bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of circadian rhythm on drug metabolism in 3D hepatic spheroids
Authors: Narayanan Vibha , Rodrigues Andre L. , Dordick Jonathan S.
Published: July 2022

Circadian rhythms are characterized as oscillations that fluctuate based on a 24 h cycle and are responsible for regulation of physiological functions. While the internal clock synchronizes gene expression using external cues like light, a similar synchronization can be induced in vitro by incubating the cells with an increased percentage of serum followed by its rapid removal. Previous studies have suggested that synchronization of HepG2 cell line induced the rhythmic expression of drug‐metabolizing enzymes (DME) most specifically the cytochrome P450 enzymes. However, there is a lack of evidence demonstrating the influence of three‐dimensional microenvironment on the rhythmicity of these genes. To understand this interplay, gene expression of the circadian machinery and CYP450s were compared using the model human hepatocarcinoma cell line, HepG2. Upon serum shock synchronization, gene and protein expression of core clock regulators was assessed and rhythmic expression of these genes was demonstrated. Further insight into the interrelations between various gene pairs was obtained using statistical analysis. Using RNA sequencing, an in‐depth understanding of the widespread effects of circadian regulation on genes involved in metabolic processes in the liver was obtained. This study aids in the better understanding of chronopharmacokinetic events in humans using physiologically relevant 3D culture systems.
Production of a high purity, C‐tagged hepatitis B surface antigen fusion protein VLP vaccine for malaria expressed in Pichia pastoris under cGMP conditions
Authors: Mukhopadhyay Ekta , Brod Florian , Angell‐Manning Philip , Green Nicola , Tarrant Richard D. , Detmers Frank J. , Bolam Emma J. , Baleanu Ioana N. , Hobson Mark , Whale Gary , Morris Susan J. , Ashfield Rebecca , Gilbert Sarah C. , Jin Jing , Draper Simon J. , Moyle Sarah P. , Berrie Eleanor L. , Hill Adrian V. S.
Published: July 2022

Virus‐like particles (VLPs) induce strong humoral and cellular responses and have formed the basis of some currently licensed vaccines. Here, we present the method used for the production of R21, a VLP‐based anti‐sporozoite malaria vaccine, under current Clinical Good Manufacturing Practice regulations (cGMP). Previous preclinical studies in BALB/c mice showed that R21 produced almost complete protection against sporozoite challenge with transgenic Plasmodium berghei parasites. Here, we have modified the preclinical production process to enable the production of sufficient quantities of highly pure, clinical‐grade material for use in human clinical trials. The R21 construct was re‐engineered to include a C‐tag to allow affinity‐based separation from the major contaminant alcohol oxidase 1 (AOX 1, ~74 kDa). To our knowledge, this is the first use of C‐tag technology to purify a VLP vaccine candidate for use in human clinical trials. The R21 vaccine has shown high‐level efficacy in an African Phase IIb trial, and multiple clinical trials are underway to assess the safety and efficacy of the vaccine. Our findings support the future use of C‐tag platform technologies to enable cGMP‐compliant biomanufacturing of high purity yeast‐expressed VLP‐based vaccines for early phase clinical trials when clinical grade material is required in smaller quantities in a quick time frame.
Preparation of CuCr1−xGaxO2 (0 ≤ x ≤ 1) nanocrystals for inorganic hole conductor of inverted perovskite solar cells
Authors: Choo Hyun Sue , Jo Ju Hee , Suh Woo Seok , Park You Jin , In Lee Wan
Published: July 2022

CuGaO2 (CGO) and CuCrO2 (CCO) belonging to the delafossite family are attracting attention as potential inorganic hole‐transporting materials (HTMs) for perovskite solar cells (PSCs). Herein, various solid solutions of CCO and CGO were prepared by hydrothermal reaction to obtain an optimal composition that leads to reproducible size control and high hole conductivity. The particle sizes of the prepared CuCr1−xGaxO2 (CCGO) were maintained at ~10 nm with a high uniformity until the Ga/Cr composition ratio was increased to 60/40, whereas the samples derived at the composition ratio of 70/30 or higher contain large disk‐like structures. When they were applied as HTMs of the inverted PSC devices employing CH3NH3PbI3, the CCGO with Ga content of 60% provided the best photovoltaic properties. The achieved photovoltaic conversion efficiency was 16.38%, which is 27% and 22% higher than that of the PSCs with bare CCO and CGO, respectively.
Antibody variable region engineering for improving cancer immunotherapy
Authors: Lou Hantao , Cao Xuetao
Published: July 2022

The efficacy and specificity of conventional monoclonal antibody (mAb) drugs in the clinic require further improvement. Currently, the development and application of novel antibody formats for improving cancer immunotherapy have attracted much attention. Variable region‐retaining antibody fragments, such as antigen‐binding fragment (Fab), single‐chain variable fragment (scFv), bispecific antibody, and bi/trispecific cell engagers, are engineered with humanization, multivalent antibody construction, affinity optimization and antibody masking for targeting tumor cells and killer cells to improve antibody‐based therapy potency, efficacy and specificity. In this review, we summarize the application of antibody variable region engineering and discuss the future direction of antibody engineering for improving cancer therapies.
Using phenomenography to unearth factors influencing the delivery of guidance services
Authors: Sedofia John , Fia Stephen Doh , Tutu‐Danquah Cecilia
Published: July 2022

Which factors influence the delivery of school guidance services in Colleges of Education (CoEs) in Ghana? The guidance needs of students in the CoEs may not be fully met if the factors that influence guidance service delivery at that level of education are not explored for effective upgrade of service quality. This phenomenographic study therefore explored factors influencing the delivery of guidance services in CoEs in Ghana. We interviewed second‐year teacher trainees (n = 24) and counsellors from three randomly selected CoEs in the Volta region of Ghana (n = 3). The findings indicate that material resources and awareness influenced guidance service delivery in the CoEs. It was also found that although students reported that confidentiality and attitude influenced service delivery in the colleges, the counsellors did not agree with this. Finally, the study discovered that human resource does not influence guidance service delivery in the colleges. It was recommended that college authorities should provide the material resources, such as offices, computers, and test batteries, that are needed for counselling, and counsellors should publicise the guidance programme to raise awareness and lead to the development of positive attitudes towards the programme. This study contributes to the guidance and counselling literature by illuminating the factors influencing guidance service delivery in CoEs. This should be of interest to practitioners, policymakers and researchers in school guidance and counselling.
Leverage your ASR to communicate the importance of your department
Authors: Sutton Halley
Published: July 2022

In a free training, Sarah Barrett, Ph.D., Director of Training and Education at the Clery Center shared best practices for Clery Compliance in a webinar series with Rave Mobile Safety. “This series was developed because institutions of higher education often set their focus on Clery crime reporting and classification and fail to account for the equally important Clery requirements that guide policy response and action,” Barrett said.
Creating law to seek information and protect the public
Authors: Rainsberger Richard
Published: July 2022

The Family Educational Rights and Privacy Act governs how student records may be used and disclosed. For campus law enforcement and safety officers, records governed by FERPA may include records pertaining to student behavior and how it may intersect with records such as sex offender registry.
Prepare a crisis communications response plan for handling complex legal, reputational issues
Authors: McCarthy Claudine
Published: July 2022

Behind every legal issue facing your campus safety department are communications issues that need to be addressed. The way you choose to address these issues will influence how they're perceived by others, whether such issues might become entangled in the legal process, and the potential reputational damage to your department and institution.
Data examines law enforcement roles in active shooter events
Authors: Sutton Halley
Published: July 2022

An in‐depth analysis by The New York Times of data from the Advanced Law Enforcement Rapid Response Training Center at Texas State University has looked at the role law enforcement played in 433 mass shootings in the country from 2000 to 2021.
Opportunities and Challenges to Profile mRNA Modifications in Escherichia coli**
Authors: Petrov Dimitar Plamenov , Kaiser Steffen , Kaiser Stefanie , Jung Kirsten
Published: July 2022

mRNA methylation is an important regulator of many physiological processes in eukaryotes but has not been studied in depth in prokaryotes. Working with bacterial mRNA is challenging because it lacks a poly(A)‐tail. However, methods for detecting RNA modifications, both sequencing and mass spectrometry, rely on efficient preparation of mRNA. Here, we compared size‐dependent separation by electrophoresis and rRNA depletion for enrichment of Escherichia coli mRNA. The purification success was monitored by qRT‐PCR and RNA sequencing. Neither method allowed complete removal of rRNA. Nevertheless, we were able to quantitatively analyze several modified nucleosides in the different RNA types. We found evidence for stress dependent RNA modification reprofiling in rRNA, but also several modified nucleosides in the mRNA enriched fractions showed significant changes.
The role of metal ions in the Golgi apparatus
Authors: Gao Jiayin , Gao Anbo , Zhou Hong , Chen Linxi
Published: July 2022

The Golgi apparatus is a membrane‐bound organelle that functions as a central role in the secretory pathway. Since the discovery of the Golgi apparatus, its structure and function have attracted ever‐increasing attention from researchers. Recently, it has been demonstrated that metal ions are necessary for the Golgi apparatus to maintain its proper structure and functions. Given that metal ions play an important role in various biological processes, their abnormal homeostasis is related to many diseases. Therefore, in this paper, we reviewed the uptake and release mechanisms of the Golgi apparatus Ca2+, Cu, and Zn2+. Furthermore, we describe the diseases associated with Golgi apparatus Ca2+, Cu, and Zn2+ imbalance.
PRospective REgistry of PAtients in REfractory cardiogenic shock—The PREPARE CardShock registry
Authors: von Lewinski Dirk , Herold Lukas , Stoffel Christian , Pätzold Sascha , Fruhwald Friedrich , Altmanninger‐Sock Siegfried , Kolesnik Ewald , Wallner Markus , Rainer Peter , Bugger Heiko , Verheyen Nicolas , Rohrer Ursula , Manninger‐Wünscher Martin , Scherr Daniel , Renz Dietmar , Yates Ameli , Zirlik Andreas , Toth Gabor G.
Published: July 2022

Aim

Cardiogenic shock (CS) is a hemodynamically complex multisystem syndrome associated with persistently high morbidity and mortality. As CS is characterized by progressive failure to provide adequate systemic perfusion, supporting end‐organ perfusion using mechanical circulatory support (MCS) seems intriguing. Since most patients with CS present in the catheterization laboratory, percutaneously implantable systems have the widest adoption in the field. We evaluated feasibility, outcomes, and complications after the introduction of a full‐percutaneous program for both the Impella CP device and venoarterial extracorporeal membrane oxygenator (VA‐ECMO).

Methods

PREPARE CardShock (PRospective REgistry of PAtients in REfractory cardiogenic shock) is a prospective single‐center registry, including 248 consecutive patients between May 2019 and April 2021, who underwent cardiac catheterization and displayed advanced cardiogenic shock. The median age was 70 (58–77) years and 28% were female. Sixty‐five percent of the cases had cardiac arrest, of which 66% were out‐of‐hospital cardiac arrest. A local standard operating procedure (SOP) indicating indications as well as relative and absolute contraindications for different means of MCS (Impella CP or VA‐ECMO) was used to guide MCS use. The primary endpoint was in‐hospital death and secondary endpoints were spontaneous myocardial infarction and major bleedings during the hospital stay.

Results

Overall mortality was 50.4% with a median survival of 2 (0–6) days. Significant independent predictors of mortality were cardiac arrest during the index event (odds ratio [OR] with 95% confidence interval [CI]: 2.53 [1.43–4.51]; p = 0.001), age > 65 years (OR: 2.05 [1.03–4.09]; p = 0.036]), pH < 7.30 (OR: 2.69 [1.56–4.66]; p < 0.001), and lactate levels > 2 mmol/L (OR: 4.51 [2.37–8.65]; p < 0.001).

Conclusions

Conclusive SOPs assist target‐orientated MCS use in CS. This study provides guidance on the implementation, validation, and modification of newly established MCS programs to aid centers that are establishing such programs.
Particle Size Effects in the Selective Hydrogenation of Alkadienes over Supported Cu Nanoparticles
Authors: Totarella Giorgio , de Rijk Jan Willem , Delannoy Laurent , de Jongh Petra E.
Published: July 2022

Copper is considered an excellent alternative to noble‐metal selective hydrogenation catalysts. Herein, we systematically studied the effect of Cu nanoparticle size (2–10 nm) in the selective hydrogenation of 1,3‐butadiene in excess of propene. The catalysts exhibited particle size‐dependent activity, with particles above 4 nm being 3 to 4 times more active than the 2 nm ones, and at the same time more selective (up to 99 % at almost full butadiene conversion for 7–10 nm particles). The higher activity of larger particles was ascribed to a higher fraction of kinks and step sites, essential to activate hydrogen. The high selectivity of nanoparticulate Cu catalysts was explained by a very strong preferential adsorption of 1,3‐butadiene compared to mono‐olefin adsorption on the Cu surface (in particular on larger particles), as proven via adsorption measurements. These findings may guide both testing and catalyst design for reactions where hydrogen surface availability and selectivity play a key role.
Selective Hydrogenation of L‐proline to L‐prolinol over Al2O3‐supported Pt‐MoOx Catalyst
Authors: Kaku Chinami , Suganuma Satoshi , Nakajima Kiyotaka , Tsuji Etsushi , Katada Naonobu
Published: July 2022

L‐proline, one of abundant amino acids, can be utilized as a biobased feedstock for the synthesis of an amino alcohol, L‐prolinol, which serves as chiral auxiliary in a variety of asymmetric synthesis. Herein we examined selective hydrogenation of L‐proline into L‐prolinol over M−MoOx/Al2O3 (M=Pt, Rh, Pd, and Ru) in aqueous H3PO4 solution. Pt‐MoOx/Al2O3 exhibited high activity among the catalysts, affording L‐prolinol in 75 % selectivity and >99.9 % enantiomeric excess, while Pt/Al2O3 was inactive. Mo species were highly dispersed as a polyoxo cluster on both Pt nanoparticles and Al2O3 support, and participated concertedly with Pt nanoparticles in the hydrogenation. Activated carboxyl group of L‐proline by MoOx species on Pt nanoparticle are readily hydrogenated with dissociative hydrogen formed on the same Pt nanoparticle with MoOx species, giving an effective route for the hydrogenation of L‐proline. Pt‐MoOx/Al2O3 could be identified as an active and reusable catalyst due to no loss of its original activity.
Exogenous Ligand‐Free Nickel‐Catalyzed Carboxylate O‐Arylation: Insight into NiI/NiIII Cycles**
Authors: Wolzak Lukas A. , de Zwart Felix J. , Oudsen Jean‐Pierre H. , Bartlett Stuart A. , de Bruin Bas , Reek Joost N. H. , Tromp Moniek , Korstanje Ties J.
Published: July 2022

Nickel‐catalyzed cross‐coupling reactions have become a powerful methodology to construct C‐heteroatom bonds. However, many protocols suffer from competitive off‐cycle reaction pathways and require non‐equimolar amounts of coupling partners to suppress them. Here, we report on mechanistic examination of carboxylate O‐arylation under thermal conditions, in both the presence and absence of an exogeneous bipyridine‐ligand. Furthermore, spectroscopic studies of the novel ligand‐free carboxylate O‐arylation reaction unveiled the resting state of the nickel catalyst, the crucial role of the alkylamine base and the formation of an off‐cycle NiI−NiII dimer upon reduction. This study provides insights into the competition between productive catalysis and deleterious pathways (comproportionation and protodehalogenation) in the commonly proposed self‐sustained NiI/NiIII catalytic cycle. Thereby we show that for productive nickel‐catalyzed carboxylate O‐arylation a choice must be made between either mild conditions or equimolar ratios of substrates.
Reaction Kinetics of an Industrial Front‐End Acetylene Hydrogenation Catalyst Using the Advanced TEMKIN Reactor
Authors: Hock Sebastian , Iser Leonhard , Lucas Martin , Rose Marcus
Published: July 2022

The front‐end process integration of the selective acetylene hydrogenation provides several advantages over the tail‐end option. But extensive knowledge of the process and reaction kinetics are required. This work combines the ideal conditions of the advanced TEMKIN reactor in a laboratory plant for gradient‐free kinetic analysis of eggshell catalyst under industrially relevant front‐end conditions. With this system an industrial state of the art Pd‐Ag/Al2O3 eggshell catalyst is investigated and the temperature dependent data under various feed compositions including information on the formation of C4‐species are reported.
Effect of Nanoscale Confinement on Ultrafast Dynamics of Singlet Fission in TIPS‐Pentacene
Authors: Silori Yogita , Chawla Sakshi , Yadav Anita , De Arijit K.
Published: July 2022

Singlet fission (SF) is a phenomenon for the generation of a pair of triplet excitons from anexcited molecule in singlet electronic state interacting with another adjacent molecule in its ground electronic state. By increasing the effective number of charge carriers and reducing thermal dissipation of excess energy, SF is promised to enhance light‐harvesting efficiency for photovoltaic applications. While SF has been extensively studied in thin films and crystals, the same has not been explored much within a confined medium. Here, we report the ultrafast SF dynamics of triisopropylsilylethynyl pentacene (TIPS‐Pn) in micellar nanocavity of varying sizes (prepared from TX‐100, CTAB, and SDS surfactants). The nanoparticles with a smaller size contain weakly coupled chromophores which are shown to be more efficient for SF followed by triplet generation as compared to the nanoparticles of larger size which contain strongly coupled chromophores which are less efficient due to the presence of singlet exciton traps. Through these studies, we delineate how a subtle interplay between short‐range and long‐range interaction among chromophores confined within nanoparticles, fine‐tuned by the curvature of the micellar interface but irrespective of the nature of the micelle (cationic or anionic or neutral), play a crucial role in SF through and generation of triplets.
DNA Tetrahedron Framework Guided Conjugation and Assembly of Gold Nanoparticles
Authors: He Wei , Zhao Yan , Xing Shu , Zhang Yinan , Wang Lihua , Liu Huajie
Published: July 2022

Au nanoparticles (AuNPs) have been extensively used to assemble programmable structures that feature various functions. One central challenge of precisely directed assembly is to make valence‐programmable building blocks. Herein, we use the DNA tetrahedron framework to stoichiometrically conjugate to Au nanoparticles, which results in monovalent building blocks at nanometer scale. We further fabricated high‐order Au‐tetrahedron structures to verify the ability of the blocks for building assemblies. These structures represent an exploration of an avenue to monovalent AuNPs, and provide the feasibility of precisely manipulating nanoparticles into prescribed assemblies.
Cross Dehydrogenative Coupling of Chloro‐ and Fluoroalkanes with Methylarenes
Authors: Xiang Jia‐Xiang , Patureau Frederic W.
Published: July 2022

Cross dehydrogenative coupling reactions (CDCs) are considerably more step‐ and atom efficient compared to classical cross coupling methods. In this context, the photochemical CDCs of hydrochlorocarbons and hydrofluorocarbons with methylarenes are herein described. This unprecedented CDC reaction concept enables a new retrosynthetic cut for the selective construction of valuable chlorinated and fluorinated organic skeletons, from industrially important dichloromethane, dichloroethane, difluoromethane (HFC‐32), and 1,1,1,2‐tetrafluoroethane (HFC‐134a).
Methods to Identify Immune Cells in Tissues With a Focus on Skin as a Model
Authors: Murphy Peter R. , Narayanan Divyaa , Kumari Snehlata
Published: July 2022

The skin protects our body from external challenges, insults, and pathogens and consists of two layers, epidermis and dermis. The immune cells of the skin are an integral part of protecting the body and essential for mediating skin immune homeostasis. They are distributed in the epidermal and dermal layers of the skin. Under homeostatic conditions, the mouse and human skin epidermis harbors immune cells such as Langerhans cells and CD8+ T cells, whereas the dermis contains dendritic cells (DCs), mast cells, macrophages, T cells, and neutrophils. Skin immune homeostasis is maintained through communication between epidermal and dermal cells and soluble factors. This communication is important for proper recruitment of immune cells in the skin to mount immune responses during infection/injury or in response to external/internal insults that alter the local cellular milieu. Imbalance in this crosstalk that occurs in association with inflammatory skin disorders such as psoriasis and atopic dermatitis can lead to alterations in the number and type of immune cells contributing to pathological manifestation in these disorders. Profiling changes in the immune cell type, localization, and number can provide important information about disease mechanisms and help design interventional therapeutic strategies. Toward this end, skin cells can be detected and characterized using basic techniques like immunofluorescence, immunohistochemistry, and flow cytometry, and recently developed methods of multiplexing. This article provides an overview on the basic techniques that are widely accessible to researchers to characterize immune cells of the skin. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.
Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID‐19
Authors: Bolla Andrea Mario , Loretelli Cristian , Montefusco Laura , Finzi Giovanna , Abdi Reza , Ben Nasr Moufida , Lunati Maria Elena , Pastore Ida , Bonventre Joseph V. , Nebuloni Manuela , Rusconi Stefano , Santus Pierachille , Zuccotti Gianvincenzo , Galli Massimo , D’Addio Francesca , Fiorina Paolo
Published: July 2022

Aims

Several reports indicate that diabetes determines an increased mortality risk in patients with coronavirus disease 19 (COVID‐19) and a good glycaemic control appears to be associated with more favourable outcomes. Evidence also supports that COVID‐19 pneumonia only accounts for a part of COVID‐19 related deaths. This disease is indeed characterised by abnormal inflammatory response and vascular dysfunction, leading to the involvement and failure of different systems, including severe acute respiratory distress syndrome, coagulopathy, myocardial damage and renal failure. Inflammation and vascular dysfunction are also well‐known features of hyperglycemia and diabetes, making up the ground for a detrimental synergistic combination that could explain the increased mortality observed in hyperglycaemic patients.

Materials and methods

In this work, we conduct a narrative review on this intriguing connection. Together with this, we also present the clinical characteristics, outcomes, laboratory and histopathological findings related to this topic of a cohort of nearly 1000 subjects with COVID‐19 admitted to a third‐level Hospital in Milan.

Results

We found an increased mortality in subjects with COVID‐19 and diabetes, together with an altered inflammatory profile.

Conclusions

This may support the hypothesis that diabetes and COVID‐19 meet at the crossroads of inflammation and vascular dysfunction. (ClinicalTrials.gov NCT04463849 and NCT04382794).
Camera trap data suggest uneven predation risk across vegetation types in a mixed farmland landscape
Authors: Laux Amelie , Waltert Matthias , Gottschalk Eckhard
Published: July 2022

Ground‐nesting farmland birds such as the grey partridge (Perdix perdix) have been rapidly declining due to a combination of habitat loss, food shortage, and predation. Predator activity is the least understood factor, especially its modulation by landscape composition and complexity. An important question is whether agri‐environment schemes such as flower strips are potentially useful for reducing predation risk, for example, from red fox (Vulpes vulpes). We employed 120 camera traps for two summers in an agricultural landscape in Central Germany to record predator activity (i.e., the number of predator captures) as a proxy for predation risk and used generalized linear mixed models (GLMMs) to investigate how the surrounding landscape affects predator activity in different vegetation types (flower strips, hedges, field margins, winter cereal, and rapeseed fields). Additionally, we used 48 cameras to study the distribution of predator captures within flower strips. Vegetation type was the most important factor determining the number of predator captures and capture rates in flower strips were lower than in hedges or field margins. Red fox capture rates were the highest of all predators in every vegetation type, confirming their importance as a predator for ground‐nesting birds. The number of fox captures increased with woodland area and decreased with structural richness and distance to settlements. In flower strips, capture rates in the center were approximately 9 times lower than at the edge. We conclude that the optimal landscape for ground‐nesting farmland birds seems to be open farmland with broad extensive vegetation elements and a high structural richness. Broad flower blocks provide valuable, comparatively safe nesting habitats, and the predation risk can further be minimized by placing them away from woods and settlements. Our results suggest that adequate landscape management may reduce predation pressure.
Heterogeneity in risk‐sensitive allocation of somatic reserves in a long‐lived mammal
Authors: Smiley Rachel A. , Wagler Brittany L. , LaSharr Tayler N. , Denryter Kristin A. , Stephenson Thomas R. , Courtemanch Alyson B. , Mong Tony W. , Lutz Daryl , McWhirter Doug , Brimeyer Doug , Hnilicka Patrick , Lowrey Blake , Monteith Kevin L.
Published: July 2022

Food quality and availability, when combined with energetic demands in seasonal environments, shape resource acquisition and allocation by animals and hold consequences for life‐history strategies. In long‐lived species with extensive maternal care, regulation of somatic reserves of energy and protein can occur in a risk‐sensitive manner, wherein resources are preferentially allocated to support survival at the cost of investment in reproduction. We investigated how Rocky Mountain bighorn sheep (Ovis canadensis), an alpine mammal in a highly seasonal environment, allocates somatic reserves across seasons. In accordance with the hypothesis of risk‐sensitive resource allocation, we expected accretion and catabolism of somatic reserves to be regulated relative to preseason nutritional state, reproductive state, and variation among populations in accordance with local environmental conditions. To test that hypothesis, we monitored seasonal changes in percent ingesta‐free body fat (IFBFat) and ingesta‐free, fat‐free body mass (IFFFBMass) in three populations of bighorn sheep in northwest Wyoming between 2015 and 2019 through repeated captures of female sheep in December and March of each year in a longitudinal study design. Regulation of somatic reserves was risk‐sensitive and varied relative to the amount of somatic reserves an animal had at the beginning of the season. Regulation of fat reserves was sensitive to reproductive state and differed by population, particularly over the summer. In one population with low rates of recruitment of young, sheep that recruited offspring lost fat over the summer in contrast to the other two populations where sheep that recruited gained fat. And yet, all populations exhibited similar changes in fat catabolism and risk sensitivity over winter. The magnitude of body fat and mass change across seasons may be indicative of sufficiency of seasonal ranges to meet energetic demands of survival and reproduction. Risk‐sensitive allocation of resources was pervasive, suggesting nutritional underpinnings are foundational to behavior, vital rates, and, ultimately, population dynamics. For species living in alpine environments, risk‐sensitive resource allocation may be essential to balance investment in reproduction with ensuring survival.
ARNI or ARB Treats Residual Left Ventricular Remodelling after Surgery for Valvular Regurgitation: ReReRe study protocol
Authors: Kang Yu , Yang Zi‐xuan , Liu Lu‐lu , Kong Hong , Wang Hua , Dong Wei , Bai Ling , Wang Jiang , Sun Zhi‐jun , Zhang Jing , Li Jing , Guo Ying‐qiang , Zhang Qing
Published: July 2022

Aims

Patients with persistent or de novo left ventricular (LV) dilation and/or reduced ejection fraction (EF) after correction for primary aortic (AR) or mitral (MR) regurgitation (i.e. residual LV remodelling) have not been well studied with regard to guideline‐directed medical therapy after successful aetiology‐reversing surgery. We aim to (i) compare the effectiveness of sacubitril/valsartan vs. valsartan in promoting LV reverse remodelling and (ii) explore the safety of medication withdrawal after LV recovery.

Methods and results

The ReReRe study is a multicentre, randomized, open‐label, parallel trial that consists of two consecutive parts. A total of 371 patients with an LV end‐diastolic diameter (LVEDD) > 60 mm or LVEF < 50%, assessed by transthoracic echocardiography (TTE) 7–14 days after valve surgery for significant AR or primary MR will be enrolled. The 1st randomization into the sacubitril/valsartan or valsartan groups and structured follow‐up (1, 3, 6, 9, and 12 months after randomization) will be conducted to observe the primary objective as the rate of complete recovery of LV remodelling (i.e. LVEDD < 55 mm and LVEF ≥ 60% by TTE at two consecutive visits). Those who have complete recovery of LV remodelling will be enrolled in Study Part 2; consequently, they will receive the 2nd randomization into the medication withdrawal or maintenance group and 6‐monthly visits for the observation of the primary objective as the rate of LV remodelling relapse (LVEDD > 60 mm or LVEF < 50%). The secondary objectives include the rate of composite clinical outcomes and the degree of change in 6‐min walk distance and Kansas City Cardiomyopathy Questionnaire scores.

Conclusions

The ReReRe study will provide new evidence for the treatment of patients with residual LV remodelling after curable unloaded surgery, as well as the duration of treatment. The study results will fill the gap in identifying an appropriate medical therapy regimen for this group of patients and perhaps for those with reversible aetiologies of heart failure.
Cardiac arrest as a manifestation of unknown Type V glycogenosis: a case report
Authors: Soria‐Navarro Raquel , Burgos Palacios Virginia , Castrillo Bustamante Cristina , Gallardo Agromayor Elena , Marcos González Sara , González‐Lamuño Leguina Domingo
Published: July 2022

Few cases have been reported to date, in which a massive rhabdomyolysis causes a cardiac arrest in a male adult suffering from undiagnosed McArdle disease. Veno‐arterial extracorporeal membrane oxygenation and cytokine adsorption filter (CytoSorb®) were required to reach a complete and successful recovery.
The influence path and dynamic relationship between economic development, industrial structure upgrading, urbanization, urban–rural income gap, and electricity consumption in China
Authors: Song Mei , Zhang Liyan , Li Mengxue
Published: July 2022

Considering China's goal of carbon neutrality, understanding the influence path and dynamic correlation between electricity consumption and relevant factors is essential for formulating a reasonable electricity development strategy and promoting high‐quality socio‐economic development. Based on panel data of 30 provinces in China from 2000 to 2019, this study adopts the panel VAR model for research, with four notable findings. (1) Economic development, urbanization, and the urban–rural income gap directly affect electricity consumption. Industrial structure upgrading can affect electricity consumption through economic development and urbanization. Electricity consumption only directly affects economic development, whereas the effect on the other three variables could be transmitted through economic development. (2) Electricity consumption first inhibits and then promotes industrial structure upgrading, and it inhibits the urban–rural income gap. (3) Industrial structure upgrading first promotes and then inhibits electricity consumption. The urban–rural income gap inhibits electricity consumption. (4) Industrial structure upgrading and the widening income gap might hinder economic development through the adverse effect on electricity consumption. Based on these findings, several policy suggestions are proposed.
Preparation of temperature‐sensitive fragrance nanocapsules and its controllable release property
Authors: Zhao Di , Zhao Qixuan , Xu Zhifei , Shi Xiaodi
Published: July 2022

Temperature‐sensitive nanocapsules with controllable release properties were synthesized through miniemulsion free radical polymerization method. Temperature‐sensitive N,N‐diethylacrylamide/N,N‐dimethylacrylamide (DEA/DMA) copolymer were systematically synthesized as shell materials, and the fragrance‐dementholized peppermint oil (DPO) was encapsulated as hydrophobic core material. The as prepared nanocapsules had high encapsulation efficiencies of more than 90% and small average diameters of less than 150 nm, as well as narrow polydispersity index (PDI) below 0.17. Furthermore, decreased DEA contents in shell material resulted in higher phase transition temperature and slower release rate of fragrance under the same temperature. By varying the copolymer composition of shell materials, the controllable release property of as prepared nanocapsules were also varied under different temperatures.
Dietary tea tree (Melaleuca alternifolia) oil supplementation enhances the expressions of amino acid transporters in goat ileal mucosa and improves intestinal immunity
Authors: Lv Xiaokang , Chen Liang , Zhou Chuanshe , Guo Yibing , Zhang Guijie , Kang Jinhe , Tan Zhiliang , Tang Shaoxun , Liu Zixin
Published: July 2022

Tea tree oil (TTO) is a plant‐derived additive with anti‐inflammatory, bactericidal, and growth‐promoting properties. However, little is known about the effects of TTO on intestinal amino acid transport and immune function in goats. Twenty‐four Ganxi goats (initial body weight of 13.5 ± 0.70 kg) were randomly allotted two treatments and fed either control (CON) or CON+TTO (0.2 ml/kg) diet. The addition of TTO to the diet significantly decreased (p < .05) tumor necrosis factor‐α content and increased (p < .05) interleukin‐2 (IL‐2) content in goat serum; significantly decreased (p < .05) IL‐12, and increased (p < .05) IL‐2 content in goat ileal mucosa; significantly increased (p < .05) secreted IgA content in the jejunal and ileal mucosa; significantly upregulated (p < .05) IL‐2 and downregulated (p < .05) IL‐12 at the mRNA level in the ileal mucosa; significantly elevated the levels of serine, arginine, and total amino acids in the ileal mucosa (p < .05); significantly upregulated (p < .05) SLC1A1 and SLC7A1 in the ileum; and significantly enhanced (p < .05) the protein expression of Claudin‐1 in the ileal mucosa. In summary, adding 0.2 ml/kg of TTO to the diet enhanced SLC1A1 and SLC7A1 mRNA expression in the ileal mucosa, and SLC1A1 and SLC7A1 could transport serine and arginine from the chyme to the ileal mucosa. Thus, increased serine and arginine content in the mucosa could improve intestinal immunity. TTO supplementation upregulated the expression of IL‐2 and Claudin‐1 in goat ileal mucosa, and enhanced immune function in the intestine.
Different functional connectivity optimal frequency in autism compared with healthy controls and the relationship with social communication deficits: Evidence from gene expression and behavior symptom analyses
Authors: Long Jinjin , Lu Fengmei , Yang Shanshan , Zhang Qianyue , Chen Xue , Pang Yajing , Wang Min , He Bifang , Liu Heng , Duan Xujun , Chen Huafu , Ye Shaobing , Chen Heng
Published: July 2022

Studies have reported that different brain regions/connections possess distinct frequency properties, which are related to brain function. Previous studies have proposed altered brain activity frequency and frequency‐specific functional connectivity (FC) patterns in autism spectrum disorder (ASD), implying the varied dominant frequency of FC in ASD. However, the difference of the dominant frequency of FC between ASD and healthy controls (HCs) remains unclear. In the present study, the dominant frequency of FC was measured by FC optimal frequency, which was defined as the intermediate of the frequency bin at which the FC strength could reach the maximum. A multivariate pattern analysis was conducted to determine whether the FC optimal frequency in ASD differs from that in HCs. Partial least squares regression (PLSR) and enrichment analyses were conducted to determine the relationship between the FC optimal frequency difference of ASD/HCs and cortical gene expression. PLSR analyses were also performed to explore the relationship between FC optimal frequency and the clinical symptoms of ASD. Results showed a significant difference of FC optimal frequency between ASD and HCs. Some genes whose cortical expression patterns are related to the FC optimal frequency difference of ASD/HCs were enriched for social communication problems. Meanwhile, the FC optimal frequency in ASD was significantly related to social communication symptoms. These results may help us understand the neuro‐mechanism of the social communication deficits in ASD.
Cdc42 promotes thyroid cancer cell proliferation and migration and tumor‐associated macrophage polarization through the PTEN/AKT pathway
Authors: Huang Deyi , Qiu Huali , Miao Lin , Guo Lin , Zhang Xiaoting , Lin Mengmeng , Li Zhongyun , Li Fang
Published: July 2022

The purpose of this study was to investigate the potential mechanism and function of Cdc42 in thyroid cancer. We found that knockdown of Cdc42 inhibited the migration and proliferation of WRO cells. This role of Cdc42 is achieved by interacting with PTEN and interfering with its PTEN nuclear translocation. The overexpression of Cdc42 enhances the production of lactic acid and promotes the polarization of M2 macrophages, and therefore M2 macrophages inhibit the function of T cells. Overall, Cdc42 can promote cell proliferation and migration through the PTEN/AKT pathway and promote tumor‐related M2 macrophage polarization and inhibit T cell activity by enhancing aerobic glycolysis, animal experiments confirmed that tumor volume increased after Cdc42 overexpressed in TBP‐3743 murine thyroid cancer cells. Increased infiltration of Treg and macrophages was also observed. taken together, our results indicate that Cdc42 can be used as a diagnostic and thyroid cancer Prognostic biomarkers and potential therapeutic targets.
IPMK modulates hepatic glucose production and insulin signaling
Authors: Jung Ik‐Rak , Anokye‐Danso Frederick , Jin Sunghee , Ahima Rexford S. , Kim Sangwon F.
Published: July 2022

Hepatic glucose production (HGP) is crucial for the maintenance of normal glucose homeostasis. Although hepatic insulin resistance contributes to excessive glucose production, its mechanism is not well understood. Here, we show that inositol polyphosphate multikinase (IPMK), a key enzyme in inositol polyphosphate biosynthesis, plays a role in regulating hepatic insulin signaling and gluconeogenesis both in vitro and in vivo. IPMK‐deficient hepatocytes exhibit decreased insulin‐induced activation of Akt‐FoxO1 signaling. The expression of messenger RNA levels of phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose 6‐phosphatase (G6pc), key enzymes mediating gluconeogenesis, are increased in IPMK‐deficient hepatocytes compared to wild type hepatocytes. Importantly, re‐expressing IPMK restores insulin sensitivity and alleviates glucose production in IPMK‐deficient hepatocytes. Moreover, hepatocyte‐specific IPMK deletion exacerbates hyperglycemia and insulin sensitivity in mice fed a high‐fat diet, accompanied by an increase in HGP during pyruvate tolerance test and reduction in Akt phosphorylation in IPMK deficient liver. Our results demonstrate that IPMK mediates insulin signaling and gluconeogenesis and may be potentially targeted for treatment of diabetes.
Quality of root canal treatment performed by undergraduate students using nickel‐titanium reciprocating versus hand instruments
Authors: Miçooğulları Kurt Seniha , Kandemir Demirci Gözde , Serefoglu Burcu , Kaval Mehmet Emin , Güneri Pelin , Çalışkan Mehmet Kemal
Published: July 2022

Purpose

To compare the technical quality of root canal treatment (RCT) depending on the incidence of procedural errors performed by undergraduate students using nickel‐titanium reciprocating and conventional hand instrumentation techniques, and to assess the impact of case difficulty and localization of the teeth (maxillary or mandibular molars).

Methods

Dental records and periapical radiographs of molars that were treated with either hand or reciprocating WaveOne (WO) instruments were evaluated retrospectively. The technical quality of RCTs, the incidence of ledge formation, perforation, instrument fracture, overinstrumentation, underfilling, overfilling, inadequate root canal filling, and the effects of case difficulty and tooth localization were compared using the chi‐square test with a significance of 5% (α = 0.05).

Results

While overinstrumentation was more frequent in the WO group (247 teeth), the incidence of inadequate root canal fillings was higher in the hand instrumentation group (245 teeth) (p < 0.01). No significant difference was observed in the incidence of other procedural errors (p > 0.05). The number of teeth with acceptable technical quality in preparation and obturation was 172 (69.6%) in the WO group, whereas it was 142 (58%) in the hand instrumentation group, presenting a significant difference between the instrumentation techniques (p < 0.01). Higher technical quality rates were observed with WO instrumentation in the high difficulty category and in maxillary teeth (p < 0.01).

Conclusion

Higher technical quality in preparation and obturation can be achieved with WO reciprocating instruments and file‐matched greater tapered gutta‐percha cones. No significant difference was observed between the groups in the incidence of procedural errors except for overinstrumentation and insufficient root canal filling. WO instrumentation and obturation with file‐matched greater tapered gutta‐percha cones provided better technical quality in the high difficulty category and in maxillary teeth.
Neuroglobin deficiency increases seizure susceptibility but does not affect basal behavior in mice
Authors: Gøtzsche Casper R. , Woldbye David P. D. , Hundahl Christian Ansgar , Hay‐Schmidt Anders
Published: July 2022

Neuroglobin (Ngb) is found in the neurones of several different brain areas and is known to bind oxygen and other gaseous molecules and reactive oxygen species (ROS) in vitro, but it does not seem to act as a respiratory molecule for neurones. Using male and female Ngb‐knockout (KO) mice, we addressed the role of Ngb in neuronal brain activity using behavioral tests but found no differences in general behaviors, memory processes, and anxiety−/depression‐like behaviors. Oxidative stress and ROS play key roles in epileptogenesis, and oxidative injury produced by an excessive production of free radicals is involved in the initiation and progression of epilepsy. The ROS binding properties led us to hypothesize that lack of Ngb could affect central coping with excitatory stimuli. We consequently explored whether exposure to the excitatory molecule kainate (KA) would increase severity of seizures in mice lacking Ngb. We found that the duration and severity of seizures were increased, while the latency time to develop seizures was shortened in Ngb‐KO compared to wildtype adult female mice. Consistently, c‐fos expression after KA was significantly increased in Ngb‐KO mice in the amygdala and piriform cortex, regions rich in Ngb and known to be centrally involved in seizure generation. Moreover, the measured c‐fos expression levels were correlated with seizure susceptibility. With these new findings combined with previous studies we propose that Ngb could constitute an intrinsic defense mechanism against neuronal hyperexcitability and oxidative stress by buffering of ROS in amygdala and other Ngb‐containing brain regions.
White wine phenolics: current methods of analysis
Authors: Clarke Sarah , Bosman Gurthwin , du Toit Wessel , Aleixandre‐Tudo Jose Luis
Published: July 2022

White wine phenolic analyses are less common in the literature than analyses of red wine phenolics. Analytical techniques for white wine phenolic analyses using spectrophotometric, chromatographic, spectroscopic, and electrochemical methods are reported. The interest of research in this area combined with the advances in technology aimed at the winemaking industry are promoting the establishment of novel approaches for identifying, quantifying, and classifying phenolic compounds in white wine. This review article provides an overview of the current research into white wine phenolics through a critical discussion of the analytical methods employed. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.