Siwy Justyna , Faguer Stanislas , Beige Joachim , Mischak Harald , Schanstra Joost P.
Published: July 2020

Urinary peptides gained significant attention as potential biomarkers especially in the context of kidney and cardiovascular disease. In this manuscript the recent literature since 2015 on urinary peptide investigation in human kidney and cardiovascular disease is reviewed. The technology most commonly used in this context is capillary electrophoresis coupled mass spectrometry, in part owed to the large database available and the well‐defined dataspace. Several studies based on over 1000 subjects are reported in the recent past, especially examining CKD273, a classifier for assessment of chronic kidney disease based on 273 urine peptides. Interestingly, the most abundant urinary peptides are generally collagen fragments, which may have gone undetected for some time as they are typically modified via proline hydroxylation. The data available suggest that urinary peptides specifically depict inflammation and fibrosis, and may serve as a non‐invasive tool to assess fibrosis, which appears to be a key driver in kidney and cardiovascular disease. The recent successful completion of the first urinary peptide guided intervention trial, PRIORITY, is expected to further spur clinical application of urinary peptidomics, aiming especially at early detection of chronic diseases, prediction of progression, and prognosis of drug response.
Redox‐Active Vanadium‐Based Polyoxometalate as an Active Element in Resistive Switching Based Nonvolatile Molecular Memory
Authors: N. S. Sterin , Basu Nivedita , Cahay Marc , M. N. Satyanarayan , Mal Sib Sankar , Das Partha Pratim
Published: July 2020

Resistive switching (RS)‐based random access memory has been envisaged as a viable alternative to existing memory technology due to its nonvolatility, high switching speed, high endurance/retention, and considerably low operating voltage. Herein, a new uniform, repetitive, and stable RS phenomenon is demonstrated based on very low‐cost two‐terminal metal–insulator–metal stack fabricated using a highly redox‐active vanadium‐based polyoxometalate (POM) molecular clusters, [V10O28]6−—belonging to polyoxovanadate (POV) family. The RS is observed to be unipolar and nonvolatile in nature, and occur at a fairly low operating bias voltage (less than 2 V), making it suitable for low‐power operations. The switching event is attributed to the cycling between formation and rupture of tiny conductive nanofilaments formed due to trapping and detrapping of positively charged ionized oxygen vacancy sites present in the active switching layer of [V10O28]6−. POMs, in their rich abundance, are highly stable early transition‐metal oxide nanosized clusters, capable of storing as well as releasing a large number of electrons. In addition, they can undergo fast and reversible redox reactions (both in solid and liquid electrolyte media) in “stepwise” manner—a property that makes them a promising candidate for ultrafast and multi‐level nonvolatile molecular memory for high‐density data storage. Preliminary investigations on the POV‐based memory cells result in device resistance ratio ≈25, endurance for more than 200 cycles, and stable retention time around 2200 s, in fully open air condition.
A Pathway to Thin GaAs Virtual Substrate on On‐Axis Si (001) with Ultralow Threading Dislocation Density
Authors: Shang Chen , Selvidge Jennifer , Hughes Eamonn , Norman Justin C. , Taylor Aidan A. , Gossard Arthur C. , Mukherjee Kunal , Bowers John E.
Published: July 2020

With recent developments in high‐speed and high‐power electronics and Si‐based photonic integration, the concept of monolithic III–V/Si integration through epitaxial methods is gaining momentum. However, the performance and reliability of epitaxially grown devices are still limited by defects in the semiconductor material, especially the threading dislocation density (TDD). Herein, a novel “asymmetric step‐graded filter” structure grown by molecular beam epitaxy (MBE) is proposed based on a systematic study of the commonly used techniques for threading dislocation reduction for high‐quality GaAs on Si (001) growth. The proposed structure greatly enhances the plastic relaxation in the filter layers. A surface TDD lower than 2 × 106 cm−2 is achieved with a total buffer thickness of only 2.55 μm. This provides a clear pathway to further reduce defect density down to the theoretical limit in the 105 cm−2 regime with a thin buffer structure.
Numerical impacts on tracer transport: A proposed intercomparison test of Atmospheric General Circulation Models
Authors: Gupta Aman , Gerber Edwin P. , Lauritzen Peter H.
Published: July 2020

The transport of trace gases by the atmospheric circulation plays an important role in the climate system and its response to external forcing. Transport presents a challenge for Atmospheric General Circulation Models (AGCMs), as errors in both the resolved circulation and the numerical representation of transport processes can bias their abundance. In this study, two tests are proposed to assess transport by the dynamical core of an AGCM. To separate transport from chemistry, the tests focus on the age‐of‐air, an estimate of the mean transport time by the circulation. The tests assess the coupled stratosphere–troposphere system, focusing on transport by the overturning circulation and isentropic mixing in the stratosphere, or Brewer–Dobson Circulation, where transport time‐scales on the order of months to years provide a challenging test of model numerics. Four dynamical cores employing different numerical schemes (finite‐volume, pseudo‐spectral, and spectral‐element) and discretizations (cubed sphere versus latitude–longitude) are compared across a range of resolutions. The subtle momentum balance of the tropical stratosphere is sensitive to model numerics, and the first intercomparison reveals stark differences in tropical stratospheric winds, particularly at high vertical resolution: some cores develop westerly jets and others easterly jets. This leads to substantial spread in transport, biasing the age‐of‐air by up to 25% relative to its climatological mean, making it difficult to assess the impact of the numerical representation of transport processes. This uncertainty is removed by constraining the tropical winds in the second intercomparison test, in a manner akin to specifying the Quasi‐Biennial Oscillation in an AGCM. The dynamical cores exhibit qualitative agreement on the structure of atmospheric transport in the second test, with evidence of convergence as the horizontal and vertical resolution is increased in a given model. Significant quantitative differences remain, however, particularly between models employing spectral versus finite‐volume numerics, even in state‐of‐the‐art cores.
Engineering the Core Units of Small‐Molecule Acceptors to Enhance the Performance of Organic Photovoltaics
Authors: Wang Hao-Cheng , Chen Chung-Hao , Li Ren-Hao , Lin Yu-Che , Tsao Cheng-Si , Chang Bin , Tan Shaun , Yang Yang , Wei Kung-Hwa
Published: July 2020

Understanding the chemical structures of next‐generation small molecules is a critical step for increasing the performance of organic photovoltaics (OPVs); an OPV's small molecule determines not only the extent of light absorption but also the morphology. Herein, four small molecules featuring different cores—indaceno dithiophene, dithienoindeno indaceno dithiophene (IDTT), substituted IDTT, and dithienothiophene‐pyrrolobenzothiadiazole—denoted as ID‐4Cl, IT‐4Cl, m‐ITIC‐OR‐4Cl, and Y7, respectively, are selected to form active layers with poly(quinoxaline) (PTQ10) and poly(benzodithiophene‐4,8‐dione) (PM6). The Y7 devices exhibit the best performance in both systems, with the power conversion efficiency (PCE) reaching 14.5%; in comparison, ID‐4Cl device gives a PCE of 10.0% for blending with PTQ10 and a relative efficiency enhancement of 45%. The same trend occurs for the cases of PM6 blend devices. This enhancement is attributed to i) the improved short‐circuit current density that is provided by the greater degree of conjugation in S, N‐heteroarenes ladder‐type fused‐ring cores of Y7, ii) an induced face‐on Y7 orientation and smaller domain sizes that result from the sp2‐hybridized nitrogen side chain, and iii) smaller energy loss. This study reveals the importance of the core structure on the device performance and provides guidelines for the design of new materials for OPV technologies.