bluuebunny/crossref_metadata_2025 huggingface dataset:
Educational gains ofin‐personvs. distance learning in primary and secondary schools: A natural experiment during theCOVID‐19 pandemic school closures in Switzerland
Authors: Tomasik Martin J. , Helbling Laura A. , Moser Urs
Published: November 2020

Using data from a computer‐based formative feedback system, we compare learning gains in the 8 weeks of school closures related to the COVID‐19 pandemic in Switzerland with learning gains in the 8 weeks before these school closures. The school performance in mathematics and language ofN = 28,685 pupils is modelled in second‐order piecewise latent growth models with strict measurement invariance for the two periods under investigation. While secondary school pupils remain largely unaffected by the school closures in terms of learning gains, for primary school pupils learning slows down and at the same time interindividual variance in learning gains increases. Distance learning arrangements seem an effective means to substitute for in‐person learning, at least in an emergency situation, but not all pupils benefit to the same degree.
Recent advances in resistive random access memory based on lead halide perovskite
Authors: Di Jiayu , Du Jianhui , Lin Zhenhua , Liu Shengzhong (Frank) , Ouyang Jianyong , Chang Jingjing
Published: November 2020

Lead halide perovskites have attracted increasing attention in photovoltaic devices, light‐emitting diodes, photodetectors, and other fields due to their excellent properties. Besides optoelectronic devices, growing numbers of studies have focused on the perovskite‐based electrical devices in the past few years, such as transistors and resistive random access memories (RRAMs). Here, this article summarizes the recent progress the researchers have made of RRAM devices. Primarily, the working mechanism and the key parameters of RRAM are introduced. Generally, the working principles, including the conductive filament model (containing the types of the model of the metal cations‐induced filament and the model of the ions migration in bulk), the interface effect, and the electronic effect are the origins of the RRAM behaviors, and hence, various factors that affect the device performance are explored. Then, RRAMs based on organolead halide perovskite and all‐inorganic perovskite are discussed in terms of different structures, different compositions, and different fabrication methods. Finally, a brief conclusion and a broad outlook are given on the progress and challenges in the field of perovskite‐based RRAMs.

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Polarization‐resolved SHG imaging as a fast screening method for collagen alterations during aging: Comparison with light and electron microscopy
Authors: Miler Irena , Rabasovic Mihailo D. , Aleksic Marija , Krmpot Aleksandar J. , Kalezic Andjelika , Jankovic Aleksandra , Korac Bato , Korac Aleksandra
Published: November 2020

Our previous study on rat skin showed that cumulative oxidative pressure induces profound structural and ultrastructural alterations in both rat skin epidermis and dermis during aging. Here, we aimed to investigate the biophotonic properties of collagen as a main dermal component in the function of chronological aging. We used second harmonic generation (SHG) and two‐photon excited fluorescence (TPEF) on 5 μm thick skin paraffin sections from 15‐day‐, 1‐month‐ and 21‐month‐old rats, respectively, to analyze collagen alterations, in comparison to conventional light and electron microscopy methods. Obtained results show that polarization‐resolved SHG (PSHG) images can detect collagen fiber alterations in line with chronological aging and that this method is consistent with light and electron microscopy. Moreover, the β coefficient calculated from PSHG images points out that delicate alterations lead to a more ordered structure of collagen molecules due to oxidative damage. The results of this study also open the possibility of successfully applying this fast and label‐free method to previously fixed samples.
Processing and characterization of phosphate glass fiber/polylactic acid commingled yarn composites for commercial production
Authors: Wang Yunqi , Fu Jiapeng , Liu Jinsong , Parsons Andrew , Ahmed Ifty , Rudd Chris , Sharmin Nusrat
Published: November 2020

This study investigated the production of phosphate glass fiber/polylactic acid (PGF/PLA) commingled yarns, textiles and composites for biomedical applications. The PGF volume contents of the composites investigated were 25% and 40%. Plain weave textiles with yarn counts of 10 warp/cm and 6 weft/cm were produced using a commercial weaving machine. An orthogonal array design (OAD) was employed as a statistical method to investigate the effects of compression molding parameters (processing temperature, preheating time, compression time, and pressure) on flexural strength and porosity of PGF/PLA textile composites. Processing temperature showed the most significant effect in achieving maximum laminate flexural strength and molecular weight of PLA. Processing models were developed using regression techniques to predict the laminate flexural strength and the molecular weight of PLA. Composites with fiber contents of 25 and 40 vol% produced using optimized processing conditions identified by the processing models, provided flexural strengths of 236 MPa and 293 MPa, respectively.
Ablation of Enpp6 Results in Transient Bone Hypomineralization
Authors: Dillon Scott , Suchacki Karla , Hsu Shun‐Neng , Stephen Louise A , Wang Rongling , Cawthorn William P , Stewart Alan J , Nudelman Fabio , Morton Nicholas M , Farquharson Colin
Published: November 2020

Biomineralization is a fundamental process key to the development of the skeleton. The phosphatase orphan phosphatase 1 (PHOSPHO1), which likely functions within extracellular matrix vesicles, has emerged as a critical regulator of biomineralization. However, the biochemical pathways that generate intravesicular PHOSPHO1 substrates are currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase 6 (ENPP6) is an upstream source of the PHOSPHO1 substrate. To test this, we characterized skeletal phenotypes of mice homozygous for a targeted deletion of Enpp6 (Enpp6−/−). Micro‐computed tomography of the trabecular compartment revealed transient hypomineralization in Enpp6−/− tibias (p < 0.05) that normalized by 12 weeks of age. Whole‐bone cortical analysis also revealed significantly hypomineralized proximal bone in 4‐ but not 12‐week‐old Enpp6−/− mice (p < 0.05) compared with WT animals. Back‐scattered SEM revealed a failure in 4‐week‐old trabecular bone of mineralization foci to propagate. Static histomorphometry revealed increased osteoid volume (p > 0.01) and osteoid surface (p < 0.05), which recovered by 12 weeks but was not accompanied by changes in osteoblast or osteoclast number. This study is the first to characterize the skeletal phenotype of Enpp6−/− mice, revealing transient hypomineralization in young animals compared with WT controls. These data suggest that ENPP6 is important for bone mineralization and may function upstream of PHOSPHO1 as a novel means of generating its substrates inside matrix vesicles. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
Unraveling individual host–guest interactions in molecular recognition from first principles quantum mechanics: Insights into the nature of nicotinic acetylcholine receptor agonist binding
Authors: Beck Michael Edmund , Riplinger Christoph , Neese Frank , Bistoni Giovanni
Published: November 2020

Drug binding to a protein target is governed by a complex pattern of noncovalent interactions between the ligand and the residues in the protein's binding pocket. Here we introduce a generally applicable, parameter‐free, computational method that allows for the identification, quantification, and analysis of the key ligand–residue interactions responsible for molecular recognition. Our strategy relies on Local Energy Decomposition analysis at the “gold‐standard” coupled cluster DLPNO‐CCSD(T) level. In the study case shown in this paper, nicotine and imidacloprid binding to the nicotinic acetylcholine receptor, our approach provides new insights into how individual amino acids in the active site determine sensitivity and selectivity of the ligands, extending and refining classical pharmacophore hypotheses. By inference, the method is applicable to any kind of host/guest interactions with potential applications in industrial biocatalysis and protein engineering.
The microarray identification circular RNA hsa_circ_0105015 up‐regulated involving inflammation pathway in essential hypertension
Authors: He Xin , Bao Xingjie , Tao Zhenbo , Sun Jihan , Zheng Shuying , Zhong Fade , Zhang Lina
Published: November 2020

Background

Essential hypertension (EH) is an inflammatory disease, and endothelial dysfunction induced by chronic inflammation is one of the pathogeneses of EH. The expression of some inflammatory mediators may be regulated by the interaction of circular RNAs (circRNAs) and microRNAs (miRNAs).

Methods

An Agilent human circRNA microarray was used to identify the expression profile of circRNAs in EH. qRT‐PCR was used to evaluate the relative expression of circRNAs in 48 pairs of human whole blood samples (sex and age ± 3 years matched) and endothelial cells. TNF‐α was applied to induce endothelial cells inflammation. CircRNA‐miRNA network was predicted by MiRanda software.

Results

There were 287 circRNAs differentially expressed in the microarray. The top 10 up‐regulated circRNAs in the EH group were hsa_circ_0014243, hsa_circ_0133228, hsa‐circRNA14116‐3, hsa_circ_0079536, hsa‐circRNA13649‐1, hsa_circ_0117886, hsa_circ_0007075, hsa‐circRNA15285‐1, hsa‐circRNA10088‐9, and hsa‐circRNA14119‐10; the top 10 down‐regulated circRNAs were hsa_circ_0100094, hsa_circ_0127342, hsa_circ_0093773, hsa_circ_0096334, hsa_circ_0131618, hsa_circ_0063886, hsa_circ_0097804, hsa_circ_0126640, hsa‐circRNA8935‐1, and hsa_circ_0039978 (fold change in descending order). Hsa_circ_0105015 has two predicted binding sites with hsa‐miR‐637. The relative expression of hsa_circ_0105015 in EH patients was significantly higher than healthy controls (P = .002), and similar results appeared in TNF‐α‐induced endothelial cells. The area under the curve after hsa_circ_0105015 combined with hsa‐miR‐637 was 0.703, P < .001.

Conclusion

Hyperexpression of hsa_circ_0105015 is a significant risk factor of EH and its association with EH involves inflammatory pathways. Hyperexpression of hsa_circ_0105015 combined with hypoexpression of hsa‐miR‐637 indicates vascular inflammation or endothelial dysfunction and has potential as a biomarker for early diagnosis of EH.
TAK1 inhibition improves myoblast differentiation and alleviates fibrosis in a mouse model of Duchenne muscular dystrophy
Authors: Xu Dengqiu , Li Sijia , Wang Lu , Jiang Jingwei , Zhao Lei , Huang Xiaofei , Sun Zeren , Li Chunjie , Sun Lixin , Li Xihua , Jiang Zhenzhou , Zhang Luyong
Published: November 2020

Background

Transforming growth factor‐β‐activated kinase 1 (TAK1) plays a key role in regulating fibroblast and myoblast proliferation and differentiation. However, the TAK1 changes associated with Duchenne muscular dystrophy (DMD) are poorly understood, and it remains unclear how TAK1 regulation could be exploited to aid the treatment of this disease.

Methods

Muscle biopsies were obtained from control donors or DMD patients for diagnosis (n = 6 per group, male, 2–3 years, respectively). Protein expression of phosphorylated TAK1 was measured by western blot and immunofluorescence analysis. In vivo overexpression of TAK1 was performed in skeletal muscle to assess whether TAK1 is sufficient to induce or aggravate atrophy and fibrosis. To explore whether TAK1 inhibition protects against muscle damage, mdx (loss of dystrophin) mice were treated with adeno‐associated virus (AAV)‐short hairpin TAK1 (shTAK1) or NG25 (a TAK1 inhibitor). Serum analysis, skeletal muscle performance and histology, muscle contractile function, and gene and protein expression were performed.

Results

We found that TAK1 was activated in the dystrophic muscles of DMD patients (n = 6, +72.2%, P < 0.001), resulting in fibrosis ( +65.9% for fibronectin expression, P < 0.001) and loss of muscle fibres (−32.5%, P < 0.01). Moreover, TAK1 was activated by interleukin‐1β, tumour necrosis factor‐α, and transforming growth factor‐β1 (P < 0.01). Overexpression of TAK1 by AAV vectors further aggravated fibrosis (n = 8, +39.6% for hydroxyproline content, P < 0.01) and exacerbated muscle wasting (−31.6%, P < 0.01) in mdx mice; however, these effects were reversed in mdx mice by treatment with AAV‐short hairpin TAK1 (shTAK1) or NG25 (a TAK1 inhibitor). The molecular mechanism underlying these effects may be related to the prevention of TAK1‐mediated transdifferentiation of myoblasts into fibroblasts, thereby reducing fibrosis and increasing myoblast differentiation.

Conclusions

Our findings show that TAK1 activation exacerbated fibrosis and muscle degeneration and that TAK1 inhibition can improve whole‐body muscle quality and the function of dystrophic skeletal muscle. Thus, TAK1 inhibition may constitute a novel therapy for DMD.
Rapid acute care genomics: Challenges and opportunities for genetic counselors
Authors: Lynch Fiona , Nisselle Amy , Gaff Clara L. , McClaren Belinda
Published: November 2020

Genomic medicine in pediatric acute care is showing great promise, with rapid results from exome and genome sequencing returned within days providing critically important information for treatment and management of seriously ill children. Many have suggested that rapid acute care genomics presents novel genetic counseling issues. This is due to the need for rapid response to referrals, the immense emotional distress that parents are likely to experience when their child is in acute care, and the unfamiliar environment of the acute care setting. To explore the practice of genetic counselors in this setting, we conducted qualitative interviews with 16 genetic counselors (GCs), representing a large proportion of GCs at the frontline of providing genetic counseling in acute care settings in Australia. Interviews revealed themes describing genetic counseling in acute care, including practical challenges of counseling within a rapid turnaround time, similarities with other contexts such as prenatal counseling, and the need for education of other health professionals. Interestingly, GCs did not raise concerns in the interviews for parents’ ability to provide informed consent for rapid genomic sequencing. GCs also encountered practical and organizational challenges with counseling in this setting where 24‐hr care is provided, at odds with traditional ‘9 to 5’ Genetics service delivery. Working closely in a multidisciplinary team was common and participants believed that GCs are well positioned to take a leading role in the education of other health professionals as rapid acute care genomics becomes routine clinical practice. Despite views that genetic counseling practice in rapid acute care genomics is unique, these exploratory data suggest that GCs are flexible, adaptable, and sufficiently skilled to deliver patient‐centered counseling in this setting. Our work indicates GCs are ready and willing to contribute at an early stage of adoption of genomic investigations in acute care.
Seroprevalence of Helicobacter pylori and its association with metabolic syndrome in a rural community of Bangladesh
Authors: Rahman M. Masudur , Kibria Md. Golam , Sultana Nigar , Akhter Mahfuza , Begum Hasina , Haque Md. Ahshanul , Haque Rashidul , Sarker Shafiqul Alam , Ahmed Faruque , Hasan Mahmud
Published: November 2020

Background and Aim

As the interrelationship between Helicobacter pylori, metabolic syndrome (MetS), and non‐alcoholic fatty liver disease (NAFLD) is controversial, we undertook a community‐based study with the aim to find the seroprevalence of H. pylori and its relationship with MetS and NAFLD.

Methods

This door‐to‐door survey was conducted among the adult subjects (≥18 years) of two villages (Charcharia of Dhaka district and Kharrah of Munshiganj district) of Bangladesh. Interviews using a structured questionnaire, clinical examination, anthropometric measurements, ultrasonogram of the liver, and biochemical tests were performed.

Results

Of 1021 subjects, 781 responded (76.49%), and 767 were included in the final analysis (mean age 40.35 ± 15.56 years; female 63.5%). Anti‐H. pylori antibodies were found in 418 of 767 (54.5%). There were no H. pylori serostatus association with MetS and diabetes mellitus (DM) in univariate or multivariate analysis (all P > 0.05). However, H. pylori seropositive subjects had lower systolic blood pressure (odds ratio [OR] = −2.95 [−5.58, −0.32]) and low density lipoprotein ‐cholesterol (OR −7.79 [−15, −0.57]) compared to seronegative subjects in the linear regression model. Seronegativity of H. pylori was associated with NALFD in univariate (P = 0.007) but not multivariate analysis (P = 0.086). There were no differences in the frequency of H. pylori seropositivity among the participants with nonobese compared to obese NAFLD (19/42 [45%] vs 43/99 [43.4%], P = 0.844).

Conclusion

In a rural community of Bangladesh, about 55% of the population were H. pylori seropositive, which was more common among the underweight than normal or obese subjects. However, there was no relationship observed between H. pylori seroprevalence and MetS, DM, or NAFLD.
Assessment of ADCY9 polymorphisms and colorectal cancer risk in the Chinese Han population
Authors: Li Haiyue , Liu Yuanwei , Liu Jianfeng , Sun Yao , Wu Jiamin , Xiong Zichao , Zhang Yi , Li Bin , Jin Tianbo
Published: November 2020

Background

Recently, ADCY9 has been found to be highly expressed in colon cancer, and high ADCY9 expressionis a poor prognostic factor of colon cancer. However, no study has reported on the relationship between single nucleotide polymorphisms (SNPs) of ADCY9 and colorectal cancer risk in the Chinese Han population.

Methods

To evaluate the association between four ADCY9 SNPs and colorectal cancer risk, we performed a case–control study including 511 colorectal cancer patients and 511 healthy controls. SNPs were genotyped using the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA). The distributions of alleles and genotypes frequencies between the case and control groups were compared using chi‐squared. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression adjusted for age and gender to assess the association between SNPs and colorectal cancer risk.

Results

The overall analysis found that rs2230742 was associated with an increased risk of colorectal cancer (AA versus GG: OR = 3.54, 95% CI = 1.16–10.86, p = 0.027; recessive model: OR = 3.55, 95% CI = 1.16–10.85, p = 0.027). Stratification analysis showed that rs2230742 was associated with an increased rectal cancer risk; rs11076810 was associated with a reduced colorectal cancer risk for age > 59 years. No association was observed between other two SNPs and colorectal cancer risk.

Conclusions

Our findings suggest that ADCY9 polymorphisms (rs2230742 and rs11076810) have an effect on colorectal cancer risk in the Chinese Han population. Future association and functional studies are required to confirm our findings and explore the mechanism of ADCY2 in colorectal cancer.
Convenient method for the synthesis of some novel chiral methyl 2‐(2‐oxo‐2H‐benzo[e][1,3]oxazin‐3(4H)‐yl)propanoate derivatives and biological evaluation of their antioxidant, cytotoxic, and molecular docking properties
Authors: Matam Sivakumar , Kaliyan Prabakaran , Selvaraj Loganathan , Muthu Seenivasa Perumal , Lohanathan Bharathi Priya , Viswanadhan Vijaya Padma , Makala Himesh , Venkatasubramanian Ulaganathan
Published: November 2020

Ten chiral methyl 2‐(2‐oxo‐2H‐benzo[e][1,3]oxazin‐3(4H)‐yl)propanoate derivatives 6a‐6j have been synthesized from optically pure amino methyl phenol 5 and 4‐nitrophenyl chloroformate. These derivatives 6a‐6j are characterized by 1H NMR, 13C NMR, FT‐IR, and HRMS spectral techniques. Optical purity of these derivatives was confirmed by chiral HPLC method. Ten synthesized ester derivatives 6a‐6j were screened for their in vitro antioxidant activity. Among the compounds 6b‐d and 6h‐j have exhibited comparable antioxidant activity with ascorbic acid as a standard. Compounds 6a and 6e‐g have shown moderate antioxidant activity. Further, the in vitro cytotoxicity of these compounds were studied through MTT cell proliferation assay in addition the effect on LDH leakage and NO release. Among the derivatives, 6j showed extremely best activity and the IC50 value (12.54 ± 0.71 μM) is very close to doxorubicin (7.2 ± 0.58 μM) as a standard. Compounds 6b, 6h, and 6i showed better inhibition next to compound 6j on the viability of HepG2 cells with an IC50 value (μM) of 56.02 ± 1.4, 41.76 ± 0.58, and 38.17 ± 0.34, respectively. Also, molecular docking studies have been carried out with STAT‐3 (PDB ID: 1BG1) and BCL‐2 (PDB ID: 4AQ3) proteins against the four active compounds 6b, 6h, 6i, and 6j. The binding energies of the tested compounds were in the range of −7.76 to −8.41 kcal/mol, which is very close to doxorubicin (−8.53 kcal/mol) as a standard. These molecular docking results are in good agreement with the in vitro studies.
Impact of Obesity and Visceral Fat on Mortality in Hematopoietic Stem Cell Transplantation
Authors: Pereira Andrea Z , de Almeida‐Pitito Bianca , Eugenio Gisele Cristine , Ruscitto do Prado Rogério , Silva Cinthya Correa , Hamerschlak Nelson
Published: November 2020

Rationale: Many studies have shown the importance of body composition parameters, muscle, and fat mass, evaluated by several methods in hematopoietic stem cell transplantation (HSCT) outcomes. Ultrasound (US) is an efficient and low‐cost method to evaluate body composition, even though there have not been many studies in HSCT. Objectives: Our goal was to investigate the muscle, visceral fat (VF), and echogenicity before HSCT and after engraftment, evaluated by US and its association with outcomes. Methods: All adult patients with hematological malignances admitted for HSCT autologous and allogeneic were eligible to enter this prospective study. Their thigh muscle thickness, VF, and echogenicity were evaluated by US on the first day of hospitalization (baseline) and after engraftment (15–25 days post‐HSCT). Results: We evaluated 50 patients; 42% were male and 58% had undergone allogeneic HSCT. Most patients were <55 years old (68%) and had normal body mass index (50%). We found a significant reduction of right and left muscle thickness (P < .001) and echogenicity (P = .002) after engraftment compared with baseline. Our elderly patients had significantly bigger right‐thigh muscle thickness (P = .02) and more VF (P = .009). The following data were higher in obese patients: right and left muscle thickness (P < .001), VF (P = .003), and echogenicity (P = .04). Death in the first 100 days had a positive association with obesity (P = 0.001) and VF (P = .002). VF was the only variable independent of HSCT type and age in mortality risk. Conclusion: Obesity and VF had an important impact in mortality. US could be a useful tool and strategy for evaluating body composition in HSCT patients.
A comparison of oncological outcomes after abdominoperineal excision before and after the implementation of a selective perineal flap closure program
Authors: Murphy Claudine , Stephens Ian , OꞌFlanagan Grace , OꞌByrne Lisa , Reynolds Ian S. , Ajmal Nadeem , O'Sullivan John Barry , OꞌNeill Brian , Deasy Joseph , Burke John P. , McNamara Deborah A.
Published: November 2020

Background and Objectives

Abdominoperineal excision (APE) is the operation chosen when a patient has low rectal cancer unamenable to sphincter preserving surgery. Perineal flap reconstruction is associated with less wound morbidity but little is known about oncological outcomes. The objective was to compare outcomes in patients undergoing APE before and after the introduction of a program that utilized flap reconstruction of the perineum.

Methods

A retrospective review of a prospectively maintained database was performed. Patients who underwent APE followed by primary closure or flap reconstruction between 1998 and 2018 were selected. The cohorts were divided according to the implementation of the flap reconstruction program in July 2009. Clinicopathological data, recurrence and survival were compared between the cohorts.

Results

One hundred and forty nine patients underwent APE for rectal adenocarcinoma between 1998 and 2018. There were 57 patients in the pre‐flap era and 92 in the post‐flap era. Forty‐six patients underwent flap reconstruction in the latter cohort (50%). More patients in the post‐flap era underwent neoadjuvant chemoradiotherapy (85.9% vs. 63.2%; p < .01). Margin positivity rates decreased from 21.1% in the pre‐flap era to 10.9% in the post‐flap era (p = .10) and there was an associated improvement in incidence and time to local recurrence (p = .03).

Conclusion

The use of perineal flap reconstruction is associated with a longer median time to local recurrence. Perineal flap reconstruction may contribute to reduced margin positivity.
A rapid and innovative extraction and enrichment method for the metaproteomic characterization of dissolved organic matter in groundwater samples
Authors: Capriotti Anna Laura , Aita Sara Elsa , Cavaliere Chiara , Cerrato Andrea , Montone Carmela Maria , Piovesana Susy , Laganà Aldo
Published: November 2020

Metaproteomic analysis of aquifer systems provides valuable information on the microbial populations, their influence on drinking water quality, and the effect on human health. In the present paper, an extraction and enrichment method by C18 extra‐wide pore cartridge was developed, optimized, and applied for the first time to the metaproteomic characterization of dissolved organic matter in groundwater samples. In particular, three elution procedures were tested and compared on water spiked with a yeast protein extract to maximize the recovery of proteins from a complex matrix. The maximum protein recovery was obtained by the use of two sequential elution buffers, one employing a denaturing agent and the other one containing an acidified organic solvent. A comprehensive metaproteomic analysis of the dissolved organic matter of groundwater was then performed by nano‐high performance liquid chromatography coupled to high‐resolution mass spectrometry. A total of 239 proteins was identified; in agreement with the current knowledge on proteins in aquifer systems, most identified sequences derived from bacteria, protobacteria, and ciliates. The paper is the first metaproteomic study applied to groundwater samples with particular emphasis on the need for sample pretreatment to obtain comprehensive information on the proteome in dissolved organic matter.
The role of the diffusion process in bimolecular reactions with neighborhood
Authors: de Souza Filho José Cândido , López‐Castillo Alejandro
Published: November 2020

We performed stochastic and deterministic calculations to study simple bimolecular chemical kinetics with a neighborhood, necessary for solid‐state and viscous medium reactions. Regarding the standard deterministic method using ordinary differential equations (ODEs) to describe a bimolecular reaction with the neighborhood, we established a comparison that indicates, in this method, an implicit diffusion process. For example, the reaction is processed in a homogeneous medium, differently from the stochastic method without diffusion. The two methods coincide at the thermodynamic limit (containing little relative fluctuation) when added with the explicit diffusion process on the stochastic model. The irreversible reaction without diffusion was emulated using the ODEs of a reversible reaction, and the inherent residual concentration of the reactions with low or no diffusion occurring in solids or strong viscous media was obtained from pseudochemical equilibrium.
Matching methods in precision oncology: An introduction and illustrative example
Authors: Weymann Deirdre , Laskin Janessa , Jones Steven J.M. , Lim Howard , Renouf Daniel J. , Roscoe Robyn , Schrader Kasmintan A. , Sun Sophie , Yip Stephen , Marra Marco A. , Regier Dean A.
Published: November 2020

Background

Randomized controlled trials (RCTs) are uncommon in precision oncology. We provide an introduction and illustrative example of matching methods for evaluating precision oncology in the absence of RCTs. We focus on British Columbia's Personalized OncoGenomics (POG) program, which applies whole‐genome and transcriptome analysis (WGTA) to inform advanced cancer care.

Methods

Our cohort comprises 230 POG patients enrolled between 2014 and 2015 and matched POG‐naive controls. We generated our matched cohort using 1:1 propensity score matching (PSM) and genetic matching prior to exploring survival differences.

Results

We find that genetic matching outperformed PSM when balancing covariates. In all cohorts, overall survival did not significantly differ across POG and POG‐naive patients (p > 0.05). Stratification by WGTA‐informed treatment indicated unmatched survival differences. Patients whose WGTA information led to treatment change were at a reduced hazard of death compared to POG‐naive controls in all cohorts, with estimated hazard ratios ranging from 0.33 (95% CI: 0.13, 0.81) to 0.41 (95% CI: 0.17, 0.98).

Conclusion

These results signal that clinical effectiveness of precision oncology approaches will depend on rates of genomics‐informed treatment change. Our study will guide future evaluations of precision oncology and support reliable effect estimation when RCT data are unavailable.
Bit‐error‐rate performance of high‐order APPM and AOPPM for non‐Kolmogorov gamma–gamma channel FSO communications
Authors: Xu Meiyong , Ullah Sibghat , Zhang Sihan , Yuan Deyu , Fu Xiujia , Wang Kaimin , Xin Xiangjun
Published: November 2020

High‐order pulse modulations in free space optics (FSO) communication are of practical value, and non‐Kolmogorov gamma–gamma (GG) channel model is the most suitable for FSO channel. However, research on a system combined with the above is rarely reported. In our work, we propose high‐order (4*32 and 4*64) amplitude and pulse position modulation (APPM) and overlapping amplitude and pulse position modulation (AOPPM) FSO communication system under a modified non‐Kolmogorov GG turbulent channel model. Simulation results present that AOPPM is obviously better than APPM in bit‐error‐rate (BER) performance, and BER performance grows with the increase of modulation order (number of pulse positions). The proposed schemes may provide a reference for system design and practical application.
Multi‐marker quantitative radiomics for mass characterization in dedicated breast CT imaging
Authors: Caballo Marco , Pangallo Domenico R. , Sanderink Wendelien , Hernandez Andrew M. , Lyu Su Hyun , Molinari Filippo , Boone John M. , Mann Ritse M. , Sechopoulos Ioannis
Published: November 2020

Purpose

To develop and evaluate the diagnostic performance of an algorithm for multi‐marker radiomic‐based classification of breast masses in dedicated breast computed tomography (bCT) images.

Methods

Over 1000 radiomic descriptors aimed at quantifying mass and border heterogeneity, morphology, and margin sharpness were developed and implemented. These included well‐established texture and shape feature descriptors, which were supplemented with additional approaches for contour irregularity quantification, spicule and lobe detection, characterization of degree of infiltration, and differences in peritumoral compartments. All descriptors were extracted from a training set of 202 bCT masses (133 benign and 69 malignant), and their individual diagnostic performance was investigated in terms of area under the receiver operating characteristics (ROC) curve (AUC) of single‐feature‐based linear discriminant analysis (LDA) classifiers. Subsequently, the most relevant descriptors were selected through a multiple‐step feature selection process (including stability analysis, statistical significance, evaluation of feature interaction, and dimensionality reduction), and used to develop a final LDA radiomic model for classification of benign and malignant masses, which was then tested on an independent test set of 82 cases (45 benign and 37 malignant).

Results

The majority of the individual radiomic descriptors showed, on the training set, an AUC value deriving from a linear decision boundary higher than 0.65, with the lower limit of the associated 95% confidence interval (C.I.) not overlapping with random chance (AUC = 0.5). The final LDA radiomic model resulted in a test set AUC of 0.90 (95% C.I. 0.80–0.96).

Conclusions

The proposed multi‐marker radiomic approach achieved high diagnostic accuracy in bCT mass classification, using a radiomic signature based on different feature types. While future studies with larger datasets are needed to further validate these results, quantitative radiomics applied to bCT shows potential to improve the breast cancer diagnosis pipeline.
Improved contrast and noise of megavoltage computed tomography (MVCT) through cycle‐consistent generative machine learning
Authors: Vinas Luciano , Scholey Jessica , Descovich Martina , Kearney Vasant , Sudhyadhom Atchar
Published: November 2020

Purpose

Megavoltage computed tomography (MVCT) has been implemented on many radiation therapy treatment machines as a tomographic imaging modality that allows for three‐dimensional visualization and localization of patient anatomy. Yet MVCT images exhibit lower contrast and greater noise than its kilovoltage CT (kVCT) counterpart. In this work, we sought to improve these disadvantages of MVCT images through an image‐to‐image‐based machine learning transformation of MVCT and kVCT images. We demonstrated that by learning the style of kVCT images, MVCT images can be converted into high‐quality synthetic kVCT (skVCT) images with higher contrast and lower noise, when compared to the original MVCT.

Methods

Kilovoltage CT and MVCT images of 120 head and neck (H&N) cancer patients treated on an Accuray TomoHD system were retrospectively analyzed in this study. A cycle‐consistent generative adversarial network (CycleGAN) machine learning, a variant of the generative adversarial network (GAN), was used to learn Hounsfield Unit (HU) transformations from MVCT to kVCT images, creating skVCT images. A formal mathematical proof is given describing the interplay between function sensitivity and input noise and how it applies to the error variance of a high‐capacity function trained with noisy input data. Finally, we show how skVCT shares distributional similarity to kVCT for various macro‐structures found in the body.

Results

Signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) were improved in skVCT images relative to the original MVCT images and were consistent with kVCT images. Specifically, skVCT CNR for muscle‐fat, bone‐fat, and bone‐muscle improved to 14.8 ± 0.4, 122.7 ± 22.6, and 107.9 ± 22.4 compared with 1.6 ± 0.3, 7.6 ± 1.9, and 6.0 ± 1.7, respectively, in the original MVCT images and was more consistent with kVCT CNR values of 15.2 ± 0.8, 124.9 ± 27.0, and 109.7 ± 26.5, respectively. Noise was significantly reduced in skVCT images with SNR values improving by roughly an order of magnitude and consistent with kVCT SNR values. Axial slice mean (S‐ME) and mean absolute error (S‐MAE) agreement between kVCT and MVCT/skVCT improved, on average, from −16.0 and 109.1 HU to 8.4 and 76.9 HU, respectively.

Conclusions

A kVCT‐like qualitative aid was generated from input MVCT data through a CycleGAN instance. This qualitative aid, skVCT, was robust toward embedded metallic material, dramatically improves HU alignment from MVCT, and appears perceptually similar to kVCT with SNR and CNR values equivalent to that of kVCT images.
Contribution of macromolecules to brain 1H MR spectra: Experts' consensus recommendations
Authors: Cudalbu Cristina , Behar Kevin L. , Bhattacharyya Pallab K. , Bogner Wolfgang , Borbath Tamas , de Graaf Robin A. , Gruetter Rolf , Henning Anke , Juchem Christoph , Kreis Roland , Lee Phil , Lei Hongxia , Marjańska Małgorzata , Mekle Ralf , Murali‐Manohar Saipavitra , Považan Michal , Rackayová Veronika , Simicic Dunja , Slotboom Johannes , Soher Brian J. , Starčuk Zenon , Starčuková Jana , Tkáč Ivan , Williams Stephen , Wilson Martin , Wright Andrew Martin , Xin Lijing , Mlynárik Vladimír
Published: November 2020

Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low molecular weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice. The aim of this consensus paper is to provide an overview and some recommendations on how to handle the MM signals in different types of studies together with a list of open issues in the field, which are all summarized at the end of the paper.
Facilitators and barriers to the provision of type 1 diabetes inpatient care: An interpretive phenomenological analysis
Authors: Nikitara Monica , Constantinou Costas S , Andreou Eleni , Latzourakis Evangelos , Diomidous Marianna
Published: November 2020

Aim

The aim and objective of this study was to understand how non‐specialized nurses understand the possible barriers and facilitators of inpatient care for type 1 diabetes.

Design

An interpretative phenomenology approach was conducted.

Methods

The sample consisted of non‐specialized nurses (N = 24) working in medical, surgical and nephrology wards in the state hospitals in Cyprus. The data were collected during 2016‐2018 from one focus group with nurses (N = 6) and individual semi‐structured interviews with nurses (N = 18) conducted. The Standards for Reporting Qualitative Research checklist used to ensure the quality of the study.

Results

It is evident from the study findings that nurses experience several barriers in diabetes inpatient care reported which are of great concern since this could have adverse effects on patients' outcomes. Only one facilitator has been reported by few nurses.
Trade, structural transformation and income convergence: The case ofEU
Authors: Jena Devasmita , Barua Alokesh
Published: November 2020

The creation of European Union (EU) was driven by the motivation to create a European Common Market that encourages free trade. As a result of Maastricht treaty of 1993, EU saw the biggest enlargement to date, from initial six founding members to now 28‐member countries comprising the union. The lower income countries have joined the EU with the hope to bridge the income gap between them and the higher income countries of the union. It has been observed in many studies that intra‐EU income convergence has happened. This article further confirms this finding. For income convergence to be sustainable, the lower income countries must also experience convergence in economic structures. Therefore, in this paper we try to assess how intra‐EU convergence in incomes is linked to intra‐EU convergence in economic structures. We observed income convergence in the EU has been mainly due to convergence in income shares of the industrial and services sector. The main contribution of this article is to examine the role of trade in income convergence via its impact on structural transformation of the EU. Using the augmented Chenery‐Syrquin model in a panel data framework, we have found that trade openness determines the sectoral shares of industry and services in income across the countries. We have also demonstrated that both the higher and lower income countries within the EU have gained in the share of industrial sector due to trade, although the gain is lesser for the lower income countries as compared to the gain in share of industries of the high‐income countries in the EU. However, structural convergence has not been fully achieved because the lower income countries of the EU are yet to gain from trade in terms of enhancing their income shares of services.
Interface engineering of ultrathin Cu(In,Ga)Se2 solar cells on reflective back contacts
Authors: Gouillart Louis , Cattoni Andrea , Chen Wei‐Chao , Goffard Julie , Riekehr Lars , Keller Jan , Jubault Marie , Naghavi Negar , Edoff Marika , Collin Stéphane
Published: November 2020

Cu(In,Ga)Se2‐based (CIGS) solar cells with ultrathin (≤500 nm) absorber layers suffer from the low reflectivity of conventional Mo back contacts. Here, we design and investigate ohmic and reflective back contacts (RBC) made of multilayer stacks that are compatible with the direct deposition of CIGS at 500°C and above. Diffusion mechanisms and reactions at each interface and in the CIGS layer are carefully analyzed by energy dispersive X‐ray (EDX)/scanning transmission electron microscopy (STEM). It shows that the highly reflective silver mirror is efficiently encapsulated in ZnO:Al layers. The detrimental reaction between CIGS and the top In2O3:Sn (ITO) layer used for ohmic contact can be mitigated by adding a 3 nm thick Al2O3 layer and by decreasing the CIGS coevaporation temperature from 550°C to 500°C. It also improves the compositional grading of Ga toward the CIGS back interface, leading to increased open‐ circuit voltage and fill factor. The best ultrathin CIGS solar cell on RBC exhibits an efficiency of 13.5% (+1.0% as compared to our Mo reference) with a short‐circuit current density of 28.9 mA/cm2 (+2.6 mA/cm2) enabled by double‐pass absorption in the 510 nm thick CIGS absorber. RBC are easy to fabricate and could benefit other photovoltaic devices that require highly reflective and conductive contacts subject to high temperature processes.
Trends in the Physical Medicine and Rehabilitation Match: Analysis of NRMP Data from 2007 to 2018
Authors: Claus Deanna , Anderson Dustin , Staley Vera , Forster Jeri , Meron Adele
Published: November 2020

Introduction

We provide an updated analysis of data about U.S. Physical Medicine and Rehabilitation (PM&R) residency program applicants collected by the National Resident Matching Program (NRMP).

Objective

Analyze trends within NRMP data for PM&R residency match rates, compare matched to unmatched applicants, and compare PM&R applicants to other medical specialties.

Design

Secondary analysis of NRMP data.

Setting

NRMP data set.

Participants

Residency program applicants who participated in the NRMP Match, 2007 to 2018.

Interventions

Not applicable.

Main Outcome Measures

Number of applicants, match rates, difference in characteristics including rank order list (ROL), U.S. Medical Licensing Examination (USMLE) Step 1 and Step 2 Clinical Knowledge (CK) scores, publications, Alpha Omega Alpha (AOA) status, PhD degree, and experiences in research, volunteer, and work.

Results

Number of applicants and residency positions increased from 2007 to 2018. Length of ROL increased and was longer for matched compared to unmatched applicants, with maximum mean difference of 7.4 in 2016 (95% confidence interval [CI] 5.6‐9.2). Matched U.S. Allopathic Seniors had higher USMLE scores compared to unmatched, with a mean difference of 12.7 for Step 1 (95% CI 8.3‐17.0) and 12.6 (95% CI 8.6‐16.6) for Step 2 CK (P < .001). Number of publications and volunteer experiences were higher for matched U.S. Allopathic Seniors (0.64, 95% CI 0.09‐1.2 and 1.5, 95% CI 0.65‐2.3, respectively). PM&R USMLE Step 1 and 2 CK scores increased at a significantly faster rate than for all other specialties, with estimated rate differences of 0.46 (95% CI 0.21‐0.71) and 0.69 (95% CI 0.45‐0.93) points per year, respectively.

Conclusions

PM&R residency has become more competitive. USMLE Step 1 and 2 CK scores have outpaced the inflation of scores in other specialties. ROL length has increased, suggesting more ranked programs to successfully match. These analyses update our knowledge about PM&R residency applicants and suggest surrogate markers for a successful match.
Solution structures of the Shewanella woodyiH‐NOX protein in the presence and absence of soluble guanylyl cyclase stimulator IWP‐051
Authors: Chen Cheng‐Yu , Lee Woonghee , Renhowe Paul A. , Jung Joon , Montfort William R.
Published: November 2020

Heme‐nitric oxide/oxygen binding (H‐NOX) domains bind gaseous ligands for signal transduction in organisms spanning prokaryotic and eukaryotic kingdoms. In the bioluminescent marine bacterium Shewanella woodyi (Sw), H‐NOX proteins regulate quorum sensing and biofilm formation. In higher animals, soluble guanylyl cyclase (sGC) binds nitric oxide with an H‐NOX domain to induce cyclase activity and regulate vascular tone, wound healing and memory formation. sGC also binds stimulator compounds targeting cardiovascular disease. The molecular details of stimulator binding to sGC remain obscure but involve a binding pocket near an interface between H‐NOX and coiled‐coil domains. Here, we report the full NMR structure for CO‐ligated Sw H‐NOX in the presence and absence of stimulator compound IWP‐051, and its backbone dynamics. Nonplanar heme geometry was retained using a semi‐empirical quantum potential energy approach. Although IWP‐051 binding is weak, a single binding conformation was found at the interface of the two H‐NOX subdomains, near but not overlapping with sites identified in sGC. Binding leads to rotation of the subdomains and closure of the binding pocket. Backbone dynamics are similar across both domains except for two helix‐connecting loops, which display increased dynamics that are further enhanced by compound binding. Structure‐based sequence analyses indicate high sequence diversity in the binding pocket, but the pocket itself appears conserved among H‐NOX proteins. The largest dynamical loop lies at the interface between Sw H‐NOX and its binding partner as well as in the interface with the coiled coil in sGC, suggesting a critical role for the loop in signal transduction.