bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors and outcomes of chronic opioid use following trauma
Authors: von Oelreich E , Eriksson M , Brattström O , Sjölund K-F , Discacciati A , Larsson E , Oldner A
Published: February 2020

Background

The growing problem of opioid misuse has become a serious crisis in many countries. The role of trauma as a gateway to opioid use is currently not determined. The study was undertaken to assess whether traumatic injury might be associated with chronic opioid use and accompanying increased long-term mortality.

Methods

Injured patients and controls from Sweden were matched for age, sex and municipality. After linkage to Swedish health registers, opioid consumption was assessed before and after trauma. Among injured patients, logistic regression was used to investigate factors associated with chronic opioid use, assessed by at least one written and dispensed prescription in the second quarter after trauma. Cox regression was employed to study excess risk of mortality. In addition, causes of death for postinjury opioid users were explored.

Results

Some 13 309 injured patients and 70 621 controls were analysed. Exposure to trauma was independently associated with chronic opioid use (odds ratio 3·28, 95 per cent c.i. 3·02 to 3·55); this use was associated with age, low level of education, somatic co-morbidity, psychiatric co-morbidity, pretrauma opioid use and severe injury. The adjusted hazard ratio for death from any cause 6–18 months after trauma for chronic opioid users was 1·82 (95 per cent c.i. 1·34 to 2·48). Findings were similar in a subset of injured patients with no pretrauma opioid exposure.

Conclusion

Traumatic injury was associated with chronic opioid use. These patients have an excess risk of death in the 6–18 months after trauma.
Environmental management capabilities for a “circular eco‐innovation”
Authors: Scarpellini Sabina , Valero‐Gil Jesus , Moneva José M. , Andreaus Michele
Published: February 2020

At a micro level, eco‐innovation marks a transition towards a circular economy (CE), and standardised routines and controls are being implemented by businesses to introduce eco‐innovative processes and thus a circular business model. Eco‐innovation applied to a circular model implies changes to companies' environmental management and accounting practices used to manage natural resources. In this context, this study analyses and measures formal and informal environmental management systems, such as certification standards and other management and environmental accounting procedures used in eco‐innovation and the CE within the dynamic capabilities theoretical framework. The study also investigates the cause‐and‐effect relationship between firms' “circular eco‐innovation” and environmental capabilities using partial least squares structural equation modelling and tests it using a sample of Spanish companies. This study offers new knowledge about the interposition of business eco‐innovation and CE‐related activities introduced by firms from the dynamic capabilities perspective.
Topical application of curcumin regulates the angiogenesis in diabetic‐impaired cutaneous wound
Authors: Dehghani Sadegh , Dalirfardouei Razieh , Jafari Najaf Abadi Mohammad Hasan , Ebrahimi Nik Maryam , Jaafari Mahmoud Reza , Mahdipour Elahe
Published: February 2020

Diabetic wound characterizes with a delayed repair as a result of the lack of neoangiogenesis and the excess of inflammation. Natural products such as curcumin have shown great promises in their regulatory potentials on inflammation and angiogenesis. However, natural agents have several shortages in their bioavailability and stability when used in vivo. In this study, we have evaluated the efficacy of a topical formulation of curcumin in the enhancement of diabetic wound repair. Streptozocin‐induced diabetic mice were wounded, and cream of curcumin (1%) was applied topically to wounds twice daily for different treatment periods. Inflammation, neoangiogenesis, and re‐epithelialization were evaluated in each experimental group. Wounds of animals treated with curcumin showed an enhanced neoangiogenesis. Application of topical curcumin also increased the expression level of RelA as the main subunit of the nuclear factor‐κB (NF‐κB) signalling pathway. However, no significant effects on macrophage polarization and re‐epithelialization were observed in the curcumin‐treated animals. Our study using a higher concentration of curcumin in the form of a topical cream further confirmed the efficacy of curcumin as an angiogenesis‐promoting agent; however, it also conveyed uncertainty over the claimed regulatory effects of curcumin on inflammation.

Significance of the study

Diabetes results in several complications such as impaired cutaneous wound repair. Excess of inflammation and lack of angiogenesis are among the main causes of delayed healing in diabetes. Curcumin is famous for its anti‐inflammatory properties. However, when in the body curcumin has shown to have a limited benefit unless in high‐dosage consumes. This is because of its poor absorption from digestive system and its bioavailability. In this study, we have used a topical formulation of curcumin at a relatively high concentration to enhance the healing of a diabetic wound in an animal model of diabetes. We also have studied different cellular and molecular mechanisms by which curcumin may help the wound repair. Our results re‐emphasize the proangiogenic potential of curcumin in diabetic wound environment.
Highly Efficient Oxygen Reduction Reaction Electrocatalysts FeCo−N−C Derived from Two Metallomacrocycles and N‐doped Porous Carbon Materials
Authors: Jin Xinxin , Xie Yan , Wang Lili , Huang Jiahui
Published: February 2020

N‐doped porous carbon (NPC) materials are beneficial to anchor desirable active sites for the oxygen reduction reaction (ORR). Herein, FeCo−N−C electrocatalysts with large specific surface areas and 3D interconnected hierarchical porous structures were prepared by pyrolysis of NPC materials with two metallomacrocycles, including iron phthalocyanine (FePc) and vitamin B12 (VB12). The onset potential (Eonset) of FePc(3)VB12(1)/NPC (900) is 0.934 V (vs. RHE), which is larger than that of commercial Pt/C (0.923 V vs. RHE). The half‐wave potential (E1/2) of FePc(3)VB12(1)/NPC (900) is 0.838 V (vs. RHE), which is almost the same with that of Pt/C electrocatalyst (0.839 V vs. RHE). Furthermore, the FePc(3)VB12(1)/NPC (900) also exhibits better durability and methanol tolerance relative to Pt/C in 0.1 M KOH solution. Such outstanding ORR performance is mainly attributed to the high proportion of both pyridinic N and graphitic N in FePc(3)VB12(1)/NPC (900) electrocatalyst.
Effect of Crystal Structures on Electrochemical Performance of Hierarchically Porous CoSe2 Spheres as Anodes for Sodium‐Ion Batteries
Authors: Liu Xin , Xu Guo B. , Cheng Ting T. , Yang Li W. , Cao Jue X.
Published: February 2020

Metal selenides with controllable crystal structures and hierarchically porous architectures have recently attracted great attention as the advanced electrode materials for sodium‐ion batteries. In present study, hierarchically porous orthogonal CoSe2 (o‐CoSe2) and cubic CoSe2 (c‐CoSe2) spheres are prepared through a controllable selenization and subsequent annealing strategy. Both types of CoSe2 spheres exhibit superior electrochemical properties resulting from hierarchical architecture, which can alleviate of the structural strain, the accelerated electron transmission and shorten the diffusion pathway of Na+. As anode materials for SIBs, the o‐CoSe2 electrode delivers a higher rate capability of 244 mAh g−1 at 3000 mA g−1 and a better cyclability of 378 mAh g−1 after 100 cycles at 1000 mA g−1 compared to the c‐CoSe2. From detailed microstructure characterization and kinetics behavior analysis, it is revealed that the o‐CoSe2 spheres exhibits larger specific surface, optimized porous nature, higher pseudocapacitive contribution, and more powerful Na+‐ions mobility. Our studies can pave the way for rational design and development of selenides electrode materials in rechargeable batteries.
An Electrochemically Synthesized Nanoporous Copper Microsensor for Highly Sensitive and Selective Determination of Glyphosate
Authors: Regiart Matias , Kumar Abhishek , Gonçalves Josué M. , Silva Junior Gilberto J. , Masini Jorge César , Angnes Lúcio , Bertotti Mauro
Published: February 2020

A nanoporous copper (NPC) film was electrodeposited on a copper microelectrode, and the generated platform was investigated for electrochemical sensing of glyphosate (Glyp). The as‐deposited NPC film was highly pure and crystalline according to results of energy dispersive spectroscopy and X‐ray diffraction experiments, respectively. Scanning electron microscopy images confirm the NPC films possess a highly porous morphology containing dendrite fractals, and the electrodeposition parameters, particularly potential (Ed) and time (td), exert a remarkable influence on the structure of the films. Such changes in the NPC morphology with Ed and td were also correlated with the electrochemical behavior investigated by cyclic voltammetry. In the presence of Glyp, the anodic oxidation is facilitated because copper ions diffuse easily through the pores of the NPC film and form a complex with the analyte at the electrode interface. On the other hand, as the amount of copper oxides decreases due to the formation of soluble Cu(II) complex with Glyp, less current is obtained during the reverse scan, allowing a relationship between the decrease in the cathodic current and the Glyp concentration to be established. The optimized NPC‐modified Cu microelectrode showed very high sensitivity (14 nA nmol−1 L), low detection limit (4 nmol L−1), excellent reproducibility, and selective response for Glyp. The applicability of the sensor was demonstrated by detecting Glyp in river water samples.
Strategies for the Controlled Covalent Double Functionalization of Graphene Oxide
Authors: Vacchi Isabella A. , Guo Shi , Raya Jésus , Bianco Alberto , Ménard‐Moyon Cécilia
Published: February 2020

Graphene oxide (GO) is a versatile platform with unique properties that have found broad applications in the biomedical field. Double functionalization is a key aspect in the design of multifunctional GO with combined imaging, targeting, and therapeutic properties. Compared to noncovalent functionalization, covalent strategies lead to GO conjugates with a higher stability in biological fluids. However, only a few double covalent functionalization approaches have been developed so far. The complexity of GO makes the derivatization of the oxygenated groups difficult to control. The combination of a nucleophilic epoxide ring opening with the derivatization of the hydroxyl groups through esterification or Williamson reaction was investigated. The conditions were selective and mild, thus preserving the structure of GO. Our strategy of double functionalization holds great potential for different applications in which the derivatization of GO with different molecules is needed, especially in the biomedical field.
Phosphorene‐Based Electrocatalysts
Authors: Dinh Khang Ngoc , Zhang Yu , Zhu Jixin , Sun Wenping
Published: February 2020

Phosphorene, generally defined as two‐dimensional (2D) black phosphorus (BP) with monolayered or few‐layered structure, has emerged as a promising member of the family of 2D materials. Since its discovery in 2014, extensive research has been focused on broadening its applications, covering the biological, photoelectric, and electrochemical fields, owing to the unique physicochemical and structural properties. As a single‐elemental material, phosphorene has demonstrated its applicability for the preparation of efficient electrocatalysts for hydrogen evolution reaction (HER), oxygen evolution reaction (OER), nitrogen reduction reaction (NRR), and other electrocatalytic applications. In this Minireview, a summary of the very recent research progresses of phosphorene in electrocatalysis is offered, with a special focus on the effective synthetic strategies towards performance improvement. In the concluding section, challenges and perspectives are also discussed.
Organizational buying behaviour for perishable‐food packaging in grocery retail
Authors: Afif Karima , Rebolledo Claudia , Roy Jacques
Published: February 2020

This qualitative study investigates the structure of the buying centre, the buying process, and the factors that influence buying decisions for perishable‐products packaging. This empirical investigation is based on the case study of a major Quebec food retailer. We show that the purchase of packaging changes significantly depending on whether the product is considered more or less strategic for the organization, which determines the required level of packaging customization. Buying centre structure becomes more complex as packaging customization increases. Given the multi‐functionality and the interdisciplinarity of packaging, we propose a multi‐criteria analysis grid to improve buying decision efficiency and to streamline communication between the various levels of the buying centre.
Extracapsular extension of neck nodes and absence of human papillomavirus 16‐DNA are predictors of impaired survival in p16‐positive oropharyngeal squamous cell carcinoma
Authors: Freitag Josefine , Wald Theresa , Kuhnt Thomas , Gradistanac Tanja , Kolb Marlen , Dietz Andreas , Wiegand Susanne , Wichmann Gunnar
Published: February 2020

Background

Human papillomavirus (HPV)‐driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV‐negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV‐driven disease. In p16‐negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16‐positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16‐positive OPSCC.

Methods

In a cohort of 92 patients with p16‐positive, lymph node (N)‐positive (stage III‐IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16‐positive/HPV16 DNA‐positive, 62 of 92 (67%) were ECE‐positive, and 45 of 62 (72.6%) were ECE‐positive, p16‐positive, and HPV16 DNA‐positive. Differences in outcome were assessed using Kaplan‐Meier plots and Cox proportional hazard regression (CoxR) for tumor‐specific survival and overall survival (OS).

Results

The mean numbers of positive lymph nodes in ECE‐positive patients (5.0 positive lymph nodes; 95% CI, 3.8‐6.4 positive lymph nodes) and ECE‐negative patients (2.4 positive lymph nodes; 95% CI, 1.8‐2.9 positive lymph nodes) were different (P = .0007). ECE affected OS and tumor‐specific survival in p16‐positive patients (P = .007 and P = .047, respectively) and in p16‐positive/HPV16 DNA‐positive patients (P = .013 and P = .026, respectively). Related to the unequal distributions of ECE‐positive/HPV16 DNA‐negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16‐positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17‐9.89; P = .025) and even greater impaired OS in those with p16‐positive/HPV16 DNA‐positive OPSCC (HR, 8.64; 95% CI, 1.12‐66.40; P = .038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors.

Conclusions

ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16‐positive OPSCC because several lines of evidence demonstrate their impact on survival.
A Dual Plasmonic Photoelectrode System for Visible‐Light Photocatalysis
Authors: Nishi Hiroyasu , Miyake Koji , Kao Kun‐Che , Tatsuma Tetsu
Published: February 2020

Plasmonic photocathodes based on plasmon‐induced charge separation (PICS) were prepared by depositing an Au nanoparticle (AuNP) ensemble on a transparent electrode and coating it with compact TiO2. Its PICS efficiency was improved by coating it further with porous TiO2 or introducing a NiO blocking layer as an underlayer of the AuNP ensemble. The former photocathode was modified further with Pt co‐catalyst nanoparticles, and combined with a PICS photoanode fabricated by depositing a AuNP ensemble on compact TiO2 and coating it with a Ni(OH)2 charge accumulation layer. The dual plasmonic photoelectrode system thus obtained exhibited a higher efficiency than the sum of the efficiencies of the single photoanode and single photocathode.
Effectiveness of motor imagery and action observation training on musculoskeletal pain intensity: A systematic review and meta‐analysis
Authors: Suso‐Martí Luis , La Touche Roy , Angulo‐Díaz‐Parreño Santiago , Cuenca‐Martínez Ferran
Published: February 2020

Background and Objective

Movement representation techniques such as motor imagery (MI) and action observation (AO) could play an important role in the field of rehabilitation of patients with musculoskeletal pain; however, the effects of these tools on clinical pain remain unclear. Our objective is therefore to develop a systematic review and meta‐analysis of the effects of MI and AO regarding the pain intensity on patients with musculoskeletal pain.

Databases and Data Treatment

MEDLINE, EMBASE, CINAHL and Google Scholar were searched. Last search was run on July 2019. Meta‐analysis was conducted to determine the effectiveness on pain intensity in patients with post‐surgical pain or chronic pain, and GRADE was used to rate the quality, certainty and applicability of the evidence.

Results

A total of 10 studies were included. AO or MI were compared versus usual rehabilitation care. The meta‐analysis showed statistically significant differences in MI and AO interventions in patients with pain after surgery in six studies, with a large clinical effect (n = 124; SMD = −0.84; 95% CI: −1.47 to −0.21). In patients with chronic pain, results showed statistically significant differences in MI and AO interventions in three studies, with a large clinical effect (n = 83; SMD = −2.14; 95% CI: −3.81 to −0.47). Risk of bias, imprecision and inconsistency decreased the GRADE level of evidence.

Conclusions

There was very low‐quality evidence regarding the effects of movement representation techniques intervention (AO and MI) on pain intensity in patients with post‐surgical pain. In addition, there was very low‐quality evidence regarding the effects of MI and AO interventions on chronic pain.

Significance

Movement representation techniques in combination with usual care are capable of producing a decrease in pain intensity compared with conventional treatment, in both post‐surgical and chronic pain. However, the very low‐quality evidence found regarding these techniques showed that more research is needed for their application in a clinical context.
Photoelectrochemical Detection of L‐Cysteine with a Covalently Grafted ZnTAPc‐Gr‐based Probe
Authors: Peng Jinyun , Huang Qing , Liu Yuxia , Huang Yingying , Zhang Cuizhong , Xiang Gang
Published: February 2020

L‐cysteine plays a vital role in organisms, and is an important biomarker for many pathological diseases that seriously affect human health. In the study, a photoelectrochemical (PEC) probe with zinc‐tetramine phthalocyanine covalently grafted to graphene oxide (ZnTAPc‐Gr) was developed for L‐cysteine detection. Graphene oxide (GO) with carboxyl was used to immobilize zinc‐tetramine phthalocyanine (ZnTAPc) with amidogen (a graft structure formed by an amide covalent bond), which could firmly immobilize ZnTAPc, thereby improving the photoelectrochemical performance and stability. L‐cysteine molecule, an electron acceptor, was specifically recognized by the PEC probe, exhibiting a decrease in the photocurrent signal. Under the optimal experimental conditions, the fabricated PEC probe exhibited excellent performance in L‐cysteine analysis within a linear range of 0.25–113 μM and a detection limit of 11.4 nM. The PEC probe showed high sensitivity, selectivity, and stability. The method described herein provides an effective strategy for PEC probe construction for L‐cysteine detection, and can also serve as a promising PEC platform for the analyses of other small molecules.
Porous Graphitic Carbon Fibers for Fast‐Charging Supercapacitor Applications
Authors: Pang Xin , Zhou Tong , Jiang Qinting , Kumar Parveen , Geng Shitao , Jia Minyu , Zhou Jin , Liu Bo , Qin Hua
Published: February 2020

Large accessible surface area, facile pore engineering, and high electrical conductivity are highly desirable properties of efficient electrode materials. Herein, porous carbon fibers with a graphitic carbon skeleton and amorphous carbon body are successfully synthesized from directly carbonized polyacrylonitrile (PAN)/FeCl3 electrospun fibers via in situ catalytic graphitization and subsequent chemical activation. Due to the graphitic carbon skeleton, which facilitates fast electron transfer, and porous carbon body, which gives a large specific surface area for charge accumulation and fast ion diffusion, optimal porous graphitic carbon fibers are developed that exhibit a fast‐charging electrochemical performance with a capacitance of 165 F g−1 at high current densities of 300 A g−1 in an alkaline electrolyte. These findings can prove to be beneficial for realizing a supercapacitor with rapid charging and discharging ability at high current densities.
A free amino acid‐based diet partially prevents symptoms of cow's milk allergy in mice after oral sensitization with whey
Authors: van Sadelhoff Joris H. J. , Hogenkamp Astrid , Wiertsema Selma P. , Harthoorn Lucien F. , Loonstra Reinilde , Hartog Anita , Garssen Johan
Published: February 2020

Background

Amino acid‐based formulas (AAFs) are used for the dietary management of cow's milk allergy (CMA). Whether AAFs have the potential to prevent the development and/or symptoms of CMA is not known.

Objective

The present study evaluated the preventive effects of an amino acid (AA)‐based diet on allergic sensitization and symptoms of CMA in mice and aimed to provide insight into the underlying mechanism.

Methods

C3H/HeOuJ mice were sensitized with whey protein or with phosphate‐buffered saline as sham‐sensitized control. Starting 2 weeks before sensitization, mice were fed with either a protein‐based diet or an AA‐based diet with an AA composition based on that of the AAF Neocate, a commercially available AAF prescribed for the dietary management of CMA. Upon challenge, allergic symptoms, mast cell degranulation, whey‐specific immunoglobulin levels, and FoxP3+ cell counts in jejunum sections were assessed.

Results

Compared to mice fed with the protein‐based diet, AA‐fed mice had significantly lower acute allergic skin responses. Moreover, the AA‐based diet prevented the whey‐induced symptoms of anaphylaxis and drop in body temperature. Whereas the AA‐based diet had no effect on the levels of serum IgE and mucosal mast cell protease‐1 (mMCP‐1), AA‐fed mice had significantly lower serum IgG2a levels and tended to have lower IgG1 levels (P = .076). In addition, the AA‐based diet prevented the whey‐induced decrease in FoxP3+ cells. In sham‐sensitized mice, no differences between the two diets were observed in any of the tested parameters.

Conclusion

This study demonstrates that an AA‐based diet can at least partially prevent allergic symptoms of CMA in mice. Differences in FoxP3+ cell counts and serum levels of IgG2a and IgG1 may suggest enhanced anti‐inflammatory and tolerizing capacities in AA‐fed mice. This, combined with the absence of effects in sham‐sensitized mice indicates that AAFs for the prevention of food allergies may be an interesting concept that warrants further research.
Role of the interferons in CD64 and CD169 expressions in whole blood: Relevance in the balance between viral‐ or bacterial‐oriented immune responses
Authors: Bourgoin Pénélope , Biéchelé Géraldine , Ait Belkacem Inès , Morange Pierre‐Emmanuel , Malergue Fabrice
Published: February 2020

Introduction

CD64 expression increases on neutrophils during bacterial infections. Recently an increase in CD169 expression has been discovered on monocytes during viral infections. Generally, interferons α (IFNsα) and IFNsγ are key drivers of the infectious host immune response. The purpose of this study was to explore if a link exists between these IFNs and both biomarkers.

Methods

Whole blood samples from healthy volunteers were stimulated with either IFNs, interleukins, or infectious extracts, to mimic an infectious state. Expressions of CD64 and CD169 were assessed in these samples by multiple flow cytometry methods, over precise kinetics.

Results

The expression of CD64 was statistically higher in samples stimulated with IFNγ, and CD169 in those stimulated with IFNα (and all other type I IFNs). Surface expressions are directly induced by their respective IFNs via Janus kinase/signal transducer and activator of transduction pathways within 6 to 8 hours of incubation. Mixing both types of IFNs seemed to indicate that they partially inhibit each other.

Conclusions

The induction of CD169 on monocytes and CD164 on neutrophils by type I and type II IFNs confirms the relevance of these markers for assessing between a viral‐ vs bacterial‐oriented immune response.
Derivation of cancer no significant risk levels and screening safety assessment for 2‐nitropropane in spray products
Authors: Gadagbui Bernard , Moore Justin , Parker Ann , McCready David , Monnot Andrew D. , Garnick Lindsey , Vincent Melissa , Spencer Pamela , Maier Andrew
Published: February 2020

Two proposition 65 no‐significant‐risk level (NSRL)‐type values were derived for 2‐nitropropane (2‐NP), in the absence of a Californian published NSRL. In addition, a safety assessment was performed based on estimated typical consumer inhalation and dermal exposure to 2‐NP during indoor application of paint from a spray can containing the solvent 1‐nitropropane. For the NSRL derivation, benchmark dose (BMD) modeling was performed using hepatocellular carcinoma incidence data from 2‐NP single exposure inhalation studies in Sprague‐Dawley rats. Several BMD models provided an acceptable fit for the male rat hepatocellular carcinoma incidence data (gamma, log‐probit, log‐logistic and multistage); therefore, the mean of the BMD lower limits from each model were used as the point of departure to derive the inhalation cancer potency. The oral human cancer potency was derived from the inhalation human cancer potency based on the ratio of the uptake factors for inhalation vs. oral routes. The derived inhalation and oral NSRLs are 67 μg/day and 32 μg/day, respectively. For the inhalation and dermal exposure assessment, three key factors were analyzed: the 2‐NP residual concentration in the spray paint product, the mass of spray paint used and the frequency of use. Based on the screening exposure assessment, potential consumer inhalation and dermal exposure to 2‐NP from indoor application of paint from a spray can does not exceed our proposed NSRLs, and a warning label is therefore not required for spray can products containing the solvent 1‐nitropropane where 2‐NP is a minor contaminant.
MicroRNA‐1 facilitates hypoxia‐induced injury by targeting NOTCH3
Authors: Xu Jinjin , Cao Dandan , Zhang Daping , Zhang Yuan , Yue Yuxia
Published: February 2020

Cell proliferation, apoptosis, and autophagy have been reported to be related to myocardial ischemia injury. MicroRNAs have attracted wide attention on regulating cell proliferation, apoptosis, and autophagy. miR‐1 expression has been reported to be dysregulated in cardiac tissue or cells with hypoxia, while the exact roles as well as underlying mechanism remain poorly understood. In this study, we investigated the potential roles of miR‐1 in cell proliferation, apoptosis, and autophagy in hypoxia‐treated cardiac injury and explored the underlying mechanism using H9c2 cells. Results showed that hypoxic stimulation inhibited cell proliferation and the expression of miR‐1 but promoted cell apoptosis in H9c2 cells. Moreover, overexpression of miR‐1 promoted cell apoptosis and inhibited cell proliferation and autophagy in H9c2 cells treated with hypoxia, while its knockdown played an opposite effect. In addition, bioinformatics, luciferase reporter, and RNA immunoprecipitation analyses indicated that NOTCH3 was a direct target of miR‐1 and its upregulation reversed the effects of miR‐1 on cell proliferation, apoptosis, and autophagy in hypoxia‐treated H9c2 cells. Taken together, our data suggested that miR‐1 promoted hypoxia‐induced injury by targeting NOTCH3, indicating novel therapeutic targets for treatment of myocardial ischemia injury.
NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer
Authors: Dong Caihua , Yin Fuqiang , Zhu Dan , Cai Xiangxue , Chen Cuilan , Liu Xia
Published: February 2020

Drug resistance, an impenetrable barrier in the treatment of ovarian cancer (OC), is often associated with poor outcomes. Hence, it is urgent to discover new factors controlling drug resistance and survival. The association between neurocalcin delta (NCALD) and cancer drug resistance is poorly understood. Here, we reveal that NCALD messenger RNA expression, probably regulated by DNA methylation and microRNAs, was significantly downregulated in at least three independent microarrays covering 633 ovarian carcinomas and 16 normal controls, which includes the Cancer Genome Atlas (TCGA) ovarian cohort. In the sub‐groups of the TCGA cohort, NCALD was suppressed in 90 platinum‐resistant tissues vs in 197 sensitive tissues. It is consistent with the quantitative reverse transcription polymerase chain reaction results revealing gene downregulation in carboplatin‐resistant SKOV3 and HeyA8 OC cells as compared with that in controls. Low expression of NCALD predicted poor overall survival (OS) in sub‐groups of 1656 patients, progression‐free survival (PFS) in 1435 patients, and post‐progression survival (PPS) in 782 patients according to Kaplan‐Meier plotter covering 1815 OC patients. Comprehensive bioinformatic analyses strongly implicated NCALD in the regulation of drug resistance, probably via competing for endogenous RNA (ceRNA) interactions with CX3CL1 and tumor immune‐microenvironment. NCALD acted as a ceRNA for CX3CL1 in 21 different cancers includes OC according to Starbase. These two genes negatively correlated with tumor purity and positively correlated with infiltration levels of neutrophils and dendritic cells in OC. The combined low expression of NCALD and CX3CL1 showed better prognosis potential for OS, PFS, and PPS in the 1815 OC patients than any of the individually tested genes. In summary, NCALD acts as a ceRNA for CX3CL1, and its downregulation may affect drug resistance and prognosis in OC. Thus, NCALD could be a new therapeutic target for anticancer therapy and a new biomarker for survival prediction in OC.
Identification immunophenotyping of lung adenocarcinomas based on the tumor microenvironment
Authors: Tan Qilong , Huang Yue , Deng Kui , Lu Mingliang , Wang Liuying , Rong Zhiwei , Zhao Weiwei , Li Shuang , Xu Zhenyi , Fan Lijun , Li Kang , Li Zhenzi
Published: February 2020

The tumor immune microenvironment is heterogeneous, and its impact on treatment responses is not well understood. It is still a challenge to analyze the interaction between malignant cells and the tumor microenvironment to apply suitable immunotherapy in lung adenocarcinoma. We performed the nonnegative matrix factorization method to 513 messenger RNA expression profiles of lung adenocarcinomas (LUADs) from The Cancer Genome Atlas (TCGA) to obtain an immune‐related expression pattern. Subsequently, we characterized the immune‐related gene signatures and clinical and survival characteristics. We used 576 patients from Gene Expression Omnibus to confirm our findings. Of the patients in the training cohort, 51% had a high immune enrichment score, high expression of immune cell signaling, cytolytic activity, and interferon (IFN)‐related signatures (all P < .05). We denoted these as the Immune Class. We further subdivided the Immune Class into two subclasses based on the tumor microenvironment. These were denoted the Active Immune Class and Exhausted Immune Class. The former showed significant IFN, T‐cells, M1 macrophage signatures, and better prognosis (all P < .05), while the latter presented an exhausted immune response with activated stromal enrichment, M2 macrophage signatures, and immunosuppressive factors such as WNT/transforming growth factor‐β (all P < .05). Furthermore, we predicted the response of our immunophenotypes to immunological checkpoint inhibitors (P < .05). Our findings provide a novel insight into the immune‐related state of LUAD and can identify the patients who will be receptive to suitable immunotherapeutic treatments.
In situ antitumor vaccination: Targeting the tumor microenvironment
Authors: Li Hanwen , Yu Jiayun , Wu Yongyao , Shao Bin , Wei Xiawei
Published: February 2020

Tumor microenvironment is known to play important roles in tumor progression. Many therapies, targeting the tumor microenvironment, are designed and applied in the clinic. One of these approaches is in situ antitumor therapy. This way, bacteria, antibodies, plasmid DNA, viruses, and cells are intratumorally delivered into the tumor site as “in‐situ antitumor vaccine,” which seeks to enhance immunogenicity and generate systemic T cell responses. In addition, this intratumoral therapy can alter the tumor microenvironment from immunosuppressive to immunostimulatory while limiting the risk of systemic exposure and associated toxicity. Contemporarily, promising preclinical results and some initial success in clinical trials have been obtained after intratumoral therapy.
Parallel evolution of regressive and constructive craniofacial traits across distinct populations of Astyanax mexicanus cavefish
Authors: Powers Amanda K. , Berning Daniel J. , Gross Joshua B.
Published: February 2020

Life in complete darkness has driven the evolution of a suite of troglobitic features in the blind Mexican cavefish Astyanax mexicanus, such as eye and pigmentation loss. While regressive evolution is a hallmark of obligate cave‐dwelling organisms, constructive (or augmented) traits commonly arise as well. The cavefish cranium has undergone extensive changes compared with closely‐related surface fish. These alterations are rooted in both cranial bones and surrounding sensory tissues such as enhancements in the gustatory and lateral line systems. Cavefish also harbor numerous cranial bone asymmetries: fluctuating asymmetry of individual bones and directional asymmetry in a dorsal bend of the skull. This asymmetry is mirrored by the asymmetrical patterning of mechanosensory neuromasts. We explored the relationship between facial bones and neuromasts using in vivo fluorescent colabeling and microcomputed tomography. We found an increase in neuromast density within dermal bone boundaries across three distinct populations of cavefish compared to surface‐dwelling fish. We also show that eye loss disrupts early neuromast patterning, which in turn impacts the development of dermal bones. While cavefish exhibit alterations in cranial bone and neuromast patterning, each population varied in the severity. This variation may reflect observed differences in behavior across populations. For instance, a bend in the dorsal region of the skull may expose neuromasts to water flow on the opposite side of the face, enhancing sensory input and spatial mapping in the dark.
An efficient synthesis of spiroacridinone derivatives from the facile reaction of isatins, dimedone, and 5‐aminoindazole (6‐aminoindazole or 5‐aminoindole)
Authors: Zhang Wen‐Ting , Sun Jian , Zhu Hong , Yue Rui‐Xue , Zhang Yi , Niu Fu‐Xiang , Rong Liangce
Published: February 2020

We have developed a simple and facil protocol for the synthesis of tetrahydrospiro(indoline‐3,11′‐pyrazolo[4,3‐a]acridine)‐2,10′(7′H)‐dione, tetrahydrospiro(indoline‐3, 11′‐pyrazolo[3,4‐a]acridine)‐2,10′(7′H)‐dione, and tetrahydrospiro (indoline‐3,11′‐pyrrolo[3,2‐a]acridine)‐2,10′(7′H)‐dione via PTSA·H2O‐induced cyclization reaction from isatins, dimedone, and 5‐aminoindazole (6‐aminoindazole or 5‐aminoindole) in mixed solvent (EtOH and CH3CN). In this research, 5‐aminoindazole, 6‐aminoindazole, and 5‐aminoindole were effectively used to react with isatins and dimedone to give spiroacridinone derivatives. The advantages of this method are mild conditions, convenient manipulation, high yields, and a wide range of substrates.
The c.1A > C start codon mutation in CLN3 is associated with a protracted disease course
Authors: Kuper Willemijn F. E. , van Alfen Claudia , van Eck Linda , de Man Stella A. , Willemsen Marjolein H. , van Gassen Koen L. I. , Losekoot Monique , van Hasselt Peter M.
Published: February 2020

Background

CLN3 disease is a disorder of lysosomal homeostasis predominantly affecting the retina and the brain. The severity of the underlying mutations in CLN3 particularly determines onset and course of neurological deterioration. Given the highly conserved start codon code among eukaryotic species, we expected a variant in the start codon of CLN3 to give rise to the classical, that is, severe, phenotype.

Case series

We present three patients with an identical CLN3 genotype (compound heterozygosity for the common 1 kb deletion in combination with a c.1A > C start codon variant) who all displayed a more attenuated phenotype than expected. While their retinal phenotype was similar to as expected in classical CLN3 disease, their neurological phenotype was delayed. Two patients had an early onset of cognitive impairment, but a particularly slow deterioration afterwards without any obvious motor impairment. The third patient also had a late onset of cognitive impairment.

Conclusions

Contrasting our initial expectations, patients with a start codon variant in CLN3 may display a protracted phenotype. Future work will have to reveal the exact mechanism behind the assumed residual protein synthesis, and determine whether this may be eligible to start codon targeted therapy.
Measured Energy Expenditure Compared With Best‐Practice Recommendations for Obese, Critically Ill Patients—A Prospective Observational Study
Authors: Ridley Emma J. , Tierney Audrey , King Susannah , Ainslie Emily , Udy Andrew , Scheinkestel Carlos , Nyulasi Ibolya
Published: February 2020

Background

This study aimed to compare recommendations in the American Society for Parenteral and Enteral Nutrition (ASPEN) Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient with measured energy expenditure in obese, critically ill adults.

Methods

After enrollment, measured energy expenditure was attempted at baseline and twice weekly to extubation or day 14. Data are reported as median [interquartile range].

Results

Twenty patients were included. The median baseline and subsequent measured energy expenditures were 2438 [1807–2703] kcal and 2919 [2318–3362] kcal, respectively. Baseline measured energy expenditures were −491 [−788 to −323] kcal lower than subsequent measurements, and week 1 measurements were lower than those of week 2. The median bias between the guideline recommendation of 11–14 kcal/kg of actual body weight and measured expenditure at baseline was −950 [−1254 to −595] kcal/d and −1618 [−1820 to −866] kcal/d at subsequent measurements.

Conclusion

Clinically significant variation was observed between measured expenditure and guideline recommendations at all time points.
Critical review on conventional spectroscopic α‐amylase activity detection methods: merits, demerits, and future prospects
Authors: Visvanathan Rizliya , Qader Mallique , Jayathilake Chathuni , Jayawardana Barana Chaminda , Liyanage Ruvini , Sivakanesan Ramiah
Published: February 2020

α‐Amylase is an endoenzyme that catalyses the hydrolysis of internal α‐l,4 glycosidic linkages in polysaccharides to produce maltose, maltotriose, and α‐limit dextrins. It is widely used in the laboratorial and industrial workflow for several applications. There are several methods utilizing different techniques and substrates to assess α‐amylase activity, among which the spectroscopic methods have found widespread applicability due to their ease of use and cost‐effectiveness. Depending upon the reaction principle, these assays are classified into four groups: reducing sugar, enzymatic, chromogenic, and amyloclastic methods. Despite the presence of numerous methods, there is no general reliable method to assess α‐amylase activity. Each method is shown to have its own merits and demerits. Many improvements have been made to make the available methods more accurate, reliable, and easy. This communication briefly discusses the basic reaction mechanisms and critically reviews the advantages and shortcomings associated with each method. Further recommendations are made for future development. © 2020 Society of Chemical Industry
Habitat and Harvesting Practices Influence Horn Growth of Male Ibex
Authors: Carvalho João , Büntgen Ulf , Pettorelli Nathalie , Mentaberre Gregorio , Olivé‐boix Xavier , Eizaguirre Oihana , Pérez Jesús M. , Fandos Paulino , Torres Rita T. , Lavín Santiago , Fonseca Carlos , Serrano Emmanuel
Published: February 2020

Size‐selective harvesting of wild ungulates can trigger a range of ecological and evolutionary consequences. It remains unclear how environmental conditions, including changes in habitat, climate, and local weather conditions, dilute or strengthen the effects of trophy hunting. We analyzed horn length measurements of 2,815 male ibex (Capra pyrenaica) that were harvested from 1995 to 2017 in Els Ports de Tortosa i Beseit National Hunting Reserve in northeastern Spain. We used linear mixed models to determine the magnitude of inter‐individual horn growth variability and partial least square path models to evaluate long‐term effects of environmental change, population size, and hunting strategy on horn growth. Age‐specific horn length significantly decreased over the study period, and nearly a quarter (23%) of its annual variation was attributed to individual heterogeneity among males. The encroachment of pine (Pinus spp.) forests had a negative effect on annual horn growth, possibly through nutritional impoverishment. The harvesting of trophy and selective individuals (e.g., small‐horned males) from the entire population increased horn growth, probably because it reduced the competition for resources and prevented breeding of these smaller males. Local weather conditions and population size did not influence horn growth. Our study demonstrates how habitat changes are altering the horn growth of male ibex. We suggest that habitat interventions, such the thinning of pine forests, can contribute to securing the sustainability of trophy hunting. Even in situations where size‐selective harvesting is not causing a detectable phenotypic response, management actions leading to the expansion of preferred land cover types, such as grass‐rich open areas, can have a positive effect on ungulate fitness. Forest encroachment on open meadows and heterogeneous grasslands is pervasive throughout Mediterranean ecosystems. Therefore, our management recommendations can be extended to the landscape level, which will have the potential to mitigate the side effects of habitat deterioration on the phenotypic traits of wild ibex. © 2020 The Wildlife Society.
The Effect of Cochlear Implantation on Vestibular Evoked Myogenic Potential in Children
Authors: Li Xin , Gong Shusheng
Published: February 2020

Objectives/Hypothesis

We conducted this study to assess the effects of unilateral cochlear implantation (CI) on otolith function by observing the changes in ocular vestibular evoked myogenic potential (oVEMP) and cervical vestibular evoked myogenic potential (cVEMP) in children.

Study Design: Prospective case series.

Methods

The oVEMP and cVEMP elicited by air‐conducted sound in 35 children were analyzed preoperatively and at 5 days, 1 month, and 2 months after surgery.

Results

Before CI, the response rates of oVEMPs and cVEMPs were 81.4% and 91.4%, respectively. In the implanted side, oVEMPs and cVEMPs were reduced by 37.1% and 68.6%, respectively, 5 days after CI. One month after CI, oVEMPs and cVEMPs were 34.6% and 72%, respectively, with the device switched off, and 50% and 73.1%, respectively, with the device switched on. Two months after CI, the oVEMPs and cVEMPs were 36% and 80%, respectively, when the implant was turned off, and 70.8% and 75%, respectively, when the implant was turned on.

Conclusions

The study confirmed the value of VEMP testing in the clinical setting and that absent VEMPs could indicate impairment of otolith function after CI.

Level of Evidence

4 Laryngoscope, 2020
Global research on Fabry's disease: Demands for a rare disease
Authors: Klingelhöfer Doris , Braun Markus , Seeger‐Zybok Rebekka K. , Quarcoo David , Brüggmann Dörthe , Groneberg David A.
Published: February 2020

Background

Fabry disease (FD), the second most prevalent lysosomal storage disorder, is classified as a rare disease. It often leads to significant quality of life impairments and premature death. Many cases remain undiagnosed due to the rarity and heterogeneity. Further, costs related to treatment often constitute a substantial financial burden for patients and health systems. While its epidemiology is still unclear, newborn screenings suggest that its actual prevalence rate is significantly higher than previously suspected.

Methods

Based on well‐established methodologies, this study gives an overview about the background of the development of FD‐related research and provides a critical view of future needs.

Results

On the grounds of benchmarking findings, an increasing research activity on FD can be observed. Most publishing countries are the USA, some European countries, Japan, Taiwan, and South Korea. In general, high‐income countries publish comparably more on FD than low‐ or middle‐income economies. The countries' financial and infrastructural background are unveiled as crucial factors for the FD research activity.

Conclusions

Overall, there is a need to foster FD research infrastructure in developing and emerging countries with focus on cost‐intensive genetic research that is independent from economic interests of big pharmaceutical companies.
A tool for symmetry breaking and multiplicity in some nonlocal problems
Authors: Musina Roberta , Nazarov Alexander I.
Published: February 2020

We prove some basic inequalities relating the Gagliardo‐Nirenberg seminorms of a symmetric function
on
and of its perturbation
, where
is a suitably chosen eigenfunction of the Laplace‐Beltrami operator on the sphere
, thus providing a technical but rather powerful tool to detect symmetry breaking and multiplicity phenomena in variational equations driven by the fractional Laplace operator. A concrete application to a problem related to the fractional Caffarelli‐Kohn‐Nirenberg inequality is given.
Spatiotemporal patterns induced by delay and cross‐fractional diffusion in a predator‐prey model describing intraguild predation
Authors: Ma Zhan‐Ping , Huo Hai‐Feng , Xiang Hong
Published: February 2020

In this article, we study a reaction‐diffusion predator‐prey model that describes intraguild predation. We mainly consider the effects of time delay and cross‐fractional diffusion on dynamical behavior. By using delay as the bifurcation parameter, we perform a detailed Hopf bifurcation analysis and derive the algorithm for determining the direction and stability of the bifurcating periodic solutions. We also demonstrate that proper cross‐fractional diffusion can induce Turing pattern, and the smaller the order of fractional diffusion is, the more easily Turing pattern is able to occur.
Local well‐posedness of the isentropic Navier‐Stokes‐Maxwell system with vacuum
Authors: Fan Jishan , Jing Lulu , Nakamura Gen , Tang Tong
Published: February 2020

In this work, we prove the local well‐posedness of strong solutions to the isentropic compressible Navier‐Stokes‐Maxwell system with vacuum in a smooth, simply connected and bounded domain
.