bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Secondary Metabolites from Mexican Plants with Antifungal Activity against Pathogenic Candida Species
Authors: Vázquez-López Nancy A. , Cruz-Jiménez Gustavo , Obregón-Herrera Armando , Ruiz-Baca Estela , Pedraza-Reyes Mario , López-Romero Everardo , Cuéllar-Cruz Mayra
Published: May 2022

In the last three decades, invasive fungal infections caused by Candida species have become an important public health problem, because they are associated with high rates of morbidity and mortality in immunocompromised and hospitalized patients. The diagnosis and treatment of candidiasis are difficult and usually inefficient. Accordingly, a diversity of available drugs, currently employed to attack candidiasis, frequently induce resistance in patients promoting toxicity due to long-term treatments. Therefore, development of accurate diagnoses and novel antifungals is of high priority to improve life’s quality and expectancy of individuals infected with this pathogen. Plants are invaluable sources of new biologically active compounds. Among the plants used in Mexico in traditional herbolary medicine which have empirically been demonstrated to have antifungal activity are Pedilanthus tithymaloides, Thymus vulgaris, and Ocimum basilicum. In the present study, we analyzed whether these plants contain metabolites with antifungal activity against five Candida species. The extracts from the different plant organs were obtained by macerating them in ethyl alcohol or hexane and filtering. The obtained extracts were preserved in amber flasks at 4°C until used. The minimum inhibitory concentrations (MICs) of the active compound were determined by a microdilution assay. In addition, the following secondary metabolites were identified: linalool (3,7-dimethylocta-1,6-dien-3-ol), eugenol (4-allyl-2-methoxyphenol), limonene (1-methyl-4-(1-methylethenyl)-cyclohexene), and borneol ([(2R)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl] formate). All these compounds were found in the three plants, traditionally used in everyday life, and proved to be effective against Candida species and therefore a viable alternative to conventional antifungals.
Maximizing the Rate of IRS-Assisted Downlink NOMA Systems
Authors: Li Xinying , Wei Haixia , Huang Haiyan , Li Cuiran , Zhang Lijun
Published: May 2022

Nonorthogonal multiple access (NOMA) techniques and intelligent reflecting surface (IRS) are being explored as potential essential technologies for future wireless communications. Accordingly, this paper provides a network framework for IRS-aided downlink NOMA transmission, in which IRS is employed to improve the NOMA system’s transmission performance, and optimization problems are raised to maximize the achievable rate. Given the fractional structure of multivariate coupling as presented in this study, the fractional problem first converts to a linear form; then, the semidefinite relaxation (SDR) algorithm is proposed to address nonconvex issues for a single-user scenario. As for a multiuser scenario, the alternating optimization (AO) algorithm is raised based on transmit beamforming and reflection phase shift matrix to settle relevant issues and mitigate computational complexity. The simulation results suggest that the algorithm described in this paper can significantly increase the signal’s achievable rate compared to the nondeployed IRS and IRS random phase-shifting schemes.
Multimodal Feature Fusion Based Hypergraph Learning Model
Authors: Yang Zhe , Xu Liangkui , Zhao Lei
Published: May 2022

Hypergraph learning is a new research hotspot in the machine learning field. The performance of the hypergraph learning model depends on the quality of the hypergraph structure built by different feature extraction methods as well as its incidence matrix. However, the existing models are all hypergraph structures built based on one feature extraction method, with limited feature extraction and abstract expression ability. This paper proposed a multimodal feature fusion method, which firstly built a single modal hypergraph structure based on different feature extraction methods, and then extended the hypergraph incidence matrix and weight matrix of different modals. The extended matrices fuse the multimodal abstract feature and an expanded Markov random walk range during model learning, with stronger feature expression ability. However, the extended multimodal incidence matrix has a high scale and high computational cost. Therefore, the Laplacian matrix fusion method was proposed, which performed Laplacian matrix transformation on the incidence matrix and weight matrix of every model, respectively, and then conducted a weighted superposition on these Laplacian matrices for subsequent model training. The tests on four different types of datasets indicate that the hypergraph learning model obtained after multimodal feature fusion has a better classification performance than the single modal model. After Laplace matrix fusion, the average time can be reduced by about 40% compared with the extended incidence matrix, the classification performance can be further improved, and the index F1 can be improved by 8.4%.
Analysis of Machine Learning Techniques for Sentinel-2A Satellite Images
Authors: Alshari Eman A. , Gawali Bharti W.
Published: May 2022

This article presents the comparative analysis of classification techniques to assign land use and land cover classes from different strategies (pixel-based, object-based, rule-based, distance-based, and neural-based) with a Sentinel-2A satellite image for 2016. The study area is the Sana’a city of Yemen which covers about 18,796.88 km2 land area. This research aims to present the fundamentals of supervised machine learning approaches, including their limitations and strengths and experimentation for twelve classifiers. The outcome of experimentation showed that the Random Forest could be a good choice as a classifier for object-based strategy. In contrast, DTC and SVM were efficient in rule-based and pixel-based strategies. Results also showed that the highest accuracy was with object-based strategy, followed by rule-based and then pixel-based and distance-based strategies.
Soil Physical Characteristics and Saturated Hydraulic Conductivity in the Landform of Barito Delta, Kalimantan, Indonesia
Authors: Arisanty Deasy , Rahmawati Novi , Rosadi Dedi
Published: May 2022

We explore the soil physical characteristics in wetland of Barito Delta from primary data of soil sample and electrical resistivity measurement with the support from some secondary data. We also estimate saturated hydraulic conductivity (Ks) in Barito Delta from soil physical characteristics applying Saxton and Rawls (1986) and Weynants et al. (2009). Soil texture profile is determined from interpolation of soil fraction in each layer applying Bayesian statistics to analyze soil physical characteristics in the landforms of Delta. Clay is the dominant soil fraction in the soil of Barito Delta. Clay fraction percentage decrease along the depth of soil profile as it reaches fine sand particles deriving from ancient sedimentation from the past. It is an opposite with soil organic matter content that has contrast value from 1st to 2nd soil depth, but a few discrepancy from 3rd depth to downward direction. The content of clay in the soil depends on the sedimentation activity in the landform. Clay is dominant soil particle in the Delta; in case, it is in flat area and there is no intensive of sea water sedimentation such as in Basin of Peat Anticline and Natural Levee. In more than 2 m depth of soil, loamy sand and silty clay textures are mostly in the landform that is influenced by sea water activity, while by river water is clay loam. Ks values from Saxton and Rawls (1986) are close to Ks values from the measurement of previous studies. Ks values are generally small in Barito Delta that is mostly ranging from 1.10−7 to 2 m s−1. Ks values are larger following the depth of soil profile. The values of Ks are smaller in Basin of Peat Anticline and Natural Levee than in Tidal Flat and Beach Ridge. It is because both landforms have clay as dominant soil particles.
Validation of Two Activity Monitors in Slow and Fast Walking Hospitalized Patients
Authors: Pedersen Britt Stævnsbo , Kristensen Morten Tange , Josefsen Christian Ohrhammer , Lykkegaard Kasper Lundberg , Jønsson Line Rokkedal , Pedersen Mette Merete
Published: May 2022

To evaluate interventions to promote physical activity, valid outcome measures are important. This study evaluated the validity and reliability of the ActivPAL3™ and the SENS motion® activity monitors with regard to the number of steps taken, walking, and sedentary behavior in hospitalized patients (n=36) (older medical patients (+65 years) (n=12), older patients (+65) with acute hip fracture (n=12), and patients (+18) who underwent acute high-risk abdominal surgery (n=12)). Both monitors showed good (≥60%) percentage agreement with direct observation for standing and no. of steps (all gait speeds) and high agreement (≥80%) for lying. For walking, ActivPAL3™ showed moderate percentage agreement, whereas SENS motion® reached high percentage agreement. The relative reliability was moderate for sedentary behavior for both monitors. The ActivPAL3™ showed poor (walking) to moderate (steps) reliability for walking and steps, whereas SENS motion® showed moderate reliability for both activities. For slow walkers, the relative reliability was moderate for SENS motion® and poor for ActivPAL3™. This trial is registered with the ClinicalTrials.gov identifier NCT04120740.
Metal Complexes in Target-Specific Anticancer Therapy: Recent Trends and Challenges
Authors: Shumi Gemechu , Desalegn Tegene , Demissie Taye B. , Ramachandran Venkatesha Perumal , Eswaramoorthy Rajalakshmanan
Published: May 2022

Cancer is characterized by abnormal cell differentiation in or on the part of the body. The most commonly used chemotherapeutic drugs are developed to target rapidly dividing cells, such as cancer cells, but they also damage healthy epithelial cells. This has serious consequences for normal cells and become responsible for the development of various disorders. Several strategies for delivering the cytotoxic drugs to cancerous sites that limit systemic toxicity and other adverse effects have recently been evolved. Among them, biomolecule-conjugated metal complexes-based cancer targeting strategies have shown tremendous advantages in cancer therapy. This review focuses on several chemoselective biomolecules-bound metal complexes as prospective cancer therapy-targeted agents. In this review, we presented the details of the various extra- and intracellular targeting mechanisms in cancer therapy. We also addressed the current clinical issues and recent therapeutic strategies in targeted cancer therapy that may pave a way for the future direction of metal complexes-based targeted cancer therapy.
Positive Weighted Symmetry Function Kernels and Some Related Inequalities for a Generalized Class of Convex Functions
Authors: Xiao Yeliang , Shah Ahsan Fareed , Zia Tariq Javed , Bonyah Ebenezer
Published: May 2022

The fractional integral inequalities are crucial to deal applied problems. The present paper deals with the generalize midpoint type inequalities for a certain class of convex functions, namely, MT-convex functions in the setting of weighted fractional integral. It can be observed from the remarks given in the paper that our results or more generalized than existing results of literature and many of them can be obtained immediately from our results.
A Case Report of Dental Implants and Site Augmentation in a Patient with Erosive Lichen Planus
Authors: Aseri Abdulrahman
Published: May 2022

Lichen planus (LP) is an autoimmune inflammatory disease that affects oral mucosal tissue, leading to complications in patients treated with dental implant therapy. This case report discusses the clinical management of a patient diagnosed with an erosive type of LP. After disease management, the patient was treated with dental implants in the upper and lower jaws with augmentation procedures around the implants. All implants were loaded after a three-month period of healing. Slight bone loss was observed in the upper premolar area following an exaggerated soft tissue response to the augmentation procedure. Within one year of implant placement, no additional complications were encountered.
Downregulation of HULC Induces Ferroptosis in Hepatocellular Carcinoma via Targeting of the miR-3200-5p/ATF4 Axis
Authors: Guan Lulu , Wang Feifei , Wang Mengjiao , Han Songfeng , Cui Zhaohai , Xi Shoumin , Xu Haixu , Li Shipeng
Published: May 2022

Hepatocellular carcinoma is a malignant tumor that poses a serious threat to human health. Ferroptosis, which represents an identified type of regulated iron-dependent cell death, may play an important role in hepatocellular carcinoma. However, it is unclear as to whether ferroptosis is involved with the mechanisms of lncRNA HULC in liver cancer cells. Here, we show that knockdown of HULC increases ferroptosis and oxidative stress in liver cancer cells. We also found changes in some related miRNAs in cells treated with HULC siRNA. Differential miRNA expression levels were determined with the use of high-throughput sequencing and prediction target genes identified using bioinformatics analysis. HULC was found to function as a ceRNA of miR-3200-5p, and miR-3200-5p regulates ferroptosis by targeting ATF4, resulting in the inhibition of proliferation and metastasis within HCC cells. In summary, these findings illuminate some of the molecular mechanisms through which downregulation of HULC induces liver cancer cell ferroptosis by targeting the miR-3200-5p/ATF4 axis to modulate the development of hepatocellular carcinoma.
Fault Diagnosis of Axle Box Bearing with Acoustic Signal Based on Chirplet Transform and Support Vector Machine
Authors: Zhang Jimin , Hu Xianting , Zhong Xujie , Zhou Hechao
Published: May 2022

Acoustic fault diagnosis technology equipment is non-contact, and the acoustic signal is easy to access. However, it is difficult to extract the feature information of the acoustic signal with low signal-to-noise ratio (SNR). In this paper, a fault diagnosis model (FDM) of axle box bearing based on Chirplet transform (CT) and support vector machine (SVM) is established to diagnose bearing fault based on acoustic signal. The availability of the model is verified by comparing with the vibration acceleration signal bearing fault diagnosis results, and the correctness of the model is verified by utilizing the open database of Western Reserve University. The acoustic-vibration comprehensive bearing fault diagnosis experiment platform (AVEP) is established to investigate the acoustic signal and acceleration signal diagnosis accuracy. The results suggest that, based on the FDM, the diagnosis accuracy and stability of acoustic signal are not as good as acceleration signal when the number of samples is small under the single condition; the diagnosis accuracy of acoustic signal is similar to that of acceleration signal when the number of samples is enough under the multiple condition, which provides a reference for the application of acoustic fault diagnosis technology in engineering in the future.
Impact of Nodal Metastases in HPV-Negative Oropharyngeal Cancer
Authors: Chang Clifford M. , Chen Michelle M. , Bellile Emily L. , Rozek Laura S. , Carey Thomas E. , Spector Matthew E. , Wolf Gregory T. , Taylor Jeremy MG , Chinn Steven B.
Published: May 2022

Background:

The updated American Joint Committee on Cancer (AJCC) 8th Edition staging manual restructured nodal classification and staging by placing less prognostic emphasis on nodal metastases for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). However, there was no change for HPV-negative OPSCC. The purpose of our study is to examine the impact of nodal metastases on survival in HPV-negative OPSCC.

Methods:

HPV-negative OPSCC was queried from the National Cancer Database (NCDB) and Surveillance, Epidemiology and End Results program (SEER) databases. Univariable and multivariable models were utilized to determine the impact of nodal status on overall survival. These patients were reclassified according to AJCC 8 HPV-positive criteria (TNM8+) and risk stratification was quantified with C-statistic.

Results:

There were 11,147 cases of HPV-negative OPSCC in the NCDB and 3,613 cases in SEER that were included in the nodal classification analysis. Unlike nonoropharyngeal malignancies, increased nodal stage is not clearly associated with survival for patients with OPSCC independent of HPV status. When the TNM8+ was applied to HPV-negative patients, there was improved concordance in the NCDB cohort, 0.561 (plus minus) 0.004 to 0.624 (plus minus) 0.004 (difference +0.063) and the SEER cohort, 0.561 (plus minus) 0.008 to 0.625 (plus minus) 0.008 (difference +0.065).

Conclusions:

We demonstrated a reduced impact of nodal metastasis on OPSCC survival, independent of HPV status and specific to OPSCC.

Impact:

We demonstrate, for the first time that when nodal staging is deemphasized as a part of overall staging, we see improved concordance and risk stratification for HPV-negative OPSCC. The exact mechanism of this differential impact remains unknown but offers a novel area of study.
PLGA–Nano-Encapsulated Disulfiram Inhibits Hypoxia-Induced NF-κB, Cancer Stem Cells, and Targets Glioblastoma In Vitro and In Vivo
Authors: Kannappan Vinodh , Liu Ying , Wang Zhipeng , Azar Karim , Kurusamy Sathishkumar , Kilari Rajagopal S. , Armesilla Angel L. , Morris Mark R. , Najlah Mohammad , Liu Peng , Bian Xiu-Wu , Wang Weiguang
Published: May 2022

Glioblastoma stem cell (GSC) is the major cause of glioblastoma multiforme (GBM) chemotherapy failure. Hypoxia is one of the determinants of GSC. NF-κB plays a pivotal link between hypoxia and cancer stem cells (CSCs). Disulfiram, an antialcoholism drug, has very strong NF-κB–inhibiting and anti-CSC activity. In this study, the in vitro anti-GSC activity of disulfiram and in vivo anti-GBM efficacy of poly lactic–co-glycolic acid nanoparticle-encapsulated disulfiram (DS-PLGA) were examined. We attempt to elucidate the molecular network between hypoxia and GSCs and also examined the anti-GSC activity of disulfiram in vitro and in vivo. The influence of GSCs and hypoxia on GBM chemoresistance and invasiveness was studied in hypoxic and spheroid cultures. The molecular regulatory roles of NF-κB, hypoxia-inducible factor-1α (HIF1α), and HIF2α were investigated using stably transfected U373MG cell lines. The hypoxia in neurospheres determines the cancer stem cell characteristics of the sphere-cultured GBM cell lines (U87MG, U251MG, U373MG). NF-κB is located at a higher hierarchical position than HIF1α/HIF2α in hypoxic regulatory network and plays a key role in hypoxia-induced GSC characters. DS inhibits NF-κB activity and targets hypoxia-induced GSCs. It showed selective toxicity to GBM cells, eradicates GSCs, and blocks migration and invasion at very low concentrations. DS-PLGA efficaciously inhibits orthotopic and subcutaneous U87MG xenograft in mouse models with no toxicity to vital organs.
Primary Duodenal Adenocarcinoma Expressing Carbonic Anhydrase IX
Authors: Kubo Kimitoshi , Kimura Noriko , Watanabe Ryosuke , Higashino Masayuki , Kato Mototsugu
Published: May 2022

Primary duodenal adenocarcinoma is a rare malignancy whose carbonic anhydrase IX (CA9) expression remains poorly understood. A 73-year-old man visited our hospital for a medical checkup. Transnasal endoscopy revealed a submucosal, tumor-like lesion with a central depression located in the descending part of the duodenum on white light imaging. On texture and color enhancement imaging mode 1, the lesion was highlighted as a reddish, elevated lesion with an irregular mucosa in its central depressed area. Pancreaticoduodenectomy was performed on the suspicion of duodenal adenocarcinoma for biopsy and endoscopic diagnosis, which led to the lesion being diagnosed as tubular adenocarcinoma, pT1b (SM). Immunohistological staining revealed an adenocarcinomatous component positive for CA9, as well as a normal duodenal mucosa. To our knowledge, this report is among the first to describe CA9-expressing primary duodenal adenocarcinoma.
Description of Methicillin-Susceptible Staphylococcus aureus Clonal Complex 30 Related to the Pandemic Phage Type 80/81 Isolated from Patients in Three Tertiary Hospitals in Jos, North Central Nigeria
Authors: Essien Unyime C. , Boswihi Samar S. , Agbakoba Nneka R. , Udo Edet E.
Published: May 2022

Objective: The prevalence of phage 80/81 Staphylococcus aureus strains, the pandemic strains that were dominant in the 1950s, had declined in the 1960s and 1970s. However, these strains have reemerged in some countries in recent years. This study investigated the antibacterial resistance, virulence, and the genetic backgrounds of CC30-MSSA isolates obtained from patients in three tertiary hospitals. Materials and Methods: Twenty-two CC30-MSSA isolates cultured from different clinical samples were investigated using antibiotic sensitivity testing, spa typing, multilocus sequence typing, and DNA microarray analysis. Results: All 22 isolates were susceptible to vancomycin (MIC ≤2 μg/mL), teicoplanin (MIC ≤2 μg/mL), and cefoxitin but were resistant to penicillin G (n = 22; 100.0%), tetracycline (n = 12; 54.5%), ciprofloxacin (n = 15; 68.2%), cadmium acetate (n = 22; 100%), mercuric chloride (n = 13; 59.1%), and ethidium bromide (n = 3; 13.6%). The isolates belonged to sequence type, ST30, and five spa types: t012 (n = 12; 54.5%), t019 (n = 5; 22.7%), t017 (n = 2; 9.1%), t037 (n = 2; 9.1%), and t318 (n = 1; 4.5%). All 22 isolates were positive for agrIII, cap8, clfA, clfB, icaA, icaC, icaD, cna, and staphylococcal enterotoxin gene clusters (seg, sei, sem, sen, seo, seu). Eight isolates carried lukS-PV and lukF-PV that code for Panton-Valentine leukocidin. Conclusion: The current CC30-MSSA isolates share phenotypic and genotypic characteristics with the pandemic phage 80/81 isolates that were common in the 1950s and 1960s. Continued surveillance is recommended to keep abreast of the changing epidemiology of S. aureus causing healthcare and community-associated infections.
Chirurgie bei oligometastasiertem Brustkrebs nach optimalem Ansprechen auf eine Therapie mit Palbociclib und Letrozol: Fallstrick der therapeutischen Bewertung per Ultraschall
Authors: Fujii Suzuka , Oura Shoji , Makimoto Shinichiro
Published: May 2022

Eine 48-jährige Frau mit regionalen Rezidiven eines Brustkrebses in der axillären und supraklavikulären Region wurde in unser Krankenhaus überwiesen. Unter der Diagnose eines rezidivierenden luminalen Brustkrebses mit einem hohen Ki-67-Markierungsindex von >30% und einem krankheitsfreien Intervall von 13 Jahren begann die Patientin mit einer Therapie bestehend aus Palbociclib, Letrozol und einem luteinisierendes Hormon freisetzenden Hormon-Agonisten, was zu einem deutlichen Ansprechen der supraklavikulären Läsion und laut Ultraschalluntersuchung zu einer stabilen Erkrankung der axillären Läsion führte. Die Positronenemissionstomographie (PET)/Computertomographie der axillären und supraklavikulären Knoten zeigte vor und nach der Behandlung hohe bzw. keine Aviditäten. Die unbewegliche Halsläsion wurde durch die Behandlung beweglich. Die Patientin wurde daher einer chirurgischen Resektion der beiden metastatischen Knoten unterzogen, um die nicht übereinstimmende therapeutische Wirksamkeit gegen die beiden metastatischen Knoten mit zwei Bildmodalitäten, d.h. US und PET, zu untersuchen und möglicherweise eine Heilung der Oligometastasierung des Brustkrebses zu erreichen. Die pathologische Untersuchung ergab eine ausgeprägte Fibrose und geringe Krebszellreste mit Mikroverkalkungen im Halstumor und eine massive Sarkoid-artige Reaktion mit geringen Krebszellresten in den Axillarknoten. Die verbleibenden Krebszellen waren positiv für Östrogen- und Progesteronrezeptoren, negativ für den humanen epidermalen Wachstumsfaktor-Rezeptor Typ 2 und wiesen einen extrem niedrigen Ki-67-Markierungsindex von 2,5% auf. Die Patientin erholte sich problemlos und setzt die Palbociclib-haltige endokrine Therapie seit einem Jahr fort, ohne dass ein Rezidiv auftrat. Brustonkologen sollten die Grundprinzipien der internen Echobildung auf dem US umfassend zur Kenntnis nehmen und das Vorhandensein einer Sarkoid-artigen Reaktion in den Krebszell-Clustern bei der therapeutischen Bewertung von metastasiertem Brustkrebs in Betracht ziehen.
Arrhythmogenic Right Ventricular Cardiomyopathy Prevalence and Arrhythmic Outcomes in At-Risk Family Members: A Systematic Review and Meta-Analysis
Authors: Sharma Apurva , Bosman Laurens P. , Tichnell Crystal , Nanavati Julie , Murray Brittney , Nonyane Bareng A.S. , Tandri Harikrishna , Calkins Hugh , James Cynthia A.
Published: May 2022

Background:

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a complex cardiomyopathy with autosomal dominant inheritance and age-related incomplete penetrance, characterized by a high risk of sudden cardiac death. Recent professional consensus guidelines recommend clinical cardiac lifelong serial screening for at-risk family members refined only by age, but family genotype might influence necessary screening. Although numerous studies report prevalence of disease and arrhythmia in family members and explore predictors of penetrance and arrhythmic risk, a systematic review consolidating this evidence is lacking.

Methods:

We searched Medline (PubMed), Embase, The Cochrane Library, and Web of Science for studies that reported prevalence of (1) diagnosis of ARVC per 2010 Task Force Criteria and/or (2) sustained ventricular arrhythmias (VA) in at least 10 family members of definite patients with ARVC.

Results:

We identified 41 studies, including 36 that reported diagnosis by Task Force Criteria and 22 VA. Meta-analysis of 1359 family members, from 13 unique cohorts showed an average prevalence estimate of 25% for diagnosis as per Task Force Criteria (95% CI, 0.15–0.35, I
2
=
96.44%). Overall prevalence of VA among gene-positive family members was 18% (95% CI, 0.13–0.23, I
2
=33.25%) in 7 independent studies (n=597). Family genotype was a significant risk factor for diagnosis of both ARVC (odds ratio, 6.91 [95% CI, 1.27–37.70];
P
=0.0005) and VA (odds ratio, 13.62 [95% CI, 0.91–204.13];
P
=0.06). Male gender was not associated with disease prevalence (odds ratio, 1.18 [95% CI, 0.72–1.95];
P
=0.42) or VA (odds ratio, 0.81 [95% CI, 0.51–1.29];
P
=0.91).

Conclusions:

The prevalence of ARVC and VA in at-risk family members differs significantly based on family genotype. Although recent recommendations provide a guideline based only on age, we propose screening every 1 to 2 years for gene-positive family members and every 3 to 5 years for first-degree relatives of gene-elusive cases, as long as they are asymptomatic and not athletes.
Mitochondrial Sirtuin-3 (SIRT3) Prevents Doxorubicin-Induced Dilated Cardiomyopathy by Modulating Protein Acetylation and Oxidative Stress
Authors: Tomczyk Mateusz M. , Cheung Kyle G. , Xiang Bo , Tamanna Nahid , Fonseca Teixeira Ana L. , Agarwal Prasoon , Kereliuk Stephanie M. , Spicer Victor , Lin Ligen , Treberg Jason , Tong Qiang , Dolinsky Vernon W.
Published: May 2022

Background:

High doses of doxorubicin put cancer patients at risk for developing dilated cardiomyopathy. Previously, we showed that doxorubicin treatment decreases SIRT3 (sirtuin 3), the main mitochondrial deacetylase and increases protein acetylation in rat cardiomyocytes. Here, we hypothesize that SIRT3 expression can attenuate doxorubicin induced dilated cardiomyopathy in vivo by preventing the acetylation of mitochondrial proteins.

Methods:

Nontransgenic, M3-SIRT3 (truncated SIRT3; short isoform), and M1-SIRT3 (full-length SIRT3; mitochondrial localized) transgenic mice were treated with doxorubicin for 4 weeks (8 mg/kg body weight per week). Echocardiography was performed to assess cardiac structure and function and validated by immunohistochemistry and immunofluorescence (n=4–10). Mass spectrometry was performed on cardiac mitochondrial peptides in saline (n=6) and doxorubicin (n=5) treated hearts. Validation was performed in doxorubicin treated primary rat and human induced stem cell derived cardiomyocytes transduced with adenoviruses for M3-SIRT3 and M1-SIRT3 and deacetylase deficient mutants (n=4–10).

Results:

Echocardiography revealed that M3-SIRT3 transgenic mice were partially resistant to doxorubicin induced changes to cardiac structure and function whereas M1-SIRT3 expression prevented cardiac remodeling and dysfunction. In doxorubicin hearts, 37 unique acetylation sites on mitochondrial proteins were altered. Pathway analysis revealed these proteins are involved in energy production, fatty acid metabolism, and oxidative stress resistance. Increased M1-SIRT3 expression in primary rat and human cardiomyocytes attenuated doxorubicin-induced superoxide formation, whereas deacetylase deficient mutants were unable to prevent oxidative stress.

Conclusions:

Doxorubicin reduced SIRT3 expression and markedly affected the cardiac mitochondrial acetylome. Increased M1-SIRT3 expression in vivo prevented doxorubicin-induced cardiac dysfunction, suggesting that SIRT3 could be a potential therapeutic target for mitigating doxorubicin-induced dilated cardiomyopathy.
Blood Pressure and Glycemic Control Among Ambulatory US Adults With Heart Failure: National Health and Nutrition Examination Survey 2001 to 2018
Authors: Rethy Leah , Vu Thanh-Huyen T. , Shah Nilay S. , Carnethon Mercedes R. , Lagu Tara , Huffman Mark D. , Yancy Clyde W. , Lloyd-Jones Donald M. , Khan Sadiya S.
Published: May 2022

Background:

Multisociety guidelines recommend a goal systolic blood pressure (BP) <130 mm Hg and a hemoglobin A1c (HbA1c) <8% in patients with heart failure (HF), regardless of ejection fraction. Few studies have described BP and glycemic control in ambulatory patients with HF and racial and ethnic disparities in this subset of the population.

Methods:

We evaluated prevalence of uncontrolled BP and HbA1c in non-Hispanic Black, non-Hispanic White, and Mexican American adults aged ≥20 years with self-reported HF (National Health and Nutrition Examination Surveys: 2001–2018). Prevalence ratios (95% CI) for uncontrolled BP and HbA1c were calculated by race and ethnicity and adjusted for sex, age, treatment, and socioeconomic status. In secondary analyses, we examined trends in the prevalence of uncontrolled BP and HbA1c.

Results:

Uncontrolled BP was present in 48% (95% CI, 49%–56%) of adults with HF (representing 2.3 million people). Non-Hispanic Black participants had a higher prevalence of uncontrolled BP compared with non-Hispanic White participants (53% [48%–58%] compared with 47% [43%–51%],
P
<0.05). In adjusted models, non-Hispanic Black participants were 1.19 (1.02–1.39) times more likely to have uncontrolled BP than non-Hispanic White participants. Overall, uncontrolled HbA1c was found in 8% (6%, 10%) with no differences by race and ethnicity. Prevalence of uncontrolled BP improved over time but uncontrolled risk factors remained high—2017 to 2018: 41% (36%, 47%) and 7% (5%, 12%) had uncontrolled BP and HbA1c, respectively.

Conclusions:

We document an unacceptably high prevalence of uncontrolled BP and HbA1c in a nationally representative, ambulatory HF sample with significant differences in BP control by race and ethnicity.
Association Between Atrial Uptake on Cardiac Scintigraphy With Technetium-99m-Pyrophosphate Labeled Bone-Seeking Tracers and Atrial Fibrillation
Authors: Hussain Muzna , Krywanczyk Alison , Donnellan Eoin , Martyn Trejeeve , Hassan Ossama Abou , Alkharabsheh Saqer , Watson Chris , Tang W.H. , Kwon Deborah , Cremer Paul , Cheng Feixiong , Kanj Mohamed , Griffin Brian , Tan Carmela , Rodriguez E. Rene , Hanna Mazen , Jaber Wael , Collier Patrick
Published: May 2022

Background:

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease, in which atrial fibrillation (AF) has been shown to be prevalent. Cardiac scintigraphy with technetium-99m-pyrophosphate (99mTc-PyP) labeled bone-seeking tracers is used to noninvasively make the diagnosis of ATTR-CA, based on ventricular myocardial uptake. Assessment of atrial wall uptake (AU) on 99mTc-PyP is currently not used in the clinical setting

Methods:

We analyzed a cohort of patients referred for 99mTc-PyP scan at a tertiary center to explore AU and associations between any and incident AF, ATTR-CA, and all-cause mortality.

Results:

Among 580 patients included, 296 patients (51%) had a diagnosis of AF; 164 patients (28%) had scans consistent with ATTR-CA while 117 patients (20%) had AU. Of 117 patients with AU, 107 (91%) had any AF. In contrast, of 463 patients without AU 191(41%) had any AF. Of those with AU, 59/117(50%) patients had a 99mTc-PyP diagnosis of ATTR-CA while 58/117(50%) patients did not have such a diagnosis (
P
=1.00). Patients with AU had significantly more any AF (hazard ratio [HR], 1.03 [95% CI, 1.02–1.04];
P
<0.001), independent of ATTR-CA diagnosis and sex. On multivariable Cox proportional hazards analyses adjusting for age, AU, ATTR-CA diagnosis, sex, smoking, hypertension, diabetes, left ventricular ejection fraction, and coronary artery disease, both age (HR, 1.03 [95% CI, 1.02–1.04];
P
<0.0001) and AU (HR, 2.68 [95% CI, 2.11–3.41];
P
<0.0001) were independently associated with the development of any AF. Freedom from incident AF at 1-year was significantly lower in patients with AU, both in patients with and without ATTR-CA respectively (HR, 2.27 [95% CI, 1.37–3.78];
P
<0.0001 versus HR, 2.21 [95% CI, 1.46–3.34];
P
<0.0001).

Conclusions:

In a consecutive cohort of patients undergoing 99mTc-PyP scans, 20% had AU, which was statistically associated with any AF, independently of ATTR-CA diagnosis and sex. AU was associated with significantly lower freedom from incident AF at 1-year. Overlooking AU on 99mTc-PyP scans could potentially miss an earlier disease manifestation, or an additional risk factor for any/incident AF.
Global Impact of Different Blood Pressure Thresholds in 4 021 690 Participants of the May Measurement Month Initiative
Authors: Nolde Janis M. , Beaney Thomas , Carnagarin Revathy , Schutte Aletta E. , Poulter Neil R. , Schlaich Markus P.
Published: May 2022

Background:

Influential guidelines currently define hypertension at different thresholds of blood pressure (BP). The global May Measurement Month initiative provides a unique opportunity to estimate the potential consequences of universal lowering of BP thresholds on the prevalence of hypertension based on a large, real-world, patient-level data set.

Methods:

The average of the second and third of 3 attended BP readings after 5 minutes of rest from 4 021 690 standardized, opportunistic BP screenings in various settings of the 2017 to 2019 May Measurement Month initiatives from 104 countries were analyzed to assess the demographic and phenotypic impact of 3 defined BP thresholds.

Results:

The age- and sex-standardized median of the relative increase in rate of hypertension with a change of thresholds from ≥140/≥90 to ≥130/≥80 mm Hg was 72.3% (interquartile range, 59.3%–91.3%) among the participating countries. With a change from ≥140/≥90 to ≥120/≥70 mm Hg, the median range was 162.6% (interquartile range, 132.8%–202.6%). The increase in rate of hypertension was most pronounced in low-income (95.3% and 203.9%) and least pronounced in high-income countries (71.6% and 167.1%).

Conclusions:

The impact of a universal application of lower BP thresholds for the definition of hypertension would have an enormous impact on the prevalence of hypertension globally with large disparities between countries and substantial heterogeneity of demographic and phenotypic patterns, which should be confirmed in dedicated population studies. While focusing on lower BP targets may constitute an opportunity for early intervention, the potential socioeconomic consequences may pose unsurmountable obstacles for most health care systems worldwide.
Effect of Environmental Change Distribution on Artificial Life Simulations
Authors: Bullinaria John A.
Published: May 2022

It is already well known that environmental variation has a big effect on real evolution, and similar effects have been found in evolutionary artificial life simulations. In particular, a lot of research has been carried out on how the various evolutionary outcomes depend on the noise distributions representing the environmental changes, and how important it is for models to use inverse power-law distributions with the right noise colour. However, there are two distinct factors of relevance—the average total magnitude of change per unit time and the distribution of individual change magnitudes—and misleading results may emerge if those factors are not properly separated. This article makes use of an existing agent-based artificial life modeling framework to explore this issue using models previously tried and tested for other purposes. It begins by demonstrating how the total magnitude and distribution effects can easily be confused, and goes on to show how it is possible to untangle the influence of these interacting factors by using correlation-based normalization. It then presents a series of simulation results demonstrating that interesting dependencies on the noise distribution remain after separating those factors, but many effects involving the noise colour of inverse power-law distributions disappear, and very similar results arise across restricted-range white-noise distributions. The average total magnitude of change per unit time is found to have a substantial effect on the simulation outcomes, but the distribution of individual changes has very little effect. A robust counterexample is thereby provided to the idea that it is always important to use accurate environmental change distributions in artificial life models.
Input Legitimacy of Voluntary Sustainability Standards and Acceptance Among Southern Producers: A Qualitative Comparative Analysis
Authors: Schouten Greetje , Toonen Hilde M. , Leeuwerik Dorine
Published: May 2022

Voluntary standards are key instruments to address sustainability concerns in value chains. The legitimacy of these initiatives has been debated, particularly related to acceptance by Global South stakeholders. The governance literature has predominantly argued that initiatives employing democratic approaches to governance are more likely to increase their legitimacy. In this article, we use a configurational approach to test this proposition in relation to standard acceptance by southern producers. A qualitative comparative analysis of eight cases was carried out, linking three elements of input legitimacy (inclusion, participation, and accountability) to the outcome of standard uptake in the Global South. While our findings suggest that an inclusive governance structure is important, overall, they show no evidence to explain the presence or absence of standard acceptance in the Global South. We conclude that theoretical assumptions about democratic legitimacy cannot be confirmed and argue for further opening up the scholarly debate to include conceptualizations, methods, and approaches inclusive of different ways of creating and perceiving legitimacy.
Orchestrating Global Climate Governance Through Data: The UNFCCC Secretariat and the Global Climate Action Platform
Authors: Mai Laura , Elsässer Joshua Philipp
Published: May 2022

Since the adoption of the Paris Agreement, the focus of the United Nations climate regime has shifted from forging consensus among national governments toward animating implementation activity across multiple levels. Based on a case study of the Global Climate Action Portal—an online database designed to document nonstate actor climate commitments and implementation efforts—we trace, conceptualize, and assess how the roles of data, data infrastructures, and actor constellations have changed as a result of this shift. We argue that in the pre-COP21 negotiation phase, the United Nations Climate Secretariat strategically used the database to orchestrate and leverage nonstate actor commitments to exert pressure on intergovernmental negotiations. By contrast, in the post-COP21 implementation phase, the Secretariat, in collaboration with climate data specialists, is seeking to develop the portal to track and animate implementation activity. Given these developments, we discuss the potential and limitations of data-driven climate governance and set out avenues for future research.
Pupil-linked Arousal Signals in the Midbrain Superior Colliculus
Authors: Wang Chin-An , White Brian , Munoz Douglas P.
Published: May 2022

The orienting response evoked by the appearance of a salient stimulus is modulated by arousal; however, neural underpinnings for the interplay between orienting and arousal are not well understood. The superior colliculus (SC), causally involved in multiple components of the orienting response including gaze and attention shifts, receives not only multisensory and cognitive inputs but also arousal-regulated inputs from various cortical and subcortical structures. To investigate the impact of moment-by-moment fluctuations in arousal on orienting saccade responses, we used microstimulation of the monkey SC to trigger saccade responses, and we used pupil size and velocity to index the level of arousal at stimulation onset because these measures correlate with changes in brain states and locus coeruleus activity. Saccades induced by SC microstimulation correlated with prestimulation pupil velocity, with higher pupil velocities on trials without evoked saccades than with evoked saccades. In contrast, prestimulation absolute pupil size did not correlate with saccade behavior. Moreover, pupil velocity correlated with evoked saccade latency and metrics. Together, our results demonstrated that small fluctuations in arousal, indexed by pupil velocity, can modulate the saccade response evoked by SC microstimulation in awake behaving monkeys.
Brain Functional Networks Involved in Different Premise Order in Conditional Reasoning: A Dynamic Causal Model Study
Authors: Wang Li , Zhang Meng , Zou Feng , Wu Xin , Wang Yufeng , Chen Jun
Published: May 2022

In conditional reasoning, the reasoner must draw a conclusion based on a conditional or “If…, then…” proposition. Previous studies have reported that reversing the premises can effectively promote modus tollens reasoning (a form of conditional reasoning), but subsequent experimental studies have found no such effect. Therefore, to further examine this issue and reveal the cognitive mechanism of conditional reasoning, we asked two groups of healthy volunteers (traditional and inverted premise order groups) to evaluate a set of visually presented conditional tasks (modus ponens/modus tollens) under fMRI. The results indicated that the inverted condition activated more brain regions associated with working memory, including the angular gyrus (BA 39), precuneus (BA 7), inferior parietal lobe, and middle frontal gyrus. The resulting common activation map was used to define the ROIs and perform dynamic causal modeling for the effective connectivity analysis, containing the medial frontal gyrus, hippocampus, cerebellum, and middle occipital gyrus in the right hemisphere and the inferior occipital gyrus in the left hemisphere. The results of intrinsic connections in the optimal model selected by Bayesian model selection showed that the connection strength was stronger in the inverted group rather than in the traditional group, which may indicate that the reversal of the premise order promotes connectivity between brain regions. Despite the lack of a premise order effect, we did discover a neuronal separation between the inverted and traditional conditions, which lends support to the mental model theory to some extent.
The Role of Action–Effect Contingency on Sensory Attenuation in the Absence of Movement
Authors: Han Nathan , Jack Bradley N. , Hughes Gethin , Whitford Thomas J.
Published: May 2022

Stimuli that have been generated by a person's own willed motor actions generally elicit a suppressed electrophysiological, as well as phenomenological, response compared with identical stimuli that have been externally generated. This well-studied phenomenon, known as sensory attenuation, has mostly been studied by comparing ERPs evoked by self-initiated and externally generated sounds. However, most studies have assumed a uniform action–effect contingency, in which a motor action leads to a resulting sensation 100% of the time. In this study, we investigated the effect of manipulating the probability of action–effect contingencies on the sensory attenuation effect. In Experiment 1, participants watched a moving, marked tickertape while EEG was recorded. In the full-contingency (FC) condition, participants chose whether to press a button by a certain mark on the tickertape. If a button press had not occurred by the mark, a sound would be played a second later 100% of the time. If the button was pressed before the mark, the sound was not played. In the no-contingency (NC) condition, participants observed the same tickertape; in contrast, however, if participants did not press the button by the mark, a sound would occur only 50% of the time (NC-inaction). Furthermore, in the NC condition, if a participant pressed the button before the mark, a sound would also play 50% of the time (NC-action). In Experiment 2, the design was identical, except that a willed action (as opposed to a willed inaction) triggered the sound in the FC condition. The results were consistent across the two experiments: Although there were no differences in N1 amplitude between conditions, the amplitude of the Tb and P2 components were smaller in the FC condition compared with the NC-inaction condition, and the amplitude of the P2 component was also smaller in the FC condition compared with the NC-action condition. The results suggest that the effect of contingency on electrophysiological indices of sensory attenuation may be indexed primarily by the Tb and P2 components, rather than the N1 component which is most commonly studied.
Hierarchical Reinforcement Learning, Sequential Behavior, and the Dorsal Frontostriatal System
Authors: Janssen Miriam , LeWarne Christopher , Burk Diana , Averbeck Bruno B.
Published: May 2022

To effectively behave within ever-changing environments, biological agents must learn and act at varying hierarchical levels such that a complex task may be broken down into more tractable subtasks. Hierarchical reinforcement learning (HRL) is a computational framework that provides an understanding of this process by combining sequential actions into one temporally extended unit called an option. However, there are still open questions within the HRL framework, including how options are formed and how HRL mechanisms might be realized within the brain. In this review, we propose that the existing human motor sequence literature can aid in understanding both of these questions. We give specific emphasis to visuomotor sequence learning tasks such as the discrete sequence production task and the M × N (M steps × N sets) task to understand how hierarchical learning and behavior manifest across sequential action tasks as well as how the dorsal cortical–subcortical circuitry could support this kind of behavior. This review highlights how motor chunks within a motor sequence can function as HRL options. Furthermore, we aim to merge findings from motor sequence literature with reinforcement learning perspectives to inform experimental design in each respective subfield.
Social Prevalence Is Rationally Integrated in Belief Updating
Authors: Orticio Evan , Martí Louis , Kidd Celeste
Published: May 2022

People rely on social information to inform their beliefs. We ask whether and to what degree the perceived prevalence of a belief influences belief adoption. We present the results of two experiments that show how increases in a person’s estimated prevalence of a belief led to increased endorsement of said belief. Belief endorsement rose when impressions of the belief’s prevalence were increased and when initial beliefs were uncertain, as predicted by a Bayesian cue integration framework. Thus, people weigh social information rationally. An implication of these results is that social engagement metrics that prompt inflated prevalence estimates in users risk increasing the believability and adoption of viral misinformation posts.