bluuebunny/crossref_metadata_2025 huggingface dataset:
‘No‐one knows how to care for LGBT community like LGBT do’1: LGBTQIA+ experiences of COVID‐19 in the United Kingdom and Brazil
Authors: Haworth Billy Tusker , Barros Cassal Luan Carpes , de Paula Muniz Tiago
Published: October 2022

The coronavirus pandemic and responses to it have had uneven impacts on different segments of societies. This study analysed the experiences of LGBTQIA+2 people during the COVID‐19 emergency, based on interviews in the United Kingdom and Brazil in 2020. The two countries are instructive cases, given the different social, cultural, economic, and political contexts. Pre‐existing marginalisation shaped COVID‐19 experiences in both settings, influencing the challenges faced, such as isolation or disruption to transgender healthcare, and coping strategies, including the important role of LGBTQIA+ volunteer and mutual aid groups. This paper argues that despite commonalities, there is no single LGBTQIA+ experience, and that disaster strategies will be ineffective until they recognise intersectionality and support the diversity of LGBTQIA+ populations. It concludes with a call for more inclusive disaster research, policy, and practice, which requires scrutinising the dominant cisgender–heteronormative structures that produce and reproduce LGBTQIA+ marginalisation.
Challenging the 50‐50 rule for the basal‐bolus insulin ratio in patients with type 2 diabetes who maintain stable glycaemic control
Authors: Harper Roy , Bashan Eran , Williams Kevin J. , Sritharan Sajitha , Willis Mark , Marriott Deanna J. , Hodish Israel
Published: October 2022

Background

For patients using basal‐bolus insulin therapy, it is widespread clinical practice to aim for a 50‐50 ratio between basal and total daily bolus. However, this practice was based on a small study of individuals without diabetes. To assess the rule in real‐world practice, we retrospectively analyzed patients on basal‐bolus therapy that was adjusted at least weekly by an artificial intelligence‐driven titration within the d‐Nav® Insulin Management Technology.

Materials and methods

We obtained de‐identified data from the Diabetes Centre of Ulster Hospital for patients with four inclusion criteria: type 2 Diabetes (T2D), on d‐Nav >6 months, on basal‐bolus insulin therapy >80% of the time (based on insulin analogs), and no gap in data >3 months.

Results

We assembled a cohort of 306 patients, followed by the d‐Nav service for 3.4 ± 1.8 years (mean ± SD), corresponding to about 180 autonomous insulin dose titrations and about 5000 autonomous individual dose recommendations per patient. After an initial run‐in period, mean glycated hemoglobin (HbA1c) values in the cohort were maintained close to 7%. Surprisingly, in just over three‐quarters of the cohort, the average basal insulin fraction was <50%; in half of the cohort average basal insulin fraction <41.2%; and in one‐quarter the basal insulin fraction was <33.6%. Further, the basal insulin fraction did not remain static over time. In half of the patients, the basal insulin fraction varied by ≥1.9×; and, in 25% of the patients, ≥2.5×.

Conclusion

Our data show that a 50‐50 ratio of basal‐to‐bolus insulin does not generally apply to patients with T2D who successfully maintain stable glycemia. Therefore, the 50‐50 ratio should not serve as an ongoing treatment guide. Moreover, our results emphasize the importance of at least weekly insulin titrations.
A multicentre, randomized, double‐blind, parallel, active‐ and placebo‐controlled Phase 3 clinical study of the glucokinase activator PB‐201 in treatment‐naive patients with type 2 diabetes mellitus: A study protocol
Authors: Du Ying , Gao Leili , Xiao Xinhua , Hou Xin , Ji Linong
Published: October 2022

Aim

To report the rationale for using PB‐201, a partial glucokinase activator (GKA), for a Phase 3 study (NCT05102149) assessing its efficacy and safety in a Chinese population and to describe the design of this GKA Phase 3 trial, the first to involve both an active control and a placebo control arm.

Materials and methods

This is an ongoing, multicentre, randomized, double‐blind, three‐arm placebo and active control study to be carried out among 672 Chinese treatment‐naive participants with type 2 diabetes mellitus (T2DM) to assess the efficacy and safety of PB‐201 for approximately 60 weeks, including a screening period and a safety follow‐up period.

Results

The primary objective of this study was to monitor change in glycated haemoglobin levels with PB‐201 in treatment‐naive T2DM participants from baseline to 24 weeks in comparison with vildagliptin and placebo. The key secondary objective was to assess the efficacy and safety of PB‐201 following treatment for a time period of 52 weeks.

Conclusion

This pivotal study will offer critical information regarding the efficacy and safety of PB‐201 in Chinese treatment‐naive T2DM participants that would help to establish robust evidence for the benefit‐risk evaluation of this drug.
Psychiatric symptoms and pain in maxillofacial injury following motor vehicle accidents: A comparative study
Authors: Hosseini Seyed Hadi , Mousavi Shalmaei Seyed Mohamad Amin , Mohtasham‐Amiri Zahra , Homaie Rad Enayatollah , Khodadadi‐Hassankiadeh Naema
Published: November 2022

Background/Aim

Post‐traumatic stress disorders, depression, and pain are rarely discussed in the literature on maxillofacial injuries, and psychiatric symptoms and pain are not identified and managed in such patients. The aim of this study was to determine the symptoms of post‐traumatic stress disorders, depression, and pain in people with maxillofacial injuries following motor vehicle accidents.

Material and Methods

In this cross‐sectional study, people injured in motor vehicle accidents from March to September 2015 who were referred to a medical educational center in the northern part of Iran for treatment follow‐up were sampled. The existing symptoms of post‐traumatic stress disorder by PSS, depression by BDI‐II, and pain by NRS were assessed. SPSS software version 21 was used for analysis.

Results

Maxillofacial injured patients had significant differences in terms of post‐traumatic stress disorder (p = .006), depression (p = .001), pain (p = .001), and length of hospital stay (p = .002) than patients without maxillofacial injuries.

Conclusions

Motor vehicle accident victims with maxillofacial injuries suffered significantly more from post‐traumatic stress disorders and depression, pain and length of hospital stay than patients with other injuries.
Difference in nutrient accumulation patterns between diapause‐destined and non‐diapause‐destined larvae of Hyphantria cunea
Authors: Wang Xinmei , Liu Zheng , Zhao Lvquan
Published: October 2022

Nutrient accumulation is crucial in insect diapause preparation because insufficient nutrient accumulation can shorten the diapause period, interfere with diapause development completion, and decrease the probability of surviving the overwintering period. The amounts of lipids and carbohydrates stored in diapausing pupae of Hyphantria cunea (Drury) (Lepidoptera: Erebidae, Arctiinae) are greater than those in the non‐diapausing pupae. In this study, we tested the hypothesis that diapause‐destined (DD) and non‐diapause‐destined (NDD) larvae of H. cunea have different nutrient accumulation patterns in penultimate and final instars. The body mass, as well as lipid, carbohydrate, and soluble protein contents, and the efficiency of converting digested food and ingested food into body matter were greater in the DD penultimate and final instars than in the NDD penultimate and final instars. Larger amounts of lipids, carbohydrates, and proteins were absorbed by DD penultimate and final instars and the final instar development period in the DD larvae was prolonged relative to NDD larvae. The activities of fatty acid synthase and glycogen synthase of DD penultimate and final instars were significantly higher than those of NDD larvae. These results suggest that the changes in nutrient accumulation patterns between DD and NDD larvae occur in penultimate and final instars, and that the DD larvae increase their nutrient accumulation during diapause preparation by the combined effect of extending their final‐instar development period and improving their digestive efficiency; they increase their lipid and carbohydrate stores by increasing the activities of fatty acid synthase and glycogen synthase in the fat body.
Structural relaxation in chalcogenide glasses
Authors: Málek Jiří
Published: October 2022

The structural relaxation of chalcogenide glasses is discussed within Tool–Narayanaswamy–Moynihan (TNM) formalism. The TNM parameters for more than 70 different glassy compositions are compared on the basis of the relaxation rate defined as Rf(ΔT) = −(dTf/dlogt)i at the inflection point of the isothermal relaxation curve plotted on a logarithmic timescale. The Rf(ΔT) depends on the TNM parameter ß and the parameter σ, combining the nonlinearity parameter x, the effective activation energy h* or the fragility m. It is shown that Rf(10) estimated at 10 K below Tg is useful for the prediction of structural relaxation kinetics in different amorphous materials. The chalcogenide glasses are, for example, compared with oxide glasses and organic polymers. For all these materials, the Rf(10) versus σ plot shows a well‐defined pattern that is thoroughly discussed.
Investigating signal modalities of aposematism in a poison frog
Authors: Stuckert Adam M. M. , Summers Kyle
Published: October 2022

Aposematic species combine a conspicuous signal with a secondary defence, the majority of which are studied in the context of a visual signal. While multimodality of the aposematic signal appears to be common in invertebrate species, we know very little about the presence or absence of multimodality in vertebrates. Here, we examine the possibility of multimodality of aposematism in the green-and-black poison frog, Dendrobates auratus. Using a non-visual predator (the cat-eyed snake, Leptodeira annulata) and extractions of chemicals in frog skins, we test whether there is sufficient non-visual information for predators to avoid this aposematic species without using visual cues. We found that experienced predators avoid chemicals in this poison frog's skin by olfactory cues alone in trials with live frogs and extracts from captive poison frogs, whereas extracts from wild poison frogs did not lead to avoidance behaviours in predators. Further, in our limited sampling, naïve predators demonstrate no avoidance. This not only indicates that predators can make informed decisions from the frog's odour, but also indicates that avoidance based on olfactory cue is a learned response.

Abstract

In this manuscript, we asked if predators avoid poison frogs by their sense of smell alone. We found that experienced predators can indeed avoid poison by smell alone, indicating the importance of examining other modalities of potential communication in aposematic vertebrates.
Racial diversity and group decision‐making in a mock jury experiment
Authors: Hakstian Anne‐Marie , Evett Sophia R. , Hoffmann James S. , Marshall Jane M. , Boyland Emory A. L. , Williams Jerome D.
Published: November 2022

The primary goal of this research was to determine whether the racial composition of a jury impacts the outcome and deliberation in a civil retail discrimination lawsuit. We presented a retail discrimination trial video to 30 separate mock juries. Of the 30 juries, 15 juries had 2 Black jurors, while the remaining 15 had no Black jurors (i.e., only White or White and Latinx participants). After watching the video, each mock jury was given 1 h to deliberate as if they were jurors deciding an actual case. Contrary to previous research, juries with Black jurors were no more likely to deliberate longer or consider more case facts. However, they were more likely to find for the plaintiff and award higher compensation. In addition, content analysis of the deliberation racial discourse revealed that some jurors espoused colorblind racial attitudes, minimizing the significance of race in this case and in society in general, and accusing the plaintiff of playing the “race card.” Other jurors encouraged understanding of the plaintiff and espoused non‐colorblind racial attitudes, recognizing the importance and damaging role of racism in American society. Implications for civil trials, jury selection, and racial discourse are discussed.
Patients with non‐functional metastatic G2 pancreatic neuroendocrine tumor benefit from palliative surgery: A 20‐year single‐center retrospective analysis
Authors: You Tingting , Tang Hui , Xu Xiuxiu , Ying Hongyan , Sun Zhao , Cheng Yuejuan , Bai Chunmei
Published: October 2022

Pancreatic neuroendocrine tumor (pNET) is the most common subset (31.5%) of gastroenteropancreatic neuroendocrine tumor in China. Based on real‐world data from a single center, the present study aimed to evaluate the influence of clinical characteristics, medical treatment and surgery on the survival of non‐functional metastatic G2 pNET. In total, 114 metastatic non‐functional G2 pNET patients, who were treated and followed up in the Department of Medical Oncology, Peking Union Medical College Hospital (PUMCH) from 2001 until 2019, were analyzed retrospectively. The primary endpoint, overall survival (OS), was calculated from the date of diagnosis to the date of death. The second endpoint, progression‐free survival (PFS), was calculated from the date of diagnosis to the date of disease progression. Statistical data were analyzed to evaluate the effects of a clinical characteristic, medical treatment and surgery on OS and PFS. Sixty‐nine (60.5%) patients were male and 87 (76.3%) were aged < 60 years. The liver was the most common metastatic organ, with a total of 84 cases (73.7%). With respect to surgery, 32 (28.1%) patients underwent radical surgery and 37 (32.5%) underwent palliative surgery. Survival analysis showed that the 5‐year and 10‐year survival rates were 79.36% and 70.0%, respectively. Univariate and multivariate Cox regression analyses suggested that both radical (p < .001/.003) and palliative surgery (p < .001/.002) significantly prolonged OS, as revealed by the Kaplan–Meier test (p < .001). Subgroup analysis showed that palliative resection also significantly improves the prognosis in patients with multiple liver metastases. However, the first‐line systemic anti‐tumor therapy option showed no statistical differences in the present study. Overall, patients with non‐functional metastatic G2 pNET receiving palliative or radical surgery demonstrated significantly better survival. Prospective clinical trials are suggested to validate our findings.
Contribution of chromosomal microarray analysis and next‐generation sequencing to genetic diagnosis in fetuses with normal karyotype
Authors: Akalın Münip , Demirci Oya , Dizdaroğulları Gizem E. , Çiftçi Erman , Karaman Ali
Published: November 2022

Aim

The aim of this study was to investigate the contribution of chromosomal microarray analysis (CMA) and next‐generation sequencing (NGS) to genetic diagnosis in fetuses with normal karyotype who underwent invasive testing for different indications.

Methods

The results of invasive genetic testing performed at a tertiary center between September 2020 and March 2022 were retrospectively analyzed. Indications for invasive tests were classified as fetal structural malformation, presence of soft markers, and high risk in screening tests. CMA results were classified as pathogenic or likely pathogenic (pCNVs), benign (bCNVs), and variants of unknown clinical significance (VOUS).

Results

A total of 830 invasive tests were performed and aneuploidy was detected in 11.2% of the fetuses. CMA was performed in 465 fetuses with normal karyotype, and pCNVs were detected in 6.9%. pCNVs were detected in 8.2% of fetuses with structural malformations, 6.5% in soft markers, and 4.7% in high risk in screening tests. Pathogenic variants were detected by NGS in 33.8% of fetuses with bCNVs.

Conclusions

pCNVs can be significantly detected not only in fetuses with structural malformations, but also in invasive testing with other indications. NGS significantly contributes to genetic diagnosis in fetuses with structural malformations.
Constraints, you, and your victims
Authors: Steuwer Bastian
Published: October 2022

Deontologists believe that it is wrong to violate a right even if this will prevent a greater number of violations of the same right. This leads to the paradox of deontology: If respecting everyone's rights is equally important, why should we not minimize the number of rights violations? One possible answer is agent‐based. This answer points out that you should not violate rights even if this will prevent someone else's violations. In this paper, I defend a relational agent‐based justification that focuses on the relation in which the agent stands to her would‐be victims. I argue that this justification can avoid two key objections levelled against agent‐based justifications: It can explain why we are not permitted to minimize our own rights violations, and the justification avoids the charge of being excessively self‐concerned.
Mobile genetic elements in Acinetobacter antibiotic‐resistance acquisition and dissemination
Authors: Noel Hannah R. , Petrey Jessica R. , Palmer Lauren D.
Published: November 2022

Pathogenic Acinetobacter species, most notably Acinetobacter baumannii, are a significant cause of healthcare‐associated infections worldwide. Acinetobacter infections are of particular concern to global health due to the high rates of multidrug resistance and extensive drug resistance. Widespread genome sequencing and analysis has determined that bacterial antibiotic resistance is often acquired and disseminated through the movement of mobile genetic elements, including insertion sequences (IS), transposons, integrons, and conjugative plasmids. In Acinetobacter specifically, resistance to carbapenems and cephalosporins is highly correlated with IS, as many ISAba elements encode strong outwardly facing promoters that are required for sufficient expression of β‐lactamases to confer clinical resistance. Here, we review the role of mobile genetic elements in antibiotic resistance in Acinetobacter species through the framework of the mechanism of resistance acquisition and with a focus on experimentally validated mechanisms.
COMT rs4818 less common allele is associated with psychological and psychiatric worse indicators in a cohort of individuals born with cleft lip and palate
Authors: Vieira Alexandre Rezende , Barros Mariana S. , Soares Maria Sueli Marques , Lacerda Rosa Helena Wanderley
Published: October 2022

Objective

Individuals born with cleft lip and palate may face difficulties in speech function, nutrition, facial aesthetics, and long‐term care. These difficulties may increase the risk of psychological and psychiatric diseases. This work aimed to test if the variant allele of COMT was carried more frequently among individuals that have psychological and psychiatric outcomes within a cohort of patients born with cleft lip and palate.

Method

DNA extraction from saliva of two hundred and fifteen individuals born with cleft lip with and/or palate and genotyping was performed, and the frequency of COMT rs4818 alleles was determined. The domain ‘Psychological Function’ of Cleft‐Q™ was used to generate scores for analysis. The scores were computed, and differences in genotype or allele frequencies between individuals with psychological function scores 60 or above and 59 or below were compared. The history of psychiatric illness (family history of psychiatric disease or self‐reported psychiatric illness) was registered.

Results

Genotype and allele frequencies were compared between individuals with and without a family history of psychiatric illness. Individuals with lower Psychological Function (Cleft‐Q™) scores were more likely to be GG (P = .04) or carriers of allele G (P < .001). The reported psychiatric illness and positive family history of psychiatric illness were compared to COMT rs4818 allele and genotype frequencies of individuals without these indicators, and individuals with psychiatric illness and positive family history of psychiatric illness were more likely to carry allele G (P = .03 and P = .008, respectively).

Conclusion

The study confirms previously suggested role of COMT rs4818 in psychiatric and psychological outcomes in a distinct cohort of patients born with cleft lip and palate.
Reduction of heat stress pressure and activation of photosystem II repairing system are crucial for citrus tolerance to multiple abiotic stress combination
Authors: Balfagón Damián , Zandalinas Sara I. , dos Reis de Oliveira Tadeu , Santa‐Catarina Claudete , Gómez‐Cadenas Aurelio
Published: October 2022

Drought, heat and high irradiance are abiotic stresses that negatively affect plant development and reduce crop productivity. The confluence of these three factors is common in nature, causing extreme situations for plants that compromise their viability. Drought and heat stresses increase the saturation of the photosystem reaction centers, increasing sensitivity to high irradiance. In addition, these stress conditions affect photosystem II (PSII) integrity, alter redox balance of the electron transport chain and decrease the photosynthetic rate. Here, we studied the effect of the stress combinations on the photosynthetic apparatus of two citrus genotypes, Carrizo citrange (Citrus sinensis × Poncirus trifoliata) and Cleopatra mandarin (Citrus reshni). Results obtained showed that physiological responses, such as modulation of stomatal aperture and transpiration rate, aimed to reduce leaf temperature, are key to diminishing heat impact on photosynthetic apparatus and increasing tolerance to double and triple combinations of drought, high irradiance and high temperatures. By using transcriptomic and proteomic analyses, we have demonstrated that under these abiotic stress combinations, Carrizo plants were able to increase expression of genes and proteins related to the photosystem repairing machinery (which better maintained the integrity of PSII) and other components of the photosynthetic apparatus. Our findings reveal crucial physiological and genetic responses in citrus to increase tolerance to the combination of multiple abiotic stresses that could be the basis for breeding programs that ensure a sustainable citrus production.
Temperature stress in psychrophilic green microalgae: Minireview
Authors: Cvetkovska Marina , Vakulenko Galyna , Smith David R. , Zhang Xi , Hüner Norman P. A.
Published: October 2022

Photosynthetic algae are the main primary producers in polar regions, form the basis of polar food webs, and are responsible for a significant portion of global carbon fixation. Many cold‐water algae are psychrophiles that thrive in the cold but cannot grow at moderate temperatures (≥20°C). Polar regions are at risk of rapid warming caused by climate change, and the sensitivity of psychrophilic algae to rising temperatures makes them, and the ecosystems they inhabit, particularly vulnerable. Recent research on the Antarctic psychrophile Chlamydomonas priscuii, an emerging algal model, has revealed unique adaptations to life in the permanent cold. Additionally, genome sequencing of C. priscuii and its relative Chlamydomonas sp. ICE‐L has given rise to a plethora of computational tools that can help elucidate the genetic basis of psychrophily. This minireview summarizes new advances in characterizing the heat stress responses in psychrophilic algae and examines their extraordinary sensitivity to temperature increases. Further research in this field will help determine the impact of climate change on psychrophiles from threatened polar environments.
Emergence of communities through interdependent dynamics of physical, cognitive and virtual contexts: the case of collaborative spaces
Authors: Capdevila Ignasi , Mérindol Valérie
Published: October 2022

Research about the emergence of communities has mainly focused on a single context of interaction, either physical or virtual. To uncover the relationships between different contexts (physical, cognitive, and virtual), the article investigates the progressive construction of different communities linked to collaborative spaces. Through a qualitative research based on a multiple case study, our analysis presents four distinct patterns of evolution, where different contexts were sequentially used, that continuously consolidated and enlarged the initial community. The results have significant implications not only to better understand community‐based collaborative dynamics, but they also offer useful insights about how to successfully develop and manage collaborative spaces for R&D and innovation activities.
Entrepreneurial new service development strategies: identifying critical success factors
Authors: Kitsios Fotis
Published: October 2022

The quickly shifting nature of the business environment generates ambiguity in the market place and poses a significant risk for decisions that will be made in the future. Managers do not know which factors are really key ingredients for the innovation process and how to allocate their resources to improve the success of service projects. This article aims to develop a predictive model which identifies the critical factors that impact the success of New Service Development (NSD) and promotes the entrepreneurial ecosystems in hospitality. In‐depth, systematic interviews with hotel managers from all over Greece, based on questionnaires, were used to look into a total of 178 service projects. Factor and discriminant analysis were employed to evaluate the relative significance of the important factors of successful NSD and to determine whether new hotel services in Greece will succeed or fail. This research led to the creation of a prediction model that takes into account the unique qualities of services and can highlight the difference between new hotel services that are successful and those that aren't, which support managers to improve the NSD process, increase service performance and therefore enhance entrepreneurial ecosystems. The findings conclude that hotels offering more successful innovative services enhance specific ecosystem‐related value. In the context of tourism, which mainly contributes to the Greek economy, service innovation might bring a competitive advantage to all the entities involved increasing the collaboration among actors, the level of employment and hotels' competitive advantage.
Exact Clustering in Tensor Block Model: Statistical Optimality and Computational Limit
Authors: Han Rungang , Luo Yuetian , Wang Miaoyan , Zhang Anru R.
Published: October 2022

High-order clustering aims to identify heterogeneous substructures in multiway datasets that arise commonly in neuroimaging, genomics, social network studies, etc. The non-convex and discontinuous nature of this problem pose significant challenges in both statistics and computation. In this paper, we propose a tensor block model and the computationally efficient methods, high-order Lloyd algorithm (HLloyd), and high-order spectral clustering (HSC), for high-order clustering. The convergence guarantees and statistical optimality are established for the proposed procedure under a mild sub-Gaussian noise assumption. Under the Gaussian tensor block model, we completely characterise the statistical-computational trade-off for achieving high-order exact clustering based on three different signal-to-noise ratio regimes. The analysis relies on new techniques of high-order spectral perturbation analysis and a ‘singular-value-gap-free’ error bound in tensor estimation, which are substantially different from the matrix spectral analyses in the literature. Finally, we show the merits of the proposed procedures via extensive experiments on both synthetic and real datasets.
A pilot study of the metabolic profiles of apheresis platelets modified by donor age and sex and in vitro short‐term incubation with sex hormones
Authors: Hadley Jamie B. , Kelher Marguerite R. , D'Alessandro Angelo , Gamboni Fabia , Hansen Kirk , Coleman Julia , Jones Kenneth , Cohen Mitchell , Moore Ernest E. , Banerjee Anirban , Silliman Christopher C.
Published: October 2022

Background

Platelets are part of innate immunity and comprise the cellular portion of hemostasis. Platelets express sex hormone receptors on their plasma membrane and sex hormones can alter their function in vitro. Little is known about how age and sex may affect platelet biology; thus, we hypothesized that platelets from males and females have different metabolomic profiles, which may be altered by age and in vitro treatment with sex hormones.

Methods

Day 1 apheresis platelets were drawn from five 18–53‐year‐old, premenopausal younger females (YF), five ≥54‐year‐old, postmenopausal, older females (OF), five 18–44‐year‐old younger males (YM), and four ≥45‐year‐old older males (OM). Platelets were normalized to a standard concentration and metabolomics analyses were completed. Unsupervised statistical analyses and hierarchical clustering with principal component analyses were completed.

Results

Platelets from OM had (1) elevated mono‐, di‐ and tri‐carboxylates, (2) increased levels of free fatty acids, acyl‐carnitines, and free amino acids, and (3) increased purine breakdown and deamination products. In vitro incubation with sex hormones only affected platelets from OM donors with trends towards increased ATP and other high‐energy purines and decreases in L‐proline and other amino acids.

Conclusion

Platelets from OM's versus YF, OF, and YM have a different metabolome implying increased energy metabolism, more free fatty acids, acylcarnitines, and amino acids, and increased breakdown of purines and deamination products. However, only platelets from OM were affected by sex hormones in vitro. Platelets from OM are metabolically distinct, which may impart functional differences when transfused.
Activation of p62-NRF2 Axis Protects against Doxorubicin-Induced Ferroptosis in Cardiomyocytes: A Novel Role and Molecular Mechanism of Resveratrol
Authors: Yu Wei , Chen Chunjuan , Xu Chenxi , Xie De , Wang Qiang , Liu Weidong , Zhao Hairong , He Furong , Chen Bingyang , Xi Yuemei , Yan Yunbo , Yu Linqian , Cheng Jidong
Published: October 2022

Doxorubicin (DOX) is a most common anthracycline chemotherapeutic agent; however, its clinical efficacy is limited due to its severe and irreversible cardiotoxicity. Ferroptosis, characterized by iron overload and lipid peroxidation, plays a pivotal role in DOX-induced cardiotoxicity. Resveratrol (RSV) displays cardioprotective and anticancer effects, owing to its antioxidative and anti-inflammatory properties. However, the role and mechanism of RSV in DOX-mediated ferroptosis in cardiomyocytes is unclear. This study showed that DOX decreased cell viability, increased iron accumulation and lipid peroxidation in H9c2 cells; however, these effects were reversed by RSV and ferroptosis inhibitor ferrostatin-1 (Fer-1) pre-treatment. Additionally, RSV significantly increased the cell viability of H9c2 cells treated with ferroptosis inducers Erastin (Era) and RSL3. Mechanistically, RSV inhibited mitochondrial reactive oxygen species (mtROS) overproduction and upregulated the p62-NRF2/HO-1 pathway. RSV-induced NRF2 activation was partially dependent on p62, and the selective inhibition of p62 (using p62-siRNA interference) or NRF2 (using NRF2 specific inhibitor, ML385) significantly abolished the anti-ferroptosis function of RSV. Furthermore, RSV treatment protected mice against DOX-induced cardiotoxicity, including significantly improving left ventricular function, ameliorating myocardial fibrosis and suppressing ferroptosis. Consistent with in vitro results, RSV also upregulated the p62-NRF2/HO-1 expression, which was inhibited by DOX, in the myocardium. Notably, the protective effect of RSV in DOX-mediated ferroptosis was similar to that of Fer-1 in vitro and in vivo. Thus, the p62-NRF2 axis plays a critical role in regulating DOX-induced ferroptosis in cardiomyocytes. RSV as a potent p62 activator has potential as a therapeutic target in preventing DOX-induced cardiotoxicity via ferroptosis modulation.
Tanshinone IIA Regulates Keap1/Nrf2 Signal Pathway by Activating Sestrin2 to Restrain Pulmonary Fibrosis
Authors: Li Hongxia , Wu Mingyu , Guo Congying , Zhai Rao , Chen Jun
Published: October 2022

Tanshinone IIA (Tan-IIA) is a major component extracted from the traditional herbal medicine Danshen, which has shown antipulmonary fibrosis by suppress reactive oxygen species-mediated activation of myofibroblast. However, the exact mechanism of Tan-IIA against pulmonary fibrosis (PF) remains unclear. This work aimed to explore the underlying mechanism of the protective effects of Tan-IIA on PF. By using high-throughput RNA-Seq analysis, we have compared the genome-wide gene expression profiles and pathway enrichment of Tan-IIA-treated NIH-3T3 cells with or without transforming growth factor beta 1 (TGF-[Formula: see text]1) induction. In normal NIH-3T3 cells, Tan-IIA treatment up-regulated 181 differential expression genes (DEGs) and down-regulated 137 DEGs. In TGF-[Formula: see text]1-induced NIH-3T3 cells, Tan-IIA treatment up-regulated 709 DEGs and down-regulated 1075 DEGs, and these DEGs were enriched in extracellular matrix organization, collagen fibril organization, cell adhesion, ECM–receptor interaction, PI3K-Akt signaling pathway and P53 signaling pathway. Moreover, there were 207 co-expressed DEGs between Tan-IIA treatment vs. the Control and TGF-[Formula: see text]1 plus Tan-IIA treatment vs. TGF-[Formula: see text]1 alone treatment, some of which were related to anti-oxidative stress. In both normal and TGF-[Formula: see text]1-induced NIH-3T3 cells, protein–protein interaction network analysis indicated that Tan-IIA can regulate the expression of several common anti-oxidant genes including Heme oxygenase 1 (Ho-1, also known as Homx1), Sestrin2 (Sesn2), GCL modifier subunit (Gclm), GCL catalytic subunit (Gclc) and Sequestosome-1 (Sqstm1). Quantitative Real-time polymerase chain reaction analysis confirmed some DEGs specifically expressing on Tan-IIA treated cells, which provided new candidates for further functional studies of Tan-IIA. In both in vitro and in vivo PF models, the protein expression of Sesn2 was significantly enhanced by Tan-IIA treatment. Overexpression and knockdown experiments showed that Sesn2 is required for Tan-IIA against TGF-[Formula: see text]1-induced myofibroblast activation by reinforcing nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated anti-oxidant response via downregulation of kelch-like ECH-associated protein 1 (Keap1). These results suggest Tan-IIA inhibits myofibroblast activation by activating Sesn2-Nrf2 signaling pathway, and provide a new insight into the essential role of Sesn2 in PF.
Impact of Buongiorno’s nanofluid model on magnetically driven non-newtonian rheological fluid capturing chemical reaction effects
Authors: Sadiq M. Adil , Waqas M. , Aziz Taha , Bahaidarah Haitham M. S.
Published: October 2022

This study aims to model two-dimensional Darcy–Forchheimer Casson nanoliquid incompressible flow confined by stretchable surface. The novel non-Fourier-Fickian (Cattaneo–Christov) heat-mass flux models are introduced. Hydromagnetic mixed convected flow is modeled. Species concentration under chemical reaction consideration is explored. Problem is formulated by employing basic fluid dynamics laws. Theory of boundary-layer (introduced by Prandtl) is utilized to simplify the highly nonlinear problems which are then rendered to ordinary differential systems under apposite transformations. Analytical solutions based on homotopy procedure are constructed. The convergence analysis is presented via [Formula: see text]-curves and tabular outcomes. The dimensionless factors are addressed in detail.
Enhanced Deep Learning Hybrid Model of CNN Based on Spatial Transformer Network for Facial Expression Recognition
Authors: Khan Nizamuddin , Singh Ajay Vikram , Agrawal Rajeev
Published: October 2022

One of the most common approaches through which people communicate is facial expressions. A large number of features documented in the literature were created by hand, with the goal of overcoming specific challenges such as occlusions, scale, and illumination variations. These classic methods are then applied to a dataset of facial images or frames in order to train a classifier. The majority of these studies perform admirably on datasets of images shot in a controlled environment, but they struggle with more difficult datasets (FER-2013) that have higher image variation and partial faces. The nonuniform features of the human face as well as changes in lighting, shadows, facial posture, and direction are the key obstacles. Techniques of deep learning have been studied as a set of methodologies for gaining scalability and robustness on new forms of data. In this paper, we look at how well-known deep learning techniques (e.g. GoogLeNet, AlexNet) perform when it comes to facial expression identification, and propose an enhanced hybrid deep learning model based on STN for facial emotion recognition, which gives the best feature extraction and classification in one go and maximizes the accuracy for a large number of samples on FERG, JAFFE, FER-2013, and CK+ datasets. It is capable of focusing on the main parts of the face and attaining extensive development over preceding fashions on the FERG, JAFFE, CK+ datasets, and the more challenging one namely FER-2013.
GLOBAL DYNAMICS, OPTIMAL CONTROL AND COST-EFFECTIVENESS ANALYSIS FOR ANTHRAX TRANSMISSION MODEL IN ANIMAL POPULATIONS WITH VACCINATION AND SANITATION
Authors: VIRIYAPONG R. , THAMMAWONG N.
Published: October 2022

In this study, we propose a deterministic model describing the dynamics of anthrax transmission in animals. It is assumed in the model that anthrax is contracted when susceptible animal comes into contact with infected animals, infected carcasses or the spores of Bacillus anthracis. Conditions for disease-free and endemic equilibria are derived and the basic reproduction number ([Formula: see text]) is computed. The disease-free equilibrium is stable when [Formula: see text] and the disease will be eliminated. If [Formula: see text], the disease persists, therefore, the endemic equilibrium is globally stable. Further, we extend our model by applying optimal control problem in which vaccination for susceptible animals and sanitation are control variables to minimize the anthrax transmission. We study three strategies to investigate the impact of the controls. Our numerical results demonstrate that both vaccination and sanitation help minimizing the transmission although vaccination alone gives more significant impact than sanitation alone. However, the combination of both controls gives the best result in wiping out the anthrax transmission overall. Further, cost-effectiveness analysis shows that the most effective strategy to control anthrax disease is a combination of vaccination and sanitation of the infected areas, therefore these two interventions should be encouraged.
A Day Ahead Electrical Appliance Planning of Residential Units in a Smart Home Network Using ITS-BF Algorithm
Authors: Dashtaki Amir Ali , Khaki Morteza , Zand Mohammad , Nasab Mostafa Azimi , Sanjeevikumar P. , Samavat Tina , Nasab Morteza Azimi , Khan Baseem
Published: October 2022

The concept of energy management in smart homes has received increasing attention in recent years, particularly on issues such as creating a balance between user privacy and reducing energy costs. Accordingly, this article proposes a user-oriented multi-objective approach, which minimizes energy costs and maximizes consumer privacy. In addition, a home energy management system is suggested for smart homes to optimize the energy consumption pattern of appliances. On the other hand, considering challenges in energy management of smart homes, the concept of demand-side management (DSM) is introduced. The objective of the proposed method is to reduce energy consumption to lower consumers’ electricity bills. Also, it improves user comfort (UC) in average waiting time conditions. In this research, a smart home equipped with an energy management system and smart home appliances that can inject electric power into the upstream network is considered the main system. This framework leads to a multi-objective optimization problem in which the two objectives mentioned above are considered two separate dimensions. To solve the problem, an ITS-BF Algorithm is used, which employs a random search to schedule home appliances and batteries based on the application of flexible devices in smart homes. The case studies show that the proposed method can considerably respect and satisfy users’ privacy and reduce the energy cost to an acceptable level. Finally, the numerical results obtained from the simulation have been analyzed to evaluate the proposed method’s efficiency. The simulation results show that an ITS-BF algorithm performs better than the existing methods in reducing costs and waiting time.
The Activity of Novel BCR-ABL Small-Molecule Degraders Containing Pyrimidine Rings and Their Role in Overcoming Drug Resistance
Authors: Zhang Xu , Tu Linglan , Chai Haohuan , Li Zilin , Fu Yuhan , Zheng Xiaoliang , Zeng Shenxin , Cheng Liyan
Published: October 2022

Inducing protein degradation by proteolysis-targeting chimeras (PROTACs) has gained tremendous momentum in the field for its promise in the discovery and development of new therapies. Based on our previously reported PROTAC BCR-ABL degraders, we designed and synthesized additional 4 PROTAC compounds with a novel linker that contains pyrimidine rings. Molecular and cellular studies have shown that different linkers affect the degradation activity of small-molecule degraders on the target protein of BCR-ABL. We screened out a lead compound, DMP11, with stable physicochemical properties and high activity. Preliminary evaluation of its pharmacodynamics in vitro model showed that it has a good inhibitory effect on imatinib-resistant chronic myeloid leukemia cell lines, as has been shown in animal models. Our preliminary research into the mechanism of DMP11 found that DMP11 can overcome drug resistance by simultaneously inhibiting the targets of BCR-ABL and SRC-family kinase (SFK).
Buyang Huanwu Decoction: A Traditional Chinese Medicine, Promotes Lactate-Induced Angiogenesis in Experimental Intracerebral Hemorrhage
Authors: Zhou Jing , Guo Hao , Yang Ali , Liu Tao , Li Pengfei , Cui Hanjin , Wang Yang , Tang Tao
Published: October 2022

Identifying the underlying mechanisms and exploring effective therapies for intracerebral hemorrhage (ICH) are urgently needed. Here, we aim to elucidate the potential roles and underlying mechanisms of Buyang Huanwu decoction (BYHWD) in ICH. In the first set of experiments, rats were randomly divided into five groups: Sham, ICH, ICH + sodium oxamate (OXA), ICH + BYHWD, and ICH + BYHWD + OXA. The lactate level around the hematoma was evaluated. PCNA+/vWF+ nuclei were observed. Additionally, an online bioinformatics analysis tool was used to predict the BYHWD druggable targets related to angiogenesis. Then, we validated these predictions. In the second set, exogenous sodium L-lactate (Lac) was infused into the intact brains of rats. Rats were randomly divided into three groups: Sham, Lac, and Lac + YC-1. The numbers of PCNA+/vWF+ nuclei and the expression of HIF-1α and VEGF were evaluated. In the first set of experiments, compared with the ICH group, the BYHWD group exhibited significantly increased numbers of PCNA+/vWF+ nuclei, and neurological dysfunction was markedly improved. Bioinformatics analysis revealed that the improvements caused by BYHWD indicated a role for the HIF-1α pathway. The HIF-1α and VEGF protein levels were upregulated after BYHWD administration. Moreover, we verified that lactate was involved in the predicted mechanisms. In the second set, lactate facilitated angiogenesis and HIF-1α and VEGF expression. Co-infusion with a HIF-1α inhibitor, YC-1, significantly inhibited these effects. Our data suggest that the pharmacological effects of BYHWD involve lactate-induced angiogenesis, these data may provide new evidence for its use in ICH.
Microbiome-Metabolome Analysis of the Immune Microenvironment of the Cecal Contents, Soft Feces, and Hard Feces of Hyplus Rabbits
Authors: Li Zhichao , He Hui , Ni Mengke , Wang Zhouyan , Guo Chaohui , Niu Yufang , Xing Shanshan , Song Mingkun , Wang Yaling , Jiang Yixuan , Yu Lei , Li Ming , Xu Huifen
Published: October 2022

The intestinal microbiota and its metabolites play vital roles in host growth, development, and immune regulation. This study analyzed the microbial community distribution and the cytokine and short-chain fatty acid (SCFA) content of cecal contents (Con group), soft feces (SF group), and hard feces (HF group) of 60-day-old Hyplus rabbits and verified the effect of soft feces on the cecal immune microenvironment by coprophagy prevention (CP). The results showed that there were significant differences in the levels of phylum and genus composition, cytokines, and SCFAs among the Con group, SF group, and HF group. The correlation analysis of cytokines and SCFAs with differential microbial communities showed that Muribaculaceae, Ruminococcaceae_UCG-014, Ruminococcaceae_NK4A214_group, and Christensenellaceae_R-7_Group are closely related to cytokines and SCFAs. After CP treatment, the contents of propionic acid, butyric acid, IL-4, and IL-10 in cecum decreased significantly, whereas TNF-α and IL-1β increased significantly. Moreover, the inhibition of coprophagy led to the downregulation of the expression levels of tight junction proteins (Claudin-1, Occludin, and ZO-1) related to intestinal inflammation and intestinal barrier function, and the ring-like structure of ZO-1 was disrupted. In conclusion, coprophagy can not only help rabbits obtain more probiotics and SCFAs but also play an essential role in improving the immune microenvironment of cecum.
Study on the Construction Waste Composition and Strength Mechanism of Recycled Mixture
Authors: Yang Sanqiang , Yang Zhenyu , Liu Jie
Published: October 2022

Recycling of construction waste has been a hot issue in road engineering research, and microscopic characteristics and composition of construction waste-recycled aggregate (RA) significantly influence their macroscopic service characteristics. In this paper, the composition, microstructure, and strength formation mechanism of natural aggregate (NA), recycled concrete aggregate (RCA), and recycled brick (RCB) were systematically studied by X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), fractal dimension and porosity determination, unconfined compressive strength test, and indirect tensile test. The results showed that RA’s microscopic morphological characteristics and chemical components were analyzed by combining XRD and SEM electron microscopy techniques. RA has prominent fractal features, and the smaller bulk density and more extensive crushing value index of RA correspond to its larger porosity as well as fractal dimension. The attributes of RA lead to the peak of 7 d unconfined compressive strength and 7 d splitting strength of the mix. The reasonable control of RA admixture benefits the improvement of mix strength. This study relies on engineering to carry out theoretical and experimental research, which provides essential support and guarantee for the application of construction waste in the field of highway transportation in Hebei Province.