bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphorus influences annual bluegrass competitiveness at seeding in perennial ryegrass and creeping bentgrass
Authors: McNally Brandon C. , Elmore Matthew T. , Kowalewski Alexander R. , Cain Alyssa B.
Published: December 2022

Annual bluegrass (AB; Poa annua L.) infestation is aided by phosphorus (P), but there is no information evaluating the effect of P on AB encroachment into turfgrass at seeded establishment. We hypothesized AB seedling survival and vigor will increase with P rates, compromising establishment of desired turfgrass species. Greenhouse pot studies evaluated the effect of P application rate on AB establishment or cover when seeded with perennial ryegrass (Lolium perenne L.) or creeping bentgrass (Agrostis stolonifera L. ‘007’). Two experimental runs were repeated in time. In perennial ryegrass, five P rates (0, 25, 50, 100, and 200 kg P ha−1) and two cultivars (‘Black Cat II’ and ‘Home Run LS’) were tested in sand media (11 mg kg−1 Mehlich‐3 extractable P). In creeping bentgrass, five P rates (0, 12.5, 25, 50, and 100 kg P ha−1), which were modified in the second run (0, 6.25, 12.5, 25, and 50 kg P ha−1), were tested in sand media (3 mg kg−1 Mehlich‐3 extractable P). Regardless of cultivar, AB establishment in perennial ryegrass improved when P was applied and was 90% of maximum at 1.7 kg P ha−1. In creeping bentgrass, both AB and creeping bentgrass cover increased when P was applied and AB was 90% of maximum at 12.1 kg P ha−1. Creeping bentgrass cover was not compromised by P application rates as low as 6.25 kg ha−1. Phosphorus enhances AB cover from seed when sown with perennial ryegrass or creeping bentgrass seed in low P soils.
Expansion of the genotypic and phenotypic spectrum of CTCF‐related disorder guides clinical management: 43 new subjects and a comprehensive literature review
Authors: Valverde de Morales Hannah Gabriela , Wang Hsiao‐Lin V. , Garber Kathryn , Cheng Xiaodong , Corces Victor G. , Li Hong
Published: December 2022

Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF‐related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed. Here, we examined the clinical features, including facial profiles, and genotypic spectrum of 107 subjects with identified CTCF variants, including 43 new and 64 previously described subjects. Among the 43 new subjects, 23 novel variants were reported. The cardinal clinical features in subjects with CRD included intellectual disability/developmental delay (91%) with speech delay (65%), motor delay (53%), feeding difficulties/failure to thrive (66%), ocular abnormalities (56%), musculoskeletal anomalies (53%), and behavioral problems (52%). Other congenital anomalies were also reported, but none of them were common. Our findings expanded the genotypic and phenotypic spectrum of CRD that will guide genetic counseling, management, and surveillance care for patients with CRD. Additionally, a newly built facial gestalt on the Face2Gene tool will facilitate prompt recognition of CRD by physicians and shorten a patient's diagnostic odyssey.
Preparative‐Scale Biocatalytic Oxygenation of N‐Heterocycles with a Lyophilized Peroxygenase Catalyst
Authors: Pogrányi Balázs , Mielke Tamara , Díaz‐Rodríguez Alba , Cartwright Jared , Unsworth William P. , Grogan Gideon
Published: December 2022

A lyophilized preparation of an unspecific peroxygenase variant from Agrocybe aegerita (rAaeUPO‐PaDa‐I‐H) is a highly effective catalyst for the oxygenation of a diverse range of N‐heterocyclic compounds. Scalable biocatalytic oxygenations (27 preparative examples, ca. 100 mg scale) have been developed across a wide range of substrates, including alkyl pyridines, bicyclic N‐heterocycles and indoles. H2O2 is the only stoichiometric oxidant needed, without auxiliary electron transport proteins, which is key to the practicality of the method. Reaction outcomes can be altered depending on whether hydrogen peroxide was delivered by syringe pump or through in situ generation using an alcohol oxidase from Pichia pastoris (PpAOX) and methanol as a co‐substrate. Good synthetic yields (up to 84 %), regioselectivity and enantioselectivity (up to 99 % ee) were observed in some cases, highlighting the promise of UPOs as practical, versatile and scalable oxygenation biocatalysts.
Investigation on mechanochemically modified calcium‐based adsorbent for flue gas HCl removal
Authors: Shen Zhen , Liu Xiaoshuo , Ning Xiang , Wang Rui , Yue Pujie , Shen Ao , Meng Lei , Wang Yuqing , Gu Xiaobing , Duan Yufeng
Published: December 2022

For purpose of reducing chlorine ions entering the wet flue gas desulfurazition (WFGD) tower to realize the WFGD waste water sequestration and the gypsum upgrading, a technical method of adsorbent injection into flue gas to remove HCl was proposed in this work. A new NaOH‐modified CaO (CA‐MC‐NA) was prepared by the mechanochemical ball milling method as a superior adsorbent for HCl removal in flue gas. The influence of particle size and Na doping on the dechlorination efficiency and chlorine capacity was investigated in a fixed bed reaction system. The experimental results demonstrated that the HCl removal performance is improved significantly under proper particle size and Na doping, as manifested by the experiment results that the chlorine capacity increases from 27.18 to 38.36 mg/g by simple mechanical ball milling, while it surprisingly reaches 75.36 mg/g by doping 5 wt.% NaOH. The surface physicochemical characteristics was explored by combined sample characterization of BET, XRD, SEM, elemental mapping, and particle size distribution. Dechlorination mechanism of the adsorbents were deduced and discussed. It shows that the mechanical ball milling process reduces the particle sizes to the submicron scale that induces the break and reconstruction of molecular interfacial bonds. It also increases the oxygen defects on the adsorbent surface. The doping of NaOH does not change the crystal structure of the dechlorinator, and Na ions can be chemically loaded over CaO in the form of ionic bonds. Free oxygen atoms or adsorbed oxygen molecules could combine with dissociated hydrogen atoms thus forming hydroxide radicals, which enhances the alkalinity of the adsorbent and boosts the removal of hydrogen chloride.
Facile fabrication of high‐performance epoxy systems with superior mechanical properties, flame retardancy, and smoke suppression
Authors: Wu Qilei , Xiao Long , Chen Junfeng , Peng Zhihe
Published: December 2022

The realization of high‐performance thermosetting polymers with superior mechanical properties, flame retardancy and smoke suppression is very necessary but not yet implemented. Herein, a flame‐retardant curing agent (BICPD) combining cyclotriphosphazene and phosphaphenanthrene groups was synthesized, and used to prepare high‐performance, flame‐retardant epoxy (EP/BICPD) systems. Our results showed that the EP/BICPD systems began to cure at 110°C and solidify rapidly under heating. In comparison to the common epoxy system, the EP/BICPD thermosets exhibited improved glass transition temperature and mechanical properties. Most impressively, the EP/BICPD thermosets possessed outstanding flame retardancy and smoke suppression. The EP/BICPD‐20 thermoset achieved the LOI value of 37.7% and passed the UL94 V‐0 rating. Additionally, compared with the common epoxy thermoset, the peak of heat release rate (pHRR) and total smoke production (TSP) of EP/BICPD‐20 thermoset were reduced by ~70.0% and ~43.4%, respectively. The significant enhancements in flame retardancy and smoke suppression was mainly due to the collaboration of cyclotriphosphazene and phosphaphenanthrene in condensed and gaseous phases. Therefore, the high‐performance EP/BICPD systems with high glass transition temperature, satisfied mechanical properties, superior flame retardancy and smoke suppression showed profound scientific and industrial significance.
Investigation of the effect of heat treatment on the inductive effect of GO membrane during the ion diffusion process
Authors: Yin Hao , Yang Haodong , Chen Zhe , Yao Lei , Wang Geming , Deng Quanrong , Wang Hongmei
Published: December 2022

The inductive effect of 2D material in an aqueous solution can be potentially applied in biological implantable electronic devices. In this paper, graphene oxide (GO) membranes were prepared via the vacuum filtration method and then treated under different heat temperatures. X‐ray diffraction and scanning electron microscopy results showed the shrinkage of the interlayer spacing in the GO membrane, while Fourier transform infrared results indicated the loss of oxygen‐containing polar groups during the heat treatment. EIS results confirmed the inductive signal of the GO membrane appeared during the ion diffusion process. And the inductive effect can be controlled by the polar groups and the interlayer spacing in the GO membrane. Moreover, at lower electrolyte concentrations (0.0100 mol/L), more polar groups lead to a stronger inductive signal, while at higher electrolyte concentrations (0.10 mol/L), narrower interlayer spacing results in a stronger inductive signal. The investigation may provide a key clue to tune the inductance of the biological electronic device based on GO.
The Michigan Histology website as an example of a free anatomical resource serving learners and educators worldwide
Authors: Hortsch Michael
Published: December 2022

With anatomical education becoming a global endeavor, free online resources offered via the Internet or other electronic venues are of increasing importance for teaching and learning communities worldwide. Students and instructors from developing countries, often limited in access to modern instructional resources by infrastructural and financial constraints, are frequent users of such online learning tools. During the recent Covid‐19 pandemic when all academic institutions were forced to quickly switch to a non‐contact mode of teaching, free online instructional resources were often essential for continuing the educational mission. However, there are a number of obstacles and issues that need to be considered when creating and offering such learning resources. These include the type, quality, and completeness of the content, their educational purpose, access to technical and financial resources, copyright and ethical issues, and more. Educators, who plan to generate and maintain free online resources, should also be aware that such projects usually require a considerable long‐term time commitment. In this article, these issues are discussed using the Michigan Histology website as an example. The discussion also addresses how e‐learning resources like the Michigan Histology website supported online learning during the recent Covid‐19 pandemic.
Organocatalytic Ring‐Opening Polymerization of ϵ‐Caprolactone with Phosphoramidimidates (PADIs) as a Bifunctional Brønsted Acid Catalyst
Authors: Zhang Xun , Sun Pan , Jiang Yu , Liao Saihu
Published: December 2022

In this study, an organocatalytic ring‐opening polymerization (ROP) of ϵ‐caprolactone (ϵ‐CL) has been developed by employing PADIs as a novel and efficient acid/base bifunctional organocatalyst, which could afford metal‐free poly(ϵ‐caprolactone) with predictable molecular weight and narrow dispersity at a low catalyst loading under mild conditions. NMR and kinetic studies indicate that the ring‐opening polymerizations of lactones catalyzed by PADIs proceed in a living and well controlled manner. Moreover, this organic Brønsted acid catalytic system could allow the synthesis of PCL with molecular weight above 60 kg/mol, as well as well‐defined star polymers.
Videoconference to supervise early intensive behavioral intervention: A preliminary evaluation of acceptability
Authors: Hay‐Hansson Aina , Eldevik Sigmund , Strømgren Børge
Published: December 2022

At present, early intensive behavioral intervention (EIBI) for children with autism spectrum disorders is the intervention that has the strongest empirical support. EIBI requires frequent supervision by qualified professionals. Norway, like many other countries, has a shortage of qualified supervisors, particularly in rural regions. This study used a reversal design to investigate how supervisors and supervisees perceive the quality of EIBI supervision and the local team's preparedness when supervision was provided either on‐site or via videoconference. Calculations were made on how much time could be saved on travel when part of the supervision was provided via videoconference. There were no significant differences in the supervisors' and supervisees' ratings of on‐site and videoconference supervision. Moreover, the supervisors found the local EIBI teams to be better prepared when supervision was provided via videoconference, and the videoconference supervision meetings were shorter. The study discusses the implications of these findings for the accessibility of EIBI and case capacity and proposes some areas for further research.
Inexpensive indoor acoustic material estimation for realistic sound propagation
Authors: Kim Taeyoung , An Inkyu , Yoon Sung‐eui
Published: December 2022

For the realistic and immersive experience in a virtual environment, it is important to estimate and reflect the acoustic characteristic of the real indoor scenes. This article proposes a method of directly measuring the reflection coefficient of a surface, which is an acoustic characteristics in the real environment. Because expensive optimization‐based studies that mainly aim to reproduce recorded sounds indirectly estimate acoustic materials, new estimates are required whenever the actual environment changes. Our approach utilizes the method of the acoustics field to enable anyone to easily and directly measure the reflection coefficient of a real environment and generate sound in a virtual environment. We obtain the impulse response (IR) for the target surface, separate the direct sound and the reflected sound, and calculate the reflection coefficient for each surface. The measurement of the IR and the reflection coefficient calculation takes about 2 s. Our result produces a sound with a similar reverberation time to the sound recorded in the real environment.
Controlled Hydrolysis of Phosphate Esters: A Route to Calixarene‐Supported Rare‐Earth Clusters
Authors: Hosseinzadeh Marjan , Sanz Sergio , van Leusen Jan , Izarova Natalya V. , Brechin Euan K. , Dalgarno Scott J. , Kögerler Paul
Published: December 2022

Phosphate ester bonds are widely present in nature (e. g. DNA/RNA) and can be extremely stable against hydrolysis without the help of catalysts. Previously, we showed how the combination of phosphoryl and calix[4]arene moieties in the same organic framework (LPO) allows isolation of single lanthanide (Ln) metal ions as [LnIII(LPO)2](O3SCF3)3. Here we report how by controlling the reaction conditions a new hydrolyzed phosphoryl‐calix[4]arene ligand (H3LHPO) is formed as a result of LnIII‐mediated P–OEt bond cleavage in three out of the eight possible sites in LPO. The chelating nature of H3LHPO traps the LnIII species in the form of [LnIII(LHPO)((EtO)2P(O)OH)]2 dimers (Ln=La, Dy, Tb, Gd), where the Dy derivative shows slow magnetization relaxation. The strategy presented herein could be extended to access a broader library of hydrolyzed platforms (HxLHPO; x=1–8) that may represent mimics of nuclease enzymes.
Development of an Analytical Method for the Determination of Trace Lead in Lake Water Samples by Flame Atomic Absorption Spectrophotometry after Vortex Assisted‐Stearic Acid Coated Magnetic Nanoparticle Based Extraction
Authors: Serbest Hakan
Published: December 2022

In the present study, a method is proposed for the determination of lead at trace levels by slotted quartz tube‐flame atomic absorption spectrophotometry (SQT‐FAAS) after preconcentration with stearic acid coated magnetic nanoparticle‐based dispersive solid phase extraction (SA‐MNP‐DSPE). The slotted quartz tube (SQT) is used to enhance the analyte atom residence time in the light path. Stearic acid coated magnetic iron oxide (Fe3O4) nanoparticles, which can be easily collected with an external magnet, are used as adsorbent in the extraction process. The limit of detection (LOD) and the limit of quantitation (LOQ) values of the proposed method are obtained as 0.90 and 2.9 µg L−1, respectively. The method allows high repeatability in a wide linear range between 5.0 and 250 µg L−1, and the relative standard deviation for six replicates is 5.8%. The detection power is enhanced by about 77‐fold compared to the regular flame atomic absorption spectrophotometry (FAAS) system. The method is validated by recovery experiments to four different lake water samples. After the spiking tests, good recovery results are calculated between 97% and 106%. These results show that lead can be detected at low levels in lake water samples with high sensitivity, accuracy, and precision.
A randomized Phase 2 study to compare erlotinib with or without bevacizumab in previously untreated patients with advanced non–small cell lung cancer with EGFR mutation
Authors: Lee Youngjoo , Kim Hye Ryun , Hong Min Hee , Lee Ki Hyeong , Park Keon Uk , Lee Geon Kook , Kim Hyae Young , Lee Soo‐Hyun , Lim Kun Young , Yoon Sung Jin , Cho Byoung Chul , Han Ji‐Youn
Published: December 2022

Background

This study evaluated whether an addition of bevacizumab to erlotinib improves clinical outcomes in patients with advanced EGFR‐mutated non–small cell lung cancer (NSCLC).

Methods

This is an open‐label, multicenter, randomized Phase 2 study in South Korea. Chemonaïve patients with Stage IIIB/IV NSCLC with EGFR 19 deletion or L858R mutation were eligible. Asymptomatic brain metastasis (BM) was enrolled without local treatment. Patients received either erlotinib plus bevacizumab or erlotinib.

Results

Between December 2016 and March 2019, 127 patients were randomly assigned to receive erlotinib plus bevacizumab (n = 64) or erlotinib (n = 63). Fifty‐nine (46.5%) patients had baseline BM. Fewer patients in the erlotinib plus bevacizumab arm received radiotherapy for BM than in the erlotinib arm (10.3% vs. 40.0%). A trend toward longer progression‐free survival (PFS) was observed in the erlotinib plus bevacizumab arm compared with the erlotinib alone arm; however, it was not statistically significant (median PFS, 17.5 months vs. 12.4 months; hazard ratio [HR], 0.74; 95% CI, 0.51–1.08; p = .119). The unplanned subgroup analysis showed a longer PFS with erlotinib plus bevacizumab in patients with BM (median PFS, 18.6 months vs. 10.3 months; HR, 0.54; 95% CI, 0.31–0.95; p = .032). Grade 3 or worse adverse events occurred in 56.6% of the erlotinib plus bevacizumab arm and 20.6% of the erlotinib arm.

Conclusions

Although it was not statistically significant, a trend to improvement in PFS was observed in patients with erlotinib plus bevacizumab compared to erlotinib alone.

Plain Language Summary

A randomized Phase 2 study compared erlotinib with or without bevacizumab in previously untreated patients with advanced non–small cell lung cancer with EGFR mutation. The erlotinib plus bevacizumab failed to improve median progression‐free survival compared with the erlotinib alone. However, the progression‐free survival benefit from erlotinib plus bevacizumab was found in patients with brain metastasis with no severe hemorrhagic adverse effects.
The local and long‐range input landscape of inhibitory neurons in mouse auditory cortex
Authors: Tasaka Gen‐ichi , Maggi Claudia , Taha Elham , Mizrahi Adi
Published: December 2022

Roughly 20% of the neurons in the mouse cortex are inhibitory interneurons (INs). Of these, the three major subtypes are parvalbumin (PV), somatostatin (SST), and vasoactive intestinal polypeptide (VIP) expressing neurons. We used monosynaptic rabies tracing to compare the presynaptic input landscape onto these three IN subtypes in the mouse primary auditory cortex (A1). We compared both local patterns of monosynaptic inputs as well as long‐range input patterns. The local monosynaptic input landscape to SST neurons was more widespread as compared to PV and VIP neurons. The brain‐wide input landscape was rich and heterogeneous with >40 brain regions connecting to all the three INs subtypes from both hemispheres. The general pattern of the long‐range input landscape was similar among the groups of INs. Nevertheless, a few differences could be identified. At low resolution, the proportion of local versus long‐range inputs was smaller for PV neurons. At mesoscale resolution, we found fewer inputs from temporal association area to VIP INs, and more inputs to SST neurons from basal forebrain and lateral amygdala. Our work can be used as a resource for a quantitative comparison of the location and level of inputs impinging onto discrete populations of neurons in mouse A1.
Reactions of Thorium Oxide Clusters with Water: The Effects of Oxygen Content
Authors: Wang Bin , Ye Shu , Zhang Si‐Yuan , Fang Hong‐Ling , Zhang Yong‐Fan , Xia Chan‐Juan , Chen Wen‐Jie
Published: December 2022

Thorium oxide has many important applications in industry. In this article, theoretical calculations have been carried out to explore the hydrolysis reactions of the ThOn (n=1–3) clusters. The reaction mechanisms of the O‐deficient ThO and the O‐rich ThO3 are compared with the stoichiometric ThO2. The theoretical results show good agreement with the prior experiments. It is shown that the hydrolysis mainly occurred on the singlet potential surface. The overall reactions consist of two hydrolysis steps which are all favourable in energy. The effects of oxygen content on the hydrolysis are elucidated. Interestingly, among them, the peroxo group O22− in ThO3 is converted to the HOO− ligand, behaving like the terminal O2− in the hydrolysis which is transformed into the HO− groups. In addition, natural bond orbital (NBO) analyses were employed to further understand the bonding of the pertinent species and to interpret the differences in hydrolysis.
Genetic variations in relation to bleeding and pharmacodynamics of dabigatran in Chinese patients with nonvalvular atrial fibrillation: A nationwide multicentre prospective cohort study
Authors: Xiang Qian , Xie Qiufen , Liu Zhiyan , Mu Guangyan , Zhang Hanxu , Zhou Shuang , Wang Zhe , Wang Zining , Zhang Yatong , Zhao Zinan , Yuan Dongdong , Guo Liping , Wang Na , Xiang Jing , Song Hongtao , Sun Jianjun , Jiang Jie , Cui Yimin
Published: December 2022

Introduction

To identify the potential factors responsible for the individual variability of dabigatran, we investigated the genetic variations associated with clinical outcomes and pharmacodynamics (PD) in Chinese patients with nonvalvular atrial fibrillation (NVAF).

Materials and methods

Chinese patients with NVAF taking dabigatran etexilate with therapeutic doses were enrolled. The primary (bleeding events) and secondary (thromboembolic and major adverse cardiac events) outcomes for a 2‐year follow‐up were evaluated. Peak and trough PD parameters (anti‐FIIa activity, activated partial thromboplastin time and prothrombin time) were detected. Whole‐exome sequencing, genome‐wide sequencing and candidate gene association analyses were performed.

Results

There were 170 patients with NVAF treated with dabigatran (110 mg twice daily) who were finally included. Two single‐nucleotide polymorphisms (SNPs) were significantly related with bleeding, which include UBASH3B rs2276408 (odds ratio [OR] = 8.79, 95% confidence interval [CI]: 2.99–25.83, p = 7.77 × 10−5 at sixth month visit) and FBN2 rs3805625 (OR = 8.29, 95% CI: 2.87–23.89, p = 9.08 × 10−5 at 12th month visit), as well as with increased trends at other visits (p < .05). Furthermore, minor allele carriers of 16 new SNPs increased PD levels, and those of one new SNP decreased PD values (p < 1.0 × 10−5). Lastly, 33 new SNPs were found to be associated with bleeding and PD among 14 candidate genes. Unfortunately, the low number of secondary outcomes precluded further association analyses.

Conclusions

Genetic variations indeed affected bleeding and PD in Chinese patients with NVAF treated with dabigatran. The functions of these suggestive genes and SNPs might further be explored and verified in more in vivo and in vitro investigations.
Reinforcement learning movement path for multiple mobile sinks in wireless sensor networks
Authors: Vahabi Shahrokh , Mojab Seyed Payam , Hozhabri Amir , Daneshvar Ali
Published: December 2022

Mobile sink nodes play a very active role in wireless sensor network (WSN) routing. Because hiring these nodes can decrease the energy consumption of each node, end‐to‐end delay, and network latency significantly. Therefore, mobile sinks can soar the network lifetime dramatically. Generally, there are three movement paths for a mobile sink, which are as follows: (1) Random/stochastic, (2) controlled, and (3) fixed/ predictable/predefined paths. In this paper, a novel movement path is introduced as a fourth category of movement paths for mobile sinks. This path is based on deep learning, so a mobile sink node can go to the appropriate region that has more data at a suitable time. Thereupon, WSN routing can improve very much in terms of end‐to‐end delay, network latency, network lifetime, delivery ratio, and energy efficiency. The new proposed routing suggests a reinforcement learning movement path (RLMP) for multiple mobile sinks. The network in the proposed work consists of a couple of regions; each region can be employed for a special purpose, so this method is hired for any application and any size of the network. All simulations in this paper are done by network simulator 3 (NS‐3). The experimental results clearly show that the RLMP overcomes other approaches by at least 32.48% in the network lifetime benchmark.
Precipitation legacies amplify ecosystem nitrogen losses from nitric oxide emissions in a Pinyon–Juniper dryland
Authors: Krichels Alexander H. , Greene Aral C. , Jenerette G. Darrel , Spasojevic Marko J. , Glassman Sydney I. , Homyak Peter M.
Published: December 2022

Climate change is increasing the variability of precipitation, altering the frequency of soil drying‐wetting events and the distribution of seasonal precipitation. These changes in precipitation can alter nitrogen (N) cycling and stimulate nitric oxide (NO) emissions (an air pollutant at high concentrations), which may vary according to legacies of past precipitation and represent a pathway for ecosystem N loss. To identify whether precipitation legacies affect NO emissions, we excluded or added precipitation during the winter growing season in a Pinyon–Juniper dryland and measured in situ NO emissions following experimental wetting. We found that the legacy of both excluding and adding winter precipitation increased NO emissions early in the following summer; cumulative NO emissions from the winter precipitation exclusion plots (2750 ± 972 μg N‐NO m−2) and winter water addition plots (2449 ± 408 μg N‐NO m−2) were higher than control plots (1506 ± 397 μg N‐NO m−2). The increase in NO emissions with previous precipitation exclusion was associated with inorganic N accumulation, while the increase in NO emissions with previous water addition was associated with an upward trend in microbial biomass. Precipitation legacies can accelerate soil NO emissions and may amplify ecosystem N loss in response to more variable precipitation.
Risk prediction of mortality for patients with heart failure in England: observational study in primary care
Authors: Bottle Alex , Newson Roger , Faitna Puji , Hayhoe Benedict , Cowie Martin R.
Published: December 2022

Aims

Many risk prediction models have been proposed for heart failure (HF), but few studies have used only information available to general practitioners (GPs) in primary care electronic health records (EHRs). We describe the predictors and performance of models built from GP‐based EHRs in two cohorts of patients 10 years apart.

Methods and results

Linked primary and secondary care data for incident HF cases in England were extracted from the Clinical Practice Research Datalink for 2001–02 and 2011–12. Time‐to‐event models for all‐cause mortality were developed using a long list of potential baseline predictors. Discrimination and calibration were calculated. A total of 5966 patients in 156 general practices were diagnosed in 2001–02, and 12 827 patients in 331 practices were diagnosed in 2011–12. The 5‐year survival rate was 40.0% in 2001–02 and 40.2% in 2011–12, though the latter population were older, frailer, and more comorbid; for 2001–02, the 10‐year survival was 20.8% and 15‐year survival 11.1%. Consistent predictors included age, male sex, systolic blood pressure, body mass index, GP domiciliary visits before diagnosis, and some comorbidities. Model performance for both time windows was modest (c = 0.70), but calibration was generally excellent in both time periods.

Conclusions

Information routinely available to UK GPs at the time of diagnosis of HF gives only modest predictive accuracy of all‐cause mortality, making it hard to decide on the type, place, and urgency of follow‐up. More consistent recording of data relevant to HF (such as echocardiography and natriuretic peptide results) in GP EHRs is needed to support accurate prediction of healthcare needs in individuals with HF.
Iridium Diphosphine Complexes Featuring Pendant Lewis Acids: Efforts toward Selective Heteroarene Borylation
Authors: Demchuk Mitchell J. , Zurakowski Joseph A. , Drover Marcus W.
Published: December 2022

The selective forging of carbon‐boron bonds via C−H borylation stands as a central means to access fine chemical precursors. Notwithstanding, achieving selectivity in this reaction is difficult, calling for the design of molecular catalysts that offer a vector for mechanistic control. This report aims to achieve such through the strategic placement of Lewis acids in the ligand periphery, permitting engagement with a substrate through non‐covalent Lewis acid/base interactions. Various diphosphine iridium(I/III) complexes having 1,2‐bis(di‐n‐propylphosphino)ethane) (dnppe), tetrakisallylphosphinoethane (tape) and 1,2‐bis(di(3‐dicyclohexylboranyl)propylphosphino)ethane (P2BCy4) ligands were prepared. The P2BCy4 ligand scaffold boasts four Lewis acidic boron groups in its secondary coordination sphere, which are shown to engage with N‐heterocycles, tape is the precursor to P2BCy4, and dnppe is a saturated n‐propyl analogue devoid of boron functionality. Select combinations of such iridium salts/diphosphine ligands were assayed in the catalytic borylation of 2‐methylpyridine using B2Pin2 (Pin=pinacol).
Effects of Lipase Immobilization Conditions and Support Materials for the Production of Structured Triacylglycerols
Authors: Causevic Ariana , Olofsson Kim , Adlercreutz Patrick , Grey Carl
Published: December 2022

Structured triacylglycerols (STAG) with desired properties can be synthesized by transesterification using immobilized lipases. Herein, the effect of immobilization conditions and support material on the immobilization yield, specific activity and regioselectivity of lipases from Rhizomucor miehei (RML) and Rhizopus oryzae (ROL) in the production of STAG, are evaluated. Four different support materials utilizing adsorption and one with covalent binding are investigated. Ammonium sulfate is found to significantly increase the activity‐based immobilization yield (12% and 38% for RML and ROL, respectively) and specific activity on Accurel MP1000 (MP1000) when used as the immobilization buffer. Furthermore, the immobilization principle and support material influenced both the activity and regiospecificity. Immobilization by adsorption is found to result in higher catalytic activity, while covalent binding resulted in lipase inactivation. For RML, the highest specific activity of 43 µmol STAG min−1 g−1 (U) is obtained on MP1000, while ROL, which exhibited higher activities in general, results in a maximum activity of 120 U on Lifetech ECR8806. The obtained specific activites are comparable to the commercial preparations Novozym 40086 (45 U) and Lipase DF “Amano” IM (147 U) while the regiospecificity of the developed preparations is even higher, forming at least 64% less byproduct.

Practical applications: There is an increasing need for lipids with specific nutritional and physical properties in health, nutrition, and food applications. In this context, STAG are highly promising products due to the possibility to tailor the composition to obtain the desired properties. Immobilized lipases are the catalyst of choice for the production of STAG, in which activity and regioselectivity are particularly important parameters for the process performance. In this study, it is shown that these parameters can be affected by the immobilization conditions and support material. Immobilized preparations with high activity and excellent regiospecificity are created on commercially available supports. This shows the possibility of STAG synthesis with high purity and beneficial properties.
Gold(I)‐Catalyzed and PTSA‐Promoted Cycloisomerization of Ynamides to Access Pyrrole Substituted α,β‐Unsaturated Ketones**
Authors: Choudhary Shivani , Gayyur  , Ghosh Nayan
Published: December 2022

Substituted pyrroles are prevalent aromatic ring systems encountered in numerous natural products and bioactive molecules. Herein, a novel ynamide scaffold has been designed, synthesized and subsequently applied to an unprecedented gold‐catalyzed and para‐toluenesulfonic acid (PTSA)‐assisted cascade cycloisomerization reaction for the synthesis of β‐pyrrole substituted α,β‐unsaturated ketones. Notably, the reaction is stereoselective, offering E‐isomer as major product with low to moderate yield.
The temporal expression of circulating microRNAs after acute experimental pain in humans
Authors: Giordano Rocco , Gerra Maria Carla , Okutani Hiroai , Lo Vecchio Silvia , Stensballe Allan , Petersen Kristian Kjær‐Staal , Arendt‐Nielsen Lars
Published: December 2022

Background

MicroRNAs (miRNAs) can modulate several biological systems, including the pain system. This study aimed to evaluate the temporal expression of circulating miRNAs in the plasma of healthy volunteers as a marker for epigenetic changes before and after an acute, experimental, pain provocation by intramuscular hypertonic saline injection.

Methods

Twenty volunteers were randomly allocated into two groups and received either hypertonic (pain) or isotonic (control) saline injection in the first dorsal interosseous muscle of their dominant hand. Pain intensity was continuously recorded for 20 minutes after injection on a VAS scale from 0 to 100 (0 indicates no pain and 100 the worst imaginable pain). Blood samples were taken at baseline, 30 minutes, 3 hours, and 24 hours post‐injection, and plasma was separated. MiRNA extracts were used for RNA sequencing with the Illumina NextSeq platform. MiRNA transcripts were compared between the pain and the no‐pain, control group at every time point. Significant differences were considered when folds were >2 and the False Discovery Rate wasp < 0.05.

Results

After 30 minutes, 4 miRNAs were significantly altered in the pain group compared to controls, which increased to 24 after 3 hours and to 42 after 24 hours from baseline (p < 0.0001). Two miRNAs were consistently upregulated throughout the experiment. Enrichment analysis showed significant miRNAs involved in brain perception of pain, brain signalling and response to stimuli.

Conclusions

This exploratory study is the first to report on the temporal expression of circulating miRNAs after an acute, human experimental muscle pain model.

Significance

This exploratory study evaluated the temporal profile of circulating miRNAs in the plasma of healthy subjects after acute experimental pain. Several miRNAs were altered in subjects at the times of follow‐up after the acute pain model when compared to controls. MiRNAs previously associated with pain processes were altered in the pain group. Our results, by showing the fast and prolonged modifications of miRNA elicited by the acute experimental pain model, add new perspectives to the topic of epigenetics and pain.
Using natural killer cell‐derived exosomes as a cell‐free therapy for leukemia
Authors: Samara Aladin , Anbar Michael , Shapira Saar , Zemlyansky Anna , Zozovsky Alla , Raanani Pia , Granot Galit , Rozovski Uri
Published: December 2022

Natural killer (NK) cells are components of the innate immune system which play a pivotal role in cancer cell surveillance. Despite promising results in clinical trials, the use of NK‐based therapies is limited due to unsatisfactory efficiencies and safety issues. In recent years, exosomes have emerged as a powerful, natural therapeutic tool. Since exosomes are known to carry cargos that reflect the cellular makeup of their cell of origin, we were prompted to test whether NK‐derived exosomes (NKexo) maintain the anti‐leukemia capacity of NK‐cells. We found NK92MI‐cells to secrete large amounts of 100–200 nm cap‐shaped particles expressing exosomal and NK biomarkers (CD63, CD81, CD56). We demonstrated that NKexo exert a potent, selective, anti‐leukemia effect on all leukemia cell‐lines tested. Furthermore, NKexo eliminated leukemia cells isolated from patients with acute and chronic leukemia and inhibited hematopoietic colony growth. While leukemia cells were targeted and severely affected by NKexo, healthy B‐cells remained unaffected, indicating a selective effect. This selectivity was further confirmed by demonstrating that NKexo were specifically taken up by leukemic cells but not by healthy B‐cells. Our in vivo data support our in vitro and ex vivo findings and demonstrate improved human‐CD45+ leukemia blast counts and overall survival in NKexo treated humanized acute myeloid leukemia (HL‐60) xenograft mice thus supporting the assumption that NKexo possess an anti‐leukemia effect. Pending further analyses, our findings provide the pre‐clinical evidence needed to test the NKexo approach in future pre‐clinical and clinical studies to ultimately develop an acellular “off‐the‐shelf” product to treat leukemia.
Testing the acceptability of stillbirth awareness messages in anSMSprogram for fathers
Authors: Fletcher Richard , Symonds Ian , StGeorge Jennifer , Warland Jane , Stark Michael
Published: December 2022

Issue addressed

To raise expectant fathers' awareness of risk factors for stillbirth.

Methods

A set of brief text messages was developed addressing recognised risk factors for stillbirth: avoidance of maternal cigarette smoking, maternal going to sleep on side messaging, awareness of the importance of noticing and reporting changes in foetal movement and fathers' involvement in shared decision making for timing of birth. Eight messages were inserted into the SMS4dads pilot program being conducted by NSW Health. Feedback on the messages was requested. Participants rated the quality of the messages on a three‐point Likert scale and provided comments.

Results

Overall, 2528 messages were sent to 626 fathers' mobile phones, 45% of fathers replied with 666 ratings and 115 comments evaluating the texts. The quantitative ratings indicated substantial overall approval of the messages. Within the coding category “Evaluation of Message Content,” three themes described fathers' reactions and feelings about the smoking, movement, side sleeping and birth timing messages: “important‐good information,” “not appropriate/anxiety provoking” and “not relevant‐obvious.” Three themes reflecting the attributes of the messages within the “Service Quality” category were “need more information,” “complements public health” and “child voice fit.”

Conclusions

Results indicate that the messages are an acceptable way to provide information and suggested actions addressing stillbirth risk factors to fathers‐to‐be.

So what?

Fathers' awareness of the risk factors for stillbirth can assist mothers to take appropriate actions for a healthy birth. Information on risk factors can be provided to fathers via a father‐focused text messaging service.
Dyslexia with and without Irlen syndrome: A study of influence on abilities and brain‐derived neurotrophic factor level
Authors: Abdelraouf Ehab R. , Kilany Ayman , Elhadidy Mohamed E. , Zeidan Hala M. , Elsaied Amal , Eid Ola M. , El‐Saied Mostafa M. , Anwar Rasha , Nashaat Neveen H.
Published: December 2022

The presence of comorbid Irlen syndrome (IS) in children with developmental dyslexia (DD) may have an impact on their reading and cognitive abilities. Furthermore, the brain‐derived neurotrophic factor (BDNF) was reported to be expressed in brain areas involved in cognitive and visual processing. The aim of this study was to evaluate some cognitive abilities of a group of dyslexic children with IS and to measure and compare the plasma BDNF level to dyslexic children without IS and neurotypical (NT) children. The participants were 60 children with DD (30 in the DD + IS group; 30 in the DD group) and 30 NT children. The Irlen reading perceptual scale, the Stanford Binet intelligence scale, 4th ed, the dyslexia assessment test, and the Illinois test of psycholinguistic abilities were used. The BDNF level was measured using the enzyme‐linked immunosorbent assay. One‐minute writing and visual closure deficits were more prevalent, while phonemic segmentation deficits were less prevalent in the DD + IS group compared to the DD group. The BDNF level in the DD groups was lower than that in NT children (p < 0.001). Some reading and non‐reading tasks were influenced by the presence of a coexisting IS. The reduced BDNF level could play a role in the deficits noticed in the abilities of children with DD.
Immunotherapies targeting neoantigens are effective in PD‐1 blockade‐resistant tumors
Authors: Sun Changbo , Nagaoka Koji , Kobayashi Yukari , Maejima Kazuhiro , Nakagawa Hidewaki , Nakajima Jun , Kakimi Kazuhiro
Published: December 2022

Only a small fraction of tumor‐infiltrating lymphocytes can specifically recognize and attack cancer cells in PD‐1/PD‐L1 blockade therapy. Here, we investigate approaches to expand the neoantigen‐specific CD8+ T cells to overcome the difficulties in treating PD‐1/PD‐L1 blockade‐resistant tumors. Mutation‐associated neoepitopes of murine nonsmall cell lung cancer ASB‐XIV were estimated by whole‐exome and RNA sequencing and predicted by MHC‐I binding affinity (FPKM >1) in silico. Using ASB‐XIV‐specific CD8+ T cells, we screened a panel of 257 neoepitope peptides derived from ASB‐XIV missense and indel mutations. Mutated Phf3 peptide (mPhf3) was successfully identified as an immunogenic neoepitope. Prophylactic mPhf3‐DC vaccination inhibited ASB‐XIV tumor growth through CD8+ T cell‐mediated antitumor immunity. Combining the mPhf3‐DC vaccine and anti‐PD‐1 treatment elicited robust antitumor activity through the induction of mPhf3‐specific CD8+ T cells in the tumor microenvironment. Furthermore, the adoptive transfer of mPhf3‐specific CD8+ T cells eradicated ASB‐XIV tumors. Likewise, the combination of mutated Cdt1 peptide (mCdt1)‐DC vaccine and anti‐PD‐1 treatment or adoptive transfer of mCdt1‐specific CD8+ T cells also led to significant regression of PD‐1 blockade‐resistant murine gastric YTN16 tumors. In conclusion, a novel immunogenic neoepitope of ASB‐XIV was identified for immunotherapy targeting neoantigens. Identification of immunogenic neoantigens can extend the therapeutic strategies by increasing the frequency of neoantigen‐specific T cells, even for PD‐1/PD‐L1 blockade‐resistant tumors.
Association between a polymorphic variant in the CDKN2B‐AS1/ANRIL gene and pancreatic cancer risk
Authors: Giaccherini Matteo , Farinella Riccardo , Gentiluomo Manuel , Mohelnikova‐Duchonova Beatrice , Kauffmann Emanuele Federico , Palmeri Matteo , Uzunoglu Faik , Soucek Pavel , Petrauskas Dalius , Cavestro Giulia Martina , Zykus Romanas , Carrara Silvia , Pezzilli Raffaele , Puzzono Marta , Szentesi Andrea , Neoptolemos John , Archibugi Livia , Palmieri Orazio , Milanetto Anna Caterina , Capurso Gabriele , van Eijck Casper H. J. , Stocker Hannah , Lawlor Rita T. , Vodicka Pavel , Lovecek Martin , Izbicki Jakob R. , Perri Francesco , Kupcinskaite‐Noreikiene Rita , Götz Mara , Kupcinskas Juozas , Hussein Tamás , Hegyi Péter , Busch Olivier R. , Hackert Thilo , Mambrini Andrea , Brenner Hermann , Lucchesi Maurizio , Basso Daniela , Tavano Francesca , Schöttker Ben , Vanella Giuseppe , Bunduc Stefania , Petrányi Ágota , Landi Stefano , Morelli Luca , Canzian Federico , Campa Daniele
Published: December 2022

Genes carrying high‐penetrance germline mutations may also be associated with cancer susceptibility through common low‐penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in our study. We conducted a multiphase study analysing 7745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high‐penetrance PDAC‐associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14 666 PDAC cases and 221 897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B‐AS1/ANRIL, showed a genome‐wide significant association with increased risk of developing PDAC (OR = 1.11, 95% CI = 1.07‐1.15, P = 5.25 × 10−9). CDKN2B‐AS1/ANRIL is a long noncoding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases.
Safety of COVID‐19 vaccination in pregnant women: A study of the adverse perinatal outcomes
Authors: Kugelman Nir , Riskin Arieh , Kedar Reuven , Riskin‐Mashiah Shlomit
Published: December 2022

Objective

To compare adverse perinatal outcome among coronavirus disease 2019 (COVID‐19)–vaccinated and –unvaccinated pregnant women.

Method

Retrospective equivalence cohort study comparing 930 women who received at least one BNT162b2 (Pfizer/BioNTech) COVID‐19 vaccine during the second or third trimester of pregnancy and 964 unvaccinated women. The primary outcome was a composite adverse perinatal outcome including at least one of the following: preterm delivery <35 weeks of gestation, intrauterine fetal death >23 weeks of gestation, intrauterine growth restriction defined as birth weight < 10th percentile, 5‐min APGAR score ≤ 7, and neonatal care unit admission.

Results

The authors found no effect of the COVID‐19 vaccine on the rate of the individual adverse perinatal outcomes. At least one adverse perinatal outcome was found in 108 (11.25%) of unvaccinated women versus 82 (8.82%) of vaccinated pregnant women (P = 0.080). The observed proportion difference (unvaccinated minus vaccinated) was 0.024. In the equivalence analysis with a margin of 0.05, the 90% confidence interval (0.01–0.05) was entirely within the equivalence zone (−0.05 to 0.05) with a P value of 0.032.

Conclusion

The present study demonstrated an equivalent rate of adverse perinatal outcomes among vaccinated and unvaccinated women, thus supporting vaccine safety during the second and third trimesters of pregnancy. The authors believe this information is useful in counseling pregnant women regarding COVID‐19 vaccination during pregnancy.