bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatocyte Notch Signaling Deregulation Related to Lipid Metabolism in Women with Obesity and Nonalcoholic Fatty Liver
Authors: Auguet Teresa , Bertran Laia , Binetti Jessica , Aguilar Carmen , Martínez Salomé , Guiu‐Jurado Esther , Sabench Fàtima , Adalid Laia , Porras José Antonio , Riesco David , Del Castillo Daniel , Richart Cristóbal
Published: July 2020

Objective

This cohort study aimed to explore the relationship between the Notch signaling pathway and the degree of nonalcoholic fatty liver disease (NAFLD). Moreover, this study intended to investigate whether this pathway is related to hepatic lipid metabolism and Toll‐like receptors (TLRs).

Methods

This study used real‐time polymerase chain reaction analysis to evaluate the hepatic expression level of all genes studied (Notch receptors NOTCH1, NOTCH2, NOTCH3, and NOTCH4, transcription factors HES1 and HES5, and Hes‐related repressor proteins HEY1 and HEY2) in hepatic tissue from two cohorts: women with severe obesity (n = 57) and normal liver structure (n = 20) or NAFLD (n = 37).

Results

In women with severe obesity and NAFLD, this study found downregulation of hepatic HES5 expression. This expression correlated positively with the hepatic expression of HES1, HEY1, and NOTCH3. This study also found a positive correlation between HES5 expression and sterol regulatory element–binding protein 1c (SREBP1c) and between NOTCH3 and several genes related to hepatic lipid metabolism (encoding liver X nuclear receptor α variant 1, farnesoid X nuclear receptor, SREBP1c, acetyl–CoA carboxylase 1, fatty acid synthase, peroxisome proliferator–activated receptor α, carnitine palmitoyltransferase 1, carnitine O‐octanoyltransferase, ATP‐binding cassette subfamily A member 1, and ATP‐binding cassette subfamily G member 1). Finally, this study found a positive correlation between NOTCH2 and TLR2, TLR4, and TLR9 and a positive relationship between NOTCH1 and TLR9.

Conclusions

Taken together, these findings suggest that hepatic expression of Notch proteins and ligands in relation to lipid metabolism pathways in the liver could have a role in NAFLD pathogenesis.
Highly flame retardant photocured paper coatings and printability behavior
Authors: Ozcan Arif , Kasikovic Nemanja , Arman Kandirmaz Emine , Durdevic Stefan , Petrovic Sasa
Published: July 2020

Due to the high flammability of the paper, its use is restricted in advanced applications. In this study, UV‐cured paper coating formulations containing silica nanoparticles and phosphinoxide were prepared and coated on paper surface. Flammability, wettability, and printability properties were investigated. For this purpose, the surface of the silica nanoparticles was first functionalized with hydroxyethyl methacrylate (HEMA) ─OH. The hydroxylated silica nanoparticles were then modified with isocyanatoethyl methacrylate. Bis fluoro phenylphosphine oxide was synthesized by Grignard reaction elsewhere and OH modified in basic medium. Acrylate groups were added to BHPPO with isocyanatoethyl methacrylate to make it suitable for UV‐curing formulation. The chemical structures of the obtained substances were illuminated by ATR‐FTIR. UV‐cured paper coating formulations containing acrylated silica, acrylated phosphinoxide, and mixtures thereof were prepared and coated on the paper surface. Chemical structure, contact angle, surface energies, surface morphology, thermogravimetric analysis, and limited oxygen index of the coatings were determined. As a result, it has been concluded that coated papers have increased thermal stability in the nitrogen atmosphere. The highest thermal stability was observed in coatings containing nanosilica and it was determined that all of the coatings ignited later. Hybrid coatings made within the scope of this study have improved the printability properties as well as adding flame retardancy properties to the paper.
Rhabdomyosarcoma associated with germline TP53 alteration in children and adolescents: The French experience
Authors: Pondrom Morgane , Bougeard Gaelle , Karanian Marie , Bonneau‐Lagacherie Jacynthe , Boulanger Cécile , Boutroux Hélène , Briandet Claire , Chevreau Christine , Corradini Nadège , Coze Carole , Defachelles Anne Sophie , Galmiche‐Roland Louise , Orbach Daniel , Piguet Christophe , Scoazec Jean Yves , Vérité Cécile , Willems Marjolaine , Frebourg Thierry , Minard Véronique , Brugières Laurence
Published: July 2020

Objective

To describe the clinical characteristics and outcome of patients with Li‐Fraumeni–associated rhabdomyosarcoma (RMS).

Method

Retrospective analysis of data from 31 French patients with RMS diagnosed before the age of 20 years associated with a TP53 pathogenic germline variant. Cases were identified through the French Li‐Fraumeni database. Central histologic review was performed in 16 cases.

Results

The median age at diagnosis was 2.3 years, and the median follow‐up was 9.1 years (0.3‐34.8). The main tumor sites were head and neck (n = 13), extremities (n = 8), and trunk (n = 8). The local pathology report classified the 31 tumors in embryonal (n = 26), alveolar (n = 1), pleomorphic (n = 1), and spindle‐cell (n = 1) RMS (missing = 2). After histological review, anaplasia (diffuse or focal) was reported in 12/16 patients. Twenty‐five patients had localized disease, three had lymph node involvement, and three distant metastases. First‐line therapy combined surgery (n = 27), chemotherapy (n = 30), and radiotherapy (n = 14) and led to RMS control in all, but one patient. Eleven patients relapsed, and 18 patients had second malignancies. The 10‐year event‐free, progression‐free, and overall survival rates were 36% (95% CI: 20‐56), 62% (95% CI: 43‐77) and 76% (95% CI: 56‐88), respectively. The 10‐year cumulative risk of second malignancies was 40% (95% CI: 22‐60).

Conclusion

The high incidence of multiple primary tumors strongly influences the long‐term prognosis of RMS associated with TP53 pathogenic germline variants. Anaplastic RMS in childhood, independently of the familial history, should lead to TP53 analysis at treatment initiation to reduce, whenever possible, the burden of genotoxic drugs and radiotherapy in carriers and to ensure the early detection of second malignancies.
Supplemental reading interventions implemented by paraprofessionals: A meta‐analysis
Authors: Jones Brian T. , Erchul William P. , Geraghty Cathleen A.
Published: July 2020

Preventative and intensive reading intervention can be administered to at‐risk students in a systematic way to help facilitate gains on literacy outcomes. Despite this fact, there are clear barriers to implementation. One solution may be to use paraprofessionals to provide supplemental reading instruction. This study employed meta‐analytic procedures to address two questions: (a) what is the overall effectiveness of paraprofessionals as implementers of reading interventions? and (b) in which areas are paraprofessionals most effective? A literature search of research from 2001 to 2017 yielded 76 studies. Nine studies meeting a priori inclusion criteria were coded for demographic information and six common reading outcomes. The mean ES across outcomes was 0.55, and spelling and decoding emerged as areas to inform future research. Although these meta‐analytic findings must be interpreted with caution due to issues of sample size and heterogeneity of variance, involving paraprofessionals as reading interventionists appears to be a highly promising strategy.
Effect of chitosan on adult longevity when fed, in no‐choice experiments, to Musca domestica L., Tabanus nigrovittatus Macquart, and Phormia regina (Meigen) adults and its consumption in adult Musca domestica L
Authors: Stoffolano John , Wong Raymond , Lo Tim , Ford Baylee , Geden Chris J
Published: July 2020

BACKGROUND

The literature reports that more research needs to be done on using chitosan as an environmentally friendly bioinsecticide, especially against dipterans. Thus, we examined the effect of chitosan when fed, in no‐choice experiments, to adult Musca domestica, Tabanus nigrovittatus, and Phormia regina.

RESULTS

A 2% chitosan solution was fed, in no‐choice experiments, to adults of Musca domestica, Tabanus nigrovittatus, and Phormia regina to study the effects on survivorship. In all species, the uptake of chitosan caused a significant decrease in survivorship. Examination of the digestive tract of house flies showed a thick material within the midgut, plus a shriveling of the midgut only in chitosan‐treated flies. A survivorship curve of adult house flies fed a 10% sucrose and 2% w/v ascorbic acid‐only solution showed that the effect of the chitosan solution was due to the chitosan and not the ascorbic acid. Intake experiments revealed that by day 2, chitosan treated house flies consumed significantly less of the diet compared to controls.

CONCLUSION

Chitosan, a biopesticide, when fed in no‐choice experiments to three species of adult flies produced severe mortality within 4–6 days of ingestion. A working hypothesis suggests that by day 2 of the chitosan diet there appears to be a malfunction of the digestive tract and possibly the midgut microbiome. © 2020 Society of Chemical Industry
Transferring biological sequence analysis tools to break‐point detection for on‐line monitoring: A control chart based on the local score
Authors: Mercier Sabine
Published: July 2020

The Lindley process defined for the queuing file domain is equivalent to the cumulative sum (CUSUM) process used for break‐point detection in process control. The maximum of the Lindley process, called local score, is used to highlight atypical regions in biological sequences, and its distribution has been established by different manners. I propose here to use the local score and also a partial maximum of the Lindley process over the immediate past to create control charts. Stopping time corresponds to the first time where the statistic achieves a statistical significance less than a given threshold α in ]0,1[, the instantaneous first error rate. The local score p value is computed using existing theoretical results. I establish here the exact distribution of the partial maximum of the Lindley process. Performance of the control charts is evaluated by Monte Carlo estimation of the average run lengths for an in‐control process (ARL0) and for an out‐of‐control process (ARL1). I also use the standard deviation of the run length (SdRL) and the extra quadratic loss (EQL). Comparison with the usual and recent control charts present in the literature shows that the local score control chart outperforms the others with a much larger ARL0 and ARL1 smaller or of the same order. Many interesting openings exist for the local score chart: not only Gaussian model but also any of them, Markovian dependance of the data, both location and dispersion monitoring at the same time can be considered.
Designing spirobifullerene core based three‐dimensional cross shape acceptor materials with promising photovoltaic properties for high‐efficiency organic solar cells
Authors: Khan Muhammad Usman , Mehboob Muhammad Yasir , Hussain Riaz , Afzal Zainab , Khalid Muhammad , Adnan Muhammad
Published: July 2020

The development of organic electron acceptor materials is one of the key factors for realizing high‐performance organic solar cells (OSCs). Nonfullerene electron acceptors, compared to traditional fullerene acceptor materials, have gained much impetus owing to their better optoelectronic tunabilities and lower cost, as well as higher stability. Therefore, 5 three‐dimensional (3D) cross‐shaped acceptor materials having a spirobifullerene core flanked with 2,1,3‐benzothiadiazole are designed from a recently synthesized highly efficient acceptor molecule SF(BR)4 and are investigated in detail with regard to their use as acceptor molecules in OSCs. The density functional theory (DFT) and time‐dependent DFT (TDDFT) calculations have been performed for the estimation of frontier molecular orbital (FMO) analysis, density of states analysis, reorganization energies of electron and hole, dipole moment, open‐circuit voltage, photo‐physical characteristics, and transition density matrix analysis. In addition, the structure‐property relationship is studied, and the influence of end‐capped acceptor modifications on photovoltaic, photo‐physical, and electronic properties of newly selected molecules (H1‐H5) is calculated and compared with reference (R) acceptor molecule SF(BR)4. The structural tailoring at terminals was found to effectively tune the FMO band gap, energy levels, absorption spectra, open‐circuit voltage, reorganization energy, and binding energy value in selected molecules H1 to H5. The 3D cross‐shaped molecules H1 to H5 suppress the intermolecular aggregation in PTB7‐Th blend, which leads to high efficiency of acceptor material H1 to H5 in OSCs. Consequently, better optoelectronic properties are achieved from designed molecules H1 to H5. It is proposed that the conceptualized molecules are superior than highly efficient spirobifullerene core‐based SF(BR)4 acceptor molecules and, thus, are recommended to experiments for future developments of highly efficient solar cells.
Fatty acid sentinels as covalently bound randomization standards for triacylglycerol (TAG) quantitative analysis
Authors: Wang Dong Hao , Wang Zhen , Martinez Secilia , Tobias Herbert J. , Brenna J. Thomas
Published: July 2020

Rationale

Quantitative analysis of triacylglycerols (TAG) is impeded by a lack of standards and the huge number of potential TAG molecular species that may be present due to the combinatorial nature of glycerolipids. Randomization of acyl groups yields TAG mixtures with profiles predictable from fatty acid profiles; however, their use as calibration mixtures has been limited.

Methods

We introduce here the principle of fatty acid isotopic sentinels that are quantitatively added prior to randomization to enable verification that randomization is complete, and that can be used as internal standards. A mixture of two isotopically labeled fatty acid methyl esters (FAME) is prepared at a ratio of 2:1 and the exact ratio is carefully measured by gas chromatography flame ionization detection (GC‐FID) and randomized covalently into the acyl groups of TAG mixtures.

Results

Reaction with catalytic amounts of NaOCH3 yields complete randomization, such that the product FAME and TAG have the same fatty acid profile. TAG mixture analysis reveals that the isotopic sentinels have been covalently incorporated into the TAG molecular species at <1% deviation from the expected proportions, thus verifying randomization within experimental error.

Conclusions

The sentinel principle demonstrated here as covalently incorporated internal standards verifies that randomization chemistry went to completion. It applies in general to use of combinatorial chemistry for quantitative standards.
Event‐triggered approach for finite‐time state estimation of delayed complex dynamical networks with random parameters
Authors: Liu Ling , Zhang Yihong , Zhou Wuneng , Ren Yuanhong , Li Xiaoli
Published: July 2020

This article emphasizes the finite‐time state estimation problem for delayed complex dynamical networks with random parameters. In order to reduce the amount of transmission process, an aperiodic sampled‐data event‐triggered mechanism is introduced to determine whether the measurement output should be released at certain time points which incorporate an appropriate triggering condition and sampling moments. Furthermore, a concept of finite‐time boundedness in the pth moment is proposed to access the performance of state estimator. The objective of this article is to design an event‐triggered state estimator to estimate the states of nodes such that, in the presence of time delays, uncertainties, and randomly changing coupling weights, the estimation error system is finite‐time bounded in the pth moment related to a given constant. Some sufficient conditions in form of linear matrix inequalities and algebraic inequalities are established to guarantee finite‐time boundedness. Finally, a numerical example is presented to show the effectiveness of the theoretical results.
Multiple gateway placement in large‐scale constellation networks with inter‐satellite links
Authors: Chen Quan , Yang Lei , Liu Xianfeng , Guo Jianming , Wu Shuai , Chen Xiaoqian
Published: July 2020

Multiple gateways are required in large satellite constellation networks (LSCNs) with inter‐satellite links (ISLs), and their placement may greatly affect the system performance. Gateway placement can be optimized to achieve better network performance under the non‐uniform ground demand distribution. This paper formulates a gateway placement optimization model for LSCN with ISLs, aiming at achieving an optimal overall performance including delay, traffic peak, and load balance. The constraints of potential gateway location, gateway‐satellite connectivity, and max hop‐count are considered. A genetic algorithm (GA)‐based method is proposed to solve the integer optimization problem with the help of quasi‐evenly distributed reference layout. A Starlink‐like constellation with ISLs is adopted in the simulation. The simulation results show that the optimized layout has better performance than the reference layout. Additionally, the locations with high user demand or at the middle of ocean are preferred by gateways. The network performance is jointly influenced by gateway placement, demand distribution, constellation configuration, node, and link capacities. The abnormally high ISL hop‐count is found in the south Indian Ocean, which is caused by constellation and ISL configuration.
Single Ni Atoms and Clusters Embedded in N‐Doped Carbon “Tubes on Fibers” Matrix with Bifunctional Activity for Water Splitting at High Current Densities
Authors: Ahn Sung Hoon , Manthiram Arumugam
Published: July 2020

Among the bifunctional catalysts for water splitting, recently emerged transition‐metal single‐atom catalysts are theoretically considered to possess high potential, while the experimental activity is not satisfactory yet. Herein, an exceptionally efficient trifunctional metal–nitrogen–carbon (M–N–C) catalyst electrode, composed of a hierarchical carbon matrix embedding isolated nickel atoms with nickel–iron (NiFe) clusters, is presented. 1D microfibers and nanotubes grow sequentially from 2D nanosheets as sacrificial templates via two stages of solution‐ and solid‐phase reactions to form a 1D hierarchy. Exceptionally efficient bifunctional activity with an overpotential of only 13 mV at 10 mA cm−2toward hydrogen evolution reaction (HER) and an overpotential of 210 mV at 30 mA cm−2toward oxygen evolution reaction (OER) is obtained, surpassing each monofunctional activity ever reported. More importantly, an overpotential of only 126 and 326 mV is required to drive 500 mA cm−2toward the HER and OER, respectively. For the first time, industrial‐scale water splitting with two bifunctional catalyst electrodes with a current density of 500 mA cm−2at a potential of 1.71 V is demonstrated. Lastly, trifunctional catalytic activity including oxygen reduction reaction is also proven with a half‐wave potential at 0.848 V.
Detection of neurokinin‐1 receptor by immunohistochemistry in canine mammary gland tumours
Authors: Song Duri , Oh Ye‐In , Kim Jeong‐Mi , Cheon Doo‐Sung , Kim Dae‐Yong , Seo Kyoung‐Won
Published: July 2020

Canine mammary gland tumour (cMGT) is the most common tumour in intact female dogs. Surgery is the only effective treatment for cMGT, and dogs with metastasis at the time of diagnosis or those diagnosed at an advanced stage have poorer prognosis. Thus, novel diagnostic biomarkers and therapeutic targets are needed. Neurokinin‐1 receptor (NK‐1 receptor) is involved in cancer progression and has been detected in various malignant tumours including breast cancer in humans. Furthermore, NK‐1 receptor antagonists inhibit cancer progression. We evaluated NK‐1 receptor expression in malignant and benign cMGT compared with that in normal mammary gland tissues and analysed the relationship between the expression of NK‐1 receptor and histopathological type or malignancy grade. Specimens from 34 malignant MGT and 35 benign MGT cases were used for immunohistochemistry and scored according to intensity and percentage. Healthy margins from each tumour were used as internal controls. The scores for NK‐1 receptor intensity, percentage of positive cells and overall immunohistochemistry were higher in malignant MGT than in benign MGT and normal tissue (p < .000). NK‐1 receptor expression was not correlated with either malignancy grade or histopathological type. Expression of the NK‐1 receptor in malignant MGT was higher than that in benign MGT and normal tissues. Thus, NK‐1 receptor could be considered a novel therapeutic target for cMGT. Further studies using other quantitative tests such as western blotting or PCR and the evaluation of substance P in patient tumour tissue or serum are needed.
Analyzing the effect of organic carbon on partial nitrification‐anammox process based on metagenomics and quorum sensing
Authors: Xing Lizhen , Liu Minglei , Zhang Yanhao , Zhang Weikang , Wang Zifan
Published: July 2020

The effects of adding organic carbon on the performance of different partial nitrification‐anammox (PNA) process (the activated sludge process and biofilm process) were studied, especially nitrogen removal, functional microbial activity, and microbial community structure. The potential influences of quorum sensing (QS) on the nitrogen metabolism were also analyzed. The results showed that the addition of organic carbon in biofilm systems could reduce total nitrogen (TN) removal percentages, while in activated systems it could increase TN removal percentages. The TN removal percentages in SBBR‐CN (the biofilm system with addition of organic carbon) and SBR‐CN (the activated sludge system with addition of organic carbon) were 15% and 45%, respectively, and those in SBBR‐N (the biofilm system without addition of organic carbon) and SBR‐N (the activated sludge system without addition of organic carbon) were 75% and 21%, respectively. Batch experiments have proved that organic carbon inhibited the activities of nitrite‐oxidizing bacteria (NOB) and anaerobic ammonia oxidation (anammox) bacteria, and organic carbon could promote the activity of denitrifying bacteria in activated sludge systems. Compared with activated sludge systems, biofilm systems could protect the activity of anammox bacteria. The relative abundances of ammonia oxidizing bacteria (AOB) and anammox bacteria were decreased, while the relative abundances of denitrifying bacteria (Thauera) were increased with the addition of organic carbon. The biofilm systems were more conducive to the growth of anammox bacteria. Metagenomics revealed that the same bacteria might be involved in different nitrogen metabolism, and nitrogen metabolism was achieved through the complex cooperation among functional bacteria. Besides, functional bacteria involving in the nitrogen metabolism had genes related to QS, indicating that QS might affect the nitrogen metabolism by regulating the functional bacteria activity.

Practitioner points

PNA was achieved through SBBR and complete nitrification was achieved through SBR under the low ammonia nitrogen concentration condition.

The effect of organic carbon on biofilm and activated sludge PNA process was different under the low ammonia nitrogen concentration condition.

QS and QQ may affect the nitrogen removal performance by regulating the expression of nitrogen metabolism‐related genes.
Generalized symmetries and holography in ABJM-type theories
Authors: Bergman Oren , Tachikawa Yuji , Zafrir Gabi
Published: July 2020

Abstract

We revisit the $$ \mathcal{N} $$
N
= 6 superconformal Chern-Simons-matter theories and their supergravity duals in the context of generalized symmetries. This allows us to finally clarify how the SU(N ) × SU(N ) and (SU(N ) × SU(N ))/ℤN theories, as well as other quotient theories that have recently been discussed, fit into the holographic framework. It also resolves a long standing puzzle regarding the di-baryon operator in the U(N ) × U(N ) theory.
The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens
Authors: Ulfig Agnes , Leichert Lars I.
Published: July 2020

Neutrophils are predominant immune cells that protect the human body against infections by deploying sophisticated antimicrobial strategies including phagocytosis of bacteria and neutrophil extracellular trap (NET) formation. Here, we provide an overview of the mechanisms by which neutrophils kill exogenous pathogens before we focus on one particular weapon in their arsenal: the generation of the oxidizing hypohalous acids HOCl, HOBr and HOSCN during the so-called oxidative burst by the enzyme myeloperoxidase. We look at the effects of these hypohalous acids on biological systems in general and proteins in particular and turn our attention to bacterial strategies to survive HOCl stress. HOCl is a strong inducer of protein aggregation, which bacteria can counteract by chaperone-like holdases that bind unfolding proteins without the need for energy in the form of ATP. These chaperones are activated by HOCl through thiol oxidation (Hsp33) or N-chlorination of basic amino acid side-chains (RidA and CnoX) and contribute to bacterial survival during HOCl stress. However, neutrophil-generated hypohalous acids also affect the host system. Recent studies have shown that plasma proteins act not only as sinks for HOCl, but get actively transformed into modulators of the cellular immune response through N-chlorination. N-chlorinated serum albumin can prevent aggregation of proteins, stimulate immune cells, and act as a pro-survival factor for immune cells in the presence of cytotoxic antigens. Finally, we take a look at the emerging role of HOCl as a potential signaling molecule, particularly its role in neutrophil extracellular trap formation.
Bone marrow concentrate injections for the treatment of osteoarthritis: evidence from preclinical findings to the clinical application
Authors: Cavallo Carola , Boffa Angelo , Andriolo Luca , Silva Simone , Grigolo Brunella , Zaffagnini Stefano , Filardo Giuseppe
Published: July 2020

Purpose

To investigate the available literature on the use of bone marrow aspirate concentrate (BMAC) and summarize the current evidence supporting its potential for the injective treatment of joints affected by osteoarthritis (OA).

Methods

A systematic literature search was conducted on three electronic databases (PubMed, Embase, and Cochrane Library) in April 2020, using the following string: “((bone marrow concentrate) OR (BMC) OR (bone marrow aspirate concentrate) OR (BMAC)) AND (osteoarthritis)”, and inclusion criteria: clinical and preclinical (animal) studies of any level of evidence, written in English language, and evaluating the intra-articular or subchondral use of BMAC for the injective treatment of OA joints.

Results

The publication trend remarkably increased over time. A total of 22 studies were included in the qualitative data synthesis: four preclinical studies and 18 clinical studies, for a total number of 4626 patients. Safety was documented by all studies, with a low number of adverse events. An overall improvement in pain and function was documented in most of the studies, but the clinical studies present significant heterogeneity, few patients, short-term follow-up, and overall poor methodology.

Conclusion

There is a growing interest in the field of BMAC injections for the treatment of OA, with promising results in preclinical and clinical studies in terms of safety and effectiveness. Nevertheless, the current knowledge is still preliminary. Preclinical research is still needed to optimize BMAC use, as well as high-level large controlled trials to better understand the real potential of BMAC injections for the treatment of patients affected by OA.
Laparoscopic Liver Resection for Hepatocellular Carcinoma in Child–Pugh A Patients With and Without Portal Hypertension: A Multicentre Study
Authors: Casellas‐Robert Margarida , Lim Chetana , Lopez‐Ben Santiago , Lladó Laura , Salloum Chady , Codina‐Font Jaume , Comas‐Cufí Marc , Ramos Emilio , Figueras Joan , Azoulay Daniel
Published: July 2020

Background

Laparoscopic liver resection (LLR) may improve outcomes for cirrhotic patients with hepatocellular carcinoma (HCC) and portal hypertension (PHT). The aim of this study was to compare the short‐term outcomes after LLR for HCC in cirrhotic patients with and without PHT.

Methods

This multicentric study included 96 HCC patients who underwent LLR. Clinically significant portal hypertension (CSPH) was defined by a hepatic venous pressure gradient ≥10 mmHg. Short‐term outcomes and liver‐specific complications including post‐hepatectomy liver failure (PHLF), ascites and encephalopathy were compared between patients with and without CSPH.

Results

Thirty‐one patients (32%) had CSPH. The CSPH group had higher post‐operative morbidity (52% vs. 15%; p < 0.001), PHLF (10% vs. 0%; p = 0.03) and encephalopathy (10% vs. 0%; p = 0.03). There was no difference in terms of post‐operative ascites between the two groups (CSPH: 16% vs. no CPSH: 8%, p = 0.28). The length of stay was longer in patients with CSPH than in those without CSPH (6 vs. 4 days; p < 0.001).

Conclusions

The laparoscopic approach is feasible in selected HCC patients with CSPH, at the price of significant increases in liver‐specific complications and length of stay.
Modified Frailty Index is Useful in Predicting Non‐home Discharge in Elderly Patients with Gastric Cancer Who Undergo Gastrectomy
Authors: Osaki Tomohiro , Saito Hiroaki , Shimizu Shota , Murakami Yuki , Miyatani Kozo , Matsunaga Tomoyuki , Tatebe Shigeru , Ikeguchi Masahide , Fujiwara Yoshiyuki
Published: July 2020

Background

Development of laparoscopic gastrectomy and the Enhanced Recovery After Surgery (ERAS) protocol enable early discharge to home of patients with gastric cancer (GC). However, a significant proportion of patients are still discharged to inpatient facilities after surgery. We aimed to identify predictive factors of non‐home discharge in patients with GC who undergo gastrectomy.

Methods

We enrolled 517 patients with histopathologically confirmed diagnosis of GC who underwent gastrectomy.

Results

The number of patients with non‐home discharge was 23 (4.4%), and non‐home discharge was only observed in patients with GC aged ≥65 years. Patients were divided into the mFIHigh (≥0.272) and mFILow (<0.272) groups according to the cut‐off value determined by ROC analysis. The mFIHigh classification was significantly more frequent in patients aged ≥75 years, who underwent either total or proximal partial gastrectomy, who underwent limited lymph node dissection, and with non‐home discharge than in patients aged <75 years (p = 0.0002), those who underwent distal partial gastrectomy (p = 0.032), those who underwent standard lymph node dissection (p = 0.036), and those without non‐home discharge (p = 0.0071). Multivariate analysis revealed mFI as an independent predictive indicator of non‐home discharge, along with postoperative complications and surgical approach, in patients with GC aged ≥65 years. The frequency of patients with non‐home discharge was significantly associated with the number of these three predictive factors in GC patients aged ≥65 years (p < 0.0001).

Conclusions

The combination of mFI, postoperative complications, and surgical approach is useful for predicting non‐home discharge in patients aged ≥65 years who underwent gastrectomy for GC.
A scan for genes associated with cancer mortality and longevity in pedigree dog breeds
Authors: Doherty Aoife , Lopes Inês , Ford Christopher T. , Monaco Gianni , Guest Patrick , de Magalhães João Pedro
Published: July 2020

Selective breeding of the domestic dog (Canis lupus familiaris) rigidly retains desirable features, and could inadvertently fix disease-causing variants within a breed. We combine phenotypic data from > 72,000 dogs with a large genotypic dataset to search for genes associated with cancer mortality and longevity in pedigree dog breeds. We validated previous findings that breeds with higher average body weight have higher cancer mortality rates and lower life expectancy. We identified a significant positive correlation between life span and cancer mortality residuals corrected for body weight, implying that long-lived breeds die more frequently from cancer compared to short-lived breeds. We replicated a number of known genetic associations with body weight (IGF1, GHR, CD36, SMAD2 and IGF2BP2). Subsequently, we identified five genetic variants in known cancer-related genes (located within SIPA1, ADCY7 and ARNT2) that could be associated with cancer mortality residuals corrected for confounding factors. One putative genetic variant was marginally significantly associated with longevity residuals that had been corrected for the effects of body weight; this genetic variant is located within PRDX1, a peroxiredoxin that belongs to an emerging class of pro-longevity associated genes. This research should be considered as an exploratory analysis to uncover associations between genes and longevity/cancer mortality.
Significant reduction of physical activity in patients with neuromuscular disease during COVID-19 pandemic: the long-term consequences of quarantine
Authors: Di Stefano Vincenzo , Battaglia Giuseppe , Giustino Valerio , Gagliardo Andrea , D’Aleo Michele , Giannini Ottavio , Palma Antonio , Brighina Filippo
Published: July 2020

Background

Quarantine was the measure taken by governments to control the rapid spread of COVID-19. This restriction resulted in a sudden change in people’s lifestyle, leading to an increase in sedentary behavior and a related decrease in the practice of physical activity (PA). However, in neuromuscular diseases patients need to perform regular PA to counteract the negative consequences of the disease. Hence, the aim of this study was to estimate the levels of PA, measured as energy expenditure (MET–minute/week), among patients with neuromuscular disease (NMD) before and during the last week of quarantine.

Methods

A total of 268 Italian subjects, living in Sicily, completed an adapted version of the IPAQ-SF. Participants comprised 149 NMD, enrolled at the Neuromuscular Clinic of Palermo and 119 healthy subjects (control group). The SF-12 questionnaire was also administered to NMD. The Mann–Whitney U and the Kruskal–Wallis rank-sum tests were used for statistical analyses.

Results

We observed a significant decrease of the total weekly PA level during COVID-19 quarantine in both patients and controls. Moreover, a significant difference in the total weekly PA level was found depending on the presence of neuromuscular disease, impaired walking, gender and BMI. Finally, we found a correlation between SF-12 scores and the entity of the reduction of PA level during quarantine, thus confirming a relevant association with the quality of life in NMD.

Conclusion

Our study confirmed that COVID-19 quarantine has affected the practice of PA among both NMD and healthy controls.
Deep learning for glioblastoma segmentation using preoperative magnetic resonance imaging identifies volumetric features associated with survival
Authors: Wan Yizhou , Rahmat Roushanak , Price Stephen J.
Published: July 2020

Background

Measurement of volumetric features is challenging in glioblastoma. We investigate whether volumetric features derived from preoperative MRI using a convolutional neural network–assisted segmentation is correlated with survival.

Methods

Preoperative MRI of 120 patients were scored using Visually Accessible Rembrandt Images (VASARI) features. We trained and tested a multilayer, multi-scale convolutional neural network on multimodal brain tumour segmentation challenge (BRATS) data, prior to testing on our dataset. The automated labels were manually edited to generate ground truth segmentations. Network performance for our data and BRATS data was compared. Multivariable Cox regression analysis corrected for multiple testing using the false discovery rate was performed to correlate clinical and imaging variables with overall survival.

Results

Median Dice coefficients in our sample were (1) whole tumour 0.94 (IQR, 0.82–0.98) compared to 0.91 (IQR, 0.83–0.94 p = 0.012), (2) FLAIR region 0.84 (IQR, 0.63–0.95) compared to 0.81 (IQR, 0.69–0.8 p = 0.170), (3) contrast-enhancing region 0.91 (IQR, 0.74–0.98) compared to 0.83 (IQR, 0.78–0.89 p = 0.003) and (4) necrosis region were 0.82 (IQR, 0.47–0.97) compared to 0.67 (IQR, 0.42–0.81 p = 0.005). Contrast-enhancing region/tumour core ratio (HR 4.73 [95% CI, 1.67–13.40], corrected p = 0.017) and necrotic core/tumour core ratio (HR 8.13 [95% CI, 2.06–32.12], corrected p = 0.011) were independently associated with overall survival.

Conclusion

Semi-automated segmentation of glioblastoma using a convolutional neural network trained on independent data is robust when applied to routine clinical data. The segmented volumes have prognostic significance.
Angular changes in implants placed in the anterior maxillae of adults: a cephalometric pilot study
Authors: Feher Balazs , Gruber Reinhard , Gahleitner Andre , Celar Ales , Necsea Philipp Luciano , Ulm Christian , Kuchler Ulrike
Published: July 2020

Objectives

Completion of adolescent growth represents the earliest time point for implant placement, yet craniofacial growth persists into adulthood and may affect implant position. We aimed to assess whether implants placed in the anterior maxillae of adults show angular changes over time.

Material and methods

We conducted a cephalometric pilot study in postpubertal patients with no growth disorders, skeletal malformations, or parafunctions. The patients received a single implant in the anterior maxilla and no orthodontic or orthognathic treatment afterwards. We measured angular changes of implants and central incisors on cephalograms taken immediately and after at least 5 years postoperatively with the Sella-Nasion line (SNL) and the nasal line (NL) as references. Changes in implant-SNL angles were the primary outcome.

Results

In 21 patients (30.2 ± 11.5 years at surgery) after a mean follow-up of 8.6 ± 1.3 years, implant-SNL angles and implant-NL angles changed in 81% and 57% of implants, respectively. Implant-SNL changes ranged from 3° counterclockwise to 4° clockwise and were more prevalent in males (100% vs. 58%) and patients under 30 at surgery (85% vs. 63%); mean absolute differences were larger in males (1.8 ± 1.0° vs. 1.3 ± 1.4°) and patients under 30 at surgery (1.5 ± 1.4° vs. 1.1 ± 1.4°). Incisor-SNL angles and incisor-NL angles changed in 89% and 32% of incisors, respectively.

Conclusions

Implants placed in the anterior maxillae of adults show modest angular changes over time.

Clinical relevance

Changes in implant angles have potential functional and esthetic consequences.
A Learning-Based Approach to Synthesizing Invariants for Incomplete Verification Engines
Authors: Neider Daniel , Madhusudan P. , Saha Shambwaditya , Garg Pranav , Park Daejun
Published: July 2020

We propose a framework for synthesizing inductive invariants for incomplete verification engines, which soundly reduce logical problems in undecidable theories to decidable theories. Our framework is based on the counterexample guided inductive synthesis principle and allows verification engines to communicate non-provability information to guide invariant synthesis. We show precisely how the verification engine can compute such non-provability information and how to build effective learning algorithms when invariants are expressed as Boolean combinations of a fixed set of predicates. Moreover, we evaluate our framework in two verification settings, one in which verification engines need to handle quantified formulas and one in which verification engines have to reason about heap properties expressed in an expressive but undecidable separation logic. Our experiments show that our invariant synthesis framework based on non-provability information can both effectively synthesize inductive invariants and adequately strengthen contracts across a large suite of programs. This work is an extended version of a conference paper titled “Invariant Synthesis for Incomplete Verification Engines”.
Violations of coalescing in parametric utility measurement
Authors: Glöckner Andreas , Renerte Baiba , Schmidt Ulrich
Published: July 2020

The majority consensus in the empirical literature is that probability weighting functions are typically inverse-S shaped, that is, people tend to overweight small and underweight large probabilities. A separate stream of literature has reported event-splitting effects (also called violations of coalescing) and shown that they can explain violations of expected utility. This leads to the questions whether (1) the observed shape of weighting functions is a mere consequence of the coalesced presentation and, more generally, whether (2) preference elicitation should rely on presenting lotteries in a canonical split form instead of the commonly used coalesced form. We analyze data from a binary choice experiment where all lottery pairs are presented in both split and coalesced forms. Our results show that the presentation in a split form leads to a better fit of expected utility theory and to probability weighting functions that are closer to linear. We thus provide some evidence that the extent of probability weighting is not an ingrained feature, but rather a result of processing difficulties.
Cerebellar Volumes Associate with Behavioral Phenotypes in Prader-Willi Syndrome
Authors: Yamada Kenichi , Watanabe Masaki , Suzuki Kiyotaka , Suzuki Yuji
Published: July 2020

The objective of this study was to investigate lobule-specific cerebellar structural alterations relevant to clinical behavioral characteristics of Prader-Willi syndrome (PWS). We performed a case-control study of 21 Japanese individuals with PWS (age; median 21.0, range 13–50 years, 14 males, 7 females) and 40 age- and sex-matched healthy controls with typical development. Participants underwent 3-Tesla magnetic resonance imaging. Three-dimensional T1-weighted images were assessed for cerebellar lobular volume and adjusted for total intracerebellar volume (TIV) using a spatially unbiased atlas template to give a relative volume ratio. A region of interest analysis included the deep cerebellar nuclei. A correlation analysis was performed between the volumetric data and the clinical behavioral scores derived from the standard questionnaires (hyperphagia, autism, obsession, and maladaptive index) for global intelligence assessment in paired subgroups. In individuals with PWS, TIV was significantly reduced compared with that of controls (p < 0.05, family-wise error corrected; mean [standard deviation], 1014.1 [93.0] mm3). Decreased relative lobular volume ratios were observed in posterior inferior lobules with age, sex, and TIV as covariates (Crus I, Crus II, lobules VIIb, VIIIa, VIIIb, and IX). However, increased ratios were found in the dentate nuclei bilaterally in individuals with PWS (p < 0.01); the mean (standard deviation) × 10−3was as follows: left, 1.58 (0.26); right, 1.67 (0.30). The altered lobular volume ratios showed negative correlations with hyperphagic and autistic characteristics and positive correlations with obsessive and intellectual characteristics. This study provides the first objective evidence of topographic patterns of volume differences in cerebellar structures consistent with clinical behavioral characteristics in individuals with PWS and strongly suggests a cerebellar contribution to altered functional brain connectivity in PWS.
Return to sports after COVID-19: a position paper from the Dutch Sports Cardiology Section of the Netherlands Society of Cardiology
Authors: Verwoert G. C. , de Vries S. T. , Bijsterveld N. , Willems A. R. , vd Borgh R. , Jongman J. K. , Kemps H. M. C. , Snoek J. A. , Rienks R. , Jorstad H. T.
Published: July 2020

The coronavirus disease 2019 (COVID-19) pandemic has led to preventive measures worldwide. With the decline of infection rates, less stringent restrictions for sports and exercise are being implemented. COVID-19 is associated with significant cardiovascular complications; however there are limited data on cardiovascular complications and long-term outcomes in both competitive (elite) athletes and highly active individuals. Based on different categories of disease severity (asymptomatic, regional/systemic symptoms, hospitalisation, myocardial damage, and/or myocarditis), in this point-of-view article we offer the (sports) cardiologist or sports physician in the Netherlands a practical guide to pre-participation screening, and diagnostic and management strategies in all athletes >16 years of age after COVID-19 infection.
Stochastic allelic expression as trigger for contractile imbalance in hypertrophic cardiomyopathy
Authors: Montag Judith , Kraft Theresia
Published: July 2020

Hypertrophic cardiomyopathy (HCM), the most common inherited cardiac disease, is caused by several mostly heterozygous mutations in sarcomeric genes. Hallmarks of HCM are cardiomyocyte and myofibrillar disarray and hypertrophy and fibrosis of the septum and the left ventricle. To date, a pathomechanism common to all mutations remains elusive. We have proposed that contractile imbalance, an unequal force generation of neighboring cardiomyocytes, may contribute to development of HCM hallmarks. At the same calcium concentration, we found substantial differences in force generation between individual cardiomyocytes from HCM patients with mutations in β-MyHC (β-myosin heavy chain). Variability among cardiomyocytes was significantly larger in HCM patients as compared with donor controls. We assume that this heterogeneity in force generation among cardiomyocytes may lead to myocardial disarray and trigger hypertrophy and fibrosis. We provided evidence that burst-like transcription of the MYH7-gene, encoding for β-MyHC, is associated with unequal fractions of mutant per wild-type mRNA from cell to cell (cell-to-cell allelic imbalance). This will presumably lead to unequal fractions of mutant per wild-type protein from cell to cell which may underlie contractile imbalance. In this review, we discuss molecular mechanisms of burst-like transcription with regard to contractile imbalance and disease development in HCM.
Experimental study and thermodynamic modelling of ethylene absorption in N-methyl-2-pyrrolidone (NMP)
Authors: Yousefi Mohammad , Azizi Shima , Peyghambarzadeh S. M. , Azizi Zoha
Published: July 2020

Determining the solubility of gases in solvents and considering non-idealities at different operating conditions are essential to design a cost-effective and energy-efficient absorption process. In this work, using a lab-made set-up, solubility of ethylene in N-methyl-2-pyrrolidone (NMP) was measured at different temperatures (278.15, 298.15, and 328.15 K) and pressures up to 14 bar, and the kinetic and equilibrium data were obtained. Accordingly, Henry’s law constants are calculated at various temperatures. Then, thermodynamic modeling was accomplished by applying Peng-Robinson equation of state (PR-EOS) and Wilson activity coefficient model, and the binary interaction parameters were estimated. By the thermodynamic modeling, positive deviation from ideal behavior was apparently observed. Due to low absolute average deviation of < 7.7%, the correlated model was able to predict the ethylene solubility in NMP with a reliable accuracy.
Measures of noncompactness and superposition operator in the space of regulated functions on an unbounded interval
Authors: Dudek Szymon , Olszowy Leszek
Published: July 2020

In this paper, we formulate necessary and sufficient conditions for relative compactness in the space $$BG({\mathbb {R}}_+,E)$$

B
G
(

R
+

,
E
)

of regulated and bounded functions defined on $${\mathbb R}_+$$

R
+

with values in the Banach space E. Moreover, we construct four new measures of noncompactness in the space $$BG({\mathbb {R}}_+,E)$$

B
G
(

R
+

,
E
)

. We investigate their properties and we describe relations between these measures. We provide necessary and sufficient conditions so that the superposition operator (Niemytskii) maps $$BG({\mathbb {R}}_+,E)$$

B
G
(

R
+

,
E
)

into $$BG({\mathbb {R}}_+,E)$$

B
G
(

R
+

,
E
)

and, additionally, be compact.