bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐Component Reaction for the Synthesis of Highly Functionalized Propargyl Ethers
Authors: Pisella Guillaume , Gagnebin Alec , Waser Jérôme
Published: March 2020

Multicomponent reactions provide efficient means to access molecular complexity. Herein, we report a copper‐catalyzed three‐component reaction of diazo compounds, alcohols and ethynyl benziodoxole (EBX) reagents for the synthesis of propargyl ethers. Extensive variations of the three partners of the reaction is possible, leading to highly functionalized and structurally diverse products under mild conditions. Alkynylation of a copper ylide intermediate is postulated as key step for this transformation.
The Bioequivalence of Tafamidis 61‐mg Free Acid Capsules and Tafamidis Meglumine 4 × 20‐mg Capsules in Healthy Volunteers
Authors: Lockwood Peter A. , Le Vu H. , O'Gorman Melissa T. , Patterson Terrell A. , Sultan Marla B. , Tankisheva Ekaterina , Wang Qiang , Riley Steve
Published: March 2020

Tafamidis, a non‐nonsteroidal anti‐inflammatory benzoxazole derivative, acts as a transthyretin (TTR) stabilizer to slow progression of TTR amyloidosis (ATTR). Tafamidis meglumine, available as 20‐mg capsules, is approved in more than 40 countries worldwide for the treatment of adults with early‐stage symptomatic ATTR polyneuropathy. This agent, administered as an 80‐mg, once‐daily dose (4 × 20‐mg capsules), is approved in the United States, Japan, Canada, and Brazil for the treatment of hereditary and wild‐type ATTR cardiomyopathy in adults. An alternative single solid oral dosage formulation (tafamidis 61‐mg free acid capsules) was developed and introduced for patient convenience (approved in the United States, United Arab Emirates, and European Union). In this single‐center, open‐label, randomized, 2‐period, 2‐sequence, crossover, multiple‐dose phase 1 study, the rate and extent of absorption were compared between tafamidis 61‐mg free acid capsules (test) and tafamidis meglumine 80‐mg (4 × 20‐mg) capsules (reference) after 7 days of repeated oral dosing under fasted conditions in 30 healthy volunteers. Ratios of adjusted geometric means (90%CI) for the test/reference formulations were 102.3 (98.0‐106.8) for area under the concentration‐time profile over the dosing interval and 94.1 (89.1‐99.4) for the maximum observed concentration, satisfying prespecified bioequivalence acceptance criteria (90%CI, 80‐125). Both tafamidis regimens had an acceptable safety/tolerability profile in this population.
Clinical practice guidelines based on evidence for cognitive‐behavioural therapy in Parkinson's disease comorbidities: A literature review
Authors: Zečević Ivan
Published: March 2020

The purpose of this review is to provide psychologists and other health care professional enough knowledge about available cognitive‐behavioural interventions for comorbidities in Parkinson's disease that include depression, anxiety, impulsive disorder, pain, and sleep disturbances. This review has clear clinical practical suggestions how to adapt psychological interventions and techniques to the motor and/or cognitive impairments of patients with Parkinson's disease, based on earlier available research results. Every available research that could be found with the help of search engines from Medline, Springer, PsychINFO, and Google Scholar, which used cognitive‐behavioural therapy to treat Parkinson's comorbidities, was cited and explained. Cognitive‐behavioural interventions and techniques are presented based on available research results for Parkinson's comorbidities. It is recommended to use treatment plans and interventions that are earlier suggested as efficient in patients with Parkinson's disease. Strongest available research based recommendations are available for depression and anxiety. There are only few available research studies that used cognitive and/or behavioural interventions for pain, impulsive disorder, or sleeping disturbances, except insomnia in Parkinson's disease. Cognitive‐behavioural therapy is safe to use and should be adapted to the specific needs of patients and with the scientific approved treatment interventions and techniques. Psychologists should be careful on how they adapt their treatment plan for patients.
Defoliation management effects on nutritive value of ‘performer’ switchgrass
Authors: Bekewe Perejitei E. , Castillo Miguel S. , Acosta Juan J. , Rivera R.
Published: March 2020

Forage species with greater nutritive value have the potential to positively affect animal responses. ‘Performer’ switchgrass (Panicum virgatum L.) was released because of greater digestibility and lower lignin concentrations as compared to ‘Alamo’ and ‘Cave‐in‐Rock.’ However, the relationship between nutritive value, canopy characteristics, and dry matter yield for this species has not yet been established. The goal of this study was to determine in vitro true digestibility (IVTD), crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF) as a function of a wide range of defoliation management strategies to aim optimize production of nutritious forage. Treatments were the factorial combination (4 × 4) of defoliation height (DH; clipped to 10, 20, 30, and 40 cm) and defoliation frequency (DF; clipped every 3, 6, 9, and 12 wk). The range of digestibility values was greater due to DF (from 590–779 g kg−1 when averaged across DH treatments) than DH treatments (from 675–692 g kg−1 when averaged across DF treatments). In general, frequent defoliation resulted in greater IVTD and CP but lower yields; however, there were interaction effects of DF × DH for all response variables. With the exception of NDF, all response variables had strong correlations with dry matter yield, canopy height, and leaf/stem ratio. Although there are tradeoffs when managing for productivity and nutritive value, there is a wide range of defoliation management options for ‘Performer’ switchgrass that provide flexibility in terms of harvesting schedules to optimize productivity and persistence of nutritious forage.
Transition Metal Phosphide‐Based Materials for Efficient Electrochemical Hydrogen Evolution: A Critical Review
Authors: Weng Chen‐Chen , Ren Jin‐Tao , Yuan Zhong‐Yong
Published: March 2020

As hydrogen has been increasingly considered as promising sustainable energy supply, electrochemical overall water splitting driven by highly efficient non‐noble metal electrocatalysts has aroused extensive attention. Transition metal phosphides (TMPs) have demonstrated remarkable electrocatalytic performance, including high activity and robust durability towards hydrogen evolution reaction (HER) in acidic and alkaline as well as neutral electrolytes. In this Review, up‐to‐date progress of TMP‐based HER electrocatalysts is summarized. Various synthesis strategies of TMPs based on selected phosphorus sources are presented, and the reaction mechanisms of HER as well as the contribution of phosphorus in the TMPs to HER activity are briefly discussed. The multiscale approaches for promoting the activity and stability of TMP‐based catalysts are discussed with respect to intrinsic electronic structure, hybrids, microstructure, and working electrode interface. Some crucial issues and future perspectives of TMPs are pointed out. These modulated approaches and challenges are also instructive for constructing other high‐activity energy‐related electrocatalysts.
Temporal patterns of macrophage‐ and neutrophil‐related markers are associated with clinical outcome in heart failure patients
Authors: Klimczak‐Tomaniak Dominika , Bouwens Elke , Schuurman Anne‐Sophie , Akkerhuis K. Martijn , Constantinescu Alina , Brugts Jasper , Westenbrink B. Daan , van Ramshorst Jan , Germans Tjeerd , Pączek Leszek , Umans Victor , Boersma Eric , Kardys Isabella
Published: March 2020

Aims

Evidence on the association of macrophage‐ and neutrophil‐related blood biomarkers with clinical outcome in heart failure patients is limited, and, with the exception of C‐reactive protein, no data exist on their temporal evolution. We aimed to investigate whether temporal patterns of these biomarkers are related to clinical outcome in patients with stable chronic heart failure (CHF).

Methods and Results

In 263 patients with CHF, we performed serial plasma measurements of scavenger receptor cysteine‐rich type 1 protein M130 (CD163), tartrate‐resistant acid phosphatase type 5 (TRAP), granulins (GRN), spondin‐1 (SPON1), peptidoglycan recognition protein 1 (PGLYRP1), and tissue factor pathway inhibitor (TFPI). The Cardiovascular Panel III (Olink Proteomics AB, Uppsala, Sweden) was used. During 2.2 years of follow‐up, we collected 1984 samples before the occurrence of the composite primary endpoint (PE) or censoring. For efficiency, we selected 567 samples for the measurements (all baseline samples, the last two samples preceding the PE, and the last sample before censoring in event‐free patients). The relationship between repeatedly measured biomarker levels and the PE was evaluated by joint models. Mean (±standard deviation) age was 67 ± 13 years; 189 (72%) were men; left ventricular ejection fraction (%) was 32 ± 11. During follow‐up, 70 (27%) patients experienced the PE. Serially measured biomarkers predicted the PE in a multivariable model adjusted for baseline clinical characteristics [hazard ratio (95% confidence interval) per 1‐standard deviation change in biomarker]: CD163 [2.07(1.47–2.98), P < 0.001], TRAP [0.62 (0.43–0.90), P = 0.009], GRN [2.46 (1.64–3.84), P < 0.001], SPON1 [3.94 (2.50–6.50), P < 0.001], and PGLYRP1 [1.62 (1.14–2.31), P = 0.006].

Conclusions

Changes in plasma levels of CD163, TRAP, GRN, SPON1, and PGLYRP1 precede adverse cardiovascular events in patients with CHF.
Electroanalysis of Carbendazim using MWCNT/Ca‐ZnO Modified Electrode
Authors: Malode Shweta J. , Keerthi Prabhu K. , Shetti Nagaraj P. , Kulkarni Raviraj M.
Published: March 2020

The present research involves the report on electrochemical deportment of Carbendazim (MBC) at multiwalled carbon nanotubes and calcium‐doped zinc oxide nanoparticles altered nanocomposite based carbon paste electrode (MWCNTs/Ca‐ZnO‐CPE). The modified carbon paste evidenced manifest electrocatalytic behavior for MBC in 0.2 M phosphate buffer (PB) solutions. Cyclic voltammetry (CV), linear sweep voltammetry (LSV), and square wave voltammetry (SWV) techniques were used for the analysis. The working electrode assembly exhibits faster electron transfer of MBC with increase in the peak current. At bare CPE, MBC showed maximum peak current of 1.098 μA at potential 0.7568 V whereas at MWCNT/Ca‐ZnO/CPE peak current of 5.203 μA was observed at potential 0.7541 V in 0.2 M PBS of pH 7.0 at the sweep rate of 50 mV s−1. The synthesized 5 % Ca‐ZnO nanoparticles (NPs) were characterized by X‐ray diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive X‐ray analysis (EDX), and Transmission electron microscopy (TEM) analysis. Various factors influencing the voltammetry of MBC such as pre‐concentration time, pH, sweep rate, and amount of MBC were studied and from the studies we observed that the response was found to be diffusion‐controlled. The concentration variation studies for MBC was watched in the linear working range of 0.01 μM to 0.45 μM and the detection limit was found by SWV technique.
New findings regarding the Fen‐Wei Graben on the southeastern margin of the Ordos Block: Evidence from the Cenozoic sedimentary record from the borehole
Authors: Fan Shuanghu , Zhang Tianyu , Chen Shu'e , Li Rongxi
Published: March 2020

In the Cenozoic, fault‐related basins, including the Wei River, Lingbao and Linfen basins, developed on the southeast margin of the Ordos Block. Based on the latest drilling data and previous research results, this article analysed the evolutionary processes, temporal and spatial relationships and tectonic background of these basins, and obtained the following results: (a) The Wei River Basin and the Lingbao Basin belong to a unified basin, which formed in the Palaeocene and developed gradually from east to west. (b) The Linfen Basin formed in the late Miocene and developed gradually from southwest to northeast. (c) The evolution of the basin systems was dominated by the westward subduction of the Pacific Plate in the Palaeogene and then by a combination effects of the subduction of the Pacific Plate and the uplift of the Tibetan Plateau. (d) The so‐called Fen‐Wei Graben is not supported by the different geological evolutionary histories of the Wei River Basin and the Linfen Basin.
Conditional depletion of Fus in oligodendrocytes leads to motor hyperactivity and increased myelin deposition associated with Akt and cholesterol activation
Authors: Guzman Kelly M. , Brink Lauren E. , Rodriguez‐Bey Guillermo , Bodnar Richard J. , Kuang Lisha , Xing Bin , Sullivan Mara , Park Hyun J. , Koppes Erik , Zhu Haining , Padiath Quasar , Cambi Franca
Published: March 2020

Fused in sarcoma (FUS) is a predominantly nuclear multifunctional RNA/DNA‐binding protein that regulates multiple aspects of gene expression. FUS mutations are associated with familial amyotrophic lateral sclerosis (fALS) and frontotemporal lobe degeneration (FTLD) in humans. At the molecular level, the mutated FUS protein is reduced in the nucleus but accumulates in cytoplasmic granules. Oligodendrocytes (OL) carrying clinically relevant FUS mutations contribute to non‐cell autonomous motor neuron disease progression, consistent with an extrinsic mechanism of disease mediated by OL. Knocking out FUS globally or in neurons lead to behavioral abnormalities that are similar to those present in FTLD. In this study, we sought to investigate whether an extrinsic mechanism mediated by loss of FUS function in OL contributes to the behavioral phenotype. We have generated a novel conditional knockout (cKO) in which Fus is selectively depleted in OL (FusOL cKO). The FusOL cKO mice show increased novelty‐induced motor activity and enhanced exploratory behavior, which are reminiscent of some manifestations of FTLD. The phenotypes are associated with greater myelin thickness, higher number of myelinated small diameter axons without an increase in the number of mature OL. The expression of the rate‐limiting enzyme of cholesterol biosynthesis (HMGCR) is increased in white matter tracts of the FusOLcKO and results in higher cholesterol content. In addition, phosphorylation of Akt, an important regulator of myelination is increased in the FusOLcKO. Collectively, this work has uncovered a novel role of oligodendrocytic Fus in regulating myelin deposition through activation of Akt and cholesterol biosynthesis.
Who belongs in school? Examining the link between Black and White racial disparities in sense of school belonging and suspension
Authors: Fisher Benjamin W. , Dawson‐Edwards Cherie , Higgins Ethan M. , Swartz Kristin
Published: March 2020

Relative to White students, Black students experience higher rates of exclusionary discipline and less welcoming school environments. However, little empirical research has examined the extent to which these two parallel racial disparities are linked. This study examines the relationship between student race and suspension and whether this relationship depends on school‐level racial disparities in students' sense of school belonging. Using data from 73,755 students (56.4% White, 43.6% Black or African–American) nested within 131 schools, this study uses a series of multilevel models with cross‐level interactions. This study finds that Black students are consistently more likely to be suspended than White students, but this difference is nonsignificant in schools where Black students' sense of school belonging is much higher than that of White students'. As such, schools' efforts toward reducing the discipline gap may benefit from making schools more welcoming to Black students.
MiR‐96‐5p promotes breast cancer migration by activating MEK/ERK signaling
Authors: Qin Wei‐yan , Feng Shi‐chun , Sun Yong‐qiang , Jiang Guo‐qin
Published: March 2020

Background

Breast cancer is the leading cause of cancer deaths in women worldwide. The purpose of the current study was to investigate the potential role of miR‐96‐5p in breast cancer.

Methods

Breast cancer tissues and matched para‐cancerous tissues were collected. The expression of microRNA‐96‐5p (miR‐96‐5p) and arginine kinase 3 (AK3) was detected by quantitative real‐time PCR (qRT‐PCR). The correlation between miR‐96‐5p and AK3 was calculated by Pearson's Chi‐square test. Moreover, mimics or inhibitors of miR‐96‐5p were applied to explore whether miR‐96‐5p influences the migration capacity in Transwell and wound healing assays. Bioinformatics analysis was performed to identify the target genes of miR‐96‐5p through the TargetScan, miRDB and miRanda databases. A luciferase reporter assay was performed to verify AK3 as a downstream target gene of miR‐96‐5p.

Results

The expression of miR‐96‐5p was significantly increased in breast cancer tissue and breast cancer cell lines compared with para‐cancerous tissue and a breast cell line, respectively. The expression of miR‐96‐5p negatively correlated with AK3 gene expression. AK3 was demonstrated to be a direct mRNA target of miR‐96‐5p. AK3 was positively associated with the overall survival of breast cancer patients. Kaplan–Meier curve and log rank test analyses revealed that decreased AK3 levels were significantly associated with reduced overall survival. miR‐96‐5p was shown to promote the migration of breast cancer cells through the MEK/ERK signaling pathway.

Conclusion

Our results identify a role for miR‐96‐5p in promoting breast cancer cell migration through activation of MEK/ERK signaling by targeting AK3.
Usefulness of 18F‐FDG‐PET/CT in the diagnosis and prediction of recurrence of pancreatic neuroendocrine neoplasms
Authors: Sato Asahi , Masui Toshihiko , Yogo Akitada , Uchida Yuichiro , Nakano Kenzo , Anazawa Takayuki , Nagai Kazuyuki , Takaori Kyoichi , Nakamoto Yuji , Uemoto Shinji
Published: March 2020

Background

Although 18F‐FDG‐PET/CT is a widely used diagnostic tool for several malignancies, its efficacy in diagnosing pancreatic neuroendocrine tumors is reported to be controversial because of the short‐term follow‐up.

Methods

We retrospectively compared demographics and pathological features between 18F‐FDG‐positive and ‐negative diseases. Additionally, we evaluated whether the avidity of 18F‐FDG‐PET/CT affected earlier recurrence after curative treatment of non‐functioning tumors. The median duration of observation was 65.6 months.

Results

Seventy‐two patients were enrolled. 18F‐FDG‐positive diseases were pathologically advanced and significantly associated with metastatic behavior. In a multivariate analysis, metastatic behavior and WHO tumor grade was independently associated with 18F‐FDG accumulation. Only 25% of functional tumors (4/16) and 8% of insulinomas (1/12) were 18F‐FDG‐positive. In a Kaplan–Meier analysis in patients with non‐functioning tumors (n = 56), 18F‐FDG‐positivity was significantly correlated with poorer recurrence‐free survival (RFS) but had no correlation with overall survival. In univariate analysis of factors associated with shorter RFS, male gender, prevalence of nodal metastasis, WHO tumor grade ≥G2, or 18F‐FDG‐positive disease were significantly higher in patients with shorter RFS, whereas only 18F‐FDG‐positivity was associated with shorter RFS in multivariate analyses.

Conclusions

The avidity of 18F‐FDG‐PET/CT was associated with metastatic behavior of pancreatic neuroendocrine tumors and recurrence after treatment of non‐functioning tumors.
Developmental brain abnormalities and acute encephalopathy in a patient with myopathy with extrapyramidal signs secondary to pathogenic variants in MICU1
Authors: Wilton Katelynn M. , Morales‐Rosado Joel A. , Selcen Duygu , Muthusamy Karthik , Ewing Sarah , Agre Katherine , Nickels Katherine , Klee Eric W. , Ho Mai‐Lan , Morava Eva
Published: March 2020

Mitochondria play a variety of roles in the cell, far beyond their widely recognized role in ATP generation. One such role is the regulation and sequestration of calcium, which is done with the help of the mitochondrial calcium uniporter (MCU) and its regulators, MICU1 and MICU2. Genetic variations in MICU1 and MICU2 have been reported to cause myopathy, developmental disability and neurological symptoms typical of mitochondrial disorders. The symptoms of MICU1/2 deficiency have generally been attributed to calcium regulation in the metabolic and biochemical roles of mitochondria. Here, we report a female child with heterozygous MICU1 variants and multiple congenital brain malformations on MRI. Specifically, she shows anterior perisylvian polymicrogyria, dysmorphic basal ganglia, and cerebellar dysplasia in addition to white matter abnormalities. These novel findings suggest that MICU1 is necessary for proper neurodevelopment through a variety of potential mechanisms, including calcium‐mediated regulation of the neuronal cytoskeleton, Miro1‐MCU complex‐mediated mitochondrial movement, or enhancing ATP production. This case provides new insight into the molecular pathogenesis of MCU dysfunction and may represent a novel diagnostic feature of calcium‐based mitochondrial disease.
Subjectively Reported Effects Experienced in an Actively Shielded 7T MRI: A Large‐Scale Study
Authors: Hansson Boel , Markenroth Bloch Karin , Owman Titti , Nilsson Markus , Lätt Jimmy , Olsrud Johan , Björkman‐Burtscher Isabella M.
Published: March 2020

Background

Ultrahigh‐field (UHF) MRI advances towards clinical use. Patient compliance is generally high, but few large‐scale studies have investigated the effects experienced in 7T MRI systems, especially considering peripheral nerve stimulation (PNS) and caregiving.

Purpose

To evaluate the quantity, the intensity, and subjective experiences from short‐term effects, focusing on the levels of comfort and compliance of subjects.

Study Type

Prospective.

Population

In all, 954 consecutive MRIs in 801 subjects for 3 years.

Field Strength

7T.

Assessment

After the 7T examination, a questionnaire was used to collect data.

Statistical Tests

Descriptive statistics, Spearman's rank correlation, Mann–Whitney U‐test, and t‐test.

Results

The majority (63%) of subjects agreed that the MRI experience was comfortable and 93% would be willing to undergo future 7T MRI as a patient (5% undecided) and 82% for research purposes (12% undecided). The most common short‐term effects experienced were dizziness (81%), inconsistent movement (68%), PNS (63%), headache (40%), nausea (32%), metallic taste (12%), and light flashes (8%). Of the subjects who reported having PNS (n = 603), 44% experienced PNS as “not uncomfortable at all,” 45% as “little or very little uncomfortable,” and 11% as “moderate to very much uncomfortable.” Scanner room temperature was experienced more comfortable before (78%) than during (58%) examinations, and the noise level was acceptable by 90% of subjects. Anxiety before the examination was reported by 43%. Patients differed from healthy volunteers regarding an experience of headache, metallic taste, dizziness, or anxiety. Room for improvement was pointed out after 117 examinations concerning given information (n = 73), communication and sound system (n = 35), or nursing care (n = 15).

Data Conclusion

Subjectively reported effects occur in actively shielded 7T MRI and include physiological responses and individual psychological issues. Although leaving room for improvement, few subjects experienced these effects being so uncomfortable that they would lead to aversion to future UHF examinations.

Level of Evidence

1

Technical Efficacy

Stage 5 J. Magn. Reson. Imaging 2020;52:1265–1276.
Noninvasive simultaneous monitoring of pH and depth using surface‐enhanced deep Raman spectroscopy
Authors: Gardner Benjamin , Stone Nicholas , Matousek Pavel
Published: March 2020

Here we demonstrate the simultaneous recovery of multiplexed physical information of surface‐enhanced Raman scattering (SERS) nanoparticles (pH and depth) using deep Raman spectroscopy. As has been shown previously and in accordance with theory, inelastically scattered photons arising from spectral peaks that are suitably separated can exhibit different optical properties in the media through which they travel. These differences can impact the relative intensities of the Raman peaks as a function of the transmission path length; thereby, the depth of signal generation is inherently encoded in the spectra; assuming the target is clustered at a single depth or location, its depth can be readily determined. Moreover, Raman spectroscopy is very sensitive to chemistry of a sample, and changes in pH are observed not only as changes in peak intensity through relevant protonation and deprotonation but also as shifts in spectral features. Here, we show it is possible to precisely predict the depth (root‐mean‐square error [RMSE] 5 %) of SERS nanoparticles in scattering media (0.5% intralipid) while also being able to noninvasively monitor simultaneously the pH levels (RMSE ~0.2 pH units) of the media surrounding the nanoparticles. This is important as it demonstrates that nanoparticles can be used to report on multiple physical properties including their depth. This opens avenues for a range of new applications including the noninvasive diagnosis and localisation of cancer lesions in clinical environment in vivo.
Short focal length tunable liquid crystal lenticular lens array based on fringe field effect
Authors: Li Rui , Chu Fan , Tian Li‐Lan , Gu Xiao‐Qing , Zhou Xiang‐Yu , Wang Qiong‐Hua
Published: March 2020

A liquid crystal (LC) lenticular lens array based on fringe field effect is proposed. The gradient refractive index (GRIN) profile can be generated in the LC layer because of the fringe field between the strip‐shaped electrodes and the bottom electrode. The proposed LC lenticular lens array possesses ideal lens‐like phase profile and shortest focal length (1.199 mm) when the driving voltage is 5.4 V. The focal length can be tuned with millisecond response time by changing the driving voltage of the proposed LC lenticular lens array. The rise time τrise and decay time τdecay of the proposed LC lenticular lens array are 162 and 94 ms, respectively.
Incidence and impact of Textbook Outcome among patients undergoing resection of pancreatic neuroendocrine tumors: Results of the US Neuroendocrine Tumor Study Group
Authors: Heidsma Charlotte M. , Hyer Madison , Tsilimigras Diamantis I. , Rocha Flavio , Abbott Daniel E. , Fields Ryan , Smith Paula M. , Poultsides George A. , Cho Clifford , Maithel Shishir K. , Pawlik Timothy M. ,   Other Members of the US Neuroendocrine Tumor Study Group
Published: March 2020

Background and Objectives

We sought to define the incidence and impact of Textbook Outcome (TO) on disease‐free survival [DFS] among patients undergoing resection of pancreatic neuroendocrine tumors (PNET).

Methods

Patients undergoing resection of a PNET between 2000 and 2016 were identified using a multi‐institutional database. TO was defined as no postoperative severe complications (Clavien‐Dindo grade ≥ III), no 90‐day mortality, no prolonged length‐of‐hospital stay (LOS) (ie, > 75th percentile), no 90‐day readmission after discharge, and R0 resection. The 5‐year DFS was calculated and the association with TO was examined.

Results

Among 821 patients with a PNET, median tumor size was 2.1 cm (IQR 1.4‐14.6). Resection consisted of pancreatoduodenectomy (PD) (n = 231, 28.1%), distal pancreatectomy (DP) (n = 492, 59.9%), and enucleation (EN) (n = 98, 11.9%). Overall TO rate was 49.3% (n = 405). The incidence of TO varied by procedure type (PD: 32.5% vs DP: 56.7% vs EN: 52.0%; P < .001). After adjusting for all competing factors, achievement of a TO was independently associated with improved DFS (hazard ratio: 0.54, 95% CI, 0.35‐0.81; P = .003).

Conclusions

Only one in two patients undergoing resection of a PNET achieved a TO, which varied markedly based on procedure type. Achievement of a TO was associated with improved DFS.
Inhibiting ubiquitin conjugating enzyme E2 N by microRNA‐590‐3p reduced cell growth of cervical carcinoma
Authors: Song Ting‐Ting , Xu Fei , Wang Wei
Published: March 2020

The ubiquitin conjugating enzyme E2 N (UBE2N) has been reported to be involved in the tumorigenesis of several tumors, but its function in cervical carcinoma has not been investigated yet. In the present study, UBE2N was found elevated in cervical carcinoma, and patients with high UBE2N had a shorter overall survival than patients with low expression. Additionally, knockdown of UBE2N decreased the activation of MEK1/2 and p38 in cervical carcinoma cells, and UBE2N knockdown also markedly inhibited cervical carcinoma cell growth. Our further studies found that microRNA‐590‐3p (miR‐590‐3p) was significantly decreased in cervical carcinoma, and patients with high miR‐590‐3p had a longer overall survival than patients with low expression. Moreover, miR‐590‐3p expression was found negatively correlated with UBE2N expression in cervical carcinoma, and our further studies showed that miR‐590‐3p targeted UBE2N and inhibited its expression in cervical carcinoma. Overexpression of miR‐590‐3p could inhibit cervical carcinoma cell growth, but enhanced UBE2N could rescue miR‐590‐3p‐induced cell growth inhibition in cervical carcinoma. This study indicated that targeting miR‐590‐3p/UBE2N axis could be a potential strategy for the treatment of cervical carcinoma.
miR‐143 inhibits renal cell carcinoma cells metastatic potential by suppressing ABL2
Authors: Xu Bin , Wang Can , Wang Ya‐Li , Chen Shu‐Qiu , Wu Jian‐Ping , Zhu Wei‐Dong , Wang Chun‐Ying , Guan Han , Guan Chao , You Zong‐Hao , Chen Ming
Published: March 2020

Although micro RNA (miRNA) expression profiles are widely investigated in renal cell carcinoma (RCC), their potential roles for affecting RCC initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs inhuman metastatic RCC tissues based on Gene Expression Omnibus (GSE37989). We further validated them iRNAs expression data in the largest clinical dataset: The Cancer Genome Atlas (TCGA). And cell adhesion and migration abilities and epithelial me senchymal transition (EMT) related proteins were assessed in both normal and tumor RCC cell lines. We suggest that hsa‐miR‐143 is a potential tumor suppressor in RCC as its down regulation positively correlated with adverse prognosis. Biologically, cell adhesion, migration, and EMT were dramatically inhibited by miR‐143. Mechanistically, we found that miR‐143 targets ABL proto‐oncogene 2 (ABL2), which was also found to be an indicator for poor survival in TCGA database. Our results have important implications in understanding functions of miRNAs in metastatic RCC and will provide a basis for further clinical application.
Soil indicators of bird activity in the temperate climatic zone – A case‐study
Authors: Ligęza Sławomir , Pranagal Jacek , Smal Halina , Gmitrowicz‐Iwan Joanna
Published: March 2020

The importance of birds to pedogenesis and their impact on soil characteristics is a long‐standing topic of research. For this reason, the ornithogenic soils (avian soils) are distinguished as a separate category in some soil classifications. The continuous progress of knowledge on and changes in the management of the Earth's resources demand constant updating of definitions and classification criteria in various fields of environmental sciences. A search of the literature revealed few studies that examine the properties of bird soils in the temperate climate zone. This paper focuses on ornithogenic material: grit and bones deposited in the topsoil. Although areas covered by such soils are limited to 1–100 ha, they are found in high abundance in Europe and Asia. The surface horizon of the soil examined in the current study in Poznań, Poland, contained ample ornithogenic material; however, the soil's phosphorus content was remarkably low. Therefore, the analysed soil may not be considered as an ornithogenic soil, nor can it be attributed to the ornithic supplementary qualifier provided by the World Reference Base (WRB). The case study presented here exemplifies that soils containing ornithogenic material but lacking phosphorous compounds may occur in the temperate climate zone. Therefore, we conclude that ornithogenic material is the only permanent indicator of the existence of large groups of birds in non‐polar climate zones.
Chitosan/Alginate Dialdehyde Multilayer Films with Modulated pH‐Responsiveness and Swelling
Authors: Huang Junhao , Moghaddam Saeed Zajforoushan , Thormann Esben
Published: March 2020

Oxidation of alginate is a promising method that creates aldehyde groups, which can form stable cross‐links with amine groups on chitosan. In this work, it is shown that a systematic variation in the oxidation degree of alginate dialdehyde allows for effective tuning of the swelling capacity of chitosan/alginate dialdehyde multilayer films. Furthermore, it is demonstrated that the pH‐responsiveness of the multilayer films can be regulated by the choice of pH at which the layer‐by‐layer assembly is conducted. The combination of these two parameters allows for the designing polysaccharide multilayer films with a tunable degree of swelling and stimuli‐responsiveness.
Retail competition using free shopping shuttle bus strategies
Authors: Wang Chan , Nie Pu‐yan
Published: March 2020

Free shopping shuttle bus (FSSB) is a common strategy in some industries such as super market and real estate. After illustrating the application conditions for FSSB, this study surveys competition effects of FSSB strategy on retailers by a duopoly spatial Bertrand model. The conclusions of this article show that the cost of FSSB and features of the market are two crucial factors to determine whether the FSSB is employed or not. When the demands are fixed, firms do not benefit from FSSB. But if the market is not fully covered, FSSB strategy has significant positive effects on market size improvement.
Utah legislature approves millions to transform mental health crisis system
Authors: Canady Valerie A.
Published: March 2020

Utah legislators this month approved more than $23 million in funding to provide better treatment options for people with mental illness, including the addition of mobile crisis centers and additional treatment beds.
New study finds link between alcohol use disorder, suicide
Authors: Canady Valerie A.
Published: March 2020

New research has found that alcohol use disorder (AUD) is a potent risk factor for suicide, underscoring the need for clinicians and physicians to be aware of suicide risk among patients with a history of AUD. The findings were published March 12 in the American Journal of Psychiatry.
Amid conference cancellations, leaders advance with support
Authors: Canady Valerie A.
Published: March 2020

In the wake of the COVID‐19 pandemic and in the interest of keeping staff, employees and consumers with mental health and substance use disorders safe, many organizations have had to cancel scheduled conferences and annual meetings. Officials and leaders, meanwhile, are moving forward with helping their members and the public stay safe during this outbreak.
Global existence and decay of solutions of a singular nonlocal viscoelastic system with a nonlinear source term, nonlocal boundary condition, and localized damping term
Authors: Boulaaras Salah , Mezouar Nadia
Published: March 2020

The paper deals with the existence of a global solution of a singular one‐dimensional viscoelastic system with a nonlinear source term, nonlocal boundary condition, and localized frictional damping a(x)ut using the potential well theory. Furthermore, the general decay result is proved. We construct a suitable Lyapunov functional and make use of the perturbed energy method.
A compact triple band circularly polarized planar antenna for wireless application
Authors: Kumari Kahani , Jaiswal Rahul K. , Srivastava Kumar V.
Published: March 2020

A compact planar triple band circularly polarized (CP) antenna loaded with parasitic elements is proposed for wireless applications. For achieving circular polarization 2 inverted L‐shaped strips are added to the longer arm of dual band monopole and ground plane. A rectangular patch and a U shaped radiator are added to increase the impedance bandwidth as well as polarization purity. Electrical size of the antenna is 0.32λ × 0.32λ, where λ is the free space wavelength at its lowest CP frequency that is, 2.4 GHz. The structure shows an impedance bandwidths (│S11│ ≤ –10 dB) of 870 MHz (1.83‐2.7 GHz), 1.17 GHz (3.27‐4.44 GHz), and 400 MHz (4.75‐5.15 GHz). The 3‐dB axial ratio bandwidths of the proposed structure are 12.2%, 5.3%, and 4.28% at 2.375, 3.47, and 4.9 GHz of center frequencies respectively. The proposed structure is fabricated and its parameters are measured. Measured results nearly match with the simulated results and it shows satisfactory gain in all the three operating CP bands.
Surface plasmon resonance‐based fiber optic sensor prepared from bilayers of indium tin oxide‐indium oxide
Authors: Kapoor Vicky , Sharma Navneet K.
Published: March 2020

Experimental investigations on fiber optic surface plasmon resonance (SPR) sensor with ITO (indium tin oxide)‐IO (indium oxide) layers are reported. Sensitivity ascends with increase in IO layer thickness till a definite thickness and begins descending with further enhancement in IO layer thickness. Maximum rise in sensitivity is observed for sensor fabricated from 40 nm ITO to 30 nm IO layers.
Heinz Gerrens Revisited: A New Look at the Impact of Reactor Type on Polymer Chain Morphology
Authors: Schork F. Joseph
Published: March 2020

The equations for predicting molecular weight distribution, copolymer composition distribution, and copolymer sequence distribution for three polymerization mechanisms (monomer linkage with termination, monomer linkage without termination, and polymer linkage), and three reactor types (batch/plug flow, homogenous continuous stirred tank, and segregated continuous stirred tank) are assembled from various sources and compared and contrasted.
An optimal‐multiphase homing methodology for powered parafoil systems
Authors: Sun Hao , Sun Qinglin , Chen Zengqiang , Tao Jin , Luo Shuzhen , Zeng Xianyi , Teng Haishan , Zhou Peng
Published: March 2020

In order to achieve the precise and agile homing control of the powered parafoil system, an optimal‐multiphase homing methodology is explored in this article. The proposed methodology is composed by a trajectory optimization method based on quantum genetic algorithm and a trajectory tracking method based on an improved active disturbance rejection control (ADRC). First, an improved optimization method combining the optimal and multiphase theory is proposed. The optimized trajectory consists of the simple trajectories, the standard lines and circles, while also satisfying the multiple constraints such as the wind disturbance, terrain avoidance, flared landing, and so on. Then, an improved active disturbance rejection controller is presented. For improving the agility of the system during the path switching and the disturbance rejection ability in windy environment, based on ADRC, a disturbance rejection control algorithm is designed for the horizontal controller of the system. By analyzing the aerodynamic characteristic of the system, the wind disturbance will be compensated previously with a feedforward compensation unit. It will be largely reduce the observation error of the extended state observer, while improving the control effect and the reaction speed. Finally, the hardware‐in‐the‐loop simulation is presented to prove the effectiveness of the proposed methodology. The results show that the optimization method can be achieved successfully and the optimized trajectory can be tracked by the improved ADRC controller precisely and agilely. The landing error is less than 15 m with the proposed homing methodology.
Sufficient optimality conditions for problems controlled by ordinary differential equations with behavior of blowup
Authors: Nowakowski Andrzej
Published: March 2020

We study the blowup problem for nonautonomous systems of ordinary differential equations. Sufficient optimality conditions for the controlled blowup time are derived, in terms of a dual dynamic programming methodology. We define an ε‐optimal value function and we construct sufficient ε‐optimality conditions for that function again in terms of a dual dynamic programming inequality.
Electrons and Hydroxyl Radicals Synergistically Boost the Catalytic Hydrogen Evolution from Ammonia Borane over Single Nickel Phosphides under Visible Light Irradiation
Authors: Song Jin , Gu Xiaojun , Zhang Hao
Published: March 2020

From the perspective of tailoring the reaction pathways of photogenerated charge carriers and intermediates to remarkably enhance the solar‐to‐hydrogen energy conversion efficiency, we synthesized the three low‐cost semiconducting nickel phosphides Ni2P, Ni12P5 and Ni3P, which singly catalyzed the hydrogen evolution from ammonia borane (NH3BH3) in the alkaline aqueous solution under visible light irradiation at 298 K. The systematic investigations showed that all the catalysts had higher activities under visible light irradiation than in the dark and Ni2P had the highest photocatalytic activity with the initial turnover frequency (TOF) value of 82.7 min−1, which exceeded the values of reported metal phosphides at 298 K. The enhanced activities of nickel phosphides were attributed to the visible‐light‐driven synergistic effect of photogenerated electrons (e−) and hydroxyl radicals (.OH), which came from the oxidation of hydroxide anions by photogenerated holes. This was verified by the fluorescent spectra and the capture experiments of photogenerated electrons and holes as well as hydroxyl radicals in the catalytic hydrogen evolution process.
Structure‐Based Design and Synthesis of Piperidinol‐Containing Molecules as New Mycobacterium abscessus Inhibitors
Authors: de Ruyck Jérôme , Dupont Christian , Lamy Elodie , Le Moigne Vincent , Biot Christophe , Guérardel Yann , Herrmann Jean‐Louis , Blaise Mickaël , Grassin‐Delyle Stanislas , Kremer Laurent , Dubar Faustine
Published: March 2020

Non‐tuberculous mycobacterium (NTM) infections, such as those caused by Mycobacterium abscessus, are increasing globally. Due to their intrinsic drug resistance, M. abscessus pulmonary infections are often difficult to cure using standard chemotherapy. We previously demonstrated that a piperidinol derivative, named PIPD1, is an efficient molecule both against M. abscessus and Mycobacterium tuberculosis, the agent of tuberculosis, by targeting the mycolic acid transporter MmpL3. These results prompted us to design and synthesize a series of piperidinol derivatives and to determine the biological activity against M. abscessus. Structure‐activity relationship (SAR) studies pointed toward specific sites on the scaffold that can tolerate slight modifications. Overall, these results identified FMD‐88 as a new promising active analogue against M. abscessus. Also, we determined the pharmacokinetics properties of PIPD1 and showed that intraperitoneal administration of this compound resulted in promising serum concentration and an elimination half‐life of 3.2 hours.
Long‐term brain status and cognitive impairment in children treated for high‐risk acute lymphoblastic leukemia with and without allogeneic hematopoietic stem cell transplantation: A single‐center study
Authors: Zając‐Spychała Olga , Pawlak Mikolaj A. , Karmelita‐Katulska Katarzyna , Pilarczyk Jakub , Jończyk‐Potoczna Katarzyna , Przepióra Agnieszka , Derwich Katarzyna , Pieczonka Anna , Wachowiak Jacek
Published: March 2020

Aim

The aim of the study was to assess long‐term consequences of central nervous system (CNS) prophylaxis in patients with high‐risk ALL (HR‐ALL) treated according to ALL IC‐BFM 2002 and to compare observed abnormalities in patients who underwent allogeneic hematopoietic stem cell transplantation (allo‐HSCT) with those who received only prophylactic CNS irradiation (12 Gy) and with control group.

Patients and methods

We studied 29 patients with HR‐ALL in CR1 after treatment according to protocol ALL IC‐BFM 2002 (14 with allo‐HSCT conditioned with fractionated total body irradiation [FTBI] and 15 without HSCT) and 16 children with newly diagnosed ALL (control group). The median time from therapy completion to evaluation was 5 years. To assess brain status, volumetric T1‐weighted sequences of magnetic resonance imaging were used. Neuropsychological assessment based on battery neuropsychological tests.

Results

Transplanted patients had significantly lower volumes of white and gray matter (P = .048 and P < .001) and also of subcortical structures, including the thalamus (P < .001), the hippocampus (P = .007), the putamen (P = .011), the globus pallidus (P = .001), and the accumbens (P < .001). In addition, these patients had generally lower cognitive performance, especially in vocabulary (P = .011), visuospatial ability (P = .047), executive functions and attention (P = .034; P = .002; P = .048), and processing speed (P = .049 and P = .037). The thalamus volume is correlated with neuropsychological performance in verbal functions (P < .001), executive functions (P < .001 and P = .024), and processing speed (P < .001).

Conclusions

In pediatric patients treated for ALL, FTBI‐based preparative regimen preceding allo‐HSCT causes reduction of subcortical structure volumes and decline in cognitive performance. The observed long‐term structural and functional CNS sequelae are significantly more pronounced in transplanted HR‐ALL patients than in those treated with prophylactic CNS‐ radiotherapy only.
Impact of vascular anomalies on the PTEN phenotype in children and young adults
Authors: Gurunathan Arun , Ricci Kiersten , Iacobas Ionela , Rednam Surya P. , Wusik Katie , Fei Lin , Hammilll Adrienne M.
Published: March 2020

Germline PTEN (phosphatase and tensin homolog) mutations lead to inappropriate cell survival and growth, and a predisposition to multiple cancers. Some patients also have vascular anomalies (VAs), and it is unclear whether these patients have different phenotypes or oncologic risks. We conducted a two‐institution retrospective cohort study to better understand the phenotypes of children and young adults with PTEN mutations, and to compare individuals with VA to those without. Almost half of the patients had thyroid tumors and nearly one quarter developed gastrointestinal tumors before 30 years of age. The presence of VA was positively associated with bulky overgrowth but did not appear to modify oncologic risk.
Pre‐pregnancy obesity and childhood malignancies: A population‐based cohort study
Authors: Kessous Roy , Wainstock Tamar , Sheiner Eyal
Published: March 2020

Objective

Exploring the effect of maternal obesity during pregnancy on the long‐term health of offspring is of great importance. The aim of this study was to evaluate the association between maternal pre‐pregnancy obesity and future risk of childhood malignancies.

Study design

A population‐based cohort analysis comparing the risk for long‐term childhood malignancies (up to the age of 18 years) in children born (1991‐2014) to mothers with and without pre‐pregnancy obesity (body mass index > 30) was conducted in July 2017. Childhood malignancies were predefined based on ICD‐9 codes, as recorded in the hospital medical files. Children with congenital malformations and multiple gestations were excluded from the analysis. The Kaplan‐Meier survival curve was constructed to compare cumulative oncological morbidity in both groups over time. The Cox proportional hazards model was used to control for confounders.

Results

During the study period, 241 273 infants met the inclusion criteria; 3268 were born to mothers with pre‐pregnancy obesity. Children of obese women had significantly increased risk for several childhood malignancies (including brain tumors) as well as increased risk for total hospitalizations with malignancy diagnoses, even after controlling for several confounders (adjusted HR 1.90, 95% CI 1.07‐3.37, P = 0.028). Cumulative incidence of oncological morbidity was also significantly increased over time in the studied group (log‐rank P = 0.023).

Conclusion

Maternal pre‐pregnancy obesity is significantly associated with an increased long‐term risk for general childhood malignancies, and specifically brain tumors in the offspring. These results are important when counseling mothers regarding potential future risks and recommended lifestyle modifications.