bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of diesel and propanol blends on regulated pollutants and polycyclic aromatic hydrocarbons under lean combustion conditions
Authors: Yilmaz Nadir , Vigil Francisco , Donaldson Burl
Published: October 2022

Alcohols such as n‐propanol and diesel fuel can be mixed to increase the rate of bioalcohol utilization while reducing harmful pollutants. Examination of exhaust emissions from diesel engines, in terms of both regulated pollutants and unregulated polycyclic aromatic hydrocarbons (PAHs), is very important to the environment, public health, and engine durability. For this purpose, in this study, diesel blends with various n‐propanol concentrations (5%, 20%, and 35% by volume) were evaluated in a diesel engine. Regulated emissions were measured using a standard 5‐gas analyzer and polycyclic aromatic hydrocarbons were detected and quantified using gas chromatography–mass spectrometry (GC–MS). The effect of blended fuels on PAH formation (total PAHs, PAH distribution, and PAH toxicity) was examined in detail and compared with baseline diesel. Nitrogen oxide (NOx) emissions were reduced by 18.30% with higher n‐propanol concentrations. The addition of n‐propanol to diesel decreased total PAHs by as much as 71.20%. The fuel blend with a 20% n‐propanol concentration stood out with a maximum reduction of 91.23% in the toxicity of PAHs. In addition, n‐propanol led to a substantial decrease in the distribution of high ring aromatic compounds. Overall, it was demonstrated that n‐propanol is an effective additive to not only reduce the total PAH emissions and toxicity but also heavier PAHs which are more carcinogenic and cause a greater risk of the wetstacking issues for engines under cold operating or low load conditions.
The beneficial effects of alpha‐tocopherol on intestinal function and the expression of tight junction proteins in differentiated segments of the intestine in piglets
Authors: Huang Yanjun , He Caimei , Hu Zheng , Chu Xuetong , Zhou Sichun , Hu Xin , Deng Jun , Xiao Di , Tao Ting , Yang Huansheng , Chen Alex F. , Yin Yulong , Yang Xiaoping
Published: October 2022

Alpha (α)‐tocopherol is a major component of dietary vitamin E. Despite being one of the most widely used food supplements in both animals and humans, its role in intestinal functions remains unknown. We were able to examine and accurately demonstrate its permeability effect in vitro and its differentiated effect on tight junction expression in different segments of the intestine in vivo using cultured intestinal porcine epithelial cell line (IPEC‐J2) and piglets. A cultured IPEC‐J2 demonstrated that α‐tocopherol upregulated the expression of tight junction proteins and improved their integrity, with a maximum effect at concentrations ranging from 20 to 40 μmol/L. In vivo data from weaned pigs fed different doses of α‐tocopherol for 2 weeks revealed that α‐tocopherol effectively increases the expression of tight junction proteins in all sections of the intestinal mucosa, with the highest effect on the duodenum at an optimum dose of 20–50 mg/kg. In contrast, α‐tocopherol did not affect intestinal inflammation. These findings suggest that α‐tocopherol maintains intestinal integrity and increases the expression of tight junction proteins both in vitro and in vivo.
Reducing toxic constituents of ginkgolic acid content and improving bioactive flavonoid content from Ginkgo biloba leaves by high‐temperature pretreatment processing
Authors: Zhao Fen , Huang Shan , Ge Liufeng , Wang Yongzhen , Liu Yuwei , Chen Cunshe , Liu Xinqi , Han Qianwen
Published: October 2022

High‐temperature pretreatment was developed in this article to remove the main toxic constituents of ginkgolic acids (GAs) from Ginkgo biloba leaves (GBLs) and improve the bioactive flavonoid content by water extraction. To optimize the effects of high‐temperature pretreatment process parameters on removing toxic GAs to a limited level and improving the content of bioactive flavonoids, a Box–Behnken design (BBD) combined with response surface methodology (RSM) was also conducted. The results showed that the content of GAs could be reduced to 4.11 ppm and the highest content of flavonoids could reach 3.51% under the optimized conditions of high‐temperature pretreatment process of 177°C with water extraction at 96°C at a liquid‐to‐solid ratio of 56:1. The content of toxic GAs substantially decreased by 83.50% while the content of bioactive flavonoids increased by 44.30% compared with the conventional water extraction method. Moreover, the new process was more efficient, environmentally friendly, and could get avoid a subsequent multi‐step process of removing toxic GAs. The crude extracts were then purified by macroporous resin to obtain the 60% ethanol fraction. After purification, the flavonoid content increased to 43.50% while the GAs were not detected. The main compounds of 60% ethanol fraction were identified by UPLC‐QTOF‐MS/MS. Antioxidant activities including reducing powder, 2,2‐diphenyl−1‐picrylhydrazyl (DPPH) radical scavenging, and OH· scavenging assays all showed that the 60% ethanol fraction was better than the butylated hydroxytoluene (BHT) standard.
Impact of Pregnancy and Vitamin A Supplementation on CYP2D6 Activity
Authors: Amaeze Ogochukwu U. , Czuba Lindsay C. , Yadav Aprajita S. , Fay Emily E. , LaFrance Jeffrey , Shum Sara , Moreni Sue L. , Mao Jennie , Huang Weize , Isoherranen Nina , Hebert Mary F.
Published: October 2022

The mechanism of cytochrome P450 2D6 (CYP2D6) induction during pregnancy has not been evaluated in humans. This study assessed the changes in CYP2D6 and CYP3A activities during pregnancy and postpartum, and the effect of vitamin A administration on CYP2D6 activity. Forty‐seven pregnant CYP2D6 extensive metabolizers (with CYP2D6 activity scores of 1 to 2) received dextromethorphan (DM) 30 mg orally as a single dose during 3 study windows (at 25 to 28 weeks of gestation, study day 1; at 28 to 32 weeks of gestation, study day 2; and at ≥3 months postpartum, study day 3). Participants were randomly assigned to groups with no supplemental vitamin A (control) or with supplemental vitamin A (10 000 IU/day orally for 3 to 4 weeks) after study day 1. Concentrations of DM and its metabolites, dextrorphan (DX) and 3‐hydroxymorphinan (3HM), were determined from a 2‐hour post‐dose plasma sample and cumulative 4‐hour urine sample using liquid chromatography–mass spectrometry. Change in CYP2D6 activity was assessed using DX/DM plasma and urine metabolic ratios. The activity change in CYP3A was also assessed using the 3HM/DM urine metabolic ratio. The DX/DM urine ratio was significantly higher (43%) in pregnancy compared with postpartum (P = .03), indicating increased CYP2D6 activity. The DX/DM plasma ratio was substantially higher in the participants, with an activity score of 1.0 during pregnancy (P = .04) compared with postpartum. The 3HM/DM urinary ratio was significantly higher (92%) during pregnancy, reflecting increased CYP3A activity (P = .02). Vitamin A supplementation did not change CYP2D6 activity during pregnancy; however, plasma all‐trans retinoic acid (atRA) concentrations were positively correlated with increased CYP2D6 activity during pregnancy and postpartum. Further research is needed to elucidate the mechanisms of increased CYP2D6 activity during pregnancy.
Synthetic strategies and medicinal perspectives of 4‐thiazolidinones: Recent developments and structure–activity relationship studies
Authors: Chawla Pooja A. , Wahan Simranpreet K. , Negi Meenakshi , Faruk Abdul , Chawla Viney
Published: October 2022

The 4‐thiazolidinone moiety is a privileged scaffold showing diversity in biological responses like antiinflammatory, antidiabetic, anticancer, antitubercular, anesthetic, hypnotic, antiviral and many more. As a result of this, researchers have been studying and synthesizing this class of heterocycles through several simple as well as complex pathways as the target scaffold for biological studies. This review recapitulates the recent advances in the chemical and biological activities of 4‐thiazolidinones that have proved to be of immense importance in the discovery and development of several molecules and, thereby, the treatment of many ailments. This study will add to previously published reviews by examining the research on various biological activities of 4‐thiazolidinones, including patents, with a focus on structure–activity relationship (SAR) investigations. Literature and patents emphasizing synthetic schemes and biological activities of 4‐thiazolidinones have covered the data in the last decade. Here, sufficient efforts have been put into place to compile the synthetic strategies, establish SARs and enlist various patents so far for this fantastic molecule. The facile synthetic schemes and a vast range of biological activity profiles possessed by this nucleus may provide researchers with new opportunities toward novel therapeutics.
Synthesis of 4‐imidoyl‐, 4‐oxiranyl‐ and 4‐propargyloxyphenyl‐substituted β‐lactam building blocks
Authors: Deketelaere Sari , Kaur Gurkirat , Piens Nicola , Deturck Daan , Depestel Robin , Van Hecke Kristof , Stevens Christian V. , Kumar Vipan , D'hooghe Matthias
Published: October 2022

In this study, the preparation of 4‐imidoyl‐, 4‐oxiranyl‐, and 4‐propargyloxyphenyl‐substituted β‐lactams as versatile building blocks in heterocyclic chemistry was realized. Efforts were made to deploy these polyvalent compounds for ensuing cyclization reactions en route to new bi‐ or polycyclic frameworks, which, in the case of a 3‐chloro‐4‐propargyloxyphenyl‐β‐lactam substrate, enabled the preparation of an unprecedented β‐lactam‐fused benzotriazolo‐oxazocane scaffold. The chemical structure of the latter polyheterocycle was unequivocally secured by means of X‐ray analysis.
V‐NeuroStack: Open‐source 3D time stack software for identifying patterns in neuronal data
Authors: Naik Ashwini G. , Kenyon Robert V. , Taheri Aynaz , BergerWolf Tanya Y. , Ibrahim Baher A. , Shinagawa Yoshitaka , Llano Daniel A.
Published: October 2022

Understanding functional correlations between the activities of neuron populations is vital for the analysis of neuronal networks. Analyzing large‐scale neuroimaging data obtained from hundreds of neurons simultaneously poses significant visualization challenges. We developed V‐NeuroStack, a novel network visualization tool to visualize data obtained using calcium imaging of spontaneous activity of neurons in a mouse brain slice as well as in vivo using two‐photon imaging. V‐NeuroStack creates 3D time stacks by stacking 2D time frames for a time‐series dataset. It provides a web interface to explore and analyze data using both 3D and 2D visualization techniques. Previous attempts to analyze such data have been limited by the tools available to visualize large numbers of correlated activity traces. V‐NeuroStack's 3D view is used to explore patterns in dynamic large‐scale correlations between neurons over time. The 2D view is used to examine any timestep of interest in greater detail. Furthermore, a dual‐line graph provides the ability to explore the raw and first‐derivative values of activity from an individual or a functional cluster of neurons. V‐NeuroStack can scale to datasets with at least a few thousand temporal snapshots. It can potentially support future advancements in in vitro and in vivo data capturing techniques to bring forth novel hypotheses by allowing unambiguous visualization of massive patterns in neuronal activity data.
Steroid injections in musculoskeletal conditions and COVID infection rates: What is the impact on positive rates following the injection?
Authors: Lethbridge Daniel , O’Shea Simon
Published: October 2022

Background and Aim

Therapeutic glucocorticosteroid injections are commonly utilised to manage musculoskeletal (MSK) complaints. Following the SARS‐CoV‐2 pandemic, national guidelines advised against their use due to potential immunosuppressant effects. The aim of the study was to determine whether steroid injections for MSK conditions impacts on positive COVID 19 infection rates.

Patients and Methods

This retrospective evaluation involved primary care participants who received a steroid injection for a MSK condition. 291 participants receiving a total of 299 steroid injections entered the study between the 25 September 2020 and the 29 April 2021.

Results

Six participants had positive polymerase chain reaction (PCR) tests, averaging 22.83 days (SD 10.48) after the injection. An infection rate of 2.06% was demonstrated in the injection group with the control group demonstrating 6.97% (p = 0.000752) with statistical significance set at p = 0.05. The odds ratio was identified as 0.27 indicating a lower odds of a positive PCR test compared with the control group.

Conclusions

This retrospective evaluation found a low risk of positive PCR tests for low and moderate COVID‐19 risk patients injected during the COVID‐19 pandemic. Glucocorticosteroid injections within the COVID‐19 pandemic were not associated with higher COVID‐19 rates compared to the local population, in fact, they were related to lower rates. For future studies, large scale studies and meta analyses are needed to provide greater generalisation to the population.
Was Hochschulen leisten können
Authors: Weinert Bastian
Published: October 2022

Das Chemiestudium muss sich weiterentwickeln und flexibler werden, wenn es für junge Menschen attraktiv bleiben soll.
Trendbericht Theoretische Chemie 2022: Maschinelles Lernen für elektronisch angeregte Zustände
Authors: Marquetand Philipp
Published: October 2022

Maschinelles Lernen eignet sich, um Photochemie und somit elektronisch angeregte Zustände zu beschreiben; klassische Molekulardynamiktechniken erlauben, bestimmte Aspekte der nuklearen Quanteneffekte in Probleme der physikalischen Chemie einzubeziehen, und was Finite‐Feld‐Methoden mit alten Sternen zu tun haben.
Nachruf: Hanns‐Peter Boehm (1928 – 2022)
Authors: Beck Wolfgang
Published: October 2022

Am 10. Mai starb Hanns‐Peter Boehm, Professor für anorganische Chemie. Er hat Graphen nicht nur entdeckt, sondern diese Entdeckung sogar geplant.
Tissue response curve‐shape analysis of dynamic glucose‐enhanced and dynamic contrast‐enhanced magnetic resonance imaging in patients with brain tumor
Authors: Seidemo Anina , Wirestam Ronnie , Helms Gunther , Markenroth Bloch Karin , Xu Xiang , Bengzon Johan , Sundgren Pia C. , van Zijl Peter C. M. , Knutsson Linda
Published: October 2022

Dynamic glucose‐enhanced (DGE) MRI is used to study the signal intensity time course (tissue response curve) after D‐glucose injection. D‐glucose has potential as a biodegradable alternative or complement to gadolinium‐based contrast agents, with DGE being comparable with dynamic contrast‐enhanced (DCE) MRI. However, the tissue uptake kinetics as well as the detection methods of DGE differ from DCE MRI, and it is relevant to compare these techniques in terms of spatiotemporal enhancement patterns. This study aims to develop a DGE analysis method based on tissue response curve shapes, and to investigate whether DGE MRI provides similar or complementary information to DCE MRI. Eleven patients with suspected gliomas were studied. Tissue response curves were measured for DGE and DCE MRI at 7 T and the area under the curve (AUC) was assessed. Seven types of response curve shapes were postulated and subsequently identified by deep learning to create color‐coded “curve maps” showing the spatial distribution of different curve types. DGE AUC values were significantly higher in lesions than in normal tissue (p < 0.007). Furthermore, the distribution of curve types differed between lesions and normal tissue for both DGE and DCE. The DGE and DCE response curves in a 6‐min postinjection time interval were classified as the same curve type in 20% of the lesion voxels, which increased to 29% when a 12‐min DGE time interval was considered. While both DGE and DCE tissue response curve‐shape analysis enabled differentiation of lesions from normal brain tissue in humans, their enhancements were neither temporally identical nor confined entirely to the same regions. Curve maps can provide accessible and intuitive information about the shape of DGE response curves, which is expected to be useful in the continued work towards the interpretation of DGE uptake curves in terms of D‐glucose delivery, transport, and metabolism.
Effects of muscle mass and muscle quality estimated by phase angle on functional outcomes in older patients undergoing rehabilitation: A prospective cohort study
Authors: Ohtsubo Takuro , Nozoe Masafumi , Kanai Masashi , Ueno Katsuhiro , Nakayama Mai
Published: October 2022

Background

Both skeletal muscle mass and muscle quality are important predictors of poor prognosis in older patients. However, the effects of muscle mass and muscle quality estimated by the phase angle (PhA) on functional outcomes in older patients undergoing rehabilitation have yet to be reported. This study aimed to investigate whether appendicular skeletal muscle index (SMI) and muscle quality estimated by PhA were independently associated with activities of daily living (ADL) and physical function in older patients undergoing rehabilitation.

Methods

This prospective cohort study included older patients in a subacute rehabilitation hospital (n = 443). Baseline SMI and PhA were measured using bioelectrical impedance analysis, and low SMI or low PhA were determined using each cutoff value. The primary outcomes were ADL abilities measured using the functional independence measure for motor function (FIM‐M) score and physical function measured using the short physical performance battery (SPPB) score at hospital discharge. Association between low SMI and low PhA and FIM‐M or SPPB scores at discharge were determined using multiple regression analysis adjusted for confounding factors.

Results

There were significant differences between the normal‐ and low‐PhA groups in the FIM‐M and SPPB scores at discharge (P < 0.001). In multiple regression analysis, low PhA was independently associated with FIM‐M (β = −0.109, P = 0.013) and SPPB scores (β = 0.535, P < 0.001) at discharge; however, low SMI was not independently associated with these functional outcomes.

Conclusion

Decreased muscle quality estimated by the PhA was independently associated with poor ADL abilities and poor physical function in older patients undergoing rehabilitation.
Characteristics of adult intestinal failure centers: An international multicenter survey
Authors: Lakananurak Narisorn , Moccia Lisa , Wall Elizabeth , Herlitz Jean , Catron Hilary , Lozano Edward , Delgado Adela , Vanuytsel Tim , Mercer David , Pevny Sophie , Berner‐Hansen Mark , Gramlich Leah
Published: October 2022

Background

Current guidelines recommend that patients with chronic intestinal failure (CIF) should be managed by a multidisciplinary team (MDT). However, the characteristics of real‐world IF centers and the patients they care for are lacking. The study aims to describe IF center characteristics as well as characteristics of patients with CIF across different global regions.

Methods

This is an international multicenter study of adult IF centers using a survey. The questionnaire survey included questions regarding program and patient characteristics. Thirty‐three investigational centers were invited to participate. Each center was asked to answer the survey questions as one MDT.

Results

The survey center response rate was 91%. The median number of patients with CIF per center was 128 (range, 30–380). The most common disciplines reported were gastroenterologist (93%), dietitian (90%), nurse (83%), and advanced practitioner (nurse practitioner and physician assistant, 77%). There were centers that did not have a pharmacist, surgeon, psychologist, and social worker (30%, 37%, 60%, and 70%, respectively). The median full‐time equivalents (FTEs) per 100 patients were 1.1 for nurses, 1 for dietitians, 1 for advanced practitioners, and 0.9 for gastroenterologists. Short bowel syndrome was the most common cause of CIF (50%) followed by intestinal dysmotility (20%).

Conclusion

The majority of centers were managing around 100 patients with CIF. Despite the widespread use of the MDT, there are some variances in team characteristics. Gastroenterologists were the most common physicians supporting MDTs. In IF centers, one FTE of each core discipline was supported to manage 100 patients with CIF.
Managing nutrition support product shortages: What have we learned?
Authors: Mulherin Diana W. , Kumpf Vanessa , Shingleton Kerri
Published: October 2022

Product shortages related to the components of parenteral nutrition (PN) therapy have been well described over the past decade. The situation has more recently worsened and expanded globally because of the impact the COVID‐19 pandemic has placed on supply chain issues and workforce demand. The impact of enteral nutrition (EN) product shortages is less well documented when compared with PN, and development of management strategies is often left up to the discretion of individual providers. The recent crisis in infant formula supply has heightened the national awareness of how a nutrition support product shortage can significantly impact patient safety. This review provides a historical perspective of PN and EN product shortages to gain insight into the lessons learned and applies this to strategies for managing current and future product shortages. Strategies for managing PN and EN shortages can best succeed if they are tailored to address aspects that are unique to the inpatient and outpatient care setting. In addition, patients who transition between care settings are vulnerable to harm related to product shortages if measures are not in place to communicate and address these shortages. Teamwork and communication within an organization and among key stakeholders are necessary to develop processes that aim to minimize patient harm related to product shortages.
Long‐term follow‐up for pediatric intestinal pseudo‐obstruction patients in China
Authors: Tang Powei , Lu Lina , Yan Weihui , Tao Yijng , Feng Haixia , Cai Wei , Wang Ying
Published: October 2022

Background

Pediatric intestinal pseudo‐obstruction (PIPO) is a heterogeneous and severe group of disorders with a high mortality rate. Patients with PIPO often develop malnutrition and need long‐term nutrition support. This study aimed to determine the nutrition status, particularly micronutrients, during the long‐term follow‐up of patients with PIPO.

Methods

Fifty‐eight patients with PIPO were followed up for at least 6 months between January 2008 and December 2020 in our hospital. PIPO was diagnosed based on the European society for pediatric gastroenterology, hepatology, and nutrition consensus. Data on clinical characteristics, medical and surgical management, nutrition support, serum vitamins, and mineral concentrations were collected. The patients were divided into the early‐onset PIPO (EO‐PIPO; neonatal‐onset) and late‐onset PIPO (LO‐PIPO; infant‐ or child‐onset) groups.

Results

The mean follow‐up was 29.5 months (6–153 months). The overall survival rate was 63.8% (37 out of 58 participants) (EO‐PIPO, 48.6% [17 out of 35 participants]; LO‐PIPO, 87.0% [20 out of 23 participants]). Mortality in the EO‐PIPO group was higher than in the LO‐PIPO group (P = 0.002). Twenty‐one patients died, of which 18 (85.7%) patients had EO‐PIPO and 14 (66.7%) patients died under 1 year of age. Infection was the major cause of death. Severe malnutrition was observed at baseline and during follow‐up in 25 (43.1%) and 6 (16.2%) patients, respectively. At baseline and during follow‐up, the zinc deficiency rates were 29.6% and 26.3%, and those of vitamin D were 26.9% and 52.6%, respectively.

Conclusions

Zinc and vitamin D deficiencies are common in patients with PIPO during follow‐up. Therefore, additional supplements should be recommended.
Experiences of living with symptomatic atrial fibrillation
Authors: Holmlund Lena , Hellström Ängerud Karin , Hörnsten Åsa , Valham Fredrik , Olsson Karin
Published: October 2022

Aim

To explore the experiences of living with symptomatic atrial fibrillation.

Design

This study, with a descriptive qualitative design, was performed using semi‐structured individual interviews.

Method

Six women and nine men with symptomatic atrial fibrillation were included. The transcribed interviews were analysed using qualitative content analysis. The COREQ checklist was followed.

Results

The analysis resulted in a main theme, namely balancing life and included the themes striving for illness control, becoming a receiver or an active partner in care and dealing with changed self‐image. The participants strived to understand their illness, prevent attacks and manage anxiety. Some of the participants were not involved in decision‐making, were uninformed about self‐care measures, reported a lack of continuity in care and felt that the doctors focused on information about the medical part of care.
Off‐label low dose amitriptyline for insomnia disorder: Patient‐reported outcomes
Authors: Bakker Mette H. , Hugtenburg Jacqueline G. , Smits Marcel G. , van der Horst Henriëtte E. , Slottje Pauline
Published: October 2022

Purpose

Low dose amitriptyline is prescribed off‐label to improve sleep maintenance in patients with insomnia disorder. Data on treatment outcomes are limited. We aimed to assess patient‐reported treatment effect and side effects of low dose amitriptyline for insomnia in routine care data.

Methods

Cross‐sectional study: Seven hundred fifty‐two consecutive patients with insomnia disorder having sleep maintenance problems were treated in an outpatient sleep clinic with low dose amitriptyline (10–20 mg based on self‐titration). Treatment was intended to improve sleep maintenance. Before the planned follow‐up consultation (approximately 6 weeks after start treatment) patients completed an online treatment evaluation questionnaire. Treatment (dose, adherence), sleep, fatigue, satisfaction and side effects were assessed by multiple‐choice questions with room for free‐text elaboration.

Results

53.7% of the patients reported to use amitriptyline up to 10 mg/day, 42.9% used a self‐increased dose of mostly 20 mg/day, while 3.5% had discontinued treatment. 73.9% of the total study population reported improvement of sleep maintenance, 31.3% improved sleep onset, 35.2% improved daytime fatigue, and 45.8% reported to be (very) satisfied with treatment results. 66.1% reported at least one side effect. The reported side effects were generally the already known side effects of amitriptyline.

Conclusion

These patient‐reported outcomes support the clinical observations that low dose amitriptyline improves sleep maintenance on the short term and that it is generally well tolerated. This further justifies randomized controlled trials in patients with insomnia disorder and sleep maintenance problems to assess the effectiveness and safety of low dose amitriptyline on the short and long term.
GeoPacker: A novel deep learning framework for protein side‐chain modeling
Authors: Liu Jiale , Zhang Changsheng , Lai Luhua
Published: October 2022

Atomic interactions play essential roles in protein folding, structure stabilization, and function performance. Recent advances in deep learning‐based methods have achieved impressive success not only in protein structure prediction, but also in protein sequence design. However, highly efficient and accurate protein side‐chain prediction methods that can give detailed atomic interactions are still lacking. In the present study, we developed a deep learning based method, GeoPacker, that uses geometric deep learning coupled ResNet for protein side‐chain modeling. GeoPacker explicitly represents atomic interactions with rotational and translational invariance for information extraction of relative locations. GeoPacker outperformed the state‐of‐the‐art energy function‐based methods in side‐chain structure prediction accuracy and runs about 10 and 700 times faster than the deep learning‐based method DLPacker and OPUS‐rota4 with comparable prediction accuracy, respectively. The performance of GeoPacker does not depend on the secondary structures that the residues belong to. GeoPacker gives highly accurate predictions for buried residues in the protein core as well as protein–protein interface, making it a useful tool for protein structure modeling, protein, and interaction design.
Signal peptide stabilizes folding and inhibits misfolding of serum amyloid A
Authors: Wu Jin‐Lin , Chen Yun‐Ru
Published: October 2022

Signal peptide (SP) plays an important role in membrane targeting for insertion of secretory and membrane proteins during translocation processes in prokaryotes and eukaryotes. Beside the targeting functions, SP has also been found to affect the stability and folding of several proteins. Serum amyloid A (SAA) proteins are apolipoproteins responding to acute‐phase inflammation. The fibrillization of SAA results in a protein misfolding disease named amyloid A (AA) amyloidosis. The main disease‐associated isoform of human SAA, SAA1.1, is expressed as a precursor protein with an N‐terminal signal peptide composed of 18 residues. The cleavage of the SP generates mature SAA1.1. To investigate whether the SP affects properties of SAA1.1, we systematically examined the structure, protein stability, and fibrillization propensity of pre‐SAA1.1, which possesses the SP, and Ser‐SAA1.1 without the SP but containing with an additional N‐terminal serine residue. We found that the presence of the SP did not significantly affect the predominant helical structure but changed the tertiary conformation as evidenced by intrinsic fluorescence and exposed hydrophobic surfaces. Pre‐SAA1.1 and Ser‐SAA1.1 formed distinct oligomeric assemblies in which pre‐SAA1.1 populated as tetramer and octamer, whereas Ser‐SAA1.1 existed as a predominant hexamer. Pre‐SAA1.1 was found significantly more stable than Ser‐SAA1.1 upon thermal and chemical unfolding. Ser‐SAA1.1, but not pre‐SAA1.1, is capable of forming amyloid fibrils in protein misfolding study, indicating a protective role of the SP. Altogether, our results demonstrated a novel role of the SP in SAA folding and misfolding and provided a novel direction for therapeutic development of AA amyloidosis.
Large‐scale identification of rodenticide resistance in Rattus norvegicus and Mus musculus in the Netherlands based on Vkorc1 codon 139 mutations
Authors: Krijger Inge M. , Strating Max , van Gent‐Pelzer Marga , van der Lee Theo A.J. , Burt Sara A. , Schroeten Fleur H. , de Vries Robin , de Cock Marieke , Maas Miriam , Meerburg Bastiaan G.
Published: October 2022

BACKGROUND

Resistance to rodenticides has been reported globally and poses a considerable problem for efficacy in pest control. The most‐documented resistance to rodenticides in commensal rodents is associated with mutations in the Vkorc1 gene, in particular in codon 139. Resistance to anticoagulant rodenticides has been reported in the Netherlands since 1989. A study from 2013 showed that 25% of 169 Norway rats (Rattus norvegicus) had a mutation at codon 139 of the Vkorc1 gene. To gain insight in the current status of rodenticide resistance amongst R. norvegicus and house mice Mus musculus in the Netherlands, we tested these rodents for mutations in codon 139 of the Vkorc1 gene. In addition, we collected data from pest controllers on their use of rodenticides and experience with rodenticide resistance.

RESULTS

A total of 1801 rodent samples were collected throughout the country consisting of 1404 R. norvegicus and 397 M. musculus. In total, 15% of R. norvegicus [95% confidence interval (CI): 13–17%] and 38% of M. musculus (95% CI: 33–43%) carried a genetic mutation at codon 139 of the Vkorc1 gene.

CONCLUSION

This study demonstrates genetic mutations at codon 139 of the Vkorc1 gene in M. musculus in the Netherlands. Resistance to anticoagulant rodenticides is present in R. norvegicus and M. musculus in multiple regions in the Netherlands. The results of this comprehensive study provide a baseline and facilitate trend analyses of Vkorc1 codon 139 mutations and evaluation of integrated pest management (IPM) strategies as these are enrolled in the Netherlands. © 2022 The Dutch Pest and Wildlife. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Differential response to the South American rice water weevil (Coleoptera: Curculionidae) damage of rice cultivars with contrasting levels of resistance: implications for field management
Authors: Pazini Juliano de B , Grützmacher Anderson D , Seidel Enio J , Vieira Afrânio M C , Padilha Aline C , de Brito Giovani G , Bernardi Daniel , Barrigossi José A F , Martins José F da S
Published: October 2022

BACKGROUND

Oryzophagus oryzae (Costa Lima) (Coleoptera: Curculionidae) is a major pest of flooded rice paddies throughout South America, and species with very similar life histories are present in many rice‐producing regions of the world (collectively rice water weevils, RWWs). The damage caused by RWW larvae on rice cultivars with contrasting levels of resistance (‘BRS Pampa CL’= ‘Pamp’: susceptible, ‘BRS Atalanta’ = ‘Atal’: resistant‐antibiosis) was evaluated in two consecutive years in the field under seven infestation levels: 0, 2, 4, 6, 8, 10 and 20 adult couples per cage with plants.

RESULTS

Higher densities of adults increased the number of leaf‐feeding scars and larvae on roots, respectively, at the rate ≤2.14 and 2.75 in Pamp and 2.23 and 2.48 in Atal, with the total number of larvae generated being lower in Atal. Grain yield was negatively impacted with increasing larval density on the roots, mainly by decreasing root volume and the number of grains per panicle. Root injury intensity and yield loss showed a nonlinear relationship. It was found that significant yield losses occurred with 8.37 larvae per plant in Pamp and 9.80 larvae per plant in Atal

CONCLUSION

The results provided the first evidence of a tolerance limit for RWW larval damage that, even though similar between cultivars of contrasting resistance, corresponds to twice the current conventional level for larval control in Brazil. We also discuss here the potential of applying tolerance limits to manage the RWW adult population in rice fields. © 2022 Society of Chemical Industry.
Fabrication of a dual pH‐responsive and photothermal microcapsule pesticide delivery system for controlled release of pesticides
Authors: Li Linhuai , Cen Jun , Huang Lingling , Luo Ling , Jiang Guangqi
Published: October 2022

BACKGROUND

The development of stimulus‐responsive and photothermally controlled‐release microcapsule pesticide delivery systems is a promising solution to enhance the effective utilization and minimize the excessive use of pesticides in agriculture.

RESULTS

In this study, an AVM@CS@TA‐Fe microcapsule pesticide delivery system was developed using avermectin as the model drug, chitosan and tannic acid as the wall materials, and tannic acid–Fe complex layer as the photothermal agent. The optical microscope, scanning electron microscope, transmission electron microscope, and Fourier‐transform infrared spectroscope were used to characterize the prepared microcapsule. The slow‐release, UV‐shielding, photothermal performance, and nematicidal activity of the microcapsule were systematically investigated. The results showed that the system exhibited excellent pH‐responsive and photothermal‐sensitive performances. In addition, the UV‐shielding performance of the delivery system was improved. The photothermal conversion efficiency (η) of the system under the irradiation of near‐infrared (NIR) light was determined to be 14.18%. Moreover, the nematicidal activities of the system against pine wood nematode and Aphelenchoides besseyi were greatly increased under the irradiation of light‐emitting diode (LED) simulated sunlight.

CONCLUSION

The release of the pesticide‐active substances in such a pesticide delivery system could be effectively regulated with the irradiation of NIR light or LED‐simulated sunlight. Thus, the developed pesticide delivery system may have broad application prospects in modern agriculture fields. © 2022 Society of Chemical Industry.
A protocol for increased throughput phenotyping of plant resistance to the pollen beetle
Authors: Bellec Laura , Hervé Maxime R , Mercier Anne‐Sophie , Lenal Pierre‐Arthur , Faure Sébastien , Cortesero Anne‐Marie
Published: October 2022

BACKGROUND

Improving crop resistance to insect herbivores is a major research objective in breeding programs. Although genomic technologies have increased the speed at which large populations can be genotyped, breeding programs still suffer from phenotyping constraints. The pollen beetle (Brassicogethes aeneus) is a major pest of oilseed rape for which no resistant cultivar is available to date, but previous studies have highlighted the potential of white mustard as a source of resistance and introgression of this resistance appears to be a promising strategy. Here we present a phenotyping protocol allowing mid‐throughput (i.e., increased throughput compared to current methods) acquisition of resistance data, which could then be used for genetic mapping of QTLs.

RESULTS

Contrasted white mustard genotypes were selected from an initial field screening and then evaluated for their resistance under controlled conditions using a standard phenotyping method on entire plants. We then upgraded this protocol for mid‐throughput phenotyping, by testing two alternative methods. We found that phenotyping on detached buds did not provide the same resistance contrasts as observed with the standard protocol, in contrast to the phenotyping protocol with miniaturized plants. This protocol was then tested on a large panel composed of hundreds of plants. A significant variation in resistance among genotypes was observed, which validates the large‐scale application of this new phenotyping protocol.

CONCLUSION

The combination of this mid‐throughput phenotyping protocol and white mustard as a source of resistance against the pollen beetle offers a promising avenue for breeding programs aiming to improve oilseed rape resistance. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Population pharmacokinetic modeling of daridorexant, a novel dual orexin receptor antagonist
Authors: Krause Andreas , Lott Dominik , Brussee Janneke M. , Muehlan Clemens , Dingemanse Jasper
Published: October 2022

The analysis aimed at identifying subject‐specific characteristics (covariates) influencing exposure to daridorexant and quantification of covariate effects to determine clinical relevance. Data from 13 phase I, two phase II, and two phase III studies were pooled to develop a population pharmacokinetic model describing daridorexant concentration over time. Covariate effects were quantified based on model predictions. A two‐compartment model with dose‐dependent bioavailability, absorption lag time, linear absorption, and nonlinear elimination described the data best. Statistically significant covariates were food status on absorption (lag time and rate constant), time of drug administration (morning, bedtime) on absorption rate constant, lean body weight on central volume of distribution and elimination, fat mass on peripheral volume of distribution and intercompartmental drug transfer, and age and alkaline phosphatase on elimination. Age, lean body weight, fat mass, and alkaline phosphatase influence exposure (area under the curve, time of maximum concentration after dose administration, maximum plasma concentration, and next‐morning concentration) to a limited extent, that is, less than 20% difference from a typical subject. Morning administration is not relevant for daridorexant use by insomnia patients. The food effect with simultaneous intake of a high‐fat, high‐calorie food is an extreme‐case scenario unlikely to occur in clinical practice. Body composition, alkaline phosphatase, and age showed clinically negligible effects on exposure to daridorexant. Lean body weight and fat mass described the pharmacokinetics of daridorexant better than other body size descriptors (body weight, height, body mass index), suggesting a convenient physiological alternative to reduce the number of covariates in population pharmacokinetic models. The results indicate that differences between subjects do not require dose adjustments.
Developmental pharmacokinetics of indomethacin in preterm neonates: Severely decreased drug clearance in the first week of life
Authors: Krzyzanski Wojciech , Stockard Bradley , Gaedigk Andrea , Scott Allison , Nolte Whitney , Gibson Kim , Leeder J. Steven , Lewis Tamorah
Published: October 2022

Indomethacin is used commonly in preterm neonates for the prevention of intracranial hemorrhage and closure of an abnormally open cardiac vessel. Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently was tested for accuracy in a validation cohort. Postnatal age was a significant covariate for hepatic clearance (CLH) and renal clearance (CLR). The typical value of the total clearance (CL, the sum of CLR and CLH) was 3.09 ml/h and expressed as CL/WTmedian = 3.96 ml/h/kg, where WTmedian is the median body weight. The intersubject variability of CLR and CLH were 61% and 207%, respectively. The typical value of the volume of distribution Vp = 366 ml (Vp/WTmedian = 470 ml/kg), and its intersubject variability was 38.8%. Half‐life was 82.1 h. Compared with more mature and older preterm populations studied previously, indomethacin CL is considerably lower in this contemporary population. Model‐informed precision dosing incorporating important covariates other than weight alone offers an opportunity to individualize dosing in a susceptible patient undergoing rapid change.
Robustness of decentralized decision‐making architectures in command and control systems
Authors: Boss Lewis N. , Gralla Erica L.
Published: October 2022

Organizations use command and control (C2) systems to collect, organize, and disseminate information in order to make decisions, impart instructions, and manage resources to accomplish a mission. C2 agility and robustness are critical to ensure that a C2 system can perform well in a variety of environments. One system design principle, decentralization, has been closely linked to desirable system characteristics such as agility and adaptability, but its relationship to system performance robustness is not well‐established. In this study, we explore C2 system architectures—ranging from fully centralized to fully decentralized archetypes—to assess their performance and robustness characteristics across a spectrum of operating environments. While the centralized archetype achieves high performance in favorable environmental conditions, its performance quickly degrades when conditions worsen, hindering its overall robustness. Conversely, the decentralized archetype achieves a lower but more stable performance profile resulting in more robustness when performance requirements are lower. Finally, we explore alternative, hybrid architectures with varying degrees of centralized and decentralized decision‐making. We find that by centralizing only certain system‐consequential functions such as resource allocation, and decentralizing more focused decision functions which can be performed suitably with only local information and resources, system performance and robustness are improved beyond that of the simple archetypes.
Creating Obstacles to Progressivity: Task Expansion in Second Language Role‐Plays
Authors: Nanbu Zachary , Greer Tim
Published: October 2022

One way that language educators can extend a role‐play is by adding a complication to encourage the learner say more. This study uses multimodal conversation analysis to explore such obstacles to progressivity among Japanese learners of English at an experiential language learning facility. We first examine an interactional practice in which the educator orients to a learner contribution as misaligned and creates a role‐play‐specific basis for rejection that expands the sequence, draws attention to linguistic form, and realigns the learner's responses with the task. We then analyze a related practice in which the educator “feigns” a next‐turn display of misunderstanding to signal trouble located in some aspect of the learner's prior turn and thereby occasions the learner's reflection on possible pragmatic, syntactic or lexical issues with their contribution. The educators therefore create a temporary interactional barrier that the learner must overcome to progress the sequence. These practices allow the educators to emulate the way that mechanisms like repair, correction and rejection operate in mundane interaction beyond the classroom (i.e., “in the wild”) and offer insight into how unscripted role‐play tasks can provide opportunities for expanded L2 use.
Overview
Authors: Semple Tara
Published: October 2022

Young adults and their conceptions and reactions to modernity, capitalism and consumerism constitute a fundamental building block to understanding society. Little sociological work has been done in the field of Hipsterism, although it can function as a paradigm for western, affluent societies. Drawing on qualitative research from two subsequent field stays in Berlin, this work utilizes Hipsterism to demonstrate contradictions of modernity, progress and counter culture in highly individualised societies, analysed through the lens of Modernity (Bauman/Giddens), Consumerism (Bauman), the New Spirit of Capitalism (Boltanski/Chiapello), and shows contradictions of urban space in reference to Lefebvre. Hipsterism demonstrates modes of identity, conceptions and a whole spectrum of activities with varying degrees of commitment. With tools such as conscious consumption, conversations and ethical or creative work within an intentional lifestyle, Hipsterism emerges as an attempt to navigate between individualism and collectivity and thus forms a kind of citizenship based on an imagined global 15 community that individuals empathize with and feel solidarity towards. Resulting from these circumstances are a variety of forms of action, while searching for better ways to contribute and engage at the same time. Attempts to try to construct spaces where milieus dissolve might fail in spatial practice, but the practices in sum still leave a trace in (consumer) culture. All these activities hint at the potential of transformative and negotiating power that Hipsterism could have.
Methodology and Methods
Authors: Semple Tara
Published: October 2022

The Hipster as an ideal type does not exist as a sociologically identifiable form, but much rather as a discursive, vague and diffuse term. It is a typological term used in social and medial discourse to describe ideal types that differ greatly across various geographic and demographic discourses, and that have subtle but significant differences in meaning. One option is to look at what these definitions have in common, which would be difficult to achieve as there are so many discourses taking place and the term itself is indefinite.
The Space of Hipsterism—The Paradox of Being and Doing
Authors: Semple Tara
Published: October 2022

One of the most interesting discourses I came upon in my research was also one of the biggest challenges for the research itself. It was on the labelling of Hipsters.