bluuebunny/crossref_metadata_2025 huggingface dataset:
Arkansas Rice: Herbicide Resistance Concerns, Production Practices, and Weed Management Costs
Authors: Butts Thomas R. , Kouame K. Badou-Jeremie , Norsworthy Jason K. , Barber L. Tom
Published: April 2022

An online survey to better understand current weed management practices and concerns in Arkansas rice was distributed in the fall of 2020. A total of 123 respondents from across the Arkansas rice growing region returned the survey covering a total of 236,414 rice hectares, representing about 40% of the planted Arkansas rice hectares in 2020. The most problematic weeds were Echinochloa crus-galli (L.) P. Beauv. (ECG), Cyperus spp., and Oryza sativa L. (weedy rice), respectively, in flooded rice, and ECG, Amaranthus palmeri S. Wats., and Cyperus spp., respectively, in furrow-irrigated rice. Most respondents (78%) reported high concern with herbicide-resistant weeds, and crop rotation (>74%) was the most common strategy listed to control and mitigate the development of herbicide-resistant weeds. A chi-square test of homogeneity showed that strategies implemented to control herbicide-resistant weeds and mitigate the evolution of herbicide-resistant weeds were not dependent on occupation type (farmer, consultant, or industry rep) nor on years of involvement in rice production. Respondents failed to control ECG 44% of the time with their first postemergence herbicide. After initial herbicide failure, 53% of respondents stated two additional herbicide applications were required to control ECG escapes while another 21% of respondents stated it was never controlled. The average ECG population at 2020 harvest was between 0.1 and 1.0 plant m−2 according to 44% of the respondents; however, 41% of respondents indicated an ECG density of 2 to 10 plants m−2 at 2020 harvest. The reported annual average cost of herbicides for rice weed control was $266.40 ha−1 with ECG accounting for 81% of the total cost. Average yield loss attributed to ECG was estimated to be 505–959 kg ha−1 (economic loss of $134–254 ha−1). However, yield loss in the most heavily infested fields was estimated to be 757–1,464 kg ha−1 (economic loss of $200–387 ha−1). Effective, non-chemical approaches to weed management were ranked as the least important current research or educational effort, indicating a paradigm shift in rice producers' weed control line of thought is needed with dwindling herbicide options due to herbicide resistance.
Vector-Controlled Wheel-Like Magnetic Swarms With Multimodal Locomotion and Reconfigurable Capabilities
Authors: Li Mu , Zhang Tao , Zhang Xiang , Mu Jinjiang , Zhang Weiwei
Published: April 2022

Inspired by the biological collective behaviors of nature, artificial microrobotic swarms have exhibited environmental adaptability and tasking capabilities for biomedicine and micromanipulation. Complex environments are extremely relevant to the applications of microswarms, which are expected to travel in blood vessels, reproductive and digestive tracts, and microfluidic chips. Here we present a strategy that reconfigures paramagnetic nanoparticles into a vector-controlled microswarm with 3D collective motions by programming sawtooth magnetic fields. Horizontal swarms can be manipulated to stand vertically and swim like a wheel by adjusting the direction of magnetic-field plane. Compared with horizontal swarms, vertical wheel-like swarms were evaluated to be of approximately 15-fold speed increase and enhanced maneuverability, which was exhibited by striding across complex 3D confinements. Based on analysis of collective behavior of magnetic particles in flow field using molecular dynamics methods, a rotary stepping mechanism was proposed to address the formation and locomotion mechanisms of wheel-like swarm. we present a strategy that actuates swarms to stand and hover in situ under a programming swing magnetic fields, which provides suitable solutions to travel across confined space with unexpected changes, such as stepped pipes. By biomimetic design from fin motion of fish, wheel-like swarms were endowed with multi-modal locomotion and load-carrying capabilities. This design of intelligent microswarms that adapt to complicated biological environments can promote the applications ranging from the construction of smart and multifunctional materials to biomedical engineering.
Reversing Epithelial Polarity in Pluripotent Stem Cell-Derived Intestinal Organoids
Authors: Kakni Panagiota , López-Iglesias Carmen , Truckenmüller Roman , Habibović Pamela , Giselbrecht Stefan
Published: April 2022

The inner surface of the intestine is a dynamic system, composed of a single layer of polarized epithelial cells. The development of intestinal organoids was a major breakthrough since they robustly recapitulate intestinal architecture, regional specification and cell composition in vitro. However, the cyst-like organization hinders direct access to the apical side of the epithelium, thus limiting their use in functional assays. For the first time, we show an intestinal organoid model from pluripotent stem cells with reversed polarity where the apical side faces the surrounding culture media and the basal side faces the lumen. These inside-out organoids preserve a distinct apico-basolateral orientation for a long period and differentiate into the major intestinal cell types. This novel model lays the foundation for developing new in vitro functional assays particularly targeting the apical surface of the epithelium and thus offers a new research tool to study nutrient/drug uptake, metabolism and host-microbiome/pathogen interactions.
Engineering Yarrowia lipolytica to Produce Itaconic Acid From Waste Cooking Oil
Authors: Rong Lanxin , Miao Lin , Wang Shuhui , Wang Yaping , Liu Shiqi , Lu Zhihui , Zhao Baixiang , Zhang Cuiying , Xiao Dongguang , Pushpanathan Krithi , Wong Adison , Yu Aiqun
Published: April 2022

Itaconic acid (IA) is a high-value organic acid with a plethora of industrial applications. In this study, we seek to develop a microbial cell factory that could utilize waste cooking oil (WCO) as raw material for circular and cost-effective production of the abovementioned biochemical. Specifically, we expressed cis-aconitic acid decarboxylase (CAD) gene from Aspergillus terreus in either the cytosol or peroxisome of Yarrowia lipolytica and assayed for production of IA on WCO. To further improve production yield, the 10 genes involved in the production pathway of acetyl-CoA, an intermediate metabolite necessary for the synthesis of cis-aconitic acid, were individually overexpressed and investigated for their impact on IA production. To minimize off-target flux channeling, we had also knocked out genes related to competing pathways in the peroxisome. Impressively, IA titer up to 54.55 g/L was achieved in our engineered Y. lipolytica in a 5 L bioreactor using WCO as the sole carbon source.
Osteogenesis Improvement of Gelatin-Based Nanocomposite Scaffold by Loading Zoledronic Acid
Authors: Abdulahy Sayed Behnam , Esmaeili Bidhendi Mona , Vaezi Mohammad Reza , Moosazadeh Moghaddam Mehrdad
Published: April 2022

Bisphosphonates (BPs) such as Zoledronic acid (ZA) are a subset of synthetic small molecules, which are now marketed as the main drugs to stimulate the growth and differentiation of osteoblast cells, thereby increasing bone formation as well as preventing bone loss. Also, Halloysite Nanotubes (HNTs)-polymer composites have attracted a lot of attention due to their high surface-to-volume ratio, low density, and high hydrophilicity, and are easily dispersed in hydrophilic biopolymers. In addition, their ability to carry enough amounts of drugs and the ability to control release has been demonstrated. Based on studies, the Gelatin-based scaffold with Halloysite nanotube (HNT) has the capacity as a drug carrier and Zoledronic acid (ZA) sustains release. Previous studies show that using ZA intravenously has some severe side effects and limitations. But by attention to the advantages of its osteogenesis, the current study has been done in order to reduce the side effects of local delivery of it. The 3-dimensional scaffolds were prepared by the Freeze-drying method. Characterization methods such as FE-SEM, FTIR, XRD, and release behavior of the scaffold has been performed to evaluate the features of the scaffolds. In fact, as-prepared Gel-HNT/ZA release 49% ZA in Phosphate Buffered Saline (PBS) within 21 days. The mechanical properties have been increased after adding HNTs and ZA from 10.27 to 26.18 MPa. Also, the water absorption has been increased after adding HNTs and ZA from 1.67 to 5.02 (g/g). Seeded human Adipose stem cells (hASCs) on the prepared scaffolds showed that the ZA effectively elevated the proliferation of the hASCs and also the MTT results proved the non-toxicity of all prepared scaffolds by high cell viability (˃80%). The osteogenic differentiation has been accelerated as displayed by ALP and Ca assay. The results propose that the HNTs-loaded Gelatin scaffold could control the releasing of ZA and its localized delivery at the defect site, simultaneously promoting the mechanical and osteogenesis ability of gelatin-based scaffolds.
Rapamycin Ameliorates Radiation-Induced Testis Damage in Mice
Authors: Yang Juan , Xu Rui , Luan Yingying , Fan Hancheng , Yang Shuo , Liu Jun , Zeng Huihong , Shao Lijian
Published: April 2022

Male infertility is an important problem in human and animal reproduction. The testis is the core of male reproduction, which is very sensitive to radiation. The decline of male reproductive ability is a common trend in the world. Radiation is a physical factor leading to abnormal male reproductive function. To investigate the potential mechanisms of testicular damage induced by radiation and explore effective strategies to alleviate radiation-induced testis injury, C57BL/6 mice were irradiated with 8.0 Gy of X-ray irradiation. Testis and epididymis were collected at days 1, 3, and 7 after radiation exposure to analyze spermatogonia and sperm function. The results showed that radiation significantly destroyed testicular structure and reduced the numbers of spermatogonia. These were associated with mTORC1 signaling activation, decreased cellular proliferation and increased apoptotic cells in the irradiated testis. Rapamycin significantly blocked mTORC1 signaling pathway in the irradiated testis. Inhibition of mTORC1 signaling pathway by rapamycin treatment after radiation could significantly improve cell proliferation in testis and alleviate radiation-induced testicular injury after radiation exposure. Rapamycin treatment benefited cell survival in testis to maintain spermatogenesis cycle at 35 days after irradiation. These findings imply that rapamycin treatment can accelerate testis recovery under radiation condition through inhibiting mTORC1 signaling pathway.
The Amazing Evolutionary Complexity of Eukaryotic Tubulins: Lessons from Naegleria and the Multi-tubulin Hypothesis
Authors: Fulton Chandler
Published: April 2022

The multi-tubulin hypothesis proposed in 1976 was motivated by finding that the tubulin to build the flagellar apparatus was synthesized de novo during the optional differentiation of Naegleria from walking amoebae to swimming flagellates. In the next decade, with the tools of cloning and sequencing, we were able to establish that the rate of flagellar tubulin synthesis in Naegleria is determined by the abundance of flagellar α- and β-tubulin mRNAs. These experiments also established that the tubulins for Naegleria mitosis were encoded by separate, divergent genes, candidates for which remain incompletely characterized. Meanwhile an unanticipated abundance of tubulin isotypes has been discovered by other researchers. Together with the surprises of genome complexity, these tubulin isotypes require us to rethink how we might utilize the opportunities and challenges offered by the evolutionary diversity of eukaryotes.
Mechanobiology in the Comorbidities of Ehlers Danlos Syndrome
Authors: Royer Shaina P. , Han Sangyoon J.
Published: April 2022

Ehlers-Danlos Syndromes (EDSs) are a group of connective tissue disorders, characterized by skin stretchability, joint hypermobility and instability. Mechanically, various tissues from EDS patients exhibit lowered elastic modulus and lowered ultimate strength. This change in mechanics has been associated with EDS symptoms. However, recent evidence points toward a possibility that the comorbidities of EDS could be also associated with reduced tissue stiffness. In this review, we focus on mast cell activation syndrome and impaired wound healing, comorbidities associated with the classical type (cEDS) and the hypermobile type (hEDS), respectively, and discuss potential mechanobiological pathways involved in the comorbidities.
Deep Metabolic Profiling Assessment of Tissue Extraction Protocols for Three Model Organisms
Authors: Gegner Hagen M. , Mechtel Nils , Heidenreich Elena , Wirth Angela , Cortizo Fabiola Garcia , Bennewitz Katrin , Fleming Thomas , Andresen Carolin , Freichel Marc , Teleman Aurelio A. , Kroll Jens , Hell Rüdiger , Poschet Gernot
Published: April 2022

Metabolic profiling harbors the potential to better understand various disease entities such as cancer, diabetes, Alzheimer’s, Parkinson’s disease or COVID-19. To better understand such diseases and their intricate metabolic pathways in human studies, model animals are regularly used. There, standardized rearing conditions and uniform sampling strategies are prerequisites towards a successful metabolomic study that can be achieved through model organisms. Although metabolomic approaches have been employed on model organisms before, no systematic assessment of different conditions to optimize metabolite extraction across several organisms and sample types has been conducted. We address this issue using a highly standardized metabolic profiling assay analyzing 630 metabolites across three commonly used model organisms (Drosophila, mouse, and zebrafish) to find an optimal extraction protocol for various matrices. Focusing on parameters such as metabolite coverage, concentration and variance between replicates we compared seven extraction protocols. We found that the application of a combination of 75% ethanol and methyl tertiary-butyl ether (MTBE), while not producing the broadest coverage and highest concentrations, was the most reproducible extraction protocol. We were able to determine up to 530 metabolites in mouse kidney samples, 509 in mouse liver, 422 in zebrafish and 388 in Drosophila and discovered a core overlap of 261 metabolites in these four matrices. To enable other scientists to search for the most suitable extraction protocol in their experimental context and interact with this comprehensive data, we have integrated our data set in the open-source shiny app “MetaboExtract”. Hereby, scientists can search for metabolites or compound classes of interest, compare them across the different tested extraction protocols and sample types as well as find reference concentration values.
Patients with Primary and Secondary Bile Duct Stones Harbor Distinct Biliary Microbial Composition and Metabolic Potential
Authors: Feng Ru , Zhang Tianyu , Kayani Masood ur Rehman , Wang Zhengting , Shen Yao , Su Kenn Liu , Bielike Kouken , Chen Lei
Published: April 2022

Introduction

Cholelithiasis has a high incidence worldwide and limited treatment options due to its poorly understood pathogenesis. Furthermore, the role of biliary microbiota in cholelithiasis remains understudied. To address these questions, we performed microbial sequencing from biliary samples from primary bile duct stone (PBDS) and secondary bile duct stone (SBDS) patients.

Results

We analyzed in total 45 biliary samples, including those from cholelithiasis patients with PBDS or SBDS and people with other digestive diseases. 16S rRNA sequencing showed the bacteria family Alcaligenaceae increased in relative abundance in the lithiasis group compared with the non-lithiasis group. In addition, the PBDS group showed significantly lower bacterial diversity than SBDS, with Propionibacteriaceae, Sphingomonadaceae, and Lactobacillaceae as the most significant bacteria families decreased in relative abundance. We further performed whole metagenomic shotgun sequencing (wMGS) and found increased ability of biofilm synthesis and the ability to sense external stimuli in PBDS based on functional annotation of mapped reads. From genome-resolved analysis of the samples, we identified 36 high-quality draft bacterial genome sequences with completion ≥70% and contamination ≤10%. Most of these genomes were classified into Proteobacteria, Firmicutes, or Actinobacteria.

Conclusions

Our findings indicated that there is a subtle impact on biliary microbiome from cholelithiasis while the difference is more pronounced between the PBDS and SBDS. It was revealed that the diversity of biliary microbiota in PBDS is lower, while some metabolic pathways are up-regulated, including those linked to higher incidence of different types of cancer, providing new insights for the understanding of cholelithiasis with different origin.
Cardioprotective Effects and Possible Mechanisms of Luteolin for Myocardial Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis of Preclinical Evidence
Authors: Pan Qinyuan , Liu Yang , Ma Wenrui , Kan Rongsheng , Zhu Hong , Li Dongye
Published: April 2022

Background

At present, effective clinical therapies for myocardial ischemia-reperfusion injury (MIRI) are lacking. We investigated if luteolin conferred cardioprotective effects against MIRI and elucidated the potential underlying mechanisms.

Method

Four databases were searched for preclinical studies of luteolin for the treatment of MIRI. The primary outcomes were myocardial infarct size (IS) and intracardiac hemodynamics. The second outcomes were representative indicators of apoptosis, oxidative stress, and inflammatory. The Stata and RevMan software packages were utilized for data analysis.

Results

Luteolin administration was confirmed to reduce IS and ameliorate hemodynamics as compared to the control groups (p < 0.01). IS had decreased by 2.50%, 2.14%, 2.54% in three subgroups. Amelioration of hemodynamics was apparent in two different myocardial infarct models (model of left anterior descending branch ligation and model of global heart ischemia), as left ventricular systolic pressure improved by 21.62 and 35.40 mmHg respectively, left ventricular end-diastolic pressure decreased by 7.79 and 4.73 mmHg respectively, maximum rate of left ventricular pressure rise increased by 737.48 and 750.47 mmHg/s respectively, and maximum rate of left ventricular pressure decrease increased by 605.66 and 790.64 mmHg/s respectively. Apoptosis of cardiomyocytes also significantly decreased, as indicated by thelevels of MDA, an oxidative stress product, and expression of the inflammatory factor TNF-α (p < 0.001).

Conclusion

Pooling of the data demonstrated that luteolin exerts cardioprotective effects against MIRI through different signaling pathways. As possible mechanisms, luteolin exerts anti-apoptosis, anti-oxidation, and anti-inflammation effects against MIRI.
Genetically Determined Lifestyle and Cardiometabolic Risk Factors Mediate the Association of Genetically Predicted Age at Menarche With Genetic Predisposition to Myocardial Infarction: A Two-Step, Two-Sample Mendelian Randomization Study
Authors: Zheng Jilin , Chen Ken , Huang Tao , Shao Chunli , Li Ping , Wang Jingjia , Wang Wenyao , Zhang Kuo , Meng Xiangbin , Gao Jun , Wang Xuliang , Liu Yupeng , Song Jingjing , Dong Eran , Tang Yi-Da
Published: April 2022

Background

Observational studies have shown an association between early age at menarche (AAM) and myocardial infarction (MI) with recorded cases. In this Mendelian randomization (MR) study, we used large amounts of summary data from genome-wide association studies (GWASs) to further estimate the association of genetically predicted AAM with genetically predicated risk of MI and investigate to what extent this association is mediated by genetically determined lifestyles, cardiometabolic factors, and estrogen exposure.

Methods

A two-step, two-sample MR study was performed by mediation analysis. Genetic variants identified by GWAS meta-analysis of reproductive genetics consortium (n = 182,416) were selected for genetically predicted AAM. Genetic variants identified by the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis plus The Coronary Artery Disease Genetics Consortium (n = 184,305) were selected for genetically predicted risk of MI. Genetic variants from other international GWAS summary data were selected for genetically determined mediators.

Results

This MR study showed that increase in genetically predicted AAM was associated with lower risk of genetically predicted MI (odds ratio 0.91, 95% confidence interval 0.84–0.98). Inverse variance weighted (IVW) MR analysis also showed that decrease in genetically predicted AAM was associated with higher genetically predicted alcohol intake frequency, current smoking behavior, higher waist-to-hip ratio, and higher levels of systolic blood pressure (SBP), fasting blood glucose, hemoglobin A1c (HbA1c), and triglycerides (TGs). Furthermore, increase in genetically predicted AAM was associated with genetically predicted longer sleep duration, higher levels of high-density lipoproteins, and older age at which hormone replacement therapy was started. The most essential mediators identified were genetically predicted current smoking behavior and levels of HbA1c, SBP, and TGs, which were estimated to genetically mediate 13.9, 12.2, 10.5, and 9.2%, respectively, with a combined mediation proportion of 37.5% in the association of genetically predicted AAM with genetically predicted increased risk of MI in an MR framework.

Conclusion

Our MR analysis showed that increase in genetically predicted AAM was associated with lower genetically predicted risk of MI, which was substantially mediated by genetically determined current smoking behavior and levels of HbA1c, SBP, and TGs. Intervening on the above mediators may reduce the risk of MI.
The Predictive Value of Left Atrial Strain Following Transcatheter Aortic Valve Implantation on Anatomical and Functional Reverse Remodeling in a Multi-Modality Study
Authors: Vattay Borbála , Nagy Anikó Ilona , Apor Astrid , Kolossváry Márton , Manouras Aristomenis , Vecsey-Nagy Milán , Molnár Levente , Boussoussou Melinda , Bartykowszki Andrea , Jermendy Ádám L. , Kováts Tímea , Zsarnóczay Emese , Maurovich-Horvat Pál , Merkely Béla , Szilveszter Bálint
Published: April 2022

Introduction

Transcatheter aortic valve implantation (TAVI) can improve left ventricular (LV) mechanics and survival. Data on the predictive value of left atrial (LA) strain following TAVI are scarce. We aimed to evaluate the association of LA strain measured shortly post-TAVI with functional and anatomical reverse remodeling of the LA and LV, and its association with mortality.

Methods

We prospectively investigated 90 patients who underwent TAVI. Transthoracic echocardiography including strain analysis was performed shortly after TAVI and repeated 6 months later. CT angiography (CTA) was performed for pre-TAVI planning and 6 months post-TAVI. Speckle tracking echocardiography was used to determine LA peak reservoir strain (LASr) and LV global longitudinal strain (LV-GL), LA volume index (LAVi) was measured by TTE. LV mass index (LVMi) was calculated using CTA images. LA reverse remodeling was based on LASr and LAVi changes, whereas LV reverse remodeling was defined as an improvement in LV-GLS or a reduction of LVMi. The association of severely reduced LASr (<20%) at baseline with changes (Δ) in LASr, LAVi, LV-GLS and LVMi were analyzed using linear regression, and Cox proportional hazard model for mortality.

Results

Mean LASr and LV-GLS were 17.7 ± 8.4 and −15.3 ± 3.4% at baseline and 20.2 ± 10.2 and −16.6 ± 4.0% at follow-up (p = 0.024 and p < 0.001, respectively). Severely reduced LASr at baseline was associated with more pronounced ΔLASr (β = 5.24, p = 0.025) and LVMi reduction on follow-up (β = 5.78, p = 0.036), however, the majority of the patients had <20% LASr on follow-up (44.4%). Also, ΔLASr was associated with ΔLV-GLS (adjusted β = 2.10, p < 0.001). No significant difference in survival was found between patients with baseline severely reduced LASr (<20%) and higher LASr (≥20%) (p = 0.054).

Conclusion

LV reverse remodeling based on LVMi was present even in patients with severely reduced LASr following TAVI, although extensive LA damage based on LA strain was demonstrated by its limited improvement over time.

Clinical Trial Registration

(ClinicalTrials.gov number: NCT02826200).
Socioeconomic Status and Prognosis of Patients With ST-Elevation Myocardial Infarction Managed by the Emergency-Intervention “Codi IAM” Network
Authors: Tizón-Marcos Helena , Vaquerizo Beatriz , Ferré Josepa Mauri , Farré Núria , Lidón Rosa-Maria , Garcia-Picart Joan , Regueiro Ander , Ariza Albert , Carrillo Xavier , Duran Xavier , Poirier Paul , Cladellas Mercè , Camps-Vilaró Anna , Ribas Núria , Cubero-Gallego Hector , Marrugat Jaume
Published: April 2022

Background

Despite the spread of ST-elevation myocardial infarction (STEMI) emergency intervention networks, inequalities in healthcare access still have a negative impact on cardiovascular prognosis. The Family Income Ratio of Barcelona (FIRB) is a socioeconomic status (SES) indicator that is annually calculated. Our aim was to evaluate whether SES had an effect on mortality and complications in patients managed by the “Codi IAM” network in Barcelona.

Methods

This is a cohort study with 3,322 consecutive patients with STEMI treated in Barcelona from 2010 to 2016. Collected data include treatment delays, clinical and risk factor characteristics, and SES. The patients were assigned to three SES groups according to FIRB score. A logistic regression analysis was conducted to estimate the adjusted effect of SES on 30-day mortality, 30-day composite cardiovascular end point, and 1-year mortality.

Results

The mean age of the patients was 65 ± 13% years, 25% were women, and 21% had diabetes mellitus. Patients with low SES were younger, more often hypertensive, diabetic, dyslipidemic (p < 0.003), had longer reperfusion delays (p < 0.03) compared to participants with higher SES. Low SES was not independently associated with 30-day mortality (OR: 0.95;9 5% CI: 0.7–1.3), 30-day cardiovascular composite end point (OR: 1.03; 95% CI: 0.84–1.26), or 1-year all-cause mortality (HR: 1.09; 95% CI: 0.76–1.56).

Conclusion

Although the low-SES patients with STEMI in Barcelona city were younger, had worse clinical profiles, and had longer revascularization delays, their 30-day and 1-year outcomes were comparable to those of the higher-SES patients.
Relationship Between Initial Urine Output and Mortality in Patients Hospitalized in Cardiovascular Intensive Care Units: More Is Not Better
Authors: Li Le , Zhang Zhenhao , Xiong Yulong , Hu Zhao , Liu Shangyu , Tu Bin , Yao Yan
Published: April 2022

Backgrounds

Decreased urine output (UO) is associated with adverse outcomes in certain patients, but this effect in patients admitted for cardiovascular diseases is still unproven. Moreover, the relationship between increased UO and prognosis is also unclear.

Objective

To investigate the relationship between decreased or increased UO and outcomes in patients with the cardiovascular intensive care unit (CICU).

Methods

This study was a retrospective cohort analysis based on the medical information mart for intensive care III (MIMIC-III) database. The patients' data were extracted from the Beth Israel Deaconess Medical Center (Boston, MA) between 2001 and 2012. With the initial 24-h UO range from 0.5 to 1.0 ml/kg/h as the reference, participants were divided into the several groups. The primary outcome was 30-day mortality. The secondary outcomes were 90-day mortality, ICU mortality, hospital mortality, use of mechanical ventilation (MV), and vasopressor agents in the first 24-h of ICU. The association between UO and mortality was assessed by multivariable logistic regression.

Results

A total of 13,279 patients admitted to CICU were included. Low UO (< 0.5 ml/kg/h) was strongly associated with 30-day mortality (unadjusted OR = 3.993, 95% CI: 3.447–4.625, p < 0.001), and very high UO (≥ 2.0 ml/kg/h) was also a significantly risk factor for 30-day mortality (Unadjusted OR = 2.069, 95% CI: 1.701–2.516, p < 0.001) compared with the reference. The same effects also were shown in the multivariable logistic regression, adjusted by age, gender, vital signs, common comorbidities, and use of diuretics, with an adjusted OR of 2.023 (95% CI: 1.693–2.417, p < 0.001) for low UO and 1.771 (95% CI: 1.389–2.256, p < 0.001) for very high UO. Moreover, both decreased UO and increased UO were risk factors for 90-day mortality, ICU mortality, hospital mortality, use of MV and vasopressor agents.

Conclusion

The decreased and increased UO both were significantly associated with short-term mortality, the relationship between UO and mortality was U-shape rather than linear.
Macrophages in Atheromatous Plaque Developmental Stages
Authors: von Ehr Alexander , Bode Christoph , Hilgendorf Ingo
Published: April 2022

Atherosclerosis is the main pathomechanism leading to cardiovascular diseases such as myocardial infarction or stroke. There is consensus that atherosclerosis is not only a metabolic disorder but rather a chronic inflammatory disease influenced by various immune cells of the innate and adaptive immune system. Macrophages constitute the largest population of inflammatory cells in atherosclerotic lesions. They play a critical role in all stages of atherogenesis. The heterogenous macrophage population can be subdivided on the basis of their origins into resident, yolk sac and fetal liver monocyte-derived macrophages and postnatal monocyte-derived, recruited macrophages. Recent transcriptomic analyses revealed that the major macrophage populations in atherosclerosis include resident, inflammatory and foamy macrophages, representing a more functional classification. The aim of this review is to provide an overview of the trafficking, fate, and functional aspects of the different macrophage populations in the “life cycle” of an atheromatous plaque. Understanding the chronic inflammatory state in atherosclerotic lesions is an important basis for developing new therapeutic approaches to abolish lesion growth and promote plaque regression in addition to general cholesterol lowering.
Cellular Heterogeneity of the Heart
Authors: Anto Michel Nathaly , Ljubojevic-Holzer Senka , Bugger Heiko , Zirlik Andreas
Published: April 2022

Recent advances in technology such as the introduction of high throughput multidimensional tools like single cell sequencing help to characterize the cellular composition of the human heart. The diversity of cell types that has been uncovered by such approaches is by far greater than ever expected before. Accurate identification of the cellular variety and dynamics will not only facilitate a much deeper understanding of cardiac physiology but also provide important insights into mechanisms underlying its pathological transformation. Distinct cellular patterns of cardiac cell clusters may allow differentiation between a healthy heart and a sick heart while potentially predicting future disease at much earlier stages than currently possible. These advances have already extensively improved and will ultimately revolutionize our knowledge of the mechanisms underlying cardiovascular disease as such. In this review, we will provide an overview of the cells present in the human and rodent heart as well as genes that may be used for their identification.
A Meta-Analysis of Early, Mid-term and Long-Term Mortality of On-Pump vs. Off-Pump in Redo Coronary Artery Bypass Surgery
Authors: Zhang Shicheng , Huang Siyuan , Tiemuerniyazi Xieraili , Song Yangwu , Feng Wei
Published: April 2022

We aimed to compare the early, mid-term, and long-term mortality between on-pump vs. off-pump redo coronary artery bypass grafting (CABG). We conducted a systematic search for studies comparing clinical outcomes of patients who underwent on-pump vs. off-pump redo CABG. We pooled the relevant studies quantitatively to compare the early (perioperative period, whether in hospital or within 30 days after discharge), mid-term (≥1 year and <5 years), and long-term (≥5 year) mortality of on-pump vs. off-pump redo CABG. A random-effect model was applied when there was high heterogeneity (I2 > 50%) between studies. Otherwise, a fixed-effect model was utilized. After systematic literature searching, 22 studies incorporating 5,197 individuals (3,215 in the on-pump group and 1,982 in the off-pump group) were identified. A pooled analysis demonstrated that compared with off-pump redo CABG, on-pump redo CABG was associated with higher early mortality (OR 2.11, 95%CI: 1.54–2.89, P < 0.00001). However, no significant difference was noted in mid-term mortality (OR 1.12, 95%CI: 0.57–2.22, P = 0.74) and long-term mortality (OR 1.12, 95%CI: 0.41–3.02, P = 0.83) between the two groups. In addition, the complete revascularization rate was higher in the on-pump group than the off-pump group (OR 2.61, 95%CI: 1.22–5.60, P = 0.01). In conclusion, the off-pump technique is a safe and efficient alternative to the on-pump technique, with early survival advantage and similar long-term mortality to the on-pump technique in the setting of redo CABG, especially in high-risk patients.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021244721.
Hydrogen Peroxide Scavenging Restores N-Type Calcium Channels in Cardiac Vagal Postganglionic Neurons and Mitigates Myocardial Infarction-Evoked Ventricular Arrhythmias in Type 2 Diabetes Mellitus
Authors: Zhang Dongze , Tu Huiyin , Hu Wenfeng , Duan Bin , Zimmerman Matthew C. , Li Yu-Long
Published: April 2022

Objective

Withdrawal of cardiac vagal activity is associated with ventricular arrhythmia-related high mortality in patients with type 2 diabetes mellitus (T2DM). Our recent study found that reduced cell excitability of cardiac vagal postganglionic (CVP) neurons is involved in cardiac vagal dysfunction and further exacerbates myocardial infarction (MI)-evoked ventricular arrhythmias and mortality in T2DM. However, the mechanisms responsible for T2DM-impaired cell excitability of CVP neurons remain unclear. This study tested if and how elevation of hydrogen peroxide (H2O2) inactivates CVP neurons and contributes to cardiac vagal dysfunction and ventricular arrhythmogenesis in T2DM.

Methods and Results

Rat T2DM was induced by a high-fat diet plus streptozotocin injection. Local in vivo transfection of adenoviral catalase gene (Ad.CAT) successfully induced overexpression of catalase and subsequently reduced cytosolic H2O2 levels in CVP neurons in T2DM rats. Ad.CAT restored protein expression and ion currents of N-type Ca2+ channels and increased cell excitability of CVP neurons in T2DM. Ad.CAT normalized T2DM-impaired cardiac vagal activation, vagal control of ventricular function, and heterogeneity of ventricular electrical activity. Additionally, Ad.CAT not only reduced the susceptibility to ventricular arrhythmias, but also suppressed MI-evoked lethal ventricular arrhythmias such as VT/VF in T2DM.

Conclusions

We concluded that endogenous H2O2 elevation inhibited protein expression and activation of N-type Ca2+ channels and reduced cell excitability of CVP neurons, which further contributed to the withdrawal of cardiac vagal activity and ventricular arrhythmogenesis in T2DM. Our current study suggests that the H2O2-N-type Ca2+ channel signaling axis might be an effective therapeutic target to suppress ventricular arrhythmias in T2DM patients with MI.
Systolic Blood Pressure and 1-Year Clinical Outcomes in Patients Hospitalized for Heart Failure
Authors: Huang Xinghe , Liu Jiamin , Zhang Lihua , Wang Bin , Bai Xueke , Hu Shuang , Miao Fengyu , Tian Aoxi , Yang Tingxuan , Li Yan , Li Jing
Published: April 2022

Background

High systolic blood pressure (SBP) is an important risk factor for the progression of heart failure (HF); however, the association between SBP and prognosis among patients with established HF was uncertain. This study aimed to investigate the association between SBP and long-term clinical outcomes in patients hospitalized for HF.

Methods

This study prospectively enrolled adult patients hospitalized for HF in 52 hospitals from 20 provinces in China. SBPs were measured in a stable condition judged by clinicians during hospitalization before discharge according to the standard research protocol. The primary outcomes included 1-year all-cause death and HF readmission. The multivariable Cox proportional hazards regression models were fitted to examine the association between SBP and clinical outcomes. Restricted cubic splines were used to examine the non-linear associations.

Results

The 4,564 patients had a mean age of 65.3 ± 13.5 years and 37.9% were female. The average SBP was 123.2 ± 19.0 mmHg. One-year all-cause death and HF readmission were 16.9 and 32.7%, respectively. After adjustment, patients with SBP < 110 mmHg had a higher risk of all-cause death compared with those with SBP of 130–139 mmHg (HR 1.71; 95% CI: 1.32–2.20). Patients with SBP < 110 mmHg (HR 1.36; 95% CI: 1.14–1.64) and SBP ≥ 150 mmHg (HR 1.26; 95% CI: 1.01–1.58) had a higher risk of HF readmission, and the association between SBP and HF readmission followed a J-curve relationship with the nadir SBP around 130 mmHg. These associations were consistent regardless of age, sex, left ventricular ejection fraction, hypertension, coronary heart disease, and medications for HF.

Conclusion

In patients hospitalized for HF, lower SBP in a stable phase during hospitalization portends an increased risk of 1-year death, and a J-curve association has been observed between SBP and 1-year HF readmission. These associations were consistent among clinically important subgroups.
In vivo Visualization of M2 Macrophages in the Myocardium After Myocardial Infarction (MI) Using 68Ga-NOTA-Anti-MMR Nb: Targeting Mannose Receptor (MR, CD206) on M2 Macrophages
Authors: Varasteh Zohreh , Braeuer Miriam , Mohanta Sarajo , Steinsiek Anna-Lena , Habenicht Andreas , Omidvari Negar , Topping Geoffrey J. , Rischpler Christoph , Weber Wolfgang A. , Sager Hendrik B. , Raes Geert , Hernot Sophie , Schwaiger Markus
Published: April 2022

Introduction and Objectives

Wound healing after myocardial infarction (MI) is a dynamic and complex multiple phase process, and a coordinated cellular response is required for proper scar formation. The current paradigm suggests that pro-inflammatory monocytes infiltrate the MI zone during the initial pro-inflammatory phase and differentiate into inflammatory macrophages, and then switch their phenotypes to anti-inflammatory during the reparative phase. Visualization of the reparative phase post-MI is of great interest because it may reveal delayed resolution of inflammation, which in turn predicts adverse cardiac remodeling. Imaging of anti-inflammatory macrophages may also be used to assess therapy approaches aiming to modulate the inflammatory response in order to limit MI size. Reparative macrophages can be distinguished from inflammatory macrophages by the surface marker mannose receptor (MR, CD206). In this study we evaluated the feasibility of 68Ga-NOTA-anti-MMR Nb for imaging of MR on alternatively activated macrophages in murine MI models.

Methods

Wildtype and MR-knockout mice and Wistar rats were subjected to MI via permanent ligation of the left coronary artery. Non-operated or sham-operated animals were used as controls. MR expression kinetics on cardiac macrophages was measured in mice using flow cytometry. PET/CT scans were performed 1 h after intravenous injection of 68Ga-NOTA-anti-MMR Nb. Mice and rats were euthanized and hearts harvested for ex vivo PET/MRI, autoradiography, and staining. As a non-targeting negative control, 68Ga-NOTA-BCII10 was used.

Results

In vivo-PET/CT scans showed focal radioactivity signals in the infarcted myocardium for 68Ga-NOTA-anti-MMR Nb which were confirmed by ex vivo-PET/MRI scans. In autoradiography images, augmented uptake of the tracer was observed in infarcts, as verified by the histochemistry analysis. Immunofluorescence staining demonstrated the presence and co-localization of CD206- and CD68-positive cells, in accordance to infarct zone. No in vivo or ex vivo signal was observed in the animals injected with control Nb or in the sham-operated animals. 68Ga-NOTA-anti-MMR Nb uptake in the infarcts of MR-knockout mice was negligibly low, confirming the specificity of 68Ga-NOTA-anti-MMR Nb to MR.

Conclusion

This exploratory study highlights the potential of 68Ga-NOTA-anti-MMR Nb to image MR-positive macrophages that are known to play a pivotal role in wound healing that follows acute MI.
Etiology and Management of Dyslipidemia in Patients With Cancer
Authors: de Jesus Mikhail , Mohammed Turab , Singh Meghana , Tiu John G. , Kim Agnes S.
Published: April 2022

Patients with cancer are now living longer than ever before due to the growth and expansion of highly effective antineoplastic therapies. Many of these patients face additional health challenges, of which cardiovascular disease (CVD) is the leading contributor to morbidity and mortality. CVD and cancer share common biological mechanisms and risk factors, including lipid abnormalities. A better understanding of the relationship between lipid metabolism and cancer can reveal strategies for cancer prevention and CVD risk reduction. Several anticancer treatments adversely affect lipid levels, increasing triglycerides and/or LDL-cholesterol. The traditional CVD risk assessment tools do not include cancer-specific parameters and may underestimate the true long-term CVD risk in this patient population. Statins are the mainstay of therapy in both primary and secondary CVD prevention. The role of non-statin therapies, including ezetimibe, PCSK9 inhibitors, bempedoic acid and icosapent ethyl in the management of lipid disorders in patients with cancer remains largely unknown. A contemporary cancer patient needs a personalized comprehensive cardiovascular assessment, management of lipid abnormalities, and prevention of late CVD to achieve optimal overall outcomes.
Mechanism and Controlling Factors on Methane Yields Catalytically Generated From Low-Mature Source Rocks at Low Temperatures (60–140°C) in Laboratory and Sedimentary Basins
Authors: Wei Lin , Yin Jia , Li Jiansheng , Zhang Kun , Li Chunzhen , Cheng Xiong
Published: April 2022

Various studies have shown that geo-catalytically mediated methanogenesis could happen in immature to early-mature source rocks at temperatures ranging from 60 to 140°C based on a series of long-term laboratory heating experimental evidences. The results of those studies show that methane yields at the given temperature are 5–11 orders of magnitude higher than the theoretically predicted yields from early thermogenic methane generation kinetic models. However, different types of source rocks in these laboratory simulation experiments generated varied CH4 and CO2 yields, which suggest that controls on CH4 generation during catalytic methanogenesis are complex. This study summarizes and compares gas yield results from laboratory low-temperature heating simulation experiments. Pre-existing trapped methane in rock chips could mimic newly generated gas during heating. The yields of catalytically generated CH4 from individual source rocks were re-quantified by subtracting the amounts of pre-existing CH4 in the closed pores of the original source rocks from the total methane amounts released from heating experiments and pre-existing CH4 in the closed pores in heated source rocks. The results show that heating temperature and time exert a positive influence on methane catalytic methanogenesis. Mowry and Second White Specks Formation Shale generated approximately ten times more CH4 than New Albany Shale and Mahogany Shale per gram of total organic carbon (TOC). Samples of Springfield Coal #1 and #2 exhibited ten times yield difference from one another at the same heating temperature. Those yield differences are not strongly associated with TOC content, heating time, temperature, metal content, or kerogen type but appear to be more influenced by maceral composition and also maceral–mineral contact area within the source rocks. We conclude that macerals in the liptinite group have a propensity for methanogenesis. Specifically, amorphous organic matter undergoes transformation into hydrocarbons earlier than alginite at low-temperature heating conditions. Sporinite also contributes to higher yields of methane released from the coal source rock. Vitrinite and inertinite show a positive influence on carbon dioxide but no significant effect on increasing methane yields compared to other macerals. The strongest catalytic methanogenesis in the studied sample produced methane yields at 60°C, which amounted to ∼2.5 μmol per gram of organic carbon during one year of heating. We suggest that geocatalytic methanogenesis could generate economically sizeable gas plays from immature to early-mature source rocks over geologic time.
Heritage Resources and Teaching Approaches. A Study With Trainee Secondary Education History Teachers
Authors: Chaparro-Sainz Álvaro , Felices-De la Fuente María del Mar , Rodríguez-Medina Jairo , Gómez-Carrasco Cosme Jesús
Published: April 2022

At present, there is a great deal of research demonstrating the educational potential of heritage for the teaching of history. However, relevant studies have shown that, although it is a resource which is widely valued by teachers, its incorporation into the classroom remains limited. The aim of this study is to analyze the opinions of teachers in initial training regarding the use of heritage in the classrooms and to inquire about their relationship with their own teaching approaches, given that these may influence the use or evaluation they make of this resource. This study, which is non-experimental and quantitative in nature, has employed as a research tool a questionnaire with the participation of 646 students of the master’s degrees in Teacher Training in Geography and History of 22 different universities, representing 70% of the universities that offer this degree in Spain. The most significant results show a broad interest in heritage among future secondary education and baccalaureate level teachers, although there is a preference for heritage resources more linked to their undergraduate studies (History, History of Art, Archeology) compared with heritage resources of a technological nature. Regarding teaching approaches, it has been observed that those who present a student-based approach (CCSF) value heritage more highly. Given these results, we consider it necessary to improve the initial training of teachers regarding existing heritage resources and to adapt teaching approaches in order to achieve a greater integration of heritage in history education.