bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex‐specific alterations in GABA receptor‐mediated responses in laterodorsal tegmentum are associated with prenatal exposure to nicotine
Authors: Eliasen Jannik Nicklas , Krall Jacob , Frølund Bente , Kohlmeier Kristi A.
Published: July 2020

Smoking during pregnancy is associated with deleterious physiological and cognitive effects on the offspring, which are likely due to nicotine‐induced alteration in the development of neurotransmitter systems. Prenatal nicotine exposure (PNE) in rodents is associated with changes in behaviors controlled in part by the pontine laterodorsal tegmentum (LDT), and LDT excitatory signaling is altered in a sex and age‐dependent manner by PNE. As effects on GABAergic LDT signaling are unknown, we used calcium imaging to evaluate GABAA receptor‐ (GABAAR as well as GABAA‐ρR) and GABAB receptor (GABABR)‐mediated calcium responses in LDT brain slices from female and male PNE mice in two different age groups. Overall, in older PNE females, changes in calcium induced by stimulation of GABAAR and GABABR, including GABAA‐ρR were shifted toward calcium rises. In both young and old males, PNE was associated with alterations in calcium mediated by all three receptors; however, the GABAAR was the most affected. These results show for the first time that PNE is associated with alterations in GABAergic transmission in the LDT in a sex‐ and age‐dependent manner, and these data are the first to show PNE‐associated alterations in functionality of GABA receptors in any nucleus. PNE‐associated alterations in LDT GABAergic transmission within the LDT would be expected to alter output to target regions and could play a role in LDT‐implicated, negative behavioral outcomes following gestational exposure to smoking. Accordingly, our data provide further supportive evidence of the importance of eliminating the consumption of nicotine during pregnancy.
Small Molecule Activation by Two‐Coordinate Acyclic Silylenes
Authors: Fujimori Shiori , Inoue Shigeyoshi
Published: July 2020

In recent decades, the chemistry of stable silylenes (R2Si:) has evolved significantly. The first major development in this chemistry was the isolation of a silicocene which is stabilized by the Cp* (Cp* = η5‐C5Me5) ligand in 1986 and subsequently the isolation of a firstN‐heterocyclic silylene (NHSi:) in 1994. Since the groundbreaking discoveries, a large number of isolable cyclic silylenes and higher coordinated silylenes, i.e. Si(II) compounds with coordination number greater than two, have been prepared and the properties investigated. However, the first isolable two‐coordinate acyclic silylene was finally reported in 2012. The achievements in the synthesis of acyclic silylenes have allowed for the utilization of silylenes in small molecule activation including inert H2activation, a process previously exclusive to transition metals. This minireview highlights the developments in silylene chemistry, specifically two‐coordinate acyclic silylenes, including experimental and computational studies which investigate the extremely high reactivity of the acyclic silylenes.
Deracemization and Stereoinversion of Alcohols Using Two Mutants of Secondary Alcohol Dehydrogenase from Thermoanaerobacter pseudoethanolicus
Authors: Nafiu Sodiq A. , Takahashi Masateru , Takahashi Etsuko , Hamdan Samir M. , Musa Musa M.
Published: July 2020

We developed a one‐pot sequential two‐step deracemization approach to chiral alcohols using two mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). This approach relies on consecutive non‐stereospecific oxidation of alcohols and stereoselective reduction of their prochiral ketones using two mutants of TeSADH with poor and good stereoselectivities, respectively. More specifically, W110G TeSADH enables a non‐stereospecific oxidation of alcohol racemates to their corresponding prochiral ketones, followed by W110V TeSADH‐catalyzed stereoselective reduction of the resultant ketone intermediates to enantiopure (S)‐configured alcohols in up to > 99 % enantiomeric excess. A heat treatment after the oxidation step was required to avoid the interference of the marginally stereoselective W110G TeSADH in the reduction step; this heat treatment was eliminated by using sol‐gel encapsulated W110G TeSADH in the oxidation step. Moreover, this bi‐enzymatic approach was implemented in the stereoinversion of (R)‐configured alcohols, and (S)‐configured alcohols with up to > 99 % enantiomeric excess were obtained by this Mitsunobu‐like stereoinversion reaction.
Stability study of α‐bromophenylacetic acid: Does it represent an appropriate model analyte for chiral separations?
Authors: Jáč Pavel , Bubáková Zuzana , Moreno‐González David , Kováčová Gabriela , Špulák Marcel , Polášek Miroslav
Published: July 2020

The stability of α‐bromophenylacetic acid (BPAA) in 50% aqueous methanol solution has been tested. CE in different running buffers was used to separate BPAA from the decomposition reaction products α‐hydroxyphenylacetic (mandelic) acid and α‐methoxyphenylacetic acid. Suitable CE separation of all three compounds and other product, bromide, was achieved in 60 mmol/L formate buffer (pH 3.0) at −30 kV in 50 μm (i.d.) poly(vinyl alcohol)‐coated fused silica capillary (30 cm/24.5 cm) with UV detection at 200 nm. The CE method was applied to determine the reaction order of the decomposition of BPAA (0.47 mmol/L) via nucleophilic substitution in 50% aqueous methanol. The first‐order reaction kinetics was confirmed by linear and non‐linear regression, giving the rate constants 1.52 × 10−4 ± 2.76 × 10−5 s−1 and 7.89 × 10−5 ± 5.02 × 10−6 s−1, respectively. Additionally, the degradation products were identified by CE coupled to mass spectrometric (MS) detection. The CE–MS experiments carried out in 60 mmol/L formate buffer (pH 3.0) and in 60 mmol/L acetate buffer (pH 5.0) confirmed the results obtained by CE–UV. Furthermore, the stability of BPAA in polar solvents was tested by 1H NMR experiments. Our results provide strong evidence of the instability and fast degradation of BPAA in 50% aqueous methanol indicating that BPAA is not suitable as the model analyte for chiral separations.
An efficient approach for whirling speeds and mode shapes of uniform and nonuniform Timoshenko shafts mounted by arbitrary rigid disks
Authors: Wu Jong‐Shyong , Hsu Tzu‐Fu
Published: July 2020

In theory, the whirling motion of a shaft‐disk system is three‐dimensional (3D), however, if the transverse displacement in the vertical principal xy‐plane and that in the horizontal principal xz‐plane for the cross‐section of the shaft located at the axial coordinate x are represented by a complex number, then the mass moment of inertia for unit shaft length (at x) and that for each rigid disk i can be combined with their associated gyroscopic moments (GMs) to form the frequency‐dependent equivalent mass moments of inertia, respectively, in the equations of motion for the rotating Timoshenko shaft carrying arbitrary rigid disks. It is found that the above‐mentioned equations for the rotating 3D shaft‐disk system take the same forms as the corresponding ones for the associated stationary two‐dimensional (2D) Timoshenko beam carrying the same number of disks, so that the approaches for the free vibration analyses of the stationary 2D beam‐disk system can be used to solve the title problem for obtaining the whirling speeds and mode shapes of a rotating 3D shaft‐disk system. Since the order of the eigenproblem equation derived from the presented approach is much smaller than that derived from the conventional finite element method (FEM), the computer time consumed by the former is much less than that by the latter. In addition, the solutions obtained from the presented approach are exact and may be the benchmark for evaluating the accuracy of solutions of the other approximate methods. Numerical examples reveal that the presented approach is available for the uniform or nonuniform shaft‐disk system, and the obtained results are very close to those obtained from existing literature or the FEM. The formulation of this article is available for a shaft‐disk system with various boundary conditions (BCs), to save space, only the cases with pinned‐pinned BCs are illustrated.
Global On Line Fellowship in head and neck surgery and oncology
Authors: Shah Jatin P. , O'Neil James P. , Brennan Murray F.
Published: July 2020

The International Federation of Head and Neck Oncologic Societies and Memorial Sloan Kettering Cancer Center in New York have partnered to create the Global On Line Fellowship program, a postgraduate fellowship training opportunity for candidates all around the world who are not able to get on‐site fellowship training at centers of excellence. This article delineates the successes, challenges, and future goals for the program.
Meso‐Substituted Tetrabenzotriazaporphyrins for Dye‐Sensitized Solar Cells
Authors: Tejerina Lara , Yamamoto Satoshi , López‐Duarte Ismael , Martínez‐Díaz M. Victoria , Kimura Mutsumi , Torres Tomás
Published: July 2020

A novel tetrabenzotriazaporphyrin (TBTAP) bearing an anchoring carboxy‐phenyl group at the meso‐carbon position (TT260) was synthesized by an efficient method, which involves the crossover condensation between phthalonitrile and aminoisoindoline precursors. Its optical and electrochemical properties were also investigated together with its use as sensitizer in dye‐sensitized solar cells (DSSCs). The performance of TT260 was compared with a benchmark molecule TT1, bearing similar bulky tert‐butyl groups at the periphery. The device, which is the first ever example of meso‐substituted TBTAP‐based DSSC, exhibits a modest maximum power conversion efficiency of 2.4±0.1 % under one‐sun conditions.
Deep transfer learning based hepatitis B virus diagnosis using spectroscopic images
Authors: Ali Safdar , Hassan Mehdi , Saleem Muhammad , Tahir Syed Fahad
Published: July 2020

Accurate identification of Hepatitis B virus (HBV) disease by analyzing the Raman spectroscopic images is a challenge for pathologists. To save precious human lives, an efficient technique is required with higher diagnostic accuracy at early‐stage of HBV. We proposed a novel method of HBV diagnosis using deep neural networks with the concept of transfer learning and Raman spectroscopic images. The proposed approach developed by utilizing pretrained convolutional neural networks ResNet101 by employing transfer learning on a real dataset of HBV‐infected blood plasma samples. Dataset consists of 1000 Raman images in which 600 are HBV‐infected blood plasma samples, and 400 are healthy ones. The developed model is capable to detect minute variation between infected and healthy samples and achieved enhanced performance. The proposed approach has been assessed and attained high classification accuracy, sensitivity, specificity, and AUC of 99.7%, 100%, 99.25%, and 98.7%, respectively. The proposed TL‐ResNet101 model outperformed the conventional approaches such as PCA‐SVM and PCA‐LDA and demonstrated improved accuracy more than 7%. High performance indicates that the developed TL‐ResNet101 model has potential to use for HBV diagnosis. Moreover, the developed automated approach can be extended for other disease.
Antimicrobial efficacy of platinum‐doped silver nanoparticles
Authors: Wongkamhaeng Kan , Wang Junnan , Banas Jeffrey A. , Dawson Deborah V. , Holloway Julie A. , Haes Amanda J. , Denry Isabelle
Published: July 2020

Silver nanoparticles (AgNPs) have been proposed to combat oral infection due to their efficient ionic silver (Ag+) release. However, concentrations required for antimicrobial efficacy may not be therapeutically viable. In this work, platinum‐doped silver nanoparticles (Pt‐AgNPs) were explored to evaluate their potential for enhanced Ag+ release, which could lead to enhanced antimicrobial efficacy against S. aureus, P. aeruginosa, and E. coli. AgNPs doped with 0.5, 1, and 2 mol% platinum (Pt0.5‐AgNPs, Pt1‐AgNPs, and Pt2‐AgNPs) were synthesized by a chemical reduction method. Transmission electron microscopy revealed mixed morphologies of spherical, oval, and ribbon‐like nanostructures. Surface‐enhanced Raman scattering revealed that the surface of Pt‐AgNPs was covered with up to 93% Pt. The amount of Ag+ released increased 16.3‐fold for Pt2‐AgNPs, compared to AgNPs. The initial lag phase in bacterial growth curve was prolonged for Pt‐AgNPs. This is consistent with a Ag+ release profile that exhibited an initial burst followed by sustained release. Doping AgNPs with platinum significantly increased the antimicrobial efficacy against all species. Pt2‐AgNPs exhibited the lowest minimum inhibitory concentrations, followed by Pt1‐AgNPs, Pt0.5‐AgNPs, and AgNPs, respectively. Doping AgNPs with a small amount of platinum promoted the release of Ag+, based on the sacrificial anodic effect, and subsequently enhanced their antimicrobial efficacy.
Red blood cell exchange to avoid intubating a COVID‐19 positive patient with sickle cell disease?
Authors: Allison David , Campbell‐Lee Sally , Crane Jason , Vidanovic Vladimir , Webb Shaun , Fraidenburg Dustin , Hussain Faiz
Published: July 2020

As the COVID‐19 pandemic continues to claim lives across the globe, insufficient data exists regarding the optimal treatment. It is well known that patients 55 years of age or older and patients with certain chronic diseases are at higher risk of severe illness, including acute respiratory distress syndrome and death. A potentially fatal pulmonary complication of sickle cell disease, acute chest syndrome, can be precipitated by acute infections, including respiratory viruses. We report the case of a patient with sickle cell disease (HbSC) who developed COVID‐19 pneumonia and acute chest syndrome who was treated with emergent red blood cell exchange in order to avoid endotracheal intubation.
Protective effect of microRNA‐134‐3p on multiple sclerosis through inhibiting PRSS57 and promotion of CD34+ cell proliferation in rats
Authors: Song Qihan , Zhao Fengli , Yao Jingfan , Dai Hailin , Hu Lei , Yu Shun
Published: July 2020

MicroRNAs (miRs) have been extensively studied for their involvement in multiple sclerosis (MS). We investigated the involvement of miR‐134‐3p on MS. The MS rat model was established, and positive expression of interleukin‐17 (IL‐17) was detected using the immunohistochemical method while the expression of miR‐134‐3p and serine protease 57 (PRSS57) was determined by means of reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and Western blot analysis. Second, the miR‐134‐3p overexpression or short hairpin RNA against PRSS57 was introduced into the CD34+ cells to investigate the levels of proliferation and apoptosis‐related genes by RT‐qPCR and Western blot analysis. In addition, analysis of the targeting relations of miR‐134‐3p and PRSS57 was conducted using online software and dual‐luciferase reporter gene assay. Furthermore, neuronal functions, inflammatory response, proliferation, and apoptosis of CD34+ cells were assayed by flow cytometry, enzyme‐linked immunosorbent assay, and methyl thiazolyl tetrazolium. IL‐17 and PRSS57 expression increased while miR‐134‐3p expression decreased in the spinal cord from MS rats. miR‐134‐3p could target PRSS57. miR‐134‐3p overexpression or PRSS57 silencing enhanced mitochondrial activity of neurons, mitochondrial membrane potential content, CD34+ cell proliferation, while decreasing Cyt C content, inflammatory response, and cell apoptosis. Collectively, overexpression of miR‐134‐3p promotes CD34+ cell proliferation via inhibition of PRSS57 in MS, which may serve as a promising target for MS intervention.
Hypermethylation of lncRNA MEG3 impairs chemosensitivity of breast cancer cells
Authors: Li Hongchang , Wang Puhua , Liu Jiazhe , Liu Weiyan , Wu Xubo , Ding Junbin , Kang Jie , Li Jindong , Lu Jingfeng , Pan Gaofeng
Published: July 2020

Background

Chemoresistance posed a barrier to successful treatment of breast cancer (BC), and lncRNA MEG3 has been documented to implicate in BC development. However, whether MEG3 methylation, which led to low MEG3 expression, was relevant to BC progression and chemoresistance remained uncertain.

Methods

In the aggregate, 374 pairs of tumor tissues and adjacent normal tissues were collected from pathologically confirmed BC patients, and four BC cell lines, including MDA‐MB‐231, Bcap‐37, MCF‐7, and SK‐BR‐3, were purchased. Moreover, methylation‐specific polymerase chain reaction (PCR) was adopted to evaluate the methylation status of BC tissues and cell lines, and chemo‐tolerance of BC cell lines was assessed by performing MTT assay. Concurrently, transwell assay and scratch assay were carried out to estimate the migratory and invasive capability of BC cell lines.

Results

Methylated MEG3, lowly expressed MEG3, large tumor size (≥2 cm), advanced TNM grade and lymphatic metastasis were potentially symbolic of poor prognosis among BC patients (P < .05). Besides, MDA‐MB‐231 cell line exhibited the strongest resistance against paclitaxel, adriamycin, and vinorelbine (P < .05), while MCF‐7 cell line seemed more sensitive against these drugs than any other BC cell line (P < .05). Furthermore, pcDNA3.1‐MEG3 and 5‐Aza‐dC markedly sensitized MDA‐MB‐231 and MCF‐7 cell lines against the drug treatments (P < .05). Simultaneously, proliferation and metastasis of the BC cell lines were slowed down under the force of pcDNA3.1‐MEG3 and 5‐Aza‐dC (P < .05).

Conclusion

Preventing methylation of MEG3 might matter in lessening BC chemoresistance, owing to its hindering proliferation and metastasis of BC cells.
Character strengths cinematherapy: Using movies to inspire change, meaning, and cinematic elevation
Authors: Niemiec Ryan M.
Published: July 2020

Good movies have the potential to capture a trifecta of meaning: they can be enjoyable, engaging, and empowering. In other words, we experience pleasure, focused attention and concentration, and are inspired toward the good or reach new insights into ourselves, others, or the human condition. Drawing on the rapidly emerging science in character strengths, areas of integration with cinematherapy are outlined and explored. A therapeutic change model for character strengths cinematherapy is discussed, with emphasis on the roles of cinematic elevation and cinematic admiration. Practical suggestions to help therapists match client goals, well‐being areas, signature strengths, lower strengths, and psychopathology or problem areas are framed. While integration into large scale projects to impact social change is possible with character strengths cinematherapy, the starting point is helping therapists to use this approach with the client in front of them to promote that change one person at a time.
Identification of novel genes in testicular cancer microenvironment based on ESTIMATE algorithm‐derived immune scores
Authors: Ke Zhi‐Bin , Wu Yu‐Peng , Huang Peng , Hou Jian , Chen Ye‐Hui , Dong Ru‐Nan , Lin Fei , Wei Yong , Xue Xue‐Yi , Ng Chi‐Fai , Xu Ning
Published: July 2020

Testicular cancer is the most common solid malignancy among young men. We downloaded data of testicular cancer patients from The Cancer Genome Atlas database to find novel genes in the testicular cancer microenviroment based on ESTIMATE algorithm‐derived immune scores. A total of 156 cases of testicular cancer were included in this study and 165 cases of normal testicular tissues were used. We divided the testicular cancer patients into high‐ and low‐score groups based on their immune scores. We identified 1,226 differentially expressed genes (fold change > 2, false discovery rate < 0.05), including 688 downregulated genes and 538 upregulated genes, between these two groups. The top Gene Ontology terms were involved in the immune response‐regulating cell surface receptor signaling pathway, immune response‐activating cell surface receptor signaling pathway, external side of the plasma membrane, and receptor ligand activity. By performing the Kyoto Encyclopedia of Genes and Genomes analysis, we demonstrated that cAMP signaling pathway was highly enriched among these differentially expressed genes. High expression of LINC01564, LINC02208, ODAM, RNA5SP111, and RNU6‐196P were found to be associated with poor overall survival. The expression of genes was further validated by the Human Protein Atlas and only ALB and IFNG were demonstrated to be differentially expressed between testis tissue and testicular cancer tissue.
Enalapril and treadmill running reduce adiposity, but only the latter causes adipose tissue browning in mice
Authors: Giori Isabele G. , Magliano D'Angelo C. , Alexandre‐Santos Beatriz , Fernandes Tiago , Oliveira Edilamar M. , Vieira Carla P. , Conte‐Junior Carlos A. , Ceddia Rolando B. , Nobrega Antonio C. L. , Frantz Eliete D. C.
Published: July 2020

This study investigated whether regulation of the renin–angiotensin system (RAS) by enalapril and/or aerobic exercise training (AET) causes browning of the subcutaneous white adipose tissue (sWAT). C57BL/6 mice were fed either a standard chow or a high‐fat (HF) diet for 16 weeks. At Week 8, HF‐fed animals were divided into sedentary (HF), enalapril (HF‐E), AET (HF‐T), and enalapril plus AET (HF‐ET) groups. Subsequently, sWAT was extracted for morphometry, determination of RAS expression, and biomarkers of WAT browning. The HF group displayed adipocyte hypertrophy and induction of the classical RAS axis. Conversely, all interventions reduced adiposity and induced the counterregulatory RAS axis. However, only AET raised plasma irisin, increased peroxisome proliferator‐activated receptor‐γ coactivator‐1α, and uncoupling protein‐1 levels, and the expression of PR‐domain containing 16 in sWAT. Therefore, we concluded that AET‐induced sWAT browning was independent of the counterregulatory axis shifting of RAS in HF diet‐induced obesity.
Predicting nitrate‐nitrogen loads in subsurface drainage as a function of fertilizer application rate and timing in southern Minnesota
Authors: Wilson Grace L. , Mulla David J. , Vetsch Jeffrey A. , Sands Gary R.
Published: July 2020

Fertilizer management practices that focus on applying N fertilizer at the right rate and time have been proposed as a practical option to reduce NO3–N losses from subsurface drained agricultural fields. In this study, regression equations were developed to predict NO3–N losses for a corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] rotation in southern Minnesota, using fertilizer application timing and rate and growing season precipitation as inputs. The equations were developed using the results of the field‐scale hydrologic and N simulation model DRAINMOD‐NII, first calibrated and validated for three sites in southern Minnesota, and then run with different combinations of N fertilizer application rates and timings. Fertilizer timing treatments included a single application in the fall or spring and a split‐spring application (half applied preplant and the remaining applied as sidedress). The predictive regression equations showed that the split fertilizer application timing could reduce regional N loads by 28% compared with spring or fall applications. Greater reductions were predicted when the split timing was combined with lower N fertilizer rates. Utilizing the split application timing and reducing the fertilizer rate by 10 and 30% showed 33 and 41% reductions in N loads, respectively, compared with current fertilizer management practices. Such reductions in fertilizer application rates could be achieved through the use of variable‐rate nitrogen (VRN) fertilizer technologies. Results of this modeling study indicate that synchronizing fertilizer application with crop requirements and utilizing VRN technologies could significantly reduce N loads to surface waters in southern Minnesota.
Impact of low‐level viraemia on virological failure among Asian children with perinatally acquired HIV on first‐line combination antiretroviral treatment: a multicentre, retrospective cohort study
Authors: Sudjaritruk Tavitiya , Teeraananchai Sirinya , Kariminia Azar , Lapphra Keswadee , Kumarasamy Nagalingeswaran , Fong Moy S , Hansudewechakul Rawiwan , Bunupuradah Torsak , Ly Penh Sun , Nallusamy Revathy A , Sohn Annette H , Sirisanthana Virat ,   TREAT Asia Pediatric HIV Observational Database of IeDEA Asia‐Pacific
Published: July 2020

Introduction

The clinical relevance of low‐level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first‐line combination antiretroviral therapy (cART).

Methods

CLHIV aged <18 years, who were on first‐line cART for ≥12 months, and had virological suppression (two consecutive plasma viral load [pVL] <50 copies/mL) were included. Those who started treatment with mono/dual antiretroviral therapy, had a history of treatment interruption >14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL < 50 copies/mL. Cox proportional hazards models were performed to assess the association between LLV and VF.

Results

From January 2008 to September 2016, 508 CLHIV (55% female) were eligible for the study. At baseline, the median age was 9.6 (IQR: 7.0 to 12.3) years, cART duration was 1.4 (IQR: 1.3 to 1.8) years, 97% of CLHIV were on non‐nucleoside reverse transcriptase inhibitor‐based regimens, and the median CD4 was 25% (IQR: 20% to 30%). Over a median follow‐up time of 6.0 (IQR: 3.1 to 8.9) years from baseline, 86 CLHIV (17%) had ever experienced LLV, of whom 32 (37%) had multiple LLV episodes. Female sex, living in Malaysia (compared to Cambodia), having family members other than biological parents/grandparents as a primary caregiver, and baseline CD4 < 25% increased risk of LLV. Overall, 115 children (23%) developed VF, corresponding to a rate of 4.0 (95%CI: 3.4 to 4.9) per 100 person‐years of follow‐up (PYFU). VF was greater among children who had ever experienced LLV compared with those who maintained virological suppression throughout the study period (8.9 vs. 3.3 per 100 PYFU;p < 0.001). In multivariable analyses, ever experiencing LLV was associated with increased risk of subsequent VF (adjusted hazard ratio: 3.01; 95%CI: 1.97 to 4.60).

Conclusions

LLV increased the risk of subsequent VF among Asian CLHIV who had previously been suppressed on first‐line cART. Adherence interventions and additional targeted pVL monitoring may be warranted among children with LLV to facilitate early detection of VF.
Moving towards clinical trials for mitochondrial diseases
Authors: Pitceathly Robert D.S. , Keshavan Nandaki , Rahman Joyeeta , Rahman Shamima
Published: July 2020

Primary mitochondrial diseases represent some of the most common and severe inherited metabolic disorders, affecting ~1 in 4,300 live births. The clinical and molecular diversity typified by mitochondrial diseases has contributed to the lack of licensed disease‐modifying therapies available. Management for the majority of patients is primarily supportive. The failure of clinical trials in mitochondrial diseases partly relates to the inefficacy of the compounds studied. However, it is also likely to be a consequence of the significant challenges faced by clinicians and researchers when designing trials for these disorders, which have historically been hampered by a lack of natural history data, biomarkers and outcome measures to detect a treatment effect. Encouragingly, over the past decade there have been significant advances in therapy development for mitochondrial diseases, with many small molecules now transitioning from preclinical to early phase human interventional studies. In this review, we present the treatments and management strategies currently available to people with mitochondrial disease. We evaluate the challenges and potential solutions to trial design and highlight the emerging pharmacological and genetic strategies that are moving from the laboratory to clinical trials for this group of disorders.
Guanylate binding proteins contained in the murine chromosome 3 are important to control mycobacterial infection
Authors: Marinho Fabio V , Fahel Julia S , de Araujo Ana Carolina V S C , Diniz Lunna T S , Gomes Marco T R , Resende Danilo P , Junqueira-Kipnis Ana P , Oliveira Sergio C
Published: July 2020

Guanylate binding proteins (GBPs) are important effector molecules of autonomous response induced by proinflammatory stimuli, mainly IFNs. The murine GBPs clustered in chromosome 3 (GBPchr3) contains the majority of human homologous GBPs. Despite intense efforts, mycobacterial-promoted diseases are still a major public health problem. However, the combined importance of GBPchr3 during mycobacterial infection has been overlooked. This study addresses the influence of the GBPchr3 in host immunity against mycobacterial infection to elucidate the relationship between cell-intrinsic immunity and triggering of an efficient anti-mycobacterial immune response. Here we show that all GBPchr3 are up-regulated in lungs of mice during Mycobacterium bovis BCG infection, resembling tissue expression of IFN-γ. Mice deficient in GBPchr3 (GBPchr3−/−) were more susceptible to infection, displaying diminished expression of autophagy-related genes (LC3B, ULK1, and ATG5) in lungs. Additionally, there was reduced proinflammatory cytokine production complementary to diminished numbers of myeloid cells in spleens of GBPchr3−/−. Higher bacterial burden in GBPchr3−/− animals correlated with increased number of tissue granulomas. Furthermore, absence of GBPchr3 hampered activation and production of TNF-α and IL-12 by dendritic cells. Concerning macrophages, lack of GBPs impaired their antimicrobial function, diminishing autophagy induction and intracellular killing efficiency. In contrast, single GBP2 deficiency did not contribute to in vivo bacterial control. In conclusion, this study shows that GBPchr3 are important not only to stimulate cell-intrinsic immunity but also for inducing an efficient immune response to control mycobacterial infection in vivo.
Growth differentiation factor‐6 attenuates inflammatory and pain‐related factors and degenerated disc‐induced pain behaviors in rat model
Authors: Cui Haowen , Zhang Jian , Li Zemin , Chen Fan , Cui Haitao , Du Xianfa , Liu Hui , Wang Jianru , Diwan Ashish D. , Zheng Zhaomin
Published: July 2020

Previous studies have indicated that growth differentiation factor 6 (GDF6) is a potential candidate for intervertebral disc (IVD) degeneration (IDD) treatment. Here, we investigated the effect of GDF6 on IDD by examining changes in disc structure and the expression of inflammatory and pain‐related factors. A rat posterior disc puncture model of single segments and three consecutive segments was constructed, and GDF6 or phosphate‐buffered solution was administered via intradiscal injection 1 or 2 weeks after surgery. Magnetic resonance imaging showed a clear degeneration signal in the punctured disc, which was inhibited by GDF6. Histological staining revealed that GDF6 did not significantly improve the structure of IVDs in rats 8 weeks after puncture surgery, but it had an inhibitory effect on expression of the tumor necrosis factor‐alpha (TNF‐α) and interleukin (IL)‐1β in the IVD. Furthermore, GDF6 was found to protect the morphology and structure of the IVD 32 weeks after surgery. Mechanical and thermal hyperalgesia tests suggested that GDF6 injection can significantly improve mechanical and thermal‐stimulated pain behavior in rats and inhibit the expression of inflammatory factors TNF‐α and IL‐1β and the pain factor calcitonin gene‐related peptide in the dorsal root ganglion. A rat protein array test indicated that GDF6 could reduce the expression of cytokines IL‐6, intercellular cell adhesion molecule‐1, matrix metalloproteinase‐13, IL‐1β, and TNF‐α and increase the expression of tissue inhibitor of metalloproteinases 1, Transforming growth factor‐beta 2, IL‐10, and resistin in a TNF‐α‐induced IDD cell model. Thus, our study demonstrates that GDF6 can improve the structure of the IVD, inhibit the expression of inflammatory and pain‐related factors, and improve pain behavior in rats. Clinical Significance: To establish further preclinical research and clinical trials, comprehensive data are needed to validate the regenerative properties of GDF6. Ideally, a regenerative agent should also be able to relieve discogenic pain, achieving the best clinical outcomes.
Association Between Anthropometric Indicators of Nutrition Status and Length of Hospital Stay in Hospitalized Patients
Authors: Pinto Ana C. , Sousa Ana S. , Amaral Teresa F. , Guerra Rita S.
Published: July 2020

Background

Undernutrition is associated with increased hospital length of stay (LOS). Anthropometrics is required for undernutrition screening and diagnosis. However, the measurements which are more strongly associated with LOS are to be specified. This study aims to measure the independent association of weight, triceps skinfold thickness (TST), mid‐upper arm circumference (MUAC), adductor pollicis muscle thickness (APMT), mid‐upper arm muscle area (AMA), mid‐upper arm muscle circumference (AMC), and body mass index (BMI) with LOS and investigating whether these indicators had similar validity in predicting LOS.

Methods

Six hundred ninety‐five patients participated in a prospective observational study. Participants were dichotomized indicators studied according to the 5th and 25th percentiles described in the literature (for APMT only the 5th percentile was used). Cox regression analysis was used to estimate adjusted hazard ratios (HRs) and corresponding 95% CIs.

Results

Patients that presented values <5th percentile for TST (HR, 0.759; 95% CI, 0.579–0.995), MUAC (HR, 0.822; 95% CI, 0.687–0.983), APMT (HR, 0.791; 95% CI, 0.671–0.933), AMA (HR, 0.797, 95% CI, 0.660–0.962), and AMC (HR, 0.746; 95% CI, 0.611–0.911) showed a lower probability of being discharged to usual residence. Patients whose TST values were <25th percentile also presented lower probability of being discharged to usual residence (HR, 0.798; 95% CI, 0.673–0.946). No associations were found between weight and BMI with LOS.

Conclusion

Depletion of TST, MUAC, APMT, AMA, and AMC was associated with lower probability of being discharged to usual residence. A thicker TST was independently associated with this outcome and thus TST should be considered for undernutrition screening and diagnosis.
Label‐free serum detection based on Raman spectroscopy for the diagnosis and classification of glioma
Authors: Zhang Chenxi , Han Ying , Sun Bo , Zhang Wenli , Liu Shujun , Liu Jiajia , Lv Hong , Zhang Guojun , Kang Xixiong
Published: July 2020

Glioma is the most prevalent malignant cancer in the central nervous system and can cause significant mortality and morbidity. A rapid, convenient, accurate, and relatively noninvasive diagnostic method for glioma is important and urgently needed. In this study, we investigated the feasibility of using Raman spectroscopy to discriminate patients with glioma from healthy individuals. Serum samples were collected from healthy individuals (n = 86) and patients with glioma [high‐grade glioma (HGG) n = 75, low‐grade glioma (LGG) n = 60]. All spectra were collected with a 785‐nm wavelength laser in the range of 400–1800 cm−1. A total of three spectra were recorded for each sample, and every spectrum was integrated for 12 s and averaged over five accumulations. Principal component analysis and linear discriminant analysis models were combined to classify the Raman spectra of different groups. The correct classification ratios were 95.35, 93.33, and 93.34% for the normal, HGG, and LGG groups, respectively, and the total accuracy was 94.12%. The sensitivity, specificity, and accuracy of differentiating the HGG group from the normal group were 96.00, 96.51, and 96.27%, respectively, with an area under the curve of 0.997; in addition, the sensitivity, specificity, and accuracy of differentiating the LGG group from the normal group were 96.67%, 98.84%, and 97.95%, respectively, with an area under the curve of 0.999. Our study results suggested that the rapid and noninvasive detection method based on principal component analysis and linear discriminant analysis combined with Raman spectroscopy is a highly promising tool for the early diagnosis of glioma.
Silicon application improves caryopsis development and yield in rice
Authors: Chaiwong Nanthana , Rerkasem Benjavan , Pusadee Tonapha , Prom‐u‐thai Chanakan
Published: July 2020

BACKGROUND

Caryopsis development consists of several processes in the production of grain yield in field crops. This study evaluated the effect of silicon (Si) on spikelet formation, spikelet fertility, and grain filling and its impact on grain yield in rice.

RESULTS

Applying Si increased grain yield by 44% in Chainat 1( CNT1) and by 23% in Pathumthani 1 (PTT1). With no Si application, CNT1 had fewer total spikelets, and the fertilized and filled spikelets responded more strongly to Si than PTT1 did. Grain yield in both genotypes increased with increasing number of spikelets and filled fertilized grains. There were close relationships between Si concentration in the shoots, flag leaf, and the husk, which were positively correlated with grain yield, the number of spikelets, and fertilized and filled grains. Applying Si fertilizer also increased the expression level of Lsi6 in both CNT1 and PTT1 by 202% and 144% respectively compared with the expression of plants with no Si supplied.

CONCLUSION

This study has shown how rice grain yield can be limited by Si deficiency through the spikelet formation, fertilization, and grain filling processes. Applying Si fertilizer could improve rice grain yield through increasing spikelet formation, fertilization, and grain filling, which is in parallel with Lsi6 gene expression. This information can be used for improving rice productivity by Si fertilization management. © 2020 Society of Chemical Industry
Rapid safety and quality control during fish shelf‐life by using a portable device
Authors: Castrica Marta , Chiesa Luca Maria , Nobile Maria , De Battisti Francesca , Siletti Elena , Pessina Davide , Panseri Sara , Balzaretti Claudia M
Published: July 2020

BACKGROUND

Fish consumption is increasing nowadays both because of its positive role for health due to the abundant presence of unsaturated fatty acids and for its use in many new food preparations (e.g. raw fillet used for uncooked sushi and sashimi dishes). The growing food industry and increased demand for the long‐term storage and preservation of food have created the need to develop methods that can easily track and preserve food freshness and safety throughout shelf‐life (production, storage, shipment, and consumption). While E‐nose technologies have already been used and tested for these purposes, scarce information is available in the literature on the feasibility of using other food devices to detect changes in perishable food like fish during shelf‐life in order to predict and correctly manage all food storage phases. The aim of the present study was to investigate the potential of Food Sniffer® portable devices to define the quality and safety of salmon fillet and burger (Salmo salar) packaged in modified atmosphere at two refrigerated conditions (4 and 8 °C).

RESULTS

An increase in biogenic amines and volatile compounds especially ketones and alcohols were observed, with large amounts at final storage times of 8 °C temperature.

CONCLUSION

The Food Sniffer® application was able to anticipate unacceptability conditions of salmon samples also correlated with chemical and microbiological parameters. This could represent a valid support for food industry and retail to manage perishable food commodities preventing possible food risk as well. © 2020 Society of Chemical Industry
Residue measurement of pendimethalin in tobacco by using heart‐cutting two dimensional liquid chromatography coupled with tandem mass spectrometry
Authors: Shen Shihao , Chen Min , Wang Xianying , Fei Ting , Yang Dianhai , Cao Miaoling , Wu Da
Published: July 2020

A novel heart‐cutting two‐dimensional liquid chromatography coupled with tandem mass spectrometry method was developed for quantitative analysis of pendimethalin residue in tobacco. The strategy of reversed phase liquid chromatography coupled with another reversed‐phase liquid chromatography was employed for high column efficiency and excellent compatibility of mobile phase. In the first dimensional chromatography, a cyano column with methanol/water as the eluent was applied to separate pendimethalin from thousands of interference components in tobacco. By heart‐cutting technique, which effectively removed interference components, the target compound was cut to the second dimensional C18 column for further separation. The pendimethalin residue was finally determined by the tandem mass spectrometry under multiple reaction monitoring reversed‐phase liquid chromatography mode. Sample pretreatment of the new method was simplified, involving only extraction and filtration. Compared with traditional methodologies, the new method showed fairly high selectivity and sensitivity with almost no matrix interference. The limit of quantitation for pendimethalin was 1.21 ng/mL, whereas the overall recoveries ranged from 95.7 to 103.3%. The new method has been successfully applied to non‐stop measure of 200 real samples, without contamination of ion source. Detection results of the samples agreed well with standard method.
Headspace solid‐phase microextraction sampling of endogenous aldehydes in biological fluids using a magnetic metal‐organic framework/polyaniline nanocomposite
Authors: Ghaedrahmati Leila , Ghiasvand Alireza , Heidari Nahid
Published: July 2020

Nanoporosity, crystal structure, good thermal and mechanical stability, high surface‐to‐volume ratio, nanoscale cavities, and uniform pore topology have made metal‐organic frameworks one of the best class of sorbents for adsorption/separation purposes. In this research, a metal‐organic framework/polyaniline magnetite nanocomposite was synthesized and intercalated by polyaniline by electrophoretic deposition on the surface of a thin steel wire, to prepare a solid‐phase microextraction fiber. It was coupled with gas chromatography‐flame ionization detection and employed for the extraction and determination of aldehydes in biological samples. The magnetic nanocomposite was characterized using scanning electron microscopy, energy dispersive X‐ray analysis, and Fourier transform infrared spectroscopy. Under the optimal experimental conditions, the calibration curves were linear in the range of 0.01‐1 and 0.1‐1 µg/L for hexanal and heptanal, respectively. The limits of detections for hexanal and heptanal were 0.001 and 0.01 µg/L, respectively. Intrafiber repeatability for six replicate analyses of 0.2 µg/L of the analytes was over the range 3.5‐7.1%. Interfiber (fiber‐to‐fiber) reproducibility, calculated by six replicate analyses of the same concentration using three different fibers, and was found to be 10.4‐15.7%. The developed procedure was successfully utilized for the analysis of hexanal and heptanal in human plasma and urine samples.
Medicare Reimbursement Trends for Facility Performed Otolaryngology Procedures: 2000–2019
Authors: Dominguez Johanny L. , Ederaine Sophia A. , Haglin Jack M. , Aragon Sierra Ana M. , Barrs David M. , Lott David G.
Published: July 2020

Objective

There is a paucity of data regarding financial trends for procedural reimbursements in otolaryngology. The purpose of this study was to evaluate monetary trends in Medicare reimbursement rates for the 20 most commonly billed otolaryngology procedures from 2000 to 2019.

Study Design

Analysis of physician reimbursement.

Methods

The American Academy of Otolaryngology–Head and Neck Surgery database was queried to determine the 20 most performed otolaryngology procedures. Next, the Physician Fee Schedule Look‐Up Tool from the Centers for Medicare and Medicaid Services was utilized to assess each of the top 20 most utilized Current Procedural Terminology (CPT) codes in otolaryngology, and reimbursement data was extracted. All monetary data was adjusted for inflation to 2019 U.S. dollars using changes to consumer price index. Average annual and total percentage change in reimbursement were calculated based on adjusted values for all included procedures.

Results

After adjusting for inflation, the average reimbursement for the total 20 procedures decreased by 37.63% from 2000 to 2019. The greatest single mean decrease was seen in CPT code 61782 for stereotaxis procedures on the skull, meninges, and brain (−59.96%), whereas the smallest mean decrease was in CPT code 30520 for septoplasty (−1.50%). From 2000 to 2019, the adjusted reimbursement rate for the combined procedures decreased by an average of 2.33% each year.

Conclusion

Medicare reimbursement for included procedures has decreased from 2000 to 2019. Increased awareness and consideration of these trends will be important for policy makers, hospitals, and surgeons in order to assure continued access to meaningful otolaryngology care in the United States.

Level of Evidence

4 Laryngoscope, 131:496–501, 2021
Proteomic and Genomic Methylation Signatures of Idiopathic Subglottic Stenosis
Authors: Schoeff Stephen S. , Shi Xudong , Young William G. , Whited Chad W. , Soni Resha S. , Liu Peng , Ong Irene M. , Dailey Seth H. , Welham Nathan V.
Published: July 2020

Objective

Idiopathic subglottic stenosis (iSGS) is a chronic inflammatory condition that causes dyspnea and affects middle‐aged women of White race and non‐Latino or Hispanic ethnicity. To better characterize its phenotype and pathogenesis, we assessed the proteomic and genomic methylation signatures of subglottic tissue collected from iSGS patients compared to controls.

Study Design

Molecular analysis of clinical biospecimens.

Methods

We collected subglottic tissue biopsies from 12 patients during direct laryngoscopy, immediately prior to surgical treatment of iSGS; as well as from 4 age‐, sex‐, and race/ethnicity‐matched control patients undergoing other direct laryngoscopic procedures. We isolated protein and genomic DNA, acquired proteomic data using label‐free quantitative mass spectrometry techniques, and acquired genome‐wide methylation data using bisulfite conversion and a microarray platform. We compared molecular profiles across the iSGS and control groups, and with respect to clinical course in the iSGS group. Eight of the 12 iSGS patients underwent subsequent blood collection and plasma isolation for further assessment.

Results

Proteomic analysis revealed 42 differentially abundant proteins in the iSGS biopsies compared to controls, inferring enrichment of biological pathways associated with early wound healing, innate immunity, matrix remodeling, and metabolism. Proteome‐based hierarchical clustering organized patients into two iSGS and one control subgroups. Methylation analysis revealed five hypermethylated genes in the iSGS biopsies compared to controls, including the biotin recycling enzyme biotinidase (BTD). Follow‐up analysis showed elevated plasma BTD activity in iSGS patients compared to both controls and published normative data.

Conclusion

iSGS exhibits distinct proteomic and genomic methylation signatures. These signatures expand current understanding of the iSGS phenotype, support the possibility of disease subgroups, and should inform the direction of future experimental studies.

Level of Evidence

Not applicable Laryngoscope, 131:E540–E546, 2021