bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyrrolyl‐Appended Zinc Porphodimethenes: Branched Oligopyrrole Products From the Templated One‐Pot Isoporphyrin Synthesis
Authors: Baş Çağla , Doettinger Florian , Klein Niels , Tschierlei Stefanie , Bröring Martin
Published: June 2021

The one‐pot synthesis of zinc isoporphyrins from pyrrole, an aryl aldehyde and zinc acetate was investigated with regard to the formation of by‐products. The optical spectra of the product mixtures differ strongly from each other depending on the aldehyde used and the water content in the solvent mixture of the condensation step. The compounds belonging to the two most prominent bands at approx. 500 nm and at approx. 640 nm could be isolated and structurally characterised. These are the homoleptic complexes (dipy)2Zn with a dipyrrolic ligand, and unexpected zinc‐tripyrrin species (trpy)ZnCl, respectively. The tripyrrin species further react under the conditions of chromatography to green intermediates and yellow end products, whose mass spectroscopic investigations indicate dimers and loss of one ZnCl2 equivalent. The final products could be crystallographically identified as zinc‐porphodimethene complexes and analysed with respect to the stereochemical situation and optical behaviour. In one case, the green intermediate form could be enriched. The investigations indicate a helical pentapyrrolic zinc complex with a non‐coordinated pyrrolyl side arm and give clues to the stereochemical course of the stepwise dimerisation.
Synthesis and Exploration of Abscisic Acid Receptor Agonists Against Dought Stress by Adding Constraint to a Tetrahydroquinoline‐Based Lead Structure
Authors: Bojack Guido , Baltz Rachel , Dittgen Jan , Fischer Christian , Freigang Jörg , Getachew Rahel , Grill Erwin , Helmke Hendrik , Hohmann Sabine , Lange Gudrun , Lehr Stefan , Porée Fabien , Schmidt Jana , Schmutzler Dirk , Yang Zhenyu , Frackenpohl Jens
Published: June 2021

New oxotetrahydroquinolinyl‐ and oxindolinyl sulfonamides interacting with RCAR/(PYR/PYL) receptor proteins were identified as lead structures against drought stress in crops starting from protein docking studies of a sulfonamide lead structure, followed by in‐depth SAR studies. Optimized five to six step synthetic approaches via substituted amino oxo‐tetrahydro‐quinolines and amino oxo‐indolines as essential intermediates gave access to the envisaged oxo‐tetrahydroquinolinyl and oxindolinyl sulfonamides. Whilst oxo‐tetrahydroquinolinyl sulfonamides with additional carbon substituents or spiro‐cycloalkyl groups exhibited only low to moderate target affinities, the corresponding spiro‐oxindolinyl and oxo‐tetrahydroquinolinyl sulfonamides carrying optimized N‐substituents revealed strong interactions with RCAR/(PYR/PYL) receptor proteins in Arabidopsis thaliana. Remarkably, the in vitro activity observed for these new compounds was on the same level as observed for the naturally occurring plant hormone in line with strong efficacy against drought stress in‐vivo (canola and wheat as broad‐acre crops).
Economic long‐term effects of intensive interdisciplinary pain treatment in paediatric patients with severe chronic pain: Analysis of claims data
Authors: Lopez Lumbi Susanne , Ruhe Ann‐Kristin , Pfenning Ingo , Wager Julia , Zernikow Boris
Published: June 2021

Objective

Chronic pain in children and adolescents gives rise to high healthcare costs. Successful treatment is supposed to reduce the economic burden. The objective of this study was to determine the changes in healthcare utilization and expenditures from 1 year before (Pre) intensive interdisciplinary pain treatment (IIPT) to the first (Post 1) and second (Post 2) years after discharge in a sample of paediatric chronic pain patients.

Methods

Claims data from one statutory health insurance company were analysed for 119 children and adolescents (mean age = 15.3, 68.9% female) who sought IIPT at the German Paediatric Pain Centre. Costs incurred for inpatient treatment, outpatient treatment, medication, remedies and aids were compared before treatment and 2 years after discharge. Healthcare utilization was compared using Wilcoxon signed‐rank test, and expenditures using trimmed means and the Yuen's t‐test.

Results

Overall costs were significantly lower in the 2 years after IIPT compared to before IIPT (Pre: 3,543€, Post 1:2,681€, Post 2:1937€ (trimmed means)). Healthcare utilization changed significantly; hospitalizations decreased in the years after discharge, while psychotherapies stayed stable in the year after discharge but lessened in the second year.

Conclusion

The results of this study support prior findings on the high economic burden of paediatric chronic pain. IIPT may contribute to a transition in healthcare utilization from somatic‐focused treatments to more psychological treatments. Overall costs were reduced as soon as the first year after discharge and decreased even further in the second year.

Significance

This study analyses original claims data from paediatric chronic pain patients in the year before and up to 2 years after intensive interdisciplinary pain treatment in a specialized paediatric pain centre. The analysis of long‐term data reveals a continuous cost reduction after intensive interdisciplinary pain treatment and a change in the subsequent outpatient treatment.
Multi‐walled Carbon Nanotubes and Gold Nanorod Decorated Biosensor for Detection of microRNA‐126
Authors: Topkaya Seda Nur , Turunc Ezgi , Cetin Arif E.
Published: June 2021

In this article, we introduced a novel electrochemical biosensor for the detection of microRNA‐126. The biosensor utilizes a hybridization assay combined with multi‐walled carbon nanotubes and gold nanorod‐decorated screen‐printed carbon electrodes. For electrode preparation, gold nanorods were first immobilized onto the surface of bare and multi‐walled carbon nanotube‐modified screen‐printed carbon electrodes, and the thiol tagged‐capture probe was immobilized on the electrode surface through gold and thiol group interaction. After the immobilization, thiol tagged‐capture probe hybridized with the target sequence. Under optimum conditions, we determined limit of detection (LOD) and limit of quantification (LOQ) as high as 11 nM and 36 nM, respectively.
The Effects of Extended Planning Time on Candidates' Performance, Processes, and Strategy Use in the LectureListening‐Into‐SpeakingTasks of theTOEFL iBT® Test
Authors: Inoue Chihiro , Lam Daniel M. K.
Published: June 2021

This study investigated the effects of two different planning time conditions (i.e., operational [20 s] and extended length [90 s]) for the lecture listening‐into‐speaking tasks of theTOEFL iBT® test for candidates at different proficiency levels. Seventy international students based in universities and language schools in the United Kingdom (35 at a lower level; 35 at a higher level) participated in the study. The effects of different lengths of planning time were examined in terms of (a) the scores given by ETS‐certified raters; (b) the quality of the speaking performances characterized by accurately reproduced idea units and the measures of complexity, accuracy, and fluency; and (c) self‐reported use of cognitive and metacognitive processes and strategies during listening, planning, and speaking. The results found neither a statistically significant main effect of the length of planning time nor an interaction between planning time and proficiency on the scores or on the quality of the speaking performance. There were several cognitive and metacognitive processes and strategies where significantly more engagement was reported under the extended planning time, which suggests enhanced cognitive validity of the task. However, the increased engagement in planning did not lead to any measurable improvement in the score. Therefore, in the interest of practicality, the results of this study provide justifications for the operational length of planning time for the lecture listening‐into‐speaking tasks in the speaking section of the TOEFL iBT test.
Identification of aroma compounds in raw and cooked broccoli
Authors: Wieczorek Martyna N. , Majcher Małgorzata A. , Jeleń Henryk H.
Published: June 2021

Broccoli is characterized by its specific flavor, which is the reason it is not tolerated by some consumers. The role of aroma in flavor is crucial; however, the characteristics of aroma‐active components in broccoli are still unclear. Solvent‐assisted flavor evaporation (SAFE) with the aid of solid‐phase microextraction (SPME) and fractionation using solid phase extraction (SPE), followed by different chromatography‐mass spectrometry approaches (GC‐MS, GC‐MS/MS, GC×GC‐ToFMS) were used to identify the compounds of interest. A total of 33 aroma‐active compounds were detected with the use of gas chromatography‐olfactometry (GC‐O) in raw, and 9 in cooked broccoli florets; in majority sulfur compounds—thiols, sulfides, and isothiocyanates prevailed. Methanethiol and 1‐pentanethiol were the key odorants characterized by the highest FD (1024) in raw broccoli, followed by dimethyl sulfide, 2,3‐butanedione, dimethyl trisulfide, dimethyl tetrasulfide, 2‐methyl methanethiosulphonate, 4‐methylpentyl isothiocyanate, hexyl isothiocyanate (all with an FD of 256). In cooked broccoli, the number and especially the intensity of detected compounds were much lower. The highest FD values (FD=4) were noted for dimethyl trisulfide and 1,4‐octadien‐3‐one. To our knowledge, this is the first detailed identification of odorants in raw and cooked broccoli.
Identification of Common Driver Gene Modules and Associations between Cancers through Integrated Network Analysis
Authors: Gao Bo , Zhao Yue , Gao Yonghang , Li Guojun , Wu Ling‐Yun
Published: June 2021

High‐throughput biological data has created an unprecedented opportunity for illuminating the mechanisms of tumor emergence and evolution. An important and challenging problem in deciphering cancers is to investigate the commonalities of driver genes and pathways and the associations between cancers. Aiming at this problem, a tool ComCovEx is developed to identify common cancer driver gene modules between two cancers by searching for the candidates in local signaling networks using an exclusivity‐coverage iteration strategy and outputting those with significant coverage and exclusivity for both cancers. The associations of the cancer pairs are further evaluated by Fisher's exact test. Being applied to 11 TCGA cancer datasets, ComCovEx identifies 13 significantly associated cancer pairs with plenty of biologically significant common gene modules. The novel results of cancer relationship and common gene modules reveal the relevant pathological basis of different cancer types and provide new clues to diagnosis and drug treatment in associated cancers.
Elective neck dissection and its extent in salivary gland cancers: A dilemma
Authors: Fatehi Khuzema Saifuddin , Malik Akshat
Published: June 2021

see page 2861‐2862
Catchments of German surface water bodies
Authors: Gericke Andreas , Mahnkopf Judith , Venohr Markus
Published: June 2021

The European Water Framework Directive demands to assess and report the chemical and ecological status of water bodies (WB). Linking their status to drivers and pressures and deriving suitable mitigation measures require knowledge of the shape and area of WB catchments. We derived a network of 26 570 WB catchments in Germany using the hydrologically‐defined drainage basins of the German federal states. We established a network of 338 149 drainage basins. This network underwent plausibility checks and a validation with the catchment areas of 348 monitoring stations across Germany. To this network, we assigned the longest intersecting or the next downstream WB code. To account for geometric inaccuracies we revised spurious intersections resulting in splittings and cycles in the WB network. As WB may be ecologically but not hydrologically well defined, we split them at confluences and intersections. The network of drainage basins matched the monitoring stations with a Nash‐Sutcliffe efficiency of 1.00. The final WB network contained 11 005 out of the 11 586 original WBs longer than 1 m. The corresponding local catchment areas range from <<0.0001 to 446 km2, with a median of 10 km2. The dataset combines the requirements of hydrological and ecological modelling applications at basin or national scales with the needs of the EU reporting which can foster their acceptance by state authorities and river‐basin management.
MakingFahrenheit 451“Come to Life”: Sound Inquiries with Youth and Teachers
Authors: Friesen Doug , Simon Rob
Published: June 2021

In this article, we describe how eighth‐grade students and teacher candidates used sound and listening to remix and attune themselves (Stewart, 2011) to the dystopian novel Fahrenheit 451 by Ray Bradbury (2011). We situate our sound inquiries in relation to critical literacy (Vasquez, Janks, & Comber, 2019; Wargo, 2019) and sound education (Schafer 1992, 2005; Oliveros, 2005). The examples we share suggest how students and teacher candidates used sound to, in the words of a participating teacher candidate, make Fahrenheit 451 “come to life.” This work demonstrates how sound inquiry can encourage students’ transformative engagement with their surroundings, with each other, and with canonical texts like Fahrenheit 451 in critical literacy classrooms.
Isoniazid Population Pharmacokinetics and Dose Recommendation for Korean Patients With Tuberculosis Based on Target Attainment Analysis
Authors: Cho Yong‐Soon , Jang Tae Won , Kim Hyo‐Jung , Oh Jee Youn , Lee Hyun‐Kyung , Park Hye Kyeong , Ghim Jong‐Lyul , Long Nguyen Phuoc , Park Yumi , Choi Young‐Kyung , Phuong Nguyen Thi Thu , Shin Jae‐Gook ,   Center for Personalized Precision Medicine of Tuberculosis
Published: June 2021

The wide variability of isoniazid (INH) pharmacokinetics is mainly attributed to the trimodal N‐acetyltransferase 2 (NAT2) acetylator phenotype, that is, rapid, intermediate, and slow. Consequently, a uniform INH dose in current clinical practice may lead to treatment failure and emergence of drug resistance. There is a lack of studies on specific doses of INH for different NAT2 acetylator phenotypes among tuberculosis (TB) patients. Therefore, we aimed to provide insight into the optimal dosing of INH for each NAT2 acetylator phenotype with respect to the probability of achieving a pharmacokinetic (PK)/pharmacodynamic target. PK, the NAT2 genotype, and clinical data were collected in a multicenter prospective cohort study conducted at 13 clinical centers in Korea. Population PK modeling and simulation were carried out. Data from 454 TB patients were divided into a training data set and a test data set at a ratio of 4 to 1. The PK of the training data were best described by a 2‐compartment model with allometric scaling for body size effect. Importantly, NAT2 acetylator phenotypes significantly affected the apparent clearance. Our model, which provided better predictive performance compared with previously published models, was evaluated by external validation using the test set. The simulation for assessing target efficacy and toxicity indicated that the best INH dosing regimens for Korean tuberculosis patients were once‐daily doses of 400, 300, and 200 mg for rapid, intermediate, and slow acetylators, respectively. In conclusion, our study provides a step forward in precision dosing for antituberculosis management.
Sparse time‐frequency analysis for aircraft target classification with low sampling rate and short observation time
Authors: Wang Yanqing , Yang Shuhui , Yin Hongcheng , Huo Chaoying , Man Liang
Published: June 2021

The traditional time‐frequency analysis (TFA) techniques are instruments for target classification, which can reflect the feature of the target in the time‐frequency domain. However, it will lead to a serious decrease in the recognition accuracy as the decline of the sampling rate. To ease this problem, in this article, the sparse time‐frequency feature analysis (STFFA) is implemented for aircraft classification, and the genetic algorithm is adopted to solve the sparse problem quickly for saving time. Firstly, the sparse time‐frequency decomposition and recovery signal are obtained by matching pursuit. Then, three novel kinds of aircraft features are extracted from the sparse time‐frequency decomposition, which are sparse recovery time‐frequency entropy (SRTFE), frequency entropy by time, and first‐order sparse time‐frequency moment. Thus, the feature combination modes based on the three features are applied to realize the classification of aircraft and compared with the traditional TFA techniques. Besides, a support vector machine is also used to classify the three kinds of aircraft. The accuracy and efficiency of the STFFA method have been investigated by employing the parametric model data and electromagnetic scattering model simulated trials. Furthermore, in contrast to the traditional TFA instrument, our method can reach a recognition accuracy of more than 90% from the numerical experiment results, which demonstrates that the feature extraction by sparse time‐frequency analysis improves the accuracy of aircraft classification under a low sampling rate.
Cost‐effectiveness of insertable cardiac monitors for diagnosis of atrial fibrillation in cryptogenic stroke in Australia
Authors: Thijs Vincent , Witte Klaus K. , Guarnieri Carmel , Makino Koji , Tilden Dominic , Gillespie John , Huynh Marianne
Published: June 2021

Introduction

Detection of atrial fibrillation (AF) is required to initiate oral anticoagulation (OAC) after cryptogenic stroke (CS). However, paroxysmal AF can be difficult to diagnose with short term cardiac monitoring. Taking an Australian payer perspective, we evaluated whether long‐term continuous monitoring for 3 years with an insertable cardiac monitor (ICM) is cost‐effective for preventing recurrent stroke in patients with CS.

Methods

A lifetime Markov model was developed to simulate the follow‐up of patients, comparing long‐term continuous monitoring with an ICM to monitoring by conventional care. We used a linked evidence approach to estimate the rates of recurrent stroke when AF detection leads to initiation of OAC, as detected using ICM during the lifetime of the device or as detected using usual care. All diagnostic and patient management costs were modeled. Other model inputs were determined by literature review. Probabilistic sensitivity analysis (PSA) was undertaken to explore the effect of parameter uncertainty according to CHADS2 score and OAC treatment effect.

Results

In the base‐case analysis, the model predicted an incremental cost‐effectiveness ratio (ICER) of A$29 570 per quality‐adjusted life year (QALY). Among CHADS2 subgroups analyses, the ICER ranged from A$26 342/QALY (CHADS2 = 6) to A$42 967/QALY (CHADS2 = 2). PSA suggested that the probabilities of ICM strategy being cost‐effective were 53.4% and 78.7%, at thresholds of $30 000 (highly cost‐effective) and $50 000 per QALY (cost‐effective), respectively.

Conclusions

Long‐term continuous monitoring with an ICM is a cost‐effective intervention to prevent recurrent stroke in patients following CS in the Australian context.
What matters most for Indian Generation Y employees? An empirical study based on work‐values
Authors: Naim Mohammad Faraz
Published: June 2021

The workplace is undergoing a major generational change as the baby boomer generation retires and younger generations replace them. Each generation brings with it a set of work values; the work values of Generation Y have been a focus of particular interest as this generation will soon form a significant proportion of the workforce. Even though Generation Y constitutes a large part of the Indian workforce, very little research has been done on this group. Using a sample of 1220 employees working in the Indian service industry, this study sets out to find the extent to which the work values of Generation Y in India are congruent with those of their global counterparts. The findings suggest that Indian employees value extrinsic and intrinsic aspects of work, and place less importance on social and prestige values; their work values are similar to those from Generation Y in the US and Slovenia, but differ significantly from those in Malaysia, Brazil, and Germany. The study provides valuable insights for international organizations where employees from various countries and cultural backgrounds work together, particularly when these involve Indian employees.
Microvesicles, blood cells, and endothelial cells mediate phosphatidylserine‐related prothrombotic state in patients with periodontitis
Authors: Zuo Nan , Liu Wenhui , Hu Tenglong , Liu Yingmiao , Li Baorong , Liu Huan , Jing Haijiao , Chen Xiaojing , Li Yueyue , Du Jingwen , Hu Tianshui , Dong Zengxiang , Niu Yumei , Shi Jialan
Published: June 2021

Background

Phosphatidylserine (PS) is essential for inflammation‐associated thrombogenesis, but the exact effect of PS on the prothrombotic state in periodontitis is uncertain. This study aimed to determine the PS‐related procoagulant state in patients with periodontitis.

Methods

A total of 138 patients with periodontitis were examined compared with 42 healthy controls. PS‐exposing cells and microvesicles in blood samples were detected by confocal microscopy and flow cytometry. The clotting time assay and prothrombinase complex formation assay were used to measure the procoagulant activity of microvesicles, blood cells and endothelial cells. Periodontal clinical parameters and laboratory characteristics of patients with severe periodontitis were recorded and analyzed at baseline and 6 months after non‐surgical periodontal therapy.

Results

Total PS‐positive (PS+) microvesicles and the percentage of PS+ blood cells increased in patients with severe periodontitis compared with patients with moderate/mild periodontitis or healthy controls. Endothelial cells cultured in serum from patients with severe periodontitis expressed more PS compared with those cultured in serum from healthy controls. Specifically, PS exposure on blood cells and endothelial cells significantly decreased after inhibiting the effect of inflammatory cytokines. The elevated levels of PS+ cells and microvesicles in severe periodontitis shortened clotting time and led to increased prothrombinase complex formation. Non‐surgical periodontal therapy significantly attenuated the release of microvesicles and the PS exposure of blood cells in severe periodontitis.

Conclusions

The prothrombotic state of patients with periodontitis is mediated by PS+ cells and microvesicles stimulated by elevated levels of inflammatory cytokines.
Comparing the long‐term effects of artificial and natural vegetation restoration strategies: A case‐study of Wuqi and its adjacent counties in northern China
Authors: Xu Xin , Zhang Daojun
Published: June 2021

The significant increase in vegetation coverage in northern China over the past two decades has attracted worldwide attention. Revegetation has been completed via artificial and natural restoration techniques, and the relative performance of each needs to be further explored. Although some studies have focused on the comparison between artificial and natural methods in vegetation restoration from a micro‐perspective, there is a lack of evidence at the regional scale. This study considers Wuqi County and its adjacent areas of the Loess Plateau in northern China as our study area. First, natural and artificial restoration areas were identified. Then, the restoration sustainability of different restoration strategies and the adjustment effect of climate factors in the relationship between vegetation restoration strategy choice and vegetation restoration sustainability were analyzed. We found that the vegetation restoration strategies employed varied between local jurisdictions. In areas dominated by artificial restoration, vegetation coverage increased over a short period, but the growth rate diminished in the long term. In comparison, in areas mainly dominated by natural restoration, although the growth rate of revegetation was not very high in the short term, it was stable in the long term. In addition, the impact of vegetation restoration strategies on vegetation restoration sustainability exhibited spatial heterogeneity, and the temperature, humidity, and wind speed further affected strategy outcomes. This study provides a new perspective for vegetation restoration strategy evaluation and is expected to serve as a reference for the optimization of relevant ecological policies in the future.
High sensitivity open‐path gas sensor based on a triangular multi‐pass cell
Authors: Wu Xu , Sang Jian , Zhou Sheng , Li Jingsong
Published: June 2021

In this article, a gas sensing technique utilizing a compact multi‐pass absorption cell in a triangular configuration was proposed for open‐path trace gases detection. To demonstrate this technique, an open‐path gas sensor system was developed by combing the innovated triangular multi‐pass cell with a near infrared distributed feedback diode laser (at 1.65 μm) for simultaneous detection of atmospheric CH4 and H2O. A Gaussian‐noise‐limited limit of detection of approximate 52 ppb and 445 ppm were achieved for CH4 and H2O, respectively, with 1 Hz sampling rate and at normal atmospheric pressure. Allan variance analysis indicates that a sensitivity of 5.5 ppb (for CH4) and 75 ppm (for H2O) could be obtained at the optimal averaging time of 300 s, which is comparative with the mid‐infrared laser based gas sensors. This technique will be a critical tool for developing low‐cost open‐path trace gas monitoring networks for environmental, industrial, and public security applications.
Gradient‐enhanced damage growth modeling of ductile fracture
Authors: Larsson Ragnar , Ertürk Ahmet S.
Published: June 2021

We present a gradient‐enhanced damage model for ductile fracture modeling, describing the degraded material response coupled to temperature. Continuum thermodynamics is used to represent components of the energy dissipation as induced by the effective material response, thermal effects, and damage evolution. The viscoplastic Johnson‐Cook constitutive model serves as prototype for the effective material. The continuum damage evolution of Lemaitre type is focusing the degradation of the shear response, eventually leading to ductile shear failure. A novel feature is the damage‐driving dissipation rate, allowing for elastic and plastic components separated by a global damage threshold for accumulation of inelastic damage‐driving energy. In the application to a dynamic split‐Hopkinson test and two quasi‐static tensile tests, the gradient damage model is compared with the corresponding local model. For isothermal conditions, the examples show that both damage models exhibit mesh convergent behavior when using the global damage threshold.
Unveiling the dynamic relationship between agriculture value addition, energy utilization, tourism and environmental degradation in South Asia
Authors: Usman Muhammad , Anwar Sofia , Yaseen Muhammad Rizwan , Makhdum Muhammad Sohail Amjad , Kousar Rakhshanda , Jahanger Atif
Published: June 2021

In the recent decade, the investigation of environmental degradation and its drivers has become a burning subject of dispute among the governments and their policymakers. However, various crucial drivers of environmental damages still have not been sufficiently analyzed in the existing literature. Considering this view, the current study investigates the impact of agricultural value‐added, economic growth, non‐renewable energy, renewable energy, and tourism on carbon dioxide emission (CO2) from 1995 to 2017 in South Asian countries. The results found that agricultural value‐added, economic growth, non‐renewable energy, and tourism sector development significantly increase the environmental degradation, depicting that these factors have a harmful contribution to the environmental quality. However, renewable energy consumption has some ability to improve the environmental quality in this region. Additionally, the results of the Dumitrescu and Hurlin casualty test confirm the feedback hypothesis between economic growth and carbon emissions. However, a conservation hypothesis exists between carbon emission, and agriculture and finally, the growth hypothesis is valid between tourism and carbon emissions. Consistent with these empirical findings, this article suggests some vital policy implications for South Asian countries to accomplish their sustainable development goals (SDGs).
Aberrant activation of Rho/ROCK signaling in impaired polarity switching of colorectal micropapillary carcinoma
Authors: Onuma Kunishige , Sato Yumi , Okuyama Hiroaki , Uematsu Hiroyuki , Homma Keiichiro , Ohue Masayuki , Kondo Jumpei , Inoue Masahiro
Published: June 2021

Micropapillary carcinoma (MPC) is a morphologically distinctive form of carcinoma, composed of small nests of cancer cells surrounded by lacunar spaces. Invasive MPC is associated with poor prognosis. The nests of tumor cells in MPC reportedly exhibit reverse polarity, although the molecular mechanisms underlying MPC patterns are poorly understood. Using the cancer tissue‐originated spheroid (CTOS) method, we previously reported polarity switching in colorectal cancer (CRC). When cultured in suspension, the apical membrane promptly switches from the outside surface of the CTOSs to the surface of the lumen inside the CTOSs under extracellular matrix (ECM)‐embedded conditions, and vice versa. Here, we investigated two CTOS lines from CRC patient tumors with MPC lesions. Xenograft tumors from the CTOSs exhibited the MPC phenotype. The MPC‐CTOSs did not switch polarity in vitro. Time‐course analysis of polarity switching using real‐time imaging of the apical membrane revealed that local switching was continually propagated in non‐MPC‐CTOSs, while MPC‐CTOSs were unable to complete the process. Integrin β4 translocated to the outer membrane when embedded in ECM in both MPC and non‐MPC‐CTOSs. Protein levels, as well as the active form of RhoA, were higher in MPC‐CTOSs. The suppression of RhoA activity by GAP overexpression enabled MPC‐CTOSs to complete polarity switching both in vitro and in vivo, while overexpression of active RhoA did not affect polarity switching in non‐MPC‐CTOSs. Pretreatment with a ROCK inhibitor enabled MPC‐CTOSs to complete polarity switching both in vitro and in vivo, although delayed treatment after becoming embedded in ECM failed to do so. Thus, the inability to switch polarity might be a cause of MPC, in which the aberrant activation of RhoA plays a critical role. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Thermo‐mechanical, rheological and morphology properties of polypropylene composites: Residual CaCO3 as a sustainable by‐product
Authors: Techawinyutham Laongdaw , Sumrith Naruemon , Srisuk Rapeeporn , Techawinyutham Wiroj , Siengchin Suchart , Mavinkere Rangappa Sanjay
Published: June 2021

This research looked into the possibility of using residual calcium carbonate (CaCO3) as a by‐product of the cane sugar production process combined with polypropylene (PP) to replace commercial CaCO3. Using a co‐rotating twin‐screw extruder, the CaCO3/PP composites were made in the following ratios: 10:90, 20:80, 30:70, 40:60, and 50:50, with the addition of maleic anhydride polypropylene at 5 wt% of CaCO3. In terms of mechanical properties, thermal properties, rheological properties, and morphology, the effect of the residual CaCO3 filler reinforced in PP matrix was compared to commercial CaCO3/PP composites. The findings showed that residual CaCO3 from the sugar production process can replace the use of industrial CaCO3 mixing in plastic and can add value to the residual CaCO3. The residual CaCO3/PP composites had better tensile modulus, flexural strength, flexural modulus, impact resistance, and thermal stability than commercial CaCO3/PP composites, according to the findings. The composites' tensile modulus, flexural modulus, hardness, thermal stability, and rheological properties improved as the CaCO3 loading increased.
An investigation on the association between sodium glucose co‐transporter 2 inhibitors use and acute pancreatitis: A VigiBase study
Authors: Frent Ioana , Bucsa Camelia , Leucuta Daniel , Farcas Andreea , Mogosan Cristina
Published: June 2021

Purpose

To characterize acute pancreatitis (AP) related to sodium glucose co‐transporter 2 inhibitors and to investigate this relationship through disproportionality analysis in an international pharmacovigilance database.

Methods

We analyzed all AP reports for canagliflozin, dapagliflozin and/or empagliflozin from the WHOs Global adverse drug reactions database VigiBase® up to July 2019. We characterized the patients, reporters, and reactions, and we present the proportional reporting ratio (PRR) and information component (IC) for each of the gliflozins. AP cases were reports containing at least one of 11 previously selected preferred terms. Gliflozin exposure was considered for all reports with at least one gliflozin as suspected/ interacting drug.

Results

Of the 19 834 180 individual case safety reports in VigiBase, in 600 reports containing 618 AP group reactions, gliflozins were suspected/ interacting drugs. Men were affected in 52.3% of the cases and 59.6% of the patients were in the 45–64 years age group. The reporters were in 417 cases healthcare professionals. Most of the reactions were reported for canagliflozin (59.7%), followed by empagliflozin (21%) and dapagliflozin (19.2%) and were serious (98.6%). Most of the reactions' outcomes (84% of the patients) were favorable. Ketoacidosis was frequently associated with the AP (21.3%). Significant PRR and IC were found for pancreatitis and pancreatitis acute for all three gliflozins, pancreatitis necrotizing for canagliflozin and empagliflozin and pancreatitis relapsing for empagliflozin.

Conclusions

Most of the AP cases were serious and with favorable outcome. We identified possible alternative causes for AP, like concomitant medication, hypertriglyceridemia, and cholelithiasis and a frequent association with ketoacidosis. We found a significant association between AP and the use of canagliflozin, dapagliflozin, and empagliflozin that would need further investigation.
Tracheostomy and long‐term mechanical ventilation in children after veno‐venous extracorporeal membrane oxygenation
Authors: Mallory Palen P. , Barbaro Ryan P. , Bembea Melania M. , Bridges Brian C. , Chima Ranjit S. , Kilbaugh Todd J. , Potera Renee M. , Rosner Elizabeth A. , Sandhu Hitesh S. , Slaven James E. , Tarquinio Keiko M. , Cheifetz Ira M. , Friedman Matthew L.
Published: June 2021

Objective

Our objective is to characterize the incidence of tracheostomy placement and of new requirement for long‐term mechanical ventilation after extracorporeal membrane oxygenation (ECMO) among children with acute respiratory failure. We examine whether an association exists between demographics, pre‐ECMO and ECMO clinical factors, and the placement of a tracheostomy or need for long‐term mechanical ventilation.

Methods

A retrospective multicenter cohort study was conducted at 10 quaternary care pediatric academic centers, including children supported with veno‐venous (V‐V) ECMO from 2011 to 2016.

Results

Among 202 patients, 136 (67%) survived to ICU discharge. All tracheostomies were placed after ECMO decannulation, in 22 patients, with 19 of those surviving to ICU discharge (14% of survivors). Twelve patients (9% of survivors) were discharged on long‐term mechanical ventilation. Tracheostomy placement and discharge on home ventilation were not associated with pre‐ECMO severity of illness or pre‐existing chronic illness. Patients who received a tracheostomy were older and weighed more than patients who did not receive a tracheostomy, although this association did not exist among patients discharged on home ventilation. ECMO duration was longer in those who received a tracheostomy compared with those who did not, as well as for those discharged on home ventilation, compared to those who were not.

Conclusion

The 14% rate for tracheostomy placement and 9% rate for discharge on long‐term mechanical ventilation after V‐V ECMO are important patient‐centered findings. This study informs anticipatory guidance provided to families of patients requiring prolonged respiratory ECMO support, and lays the foundation for future research.
Muon Discrepancy Within D‐brane String Compactifications
Authors: Anchordoqui Luis A. , Antoniadis Ignatios , Huang Xing , Lüst Dieter , Taylor Tomasz R.
Published: June 2021

Very recently, the Muon g − 2 experiment at Fermilab has confirmed the E821 Brookhaven result, which hinted at a deviation of the muon anomalous magnetic moment from the Standard Model (SM) expectation. The combined results from Brookhaven and Fermilab show a difference with the SM prediction δaμ = (251 ± 59) × 10−11 at a significance of 4.2σ, strongly indicating the presence of new physics. Motivated by this new result we reexamine the contributions to δaμ from both: (i) the ubiquitous U(1) gauge bosons of D‐brane string theory constructions and (ii) the Regge excitations of the string. We show that, for a string scale , the contribution from anomalous U(1) gauge bosons which couple to hadrons could help to reduce (though not fully eliminate) the discrepancy reported by the Muon g − 2 Collaboration. Consistency with null results from LHC searches of new heavy vector bosons imparts the dominant constraint. We demonstrate that the contribution from Regge excitations is strongly suppressed as it was previously conjectured. We also comment on contributions from Kaluza‐Klein (KK) modes, which could help resolve the δaμ discrepancy. In particular, we argue that for 4‐stack intersecting D‐brane models, the KK excitations of the U(1) boson living on the lepton brane would not couple to hadrons and therefore can evade the LHC bounds while fully bridging the δaμ gap observed at Brookhaven and Fermilab.
Anti‐gastric cancer activity and mechanism of natural compound “Heilaohulignan C” isolated from Kadsura coccinea
Authors: Daniyal Muhammad , Liu Yongbei , Yang Yupei , Xiao Feng , Fan Jialong , Yu Huanghe , Qiu Yixing , Liu Bin , Wang Wei , Yuhui Qin
Published: June 2021

In this research, we analyzed the antitumor activity of one new compound Heilaohulignan C (B‐6) on the human gastric carcinoma cells. MTT, cell migration, Calcein AM/Propidium Iodide (PI), and flow cytometry in BGC‐823 cell line (gastric tumor). Western blot was utilized to distinguish the protein level. Xenografts nude mice were used for in vivo anticancer analysis. H&E staining and laboratory investigation was accomplished for toxicity study. MTT test demonstrated the cytotoxicity of BGC‐823 cells, Calcein AM/Propidium Iodide (PI) examine indicated increment dead cells proportion with a high dose of B‐6, Flow cytometry (FACS) measure showed that B‐6 influenced gastric cancer cells by initiating apoptosis. Western blot analysis confirmed that (B‐6) decrease the level of Bcl‐2 and increase the level of p53, Bax, and cleaved Caspase‐3, this confirms that the B‐6 doing the apoptosis through caspase and cytochrome C apoptotic pathways. Also, B‐6 particularly decline the tumor volume and tumor size in the xenograft mice. H&E staining additionally supports that B‐6 does not have any toxic impact on the normal tissues. This research supports that B‐6 have pharmacological activity against gastric cancer, by p53 and mitochondrial dependent apoptotic pathway, and have no toxicity on normal tissues.
Variable selection for censored data using Modified Correlation Adjusted coRrelation (MCAR) scores
Authors: Mimi Afsana , Khan Md Hasinur Rahaman
Published: June 2021

Dealing with high‐dimensional censored data is very challenging because of the complexities in data structure. This article focuses on developing a variable selection procedure for censored high‐dimensional data with the AFT models using the Modified Correlation Adjusted coRrelation (MCAR) scores method. The latter is developed based on CAR scores method that provides a canonical ordering that encourages grouping of correlated predictors and down‐weights antagonistic variables. The proposed MCAR scores method is developed as an extension of the CAR scores method using NOVEL integration of the sample and threshold estimator of the correlation matrix as suggested by Huang and Frylewicz. The proposed MCAR exhibits computationally more efficient estimates under model sparsity and can provide a canonical ordering among the predictors. The MCAR method is a greedy method that is also easy to understand and can perform estimation and variable selection simultaneously. Performances of variable selection by the MCAR method have been compared with other existing regularized techniques in literature—such as the lasso, elastic net and with a machine learning technique called boosting and with the censored CAR by a number of simulation studies and a real microarray data set called diffuse large‐B‐cell lymphoma. Results indicate that when correlation exists among the covariates, the MCAR method outperforms all five techniques while for uncorrelated data, the MCAR performs quite similar to the CAR method but clearly outperforms the other three methods. The empirical study further reveals that the MCAR method exhibits the best predictive performance among the methods.
Borrowing from supplemental sources to estimate causal effects from a primary data source
Authors: Boatman Jeffrey A. , Vock David M. , Koopmeiners Joseph S.
Published: June 2021

The increasing multiplicity of data sources offers exciting possibilities in estimating the effects of a treatment, intervention, or exposure, particularly if observational and experimental sources could be used simultaneously. Borrowing between sources can potentially result in more efficient estimators, but it must be done in a principled manner to mitigate increased bias and Type I error. Furthermore, when the effect of treatment is confounded, as in observational sources or in clinical trials with noncompliance, causal effect estimators are needed to simultaneously adjust for confounding and to estimate effects across data sources. We consider the problem of estimating causal effects from a primary source and borrowing from any number of supplemental sources. We propose using regression‐based estimators that borrow based on assuming exchangeability of the regression coefficients and parameters between data sources. Borrowing is accomplished with multisource exchangeability models and Bayesian model averaging. We show via simulation that a Bayesian linear model and Bayesian additive regression trees both have desirable properties and borrow under appropriate circumstances. We apply the estimators to recently completed trials of very low nicotine content cigarettes investigating their impact on smoking behavior.
Christmas‐Tree‐Shaped Palladium Nanostructures Decorated on Glassy Carbon Electrode for Ascorbic Acid Oxidation in Alkaline Condition
Authors: Hasan Mahmudul , Nagao Yuki
Published: June 2021

Christmas‐tree‐shaped Pd nanostructures were synthesized using a simple one‐step electrodeposition method with no additives on a glassy carbon electrode (GCE) surface. Growth of the hierarchical nanostructures was optimized through the applied potential, deposition time, and precursor concentration. Comprehensive characterization techniques such as scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDX), X‐ray photoelectron spectroscopy (XPS), X‐ray powder diffraction (XRD), and cyclic voltammetry (CV) were used to characterize structural features of the Christmas‐tree‐shaped Pd nanostructures. Our Christmas‐tree‐shaped Pd nanostructures showed excellent catalytic activity for ascorbic acid (AA) electro‐oxidation in the alkaline condition. The modified electrode exhibited current density of 4.5 mA cm−2: much higher than that of unmodified GCE (0.6 mA cm−2). This simple electrodeposition technique with well‐defined hierarchical Pd nanostructures is expected to offer new perspectives using Pd‐based nanostructured surfaces in different research areas.
Highly Selective Hydrogenation of Phenol Catalyzed by Porous BN Supported Ni−Pd Catalysts
Authors: Zhang Lei , Fang Yi , Du Zhao , Bi Dandan , Guo Zhonglu , Liu Zhenya , Huang Yang , Lin Jing , Tang Chengchun
Published: June 2021

Phenol, as a phenolic organic substance, is widely present in industrial wastewater and is an important organic pollutant. Porous boron nitride (p‐BN) is an ideal material as catalyst support because it has a large specific surface area and a variety of pore structures. In this paper, a series of Ni−Pd/p‐BN catalysts were prepared by precipitation method. Meanwhile, the catalytic performance of the catalysts for the hydrogenation of phenol to cyclohexanol was systematical and comprehensive studied. Significantly, with the optimal catalyst, the conversion of phenol was greatly improved to reach more than 99.9 %, and the selectivity of cyclohexanol could almost exceed 99.8 %. In addition, the Ni−Pd/p‐BN catalyst can be reused as an effective catalyst for numerous cycles, indicating superior reusability and recyclability. After five cycles, the conversion of phenol and the selectivity of cyclohexanol is only reduced to ∼80 %. This catalyst will be a promising material in the field of industrial catalysis applications.
NMR Analysis of a Series of 6,14‐Ethenomorphinan Derivatives as PET Precursors and Reference Substances**
Authors: Marton János , Sipos Attila , Henriksen Gjermund , Cumming Paul , Berényi Sándor , Schmitt Bettina M. , Szabó Zoltán
Published: June 2021

The new semisynthetic oripavine derivative 3‐O‐trityl‐6‐O‐desmethyl‐dihydroetorphine was synthesized from the poppy alkaloid thebaine in a six‐step procedure. This compound can be applied as precursor for the radiosynthesis of [6‐O‐methyl‐11C]‐dihydroetorphine ([11C]DHE). We present a detailed description of 1H and 13C NMR data of reference standards and precursors for [6‐O‐methyl‐11C]‐ and [6‐O‐(2‐[18F]fluoroethyl]orvinols. This includes the complete assignment for 19 oripavine derivatives examined in 1D and 2D NMR experiments. We also investigated the molecular basis for regioselectivity of fluoroalkylation of 3‐O‐trityl‐6‐O‐desmethyl‐phenethyl‐orvinol (TDPEO) using computational methods.
Report of the Nomenclature Committee for Fossils: 14
Authors: Herendeen Patrick S.
Published: June 2021

The following eight generic names are recommended for conservation: Camptopteris with a conserved type, Clathropteris against Meniscites, Dictyophyllum against Quercites, Eristophyton against Ullmannites, Leptopteris C. Presl against Leptopteris Brongn., Lonchopteris with a conserved type, Otozamites against Otopteris, and Pirea Vavrdová against Pirea T. Durand. The following two species names are recommended for conservation: Glyptolepis keuperiana with a conserved type and Palaeospathe daemonorops against Chamaerops teutonica. The Committee supports the addition of A. Richard's 1822 publication to the list of suppressed works. The Committee judged the descriptive statement associated with “Rhyniales Němejc” to not be adequate for valid publication.