bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting G protein‐coupled receptors for heart failure treatment
Authors: Thai Bui San , Chia Ling Yeong , Nguyen Anh T. N. , Qin Chengxue , Ritchie Rebecca H. , Hutchinson Dana S. , Kompa Andrew , White Paul J. , May Lauren T. 
Published: April 2023

Heart failure remains a leading cause of morbidity and mortality worldwide. Current treatment for patients with heart failure include drugs targeting G protein‐coupled receptors such as β‐adrenoceptor antagonists (β‐blockers) and angiotensin II type 1 receptor antagonists (or angiotensin II receptor blockers). However, many patients progress to advanced heart failure with persistent symptoms, despite treatment with available therapeutics that have been shown to reduce mortality and mortality. GPCR targets currently being explored for the development of novel heart failure therapeutics include adenosine receptor, formyl peptide receptor, relaxin/insulin‐like family peptide receptor, vasopressin receptor, endothelin receptor and the glucagon‐like peptide 1 receptor. Many GPCR drug candidates are limited by insufficient efficacy and/or dose‐limiting unwanted effects. Understanding the current challenges hindering successful clinical translation and the potential to overcome existing limitations will facilitate the future development of novel heart failure therapeutics.LINKED ARTICLESThis article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc
PPARγ inhibited tumor immune escape by inducing PD‐L1 autophagic degradation
Authors: Gou Qian , Che Suning , Chen Mingjun , Chen Huiqing , Shi Juanjuan , Hou Yongzhong 
Published: April 2023

AbstractBlockade of the programmed death 1 (PD‐1)/ programmed death ligand 1 (PD‐L1) immune checkpoint could increase antitumor immunotherapy for multiple types of cancer, but the response rate of patients is about 10%–40%. Peroxisome proliferator activated receptor γ (PPARγ) plays an important role in regulating cell metabolism, inflammation, immunity, and cancer progression, while the mechanism of PPARγ on cancer cell immune escape is still unclear. Here we found that PPARγ expression exhibits a positive correlation with activation of T cells in non‐small‐cell lung cancer (NSCLC) by clinical analysis. Deficiency of PPARγ promoted immune escape of NSCLC by inhibiting T‐cell activity, which was associated with increased PD‐L1 protein level. Further analysis showed that PPARγ reduced PD‐L1 expression independent of its transcriptional activity. PPARγ contains the microtubule‐associated protein 1A/1B‐light chain 3 (LC3) interacting region motif, which acts as an autophagy receptor for PPARγ binding to LC3, leading to degradation of PD‐L1 in lysosomes, which in turn suppresses NSCLC tumor growth by increasing T‐cell activity. These findings suggest that PPARγ inhibits the tumor immune escape of NSCLC by inducing PD‐L1 autophagic degradation.
Determining optimal forest rotation ages and carbon offset credits: Accounting for post‐harvest carbon storehouses
Authors: van Kooten G. Cornelis 
Published: April 2023

AbstractSequestering carbon in forest ecosystems is important for mitigating climate change. A major policy concern is whether forests should be left unharvested to avoid carbon dioxide (CO2) emissions and store carbon, or harvested to take advantage of potential carbon storage in post‐harvest wood product sinks and removal of CO2from the atmosphere by new growth. The issue is addressed in this paper by examining carbon rotation ages that consider commercial timber as well as carbon values. A discrete‐time optimal rotation age model is developed that employs data on carbon fluxes stored in both living and dead biomass as opposed to carbon as a function of timber growth. Carbon is allocated to several ecosystem and post‐harvest product pools that decay over time at different rates. In addition, the timing of carbon fluxes is taken into account by weighting future carbon fluxes as less important than current ones. Using simple formulae for determining optimal rotation ages, we find that: (1) Reducing the price of timber while increasing the price of carbon will increase rotation age, perhaps to infinity (stand remains unharvested). (2) An increase in the rate used to discount physical carbon generally reduces the rotation age, but not in all cases. (3) As a corollary, an increase in the price of carbon increases or reduces rotation age depending on the weight chosen to discount future carbon fluxes. (4) Site characteristics and the mix of species on the site affect conclusions (2) and (3). (5) A large variety of carbon offset credits from forestry activities could be justified, which makes it difficult to accept any.
Generation of Rh D‐negative blood using CRISPR/Cas9
Authors: Xu Lei , Zeng Quan , Liang Liqing , Yang Zhou , Qu Mingyi , Li Huilin , Zhang Bowen , Zhang Jing , Yuan Xin , Chen Lin , Fan Zeng , He Lijuan , Nan Xue , Yue Wen , Xie Xiaoyan , Pei Xuetao 
Published: April 2023

AbstractBlood supply shortages, especially the shortage of rare blood types, threaten the current medical system. Research on stem cells has shed light on in vitro blood cell manufacturing. The in vitro production of universal red blood cells (RBCs) from induced pluripotent stem cells (iPSCs) has become the focus of transfusion medicine. To obtain O‐type Rh D‐negative blood, we developed O‐type Rh D‐negative human (h)iPSCs using homology‐directed repair (HDR)‐based CRISPR/Cas9. HuAiPSCs derived from human umbilical arterial endothelial cells and showing haematopoietic differentiation preferences were selected for gene modification. Guide RNAs (gRNAs) were selected, and a donor template flanked by gRNA‐directed homologous arms was set to introduce a premature stop code to RHD exon 2. CRISPR/Cas9 gene editing has resulted in the successful generation of an RHD knockout cell line. The HuAiPSC‐A1‐RHD−/− cell line was differentiated into haematopoietic stem/progenitor cells and subsequently into erythrocytes in the oxygen concentration‐optimized differentiation scheme. HuAiPSC‐A1‐RHD−/− derived erythrocytes remained positive for the RBC markers CD71 and CD235a. These erythrocytes did not express D antigen and did not agglutinate in the presence of anti‐Rh D reagents. In conclusion, taking the priority of haematopoietic preference hiPSCs, the HDR‐based CRISPR/Cas9 system and optimizing the erythroid‐lineage differentiation protocol, we first generated O‐type Rh D‐negative universal erythrocytes from RHD knockout HuAiPSCs. Its production is highly efficient and shows great potential for clinical applications.
Finding harmony inMarine Protected Areadesign guidelines
Authors: Burns Echelle S. , Lopazanski Cori , Flower Jason , Thomas Lennon R. , Bradley Darcy , Lester Sarah E. 
Published: April 2023

AbstractWidespread degradation of marine ecosystems and ecosystem services, coupled with national and global commitments to improve protection of the oceans, has led to a proliferation of efforts to designate new marine protected areas (MPAs) and MPA networks. A range of design features must be considered when designating MPAs, including MPA size and shape, level of protection, and the species and habitats protected, and evidence suggests these design elements can be crucial in determining MPA effectiveness. Over the past several decades, expansive literature has emerged providing recommendations for MPA design, and yet collectively these recommendations can be overwhelming and even contradictory for MPA planners. To address this barrier, we reviewed and synthesized 307 unique MPA design recommendations across 56 peer‐reviewed and gray literature publications. We created a new set of 24 condensed design guidelines grouped by conservation objectives: ecological spatial connectivity (e.g., genetic, larval, community); habitat representation; species or population persistence; mitigation of and complementarity to human activities; and permanence and adaptability. We then discuss examples of datasets, models, and tools that can be utilized to implement specific guidelines. Our review and novel synthesis can help decision‐makers understand and apply MPA design recommendations to achieve desired conservation objectives.
Predicting new onset atrial fibrillation post acute myocardial infarction: Echocardiographic assessment of left atrial size
Authors: Lancini Daniel , Prasad Aveechal , Thomas Liza , Atherton John , Martin Paul , Prasad Sandhir 
Published: April 2023

AbstractBackgroundAtrial fibrillation (AF) commonly occurs following acute myocardial infarction (AMI). Left atrial (LA) size has been reported to predict new onset AF in this cohort, however, the optimal metric of left atrial size for risk stratification following AMI is unknown.MethodsPatients presenting to a tertiary hospital with incident AMI (NSTEMI or STEMI) and no history of AF were recruited. All patients underwent guideline‐based workup and management for AMI, including transthoracic echocardiographic assessment. Three alternative metrics of left atrial size were determined: LA area, maximal and minimal LA volume indexed to body surface area (LAVImax and LAVImin). The primary endpoint was new onset AF diagnoses.ResultsFour hundred thirty three patients were included in the analysis, of which 7.1% had a new diagnosis of AF within a median follow‐up of 3.8 years. Univariate predictors of incident AF included age, hypertension, revascularization with CABG, NSTEMI presentation, right atrial area, and all three metrics of LA size. Among three multivariable models created for the prediction of new onset AF utilizing alternate metrics of LA size, LAVImin was the only LA size metric found to be an independent predictor.ConclusionsLAVImin is an independent predictor of new onset AF post AMI. LAVImin outperforms echocardiographic assessment of diastolic dysfunction and alternative metrics of LA size (including LA area and LAVImax) for risk stratification. Further studies are needed to validate our findings in post AMI patients, and evaluate whether LAVImin holds similar advantages over LAVImax in other cohorts.
One‐hour post‐load glucose and subclinical left atrial myocardial dysfunction in hypertensive patients
Authors: Miceli Sofia , Cassano Velia , Clausi Elvira , Armentaro Giuseppe , Tallarico Valeria , Dallimonti Perini Daniele , Succurro Elena , Maio Raffaele , Perticone Maria , Hribal Marta L. , Montalcini Tiziana , Andreozzi Francesco , Sesti Giorgio , Sciacqua Angela 
Published: April 2023

AbstractBackgroundRecently, studies demonstrated that normal glucose‐tolerant subjects (NGT) with 1‐h post‐load plasma glucose value ≥155 mg/dL during oral glucose tolerance test (OGTT) (NGT ≥ 155) present an impaired cardio‐metabolic profile, with subclinical myocardial damage. Atrial morphological and functional alterations, closely related to diastolic dysfunction, are important predictors of atrial fibrillation (AF), cardiovascular (CV) events and mortality in the entire population as well as in diabetic patients. The aim of our study was to evaluate subclinical atrial myocardial damage, assessed with speckle tracking echocardiography, in NGT≥155 mg/dL patients, comparing to NGT < 155 mg/dL subjects, impaired glucose tolerant (IGT) individuals and patients with newly diagnosed type 2 diabetes (T2DM).MethodsWe enrolled 229 Caucasian patients. All subjects underwent anthropometrical and haemodynamic parameters evaluation, OGTT, advanced Colour‐Doppler echocardiography with evaluation of main atrial and ventricular parameters.ResultsAs expected, from first to the fourth group there was a worsening of the metabolic profile as attested by fasting, 1‐ and 2‐h post‐load plasma glucose levels, during OGTT. Moreover, from NGT < 155 to T2DM group there was an impairment in reservoir and pump atrial function (PALS and PACS, respectively) (p < .0001).ConclusionPresent data demonstrated for the first time that NGT≥155 subjects present subclinical atrial dysfunction. These results may be clinically relevant because they highlight how atrial myopathy occurs early in pre‐diabetes stage regardless of fibrotic and morphological alterations of the ventricular myocardium.
Risk factors and outcomes of COVID‐19 in adult patients with hematological malignancies: A single‐center study showing lower than expected rates of hospitalization and mortality
Authors: Aumann Shlomzion , Tsubary Uria , Nachmias Boaz , Ben Yehuda Dina , Lavie David , Goldschmidt Neta , Vainstein Vladimir , Libster Diana , Saban Revital , Shaulov Adir , Israel Sarah , Avni Batia , Grisariu Sigal , Bdolah‐Amram Tali , Gatt Moshe , Zimran Eran 
Published: April 2023

AbstractBackgroundStudies addressing coronavirus disease 2019 (COVID‐19) in patients with hematological malignancies have reported mortality rates of up to 40%; however, included predominantly hospitalized patients.MethodsDuring the first year of the pandemic, we followed adult patients with hematological malignancies treated at a tertiary center in Jerusalem, Israel, who contracted COVID‐19, with the aim of studying risk factors for adverse COVID‐19‐related outcomes. We used remote communication to track patients managed at home‐isolation, and patient questioning to assess the source of COVID‐19 infection, community versus nosocomial.ResultsOur series included 183 patients, median age was 62.5 years, 72% had at least one comorbidity and 39% were receiving active antineoplastic treatment. Hospitalization, critical COVID‐19, and mortality rates were 32%, 12.6%, and 9.8%, respectively, remarkably lower than previously reported. Age, multiple comorbidities, and active antineoplastic treatment were significantly associated with hospitalization due to COVID‐19. Treatment with monoclonal antibodies was strongly associated with both hospitalization and critical COVID‐19. In older (≥60) patients not receiving active antineoplastic treatment, mortality, and severe COVID‐19 rates were comparable to those of the general Israeli population. We did not detect patients that contracted COVID‐19 within the Hematology Division.ConclusionThese findings are relevant for the future management of patients with hematological malignancies in COVID‐19‐affected regions.
Familial adult myoclonus epilepsy: Neuroimaging and neuropathological findings
Authors: van Rootselaar Anne‐Fleur , Cocozza Sirio , Aronica Eleonora , Striano Pasquale 
Published: April 2023

AbstractFamilial adult myoclonus epilepsy (FAME) is characterized by cortical myoclonus and often epileptic seizures, but the pathophysiology of this condition remains uncertain. Here, we review the neuroimaging and neuropathological findings in FAME. Imaging findings, including functional magnetic resonance imaging, are in line with a cortical origin of involuntary tremulous movements (cortical myoclonic tremor) and indicate a complex pattern of cerebellar functional connectivity. Scarce neuropathological reports, mainly from a single family, provide evidence of morphological changes in the Purkinje cells. Cerebellar changes seem to be part of the syndrome, in at least some FAME pedigrees. Cortical hyperexcitability in FAME, resulting in the cardinal clinical symptoms, might be the result of decreased cortical inhibition via the cerebellothalamocortical loop. The pathological findings might share some similarities with other pentanucleotide repeat disorders. The relation with genetic findings in FAME needs to be elucidated.
A major 6 Mb superlocus is involved in pyrethroid resistance in the common bed bug Cimex lectularius
Authors: Haberkorn Chloé , David Jean‐Philippe , Henri Hélène , Delpuech Jean‐Marie , Lasseur Romain , Vavre Fabrice , Varaldi Julien 
Published: April 2023

AbstractIn the last few years, the bed bug Cimex lectularius has been an increasing problem worldwide, mainly due to the development of insecticide resistance to pyrethroids. The characterization of resistance alleles is a prerequisite to improve surveillance and resistance management. To identify genomic variants associated with pyrethroid resistance in Cimex lectularius, we compared the genetic composition of two recent and resistant populations with that of two ancient‐susceptible strains using a genome‐wide pool‐seq design. We identified a large 6 Mb “superlocus” showing particularly high genetic differentiation and association with the resistance phenotype. This superlocus contained several clustered resistance genes and was also characterized by a high density of structural variants (inversions, duplications). The possibility that this superlocus constitutes a resistance “supergene” that evolved after the clustering of alleles adapted to insecticide and after reduction in recombination is discussed.
Technological innovation and stock returns: Innovative skill versus innovative luck
Authors: Angelo Ben , Johnston Mitchell 
Published: April 2023

AbstractPrior studies conclude that investors undervalue innovative ability. These studies do not fully capture the prominent role that industry and market trends play in contextualizing innovations. We disaggregate the value generated by innovative skill from the value generated by industry and market trends and find that innovative skill is positively associated with profitability. Further, our results are consistent with a risk explanation as innovative skill is negatively associated with returns, consistent with investors using patent value to identify innovative skill and adjusting the riskiness of the firm accordingly.
Mi casa de los Espíritus (My house of spirits): Challenging patriarchy with magical feminism
Authors: Clavijo Nathalie 
Published: April 2023

AbstractThis paper draws onmagical feminism, a writing that engages in a critic of patriarchy through inexplicable events that address gender inequality and the power of the oppressed. This magic has always been in me but always dormant in my academic writing. To let this magic out has required to let myself go into a form ofmagical embodimentin my methods: I engage in a spiritual excavation to let emerge three Latin American feminist myths and legends that are in me to recover from vicarious violence and come back to the world. This experience opens the gates to engage with a colonial past and to celebrate other systems of belief. This paper is an invitation for those who will join to mobilize our magical forces for the recognition of knowledge production in moments of magic as legitimate.
Risk factors, treatment and survival rates of late‐onset acquired haemophilia A: A cohort study from the Shizuoka Kokuho Database
Authors: Shoji‐Asahina Aya , Nakatani Eiji , Imaichi Yutaro , Ohata Emi , Oshima Michiko , Miyakoshi Akinori , Miyake Hiromu , Ichikawa Yoshikazu , Dote Hisashi , Ubukata Nanako , Funaki Daito , Urano Tetsumei 
Published: April 2023

AbstractIntroductionAcquired haemophilia A (AHA) is a rare disease. The risk factors have yet to be studied.AimWe aimed to identify risk factors for late‐onset AHA in Japan.MethodsA population‐based cohort study was conducted using data from the Shizuoka Kokuho Database. The study population was defined as individuals aged ≥60 years. Cause‐specific Cox regression analysis was performed to calculate hazard ratios.ResultsOf 1,160,934 registrants, there were 34 patients with newly diagnosed AHA. The mean follow‐up period was 5.6 years, and the incidence of AHA was 5.21 per million person‐years. Myocardial infarction, diabetes mellitus, solid tumors, antimicrobial agents, phenytoin and anti‐dementia drugs, which showed significant differences in the univariate analysis, were excluded from the multivariable analysis because of the small number of cases. Multivariable regression analysis showed that the presence of Alzheimer's disease (hazard ratio [HR]:4.28, 95% confidence interval [CI]:1.67‐10.97) and rheumatic disease (HR:4.65, 95% CI:1.79‐12.12) increased the risk of AHA development.ConclusionWe found that comorbid Alzheimer's disease is a risk factor of AHA incidence in the general population. Our findings provide insight into the etiology of AHA, and the proof of the coexistence of Alzheimer's disease may support the recent notion that Alzheimer disease is an autoimmune disease.
Physicochemical and sensory properties of Sacha Inchi oil‐functionalised stirred yogurt
Authors: Villamil Ruby‐Alejandra , Cortés Lilia‐Yadira , Gutiérrez Luis‐Felipe 
Published: April 2023

SummaryIn this study, the effects of replacing the total milk fat by Sacha Inchi oil (SIO) at different concentrations (1.5, 2.5 and 3.5%w/w), on the physicochemical and sensory properties of stirred yogurts were investigated. Addition of SIO did not significant affect the yogurts fermentation processing, but significantly increased the pH‐value, acidity, water holding capacity and viscosity of obtained yogurts. In comparison with control samples (yogurts with ~3.3% milk fat), SIO‐functionalised yogurts displayed higher concentrations of α‐linolenic and linoleic acids (~50% and ~33% of the total fatty acids), and lower values of saturated fatty acids, omega‐6/omega‐3 ratios and atherogenic indices. Samples with 3.5% SIO showed a sensorial acceptance above of 60%, and a peroxide value of 2.14 after 21 days of storage at 4 °C. These results indicate that SIO could be used for producing yogurts with improved fatty acid profile and physicochemical and sensory properties acceptable to consumers.
Afternoon school shift is associated with increased risk of overweight/obesity in 11–14‐year‐old females with early and intermediate chronotype
Authors: Borisenkov Mikhail F. , Tserne Tatyana , Bakutova Larisa , Smirnov Vasily , Popov Sergey 
Published: April 2023

SummaryObjectiveThe purpose of this study was to compare the anthropometric and sleep–wake rhythm characteristics of schoolchildren that attend school in morning and afternoon school shifts.MethodsWe recruited 18 481 individuals (females: 56.4%) aged 11 to 18 years old with an average age of 14.4 ± 1.7 years old. In total, 812 (4.2%) questionnaires were incomplete. The self‐reported height and weight were used to assess the sex‐ and age‐corrected body mass index of the participants. The Munich ChronoType Questionnaire was used to assess the chronotype, social jetlag, and sleep duration of the participants.ResultsIn total, 12.6% of the participants were affected by overweight or obesity. The overweight and obesity incidence rate was higher among the students studying in the afternoon (odd ratio [95%CI]: 1.33 [1.16–1.52]). The afternoon school shift had a negative impact on the anthropometric indicators only in the 11–14‐year‐olds (1.29 [1.11–1.50]) and girls (1.26 [1.04–1.54]) with an early (1.27 [1.03–1.56]) and intermediate (1.30 [1.07–1.58]) chronotype.ConclusionThe data obtained indicated that the afternoon school shift is not ideal, especially for female children and adolescents under 15 years old with an early and intermediate chronotype.