bluuebunny/crossref_metadata_2025 huggingface dataset:
Renalase peptides reduce pancreatitis severity in mice
Authors: Kolodecik Thomas R. , Guo Xiaoyu , Shugrue Christine A. , Guo Xiaojia , Desir Gary V. , Wen Li , Gorelick Fred
Published: July 2024

Renalase is a secretory protein. The prosurvival and anti-inflammatory effects of the whole molecule are contained in a 20 aa renalase site (RP220). Systemic treatment with peptides containing this renalase site reduced the severity of post-endoscopic retrograde cholangiopancreatography (ERCP) and severe cerulein pancreatitis in mouse models.
Meta‐Analysis: Characteristics of Retinal Vasculature in Obstructive Sleep Apnea Syndrome Humans
Authors: Ji Kaibao , Yang Yang , Zhang Qinglin , Xing Yiqiao , Wan Wei
Published: July 2024

Background. The objective of this study is to determine optic nerve head vascular changes in patients with obstructive sleep apnea‐hypopnea syndrome (OSAS) by utilizing an optical coherence tomography angiography (OCTA) device. Methods. A detailed studies search was screened in the PubMed, Embase, the Cochrane Library, and Web of Science databases from inception to August 2023. We reviewed and examined optic nerve head vascular density in eyes with OSAS and controls. The mean difference and 95% confidence interval were calculated to evaluate continuous outcomes. Review Manager version 5.4.1 was applied for analysing pooled data. Results. Six eligible studies were included in our meta‐analysis. The radial peripapillary capillary (RPC) whole enface vessel density (VD) measured by OCTA in the mild‐to‐moderate and severe OSAS groups was significantly lower compared to the controls (MD = −0.96, P = 0.03; MD = −1.42, P = 0.001, respectively). For RPC peripapillary VD, eyes in mild‐to‐moderate OSAS showed a trending decrease compared to the controls (MD = −1.71, P = 0.05), and there was a remarkable difference between eyes with severe OSAS and the controls (MD = −3.08, P = 0.004). In addition, the RPC inside disc VD was decreased in severe OSAS eyes than in the controls (MD = −0.07, P = 0.94). Conclusions. Our results revealed that peripapillary vascular density was attenuated in patients with OSAS. Moreover, on the basis of these findings, we suggest that optic nerve head vascular density measured by OCTA may be used as a potential tool to diagnose and monitor the severity of patients with OSAS.
Peripheral Injection of hUC‐MSCs in the Treatment of Acute Liver Failure: A Pre‐Clinical Cohort Study in Rhesus Monkeys
Authors: Zeng Yuting , Wu Zhenru , Chen Gen , Liu Guoqiang , Zhang Bo , Zhou Yongjie , Chen Menglin , Yao Rong , Shi Yujun
Published: July 2024

Background. Using a toxin‐induced lethal acute liver failure (ALF) monkey model, we have recently shown that early peripheral infusion of human umbilical cord mesenchymal stem cells (hUC‐MSCs) can alleviate liver damage and improve animal survival by suppressing the activation of circulating monocytes and the subsequent cytokine storm. Here, we explored whether the administration of hUC‐MSCs could still improve ALF when the cytokine storm is fully developed. Method. We treated ALF monkeys with peripheral delivery of hUC‐MSCs at 48 hr after toxin challenge. Liver indices, histology, imaging, and animal survival were recorded and analyzed. Results. In our cohort study, we conducted and demonstrated that the infusion of hUC‐MSCs significantly improved liver histology, effectively controlled inflammatory cytokine storms, and increased survival rates. Additionally, the administration of a higher dose of hUC‐MSCs (2 × 107/monkey) yielded superior outcomes compared to a lower dose (1 × 107/monkey). Conclusion. Treatment of hUC‐MSCs can significantly improve the pathological and survival outcomes of ALF even when the cytokine storm has been fully developed, indicating a promising clinical solution for ALF.
Characteristics of Leadership Competency in Nurse Managers: A Scoping Review
Authors: Perez-Gonzalez Silvia , Marques-Sanchez Pilar , Pinto-Carral Arrate , Gonzalez-Garcia Alberto , Liebana-Presa Cristina , Benavides Carmen
Published: July 2024

Aim. Identify the characteristics of leadership competency for the nurse manager and describe the most cited leadership styles in the literature. Background. Leadership is a fundamental competency for nurse managers, as it plays an important role in the healthcare environment to achieve Sustainable Development Goals and promote people‐centered organizations. Therefore, understanding the characteristics of leadership and the leadership style to be employed is important. Methods. A scoping review was conducted from January 2009 to January 2024 using the design of González Garcia et al., the Arksey and O’Malley framework, and databases including Web of Science, Scopus, and PubMed. Articles reporting on the characteristics of leadership for nurse managers were reviewed. The authors performed the review based on a search syntax, inclusion and exclusion criteria, and the data extraction process. Results. Sixty‐two studies were included in the final review. The review identified 38 characteristics related to leadership competency, among which we highlighted caring for nurses as individuals, being a visionary, knowledgeable, a change agent, and a communicator. This review highlights the prevalence of transformational leadership, which constitutes 69.57% of the leadership styles cited, and underscores its pivotal role in improving the work environment, effectiveness in nursing care, conflict management, team commitment, and adaptability to change within healthcare settings. Conclusions. The most commonly cited characteristics of leadership include caring for the team, effective communication, and a vision for change. Transformational, people‐centered, and motivational leadership is the most appropriate style. Implications for Nursing Management. The characterization of leadership competency will allow the development of training adapted to the current requirements for nursing leaders. This training could be developed in simulation and virtual reality environments. It also allows for a deeper understanding of how leadership competency affects teams and their functioning.
Infectivity and Potential Zoonotic Characteristics of Porcine Pseudorabies Virus in Human Cells
Authors: Li Xue , Li Nan , Zheng Jiawei , Lv Xinru , Han Yaqi , Zhang Huimin , Ren Ying , Yin Gefen , Ren Linzhu
Published: July 2024

Pseudorabies virus (PRV) is widely spread, characterized by high contagiousness, high viral load, and strong infectivity, and poses severe threats to the global pig farming industry. Apart from pigs, PRV can also infect several other mammals, including mice, cattle, cats, dogs, and wolves, with diverse clinical symptoms. Notably, approximately more than 20 cases of human PRV infection have been reported in recent years, with fever, seizures, human encephalitis, intraocular inflammation, and severe central nervous system symptoms. However, whether PRV can infect humans or belongs to a zoonotic virus is still controversial. In this study, human neuronal cells were infected with PRV and blindly passaged to obtain human cell‐adapted PRV, followed by comparing the characteristics of human cell‐adapted PRV and pig‐derived PRV in vitro and in vivo, to determine whether PRV has the potential to infect humans. The results showed that PRV could be stably passaged in human cells and produced progeny viruses similar to the parental virus, including morphology, infectivity, and pathogenicity. The human cell‐adapted PRV can also cross‐transmit to cells from other origins, including humans, mice, pigs, and monkeys, causing different cytopathic effects. Moreover, multiple tissue damage can be detected in mice infected with human cell‐adapted PRV. These results demonstrate that PRV is a potential zoonotic virus, and it is necessary to pay close attention to the spread and variation of the virus in animals and humans.
Efficacy of Different Pesticides against Fall Armyworm (Spodoptera frugiperda (J.E. Smith) Lepidoptera: Noctuidae) under Laboratory Conditions in Rupandehi, Nepal
Authors: Khanal Dipak , Subedi Dipesh , Banjade Gaurave , Lamichhane Manila , Shrestha Sapana , Chaudhary Prashant
Published: July 2024

The fall armyworm (FAW), Spodoptera frugiperda, is a highly destructive pest recently reported in various Asian countries and originated in the subtropical regions of America. It was first recorded in Nepal on May 9, 2019. This invasive species poses a significant threat to maize production because it can undergo multiple generations, migrate, and feed on a wide range of host plants. A laboratory study was conducted with 3 categories of pesticides: conventional, newer, and bio‐rational. The study focused on evaluating the efficacy of these pesticides on the third‐instar larvae of S. frugiperda. The treatments included (1) newer chemical pesticides: spinosad 45% suspension concentrate (SC) (Tracer 1 ml/3 L of water), spinetoram 11.7% SC (Delegate 0.5 ml/L of water), chlorantraniliprole 18.5% SC (Allcora 1 ml/2.5 L of water), emamectin benzoate 5.7% water dispersible granules (WDG) (top killer 1 g/2.5 L), (2) conventional pesticide: chlorpyrifos 50% EC (Predator 2 ml/L), and (3) bio‐rational pesticides: Bacillus thuringiensis var kurstaki 0.5% wettable powder (WP) (Maharashtra 2gm/L), Metarhizium anisopliae 1.0% WP (Kalichakra 5 ml/L), Beauveria bassiana 2% AS (DamanL 5 ml/L), Azadirachta indica 4.5% (Neemix 5 ml/L), Syzygium aromaticum 100% v/v (Kanti herbal Clove oil 3 ml/L), and spinosad 45% SC (Tracer 0.3 ml/L). Fresh maize leaves were treated using the leaf dip method and then fed to 3rd instar larvae of FAW. The results revealed that spinetoram and spinosad caused 100% larval mortality within the first 24 hours after treatment. Similarly, spinosad (99.99%) and clove oil (76.64%) were the most effective bio‐rational pesticides followed by B. bassiana and B. thuringiensis. The newer and bio‐rational pesticides that showed high efficacy could be suggested for further study in farmers’ fields. They could be recommended for testing as a component of integrated pest management for effective management of FAW in Nepal.
Clinical Experience with Dimethyl Fumarate and Natalizumab in Pregnant Women with Multiple Sclerosis: A Four‐Patient Case Series
Authors: Saito Satoshi , Ikeguchi Ryotaro , Kitagawa Kazuo , Shimizu Yuko
Published: July 2024

Interferon β and glatiramer acetate are the disease‐modifying drugs (DMDs) considered relatively safe for use in pregnant women with multiple sclerosis (MS); however, the safety profile of dimethyl fumarate (DMF) and natalizumab (NTZ) in this population remains inconclusive. Here, we present four cases of pregnant women with MS who were treated with DMF and NTZ (n = 2 patients, each) during their pregnancy and discuss our observations with the use of these drugs and the clinical courses of the patients. We retrospectively examined relapse of MS during pregnancy and after delivery; duration of exposure to DMDs; maternal, fetal, and neonatal adverse events; breastfeeding; and timing of resumption of DMDs. The two patients treated with DMF discontinued treatment 5 or 6 weeks after the discovery of pregnancy. DMF was resumed 1 week postpartum, and mixed breastfeeding was initiated. Brain magnetic resonance imaging in one patient 9 months after delivery revealed a new lesion; however, it was not classified as a clinical relapse. In two patients treated with NTZ, the dosing interval was extended to 6 weeks after the discovery of pregnancy. One patient discontinued NTZ at 30 weeks and the other at 25 weeks of gestation, as a slight restriction in fetal growth was observed owing to hyperemesis gravidarum. Both patients opted for formula feeding, and no relapse was observed within 1 year postpartum. Additionally, no abnormalities were observed in any of the patients during the perinatal period, and their development was normal. Investigation of drug safety in pregnant and parturient women primarily relies on registries, postmarketing surveillance, and case reports due to ethical limitations on conducting randomized controlled trials. Our findings demonstrated that DMF and NTZ were not contraindicated during pregnancy or the perinatal period in women with MS; nevertheless, vigilant monitoring is essential to ensure the safety of these drugs.
Galerkin Spectral Method of Stochastic Partial Differential Equations Driven by Multivariate Poisson Measure
Authors: Xie Hongling
Published: July 2024

A considerable body of prior research has been dedicated to devising efficient and high‐order numerical methods for solving stochastic partial differential equations (SPDEs) driven by discrete or continuous random variables. The majority of these efforts have concentrated on introducing numerical approaches for SPDEs involving independent random variables, with limited exploration into solving SPDEs driven by dependent and discrete random variables. In this paper, we introduce a Galerkin spectral method tailored for addressing SPDEs driven by multivariate Poisson variables. Our novel numerical method is applied to solve the one‐ and two‐dimensional stochastic Poisson equations, as well as the one and two‐dimensional stochastic heat equation, stochastic KdV equation, and stochastic Burgers equation, respectively. Notably, all the presented stochastic equations are governed by two dependent Poisson random variables.
Data from A Galaxy Implementation of Next-Generation Clustered Heatmaps for Interactive Exploration of Molecular Profiling Data
Authors: Broom Bradley M. , Ryan Michael C. , Brown Robert E. , Ikeda Futa , Stucky Mark , Kane David W. , Melott James , Wakefield Chris , Casasent Tod D. , Akbani Rehan , Weinstein John N.
Published: July 2024

Abstract
Clustered heatmaps are the most frequently used graphics for visualization of molecular profiling data in biology. However, they are generally rendered as static, or only modestly interactive, images. We have now used recent advances in web technologies to produce interactive “next-generation” clustered heatmaps (NG-CHM) that enable extreme zooming and navigation without loss of resolution. NG-CHMs also provide link-outs to additional information sources and include other features that facilitate deep exploration of the biology behind the image. Here, we describe an implementation of the NG-CHM system in the Galaxy bioinformatics platform. We illustrate the algorithm and available computational tool using RNA-seq data from The Cancer Genome Atlas program's Kidney Clear Cell Carcinoma project. Cancer Res; 77(21); e23–26. ©2017 AACR.
Interim Phase II Results Using Panitumumab-IRDye800CW during Transoral Robotic Surgery in Patients with Oropharyngeal Cancer
Authors: Stone Logan D. , Kasten Benjamin B. , Rao Shilpa , Gonzalez Manuel. L. , Stevens Todd M. , Lin Diana , Carroll William , Greene Benjamin , Moore Lindsay S. , Fuson Andrew , James Sherin , Hartman Yolanda E. , McCammon Susan , Panuganti Bharat , Nabell Lisle M. , Li Yufeng , Li Mei , Bailey Luke , Rosenthal Eben L. , Jeyarajan Harishanker , Thomas Carissa M. , Warram Jason M.
Published: July 2024

Purpose:

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence-guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but exhibit the greatest potential impact for improving patient care when the surgeon receives limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in patients with OPSCC.

Patients and Methods:

Twelve consecutive patients with OPSCC were enrolled as part of a nonrandomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology.

Results:

Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach.

Conclusions:

The results from this patient with OPSCC cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.
Supplementary Figure 2 from Noninvasive Lung Cancer Subtype Classification Using Tumor-Derived Signatures and cfDNA Methylome
Authors: Li Shuo , Li Wenyuan , Liu Bin , Krysan Kostyantyn , Dubinett Steven M.
Published: July 2024

Tumor copy number variations identified from 106 cfDNA samples for model training and cross-validation
Figure 2 from Noninvasive Lung Cancer Subtype Classification Using Tumor-Derived Signatures and cfDNA Methylome
Authors: Li Shuo , Li Wenyuan , Liu Bin , Krysan Kostyantyn , Dubinett Steven M.
Published: July 2024

Identification and validation of the subtype-specific methylation markers. A, Heatmap of the logarithm-scaled normalized read count at the markers in the tumor tissue RRBS data. For lung adenocarcinoma and LUSC, we selected the top 2,500 hypermethylation and hypomethylation regions using the fragment-based marker discovery method. The color in the heatmap represents the logarithm-scaled normalized count of the hypermethylated (hypomethylated) reads at the hypermethylation (hypomethylation) markers. B, Heatmap of the logarithm-scaled normalized read count at the markers in the independent tumor tissue RRBS data. C, Heatmap of the methylation levels at the markers in TCGA methylation data. Methylation levels were quantified as the average β value across all probes covered by a marker. D, Heatmap of the logarithm-scaled transcription level at the marker-associated genes in the TCGA RNA-seq data. A gene is marker-associated if its promoter has more than 50% overlap with a marker. Every row in the heatmap represents a marker-associated gene, and every column represents a patient with cancer. A transcription level was quantified as the TPM. E, Differential gene expression between lung adenocarcinoma and LUSC in TCGA RNA-seq data. The statistical significance of the genes was determined by the Benjamini–Hochberg adjusted P values at 0.05. The adjusted P values are shown in a negative logarithm (base 10) scale. F, The discriminative power of the whole marker set was evaluated using a 10-fold cross-validation on tumor tissues. The discriminative power was quantified as the ROC curve, shown as the bold black curve. The gray area represents the CI of the ROC curve. The AUC was calculated, and the corresponding 95% DeLong CI is shown in the parentheses.
Dysferlin Enables Tubular Membrane Proliferation in Cardiac Hypertrophy
Authors: Paulke Nora Josefine , Fleischhacker Carolin , Wegener Justus B. , Riedemann Gabriel C. , Cretu Constantin , Mushtaq Mufassra , Zaremba Nina , Möbius Wiebke , Zühlke Yannik , Wedemeyer Jasper , Liebmann Lorenz , Gorshkova Anastasiia A. , Kownatzki-Danger Daniel , Wagner Eva , Kohl Tobias , Wichmann Carolin , Jahn Olaf , Urlaub Henning , Toischer Karl , Hasenfuß Gerd , Moser Tobias , Preobraschenski Julia , Lenz Christof , Rog-Zielinska Eva A. , Lehnart Stephan E. , Brandenburg Sören
Published: July 2024

BACKGROUND:

Cardiac hypertrophy compensates for increased biomechanical stress of the heart induced by prevalent cardiovascular pathologies but can result in heart failure if left untreated. Here, we hypothesized that the membrane fusion and repair protein dysferlin is critical for the integrity of the transverse-axial tubule (TAT) network inside cardiomyocytes and contributes to the proliferation of TAT endomembranes during pressure overload–induced cardiac hypertrophy.

METHODS:

Stimulated emission depletion and electron microscopy were used to localize dysferlin in mouse and human cardiomyocytes. Data-independent acquisition mass spectrometry revealed the cardiac dysferlin interactome and proteomic changes of the heart in dysferlin-knockout mice. After transverse aortic constriction, we compared the hypertrophic response of wild-type versus dysferlin-knockout hearts and studied TAT network remodeling mechanisms inside cardiomyocytes by live-cell membrane imaging.

RESULTS:

We localized dysferlin in a vesicular compartment in nanometric proximity to contact sites of the TAT network with the sarcoplasmic reticulum, a.k.a. junctional complexes for Ca
2+
-induced Ca
2+
release. Interactome analyses demonstrated a novel protein interaction of dysferlin with the membrane-tethering sarcoplasmic reticulum protein juncophilin-2, a putative interactor of L-type Ca
2+
channels and ryanodine receptor Ca
2+
release channels in junctional complexes. Although the dysferlin-knockout caused a mild progressive phenotype of dilated cardiomyopathy, global proteome analysis revealed changes preceding systolic failure. Following transverse aortic constriction, dysferlin protein expression was significantly increased in hypertrophied wild-type myocardium, while dysferlin-knockout animals presented markedly reduced left-ventricular hypertrophy. Live-cell membrane imaging showed a profound reorganization of the TAT network in wild-type left-ventricular myocytes after transverse aortic constriction with robust proliferation of axial tubules, which critically depended on the increased expression of dysferlin within newly emerging tubule components.

CONCLUSIONS:

Dysferlin represents a new molecular target in cardiac disease that protects the integrity of tubule-sarcoplasmic reticulum junctional complexes for regulated excitation-contraction coupling and controls TAT network reorganization and tubular membrane proliferation in cardiomyocyte hypertrophy induced by pressure overload.
Glucagon Receptor Antagonist for Heart Failure With Preserved Ejection Fraction
Authors: Gao Chen , Xiong Zhaojun , Liu Yunxia , Wang Meng , Wang Menglong , Liu Tian , Liu Jianfang , Ren Shuxun , Cao Nancy , Yan Hai , Drucker Daniel J. , Rau Christoph Daniel , Yokota Tomohiro , Huang Jijun , Wang Yibin
Published: July 2024

BACKGROUND:

Heart failure with preserved ejection fraction (HFpEF) is an emerging major unmet need and one of the most significant clinic challenges in cardiology. The pathogenesis of HFpEF is associated with multiple risk factors. Hypertension and metabolic disorders associated with obesity are the 2 most prominent comorbidities observed in patients with HFpEF. Although hypertension-induced mechanical overload has long been recognized as a potent contributor to heart failure with reduced ejection fraction, the synergistic interaction between mechanical overload and metabolic disorders in the pathogenesis of HFpEF remains poorly characterized.

METHOD:

We investigated the functional outcome and the underlying mechanisms from concurrent mechanic and metabolic stresses in the heart by applying transverse aortic constriction in lean C57Bl/6J or obese/diabetic B6.Cg-Lep
ob
/J (ob/ob) mice, followed by single-nuclei RNA-seq and targeted manipulation of a top-ranked signaling pathway differentially affected in the 2 experimental cohorts.

RESULTS:

In contrast to the post-transverse aortic constriction C57Bl/6J lean mice, which developed pathological features of heart failure with reduced ejection fraction over time, the post-transverse aortic constriction ob/ob mice showed no significant changes in ejection fraction but developed characteristic pathological features of HFpEF, including diastolic dysfunction, worsened cardiac hypertrophy, and pathological remodeling, along with further deterioration of exercise intolerance. Single-nuclei RNA-seq analysis revealed significant transcriptome reprogramming in the cardiomyocytes stressed by both pressure overload and obesity/diabetes, markedly distinct from the cardiomyocytes singularly stressed by pressure overload or obesity/diabetes. Furthermore, glucagon signaling was identified as the top-ranked signaling pathway affected in the cardiomyocytes associated with HFpEF. Treatment with a glucagon receptor antagonist significantly ameliorated the progression of HFpEF-related pathological features in 2 independent preclinical models. Importantly, cardiomyocyte-specific genetic deletion of the glucagon receptor also significantly improved cardiac function in response to pressure overload and metabolic stress.

CONCLUSIONS:

These findings identify glucagon receptor signaling in cardiomyocytes as a critical determinant of HFpEF progression and provide proof-of-concept support for glucagon receptor antagonism as a potential therapy for the disease.
Asymptomatic Intracranial Artery Stenosis/Occlusion in Heterozygous Familial Hypercholesterolemia: Its Frequency and Implications for Cerebrovascular and Cardiovascular Events
Authors: Funabashi Sayaka , Kataoka Yu , Hori Mika , Ogura Masatsune , Doi Takahito , Morita Yoshiaki , Kiyoshige Eri , Nishimura Kunihiro , Noguchi Teruo , Harada‐Shiba Mariko
Published: July 2024

Background

The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH.

Methods and Results

This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging/magnetic resonance angiography imaging for evaluation of IASO (≥50% diameter stenosis). Major adverse cerebrovascular and cardiovascular events (cardiac death, ischemic stroke, and acute coronary syndrome) were compared in patients with HeFH with and without asymptomatic IASO. Asymptomatic IASO was observed in 13.6% of patients with HeFH. The untreated low‐density lipoprotein cholesterol level (240±95 versus 244±75 mg/dL;
P
=0.67) did not differ between the 2 groups. Despite the use of lipid‐lowering therapies (statin,
P
=0.71; high‐intensity statin,
P
=0.81; ezetimibe,
P
=0.33; proprotein convertase subxilisin/kexin type 9 inhibitor,
P
=0.39; low‐density lipoprotein apheresis,
P
=0.14), on‐treatment low‐density lipoprotein cholesterol level in patients with both HeFH and IASO was still suboptimally controlled (97±62 versus 105±50 mg/dL;
P
=0.17), accompanied by a higher triglyceride level (median, 109 versus 79 mg/dL;
P
=0.001). During the 12.4‐year observational period (interquartile range, 6.2–24.6 years), asymptomatic IASO exhibited a 4.04‐fold greater likelihood of experiencing a major adverse cardiovascular event (95% CI, 1.71–9.55;
P
=0.001) in patients with HeFH. This increased risk of a major adverse cardiovascular event was consistently observed in a multivariate Cox proportional hazards model adjusting clinical characteristics (hazard ratio, 4.32 [95% CI, 1.71–10.9];
P
=0.002).

Conclusions

A total of 13.6% of Japanese subjects with HeFH presented with asymptomatic IASO. Despite lipid‐lowering therapies, patients with both HeFH and IASO more likely had elevated risk of cerebrovascular and cardiovascular events. Our findings highlight asymptomatic IASO as a phenotypic feature of HeFH‐related atherosclerosis, which ultimately affects future outcomes.
Tropical Cyclones in the GEOS-S2S-2 Subseasonal Forecasts
Authors: García-Franco Jorge L. , Lee Chia-Ying , Camargo Suzana J. , Tippett Michael K. , Emlaw Geraldine N. , Kim Daehyun , Lim Young-Kwon , Molod Andrea
Published: July 2024

This paper analyzes the climatology, prediction skill, and predictability of tropical cyclones (TCs) in NASA’s Goddard Earth Observing System Subseasonal to Seasonal (GEOS-S2S) forecast system version 2. GEOS reasonably simulates the number and spatial distribution of TCs compared to observations except in the Atlantic where the model simulates too few TCs due to low genesis rates in the Caribbean Sea and Gulf of Mexico. The environmental conditions, diagnosed through a genesis potential index, do not clearly explain model biases in the genesis rates, especially in the Atlantic. At the storm scale, GEOS reforecasts replicate several key aspects of the thermodynamic and dynamic structures of observed TCs, such as a warm core and the secondary circulation. The model, however, fails to simulate an off-center eyewall when evaluating vertical velocity, precipitation, and moisture. The analysis of the prediction skill of TC genesis and occurrence shows that GEOS has comparable skill to other global models in WMO S2S archive and that its skill could be further improved by increasing the ensemble size. After calibration, GEOS forecasts are skillful in the western North Pacific and southern Indian Ocean up to 20 days in advance. A model-based predictability analysis demonstrates the importance of the Madden–Julian oscillation (MJO) as a source of predictability of TC occurrence beyond the 14-day lead time. Forecasts initialized under strong MJO conditions show evidence of predictability beyond week 3. However, due to model biases in the forecast distribution, there are notable gaps between the MJO-related prediction skill and predictability, which require further study.
Inhibition of 2-AG hydrolysis alleviates posttraumatic headache attributed to mild traumatic brain injury
Authors: Wen Jie , Tanaka Mikiei , Zhang Yumin
Published: July 2024

Background

Posttraumatic headache (PTH) is a common and debilitating symptom following repetitive mild traumatic brain injury (rmTBI), and it mainly resembles a migraine-like phenotype. While modulation of the endocannabinoid system (ECS) is effective in treating TBI and various types of pain including migraine, the role of augmentation of endocannabinoids in treating PTH has not been investigated.

Methods

Repetitive mild TBI was induced in male C57BL/6J mice using the non-invasive close-head impact model of engineered rotational acceleration (CHIMERA). Periorbital allodynia was assessed using von Frey filaments and determined by the “Up-Down” method. Immunofluorescence staining was employed to investigate glial cell activation and calcitonin gene-related peptide (CGRP) expression in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) of the rmTBI mice. Levels of 2-arachidonoyl glycerol (2-AG), anandamide (AEA), and arachidonic acid (AA) in the TG, medulla (including TNC), and periaqueductal gray (PAG) were measured by mass spectrometry. The therapeutic effect of endocannabinoid modulation on PTH was also assessed.

Results

The rmTBI mice exhibited significantly increased cephalic pain hypersensitivity compared to the sham controls. MJN110, a potent and selective inhibitor of the 2-AG hydrolytic enzyme monoacylglycerol lipase (MAGL), dose-dependently attenuated periorbital allodynia in the rmTBI animals. Administration of CGRP at 0.01 mg/kg reinstated periorbital allodynia in the rmTBI animals on days 33 and 45 post-injury but had no effect in the sham and MJN110 treatment groups. Activation of glial cells along with increased production of CGRP in the TG and TNC at 7 and 14 days post-rmTBI were attenuated by MJN110 treatment. The anti-inflammatory and anti-nociceptive effects of MJN110 were partially mediated by cannabinoid receptor activation, and the pain-suppressive effect of MJN110 was completely blocked by co-administration of DO34, an inhibitor of 2-AG synthase. The levels of 2-AG in TG, TNC and PAG were decreased in TBI animals, significantly elevated and further reduced by the selective inhibitors of 2-AG hydrolytic and synthetic enzymes, respectively.

Conclusion

Enhancing endogenous levels of 2-AG appears to be an effective strategy for the treatment of PTH by attenuating pain initiation and transmission in the trigeminal pathway and facilitating descending pain inhibitory modulation.
The interactive effects of different exercises and hawthorn consumption on the pain threshold of TMT-induced Alzheimer male rats
Authors: Almasi Ensiyeh , Heidarianpour Ali , Keshvari Maryam
Published: July 2024

Exercise increases the pain threshold in healthy people. However, the pain threshold modulation effect of exercise and hawthorn is unclear because of its potential benefits in people with persistent pain, including those with Alzheimer's disease. Accordingly, after the induction of Alzheimer's disease by trimethyl chloride, male rats with Alzheimer's disease were subjected to a 12-week training regimen consisting of resistance training, swimming endurance exercises, and combined exercises. In addition, hawthorn extract was orally administered to the rats. Then, their pain threshold was evaluated using three Tail-flick, Hot-plate, and Formalin tests. Our results showed that Alzheimer's decreased the pain threshold in all three behavioral tests. Combined exercise with hawthorn consumption had the most statistically significant effect on Alzheimer's male rats' pain threshold in all three experiments. A combination of swimming endurance and resistance exercises with hawthorn consumption may modulate hyperalgesia in Alzheimer's rats. Future studies need to determine the effects of these factors on the treatment and/or management of painful conditions.

Graphical Abstract
PyChelator: a Python-based Colab and web application for metal chelator calculations
Authors: Spahiu Emrulla , Kastrati Esra , Amrute-Nayak Mamta
Published: July 2024

Background

Metal ions play vital roles in regulating various biological systems, making it essential to control the concentration of free metal ions in solutions during experimental procedures. Several software applications exist for estimating the concentration of free metals in the presence of chelators, with MaxChelator being the easily accessible choice in this domain. This work aimed at developing a Python version of the software with arbitrary precision calculations, extensive new features, and a user-friendly interface to calculate the free metal ions.

Results

We introduce the open-source PyChelator web application and the Python-based Google Colaboratory notebook, PyChelator Colab. Key features aim to improve the user experience of metal chelator calculations including input in smaller units, selection among stability constants, input of user-defined constants, and convenient download of all results in Excel format. These features were implemented in Python language by employing Google Colab, facilitating the incorporation of the calculator into other Python-based pipelines and inviting the contributions from the community of Python-using scientists for further enhancements. Arbitrary-precision arithmetic was employed by using the built-in Decimal module to obtain the most accurate results and to avoid rounding errors. No notable differences were observed compared to the results obtained from the PyChelator web application. However, comparison of different sources of stability constants showed substantial differences among them.

Conclusions

PyChelator is a user-friendly metal and chelator calculator that provides a platform for further development. It is provided as an interactive web application, freely available for use at https://amrutelab.github.io/PyChelator, and as a Python-based Google Colaboratory notebook at https://colab.research.google.com/github/AmruteLab/PyChelator/blob/main/PyChelator_Colab.ipynb.
AFITbin: a metagenomic contig binning method using aggregate l-mer frequency based on initial and terminal nucleotides
Authors: Darabi Amin , Sobhani Sayeh , Aghdam Rosa , Eslahchi Changiz
Published: July 2024

Background

Using next-generation sequencing technologies, scientists can sequence complex microbial communities directly from the environment. Significant insights into the structure, diversity, and ecology of microbial communities have resulted from the study of metagenomics. The assembly of reads into longer contigs, which are then binned into groups of contigs that correspond to different species in the metagenomic sample, is a crucial step in the analysis of metagenomics. It is necessary to organize these contigs into operational taxonomic units (OTUs) for further taxonomic profiling and functional analysis. For binning, which is synonymous with the clustering of OTUs, the tetra-nucleotide frequency (TNF) is typically utilized as a compositional feature for each OTU.

Results

In this paper, we present AFIT, a new l-mer statistic vector for each contig, and AFITBin, a novel method for metagenomic binning based on AFIT and a matrix factorization method. To evaluate the performance of the AFIT vector, the t-SNE algorithm is used to compare species clustering based on AFIT and TNF information. In addition, the efficacy of AFITBin is demonstrated on both simulated and real datasets in comparison to state-of-the-art binning methods such as MetaBAT 2, MaxBin 2.0, CONCOT, MetaCon, SolidBin, BusyBee Web, and MetaBinner. To further analyze the performance of the purposed AFIT vector, we compare the barcodes of the AFIT vector and the TNF vector.

Conclusion

The results demonstrate that AFITBin shows superior performance in taxonomic identification compared to existing methods, leveraging the AFIT vector for improved results in metagenomic binning. This approach holds promise for advancing the analysis of metagenomic data, providing more reliable insights into microbial community composition and function.

Availability

A python package is available at: https://github.com/SayehSobhani/AFITBin.
Effective population size in field pea
Authors: Johnson Josephine Princy , Piche Lisa , Worral Hannah , Atanda Sikiru Adeniyi , Coyne Clarice J. , McGee Rebecca J. , McPhee Kevin , Bandillo Nonoy
Published: July 2024

Background

Effective population size (Ne) is a pivotal parameter in population genetics as it can provide information on the rate of inbreeding and the contemporary status of genetic diversity in breeding populations. The population with smaller Ne can lead to faster inbreeding, with little potential for genetic gain making selections ineffective. The importance of Ne has become increasingly recognized in plant breeding, which can help breeders monitor and enhance the genetic variability or redesign their selection protocols. Here, we present the first Ne estimates based on linkage disequilibrium (LD) in the pea genome.

Results

We calculated and compared Ne using SNP markers from North Dakota State University (NDSU) modern breeding lines and United States Department of Agriculture (USDA) diversity panel. The extent of LD was highly variable not only between populations but also among different regions and chromosomes of the genome. Overall, NDSU had a higher and longer-range LD than the USDA that could extend up to 500 Kb, with a genome-wide average r2 of 0.57 (vs 0.34), likely due to its lower recombination rates and the selection background. The estimated Ne for the USDA was nearly three-fold higher (Ne = 174) than NDSU (Ne = 64), which can be confounded by a high degree of population structure due to the selfing nature of pea.

Conclusions

Our results provided insights into the genetic diversity of the germplasm studied, which can guide plant breeders to actively monitor Ne in successive cycles of breeding to sustain viability of the breeding efforts in the long term.
Preoperative psychological factors influence analgesic consumption and self-reported pain intensity following breast cancer surgery
Authors: Masaud Khaled , Galvin Audrey Dunn , De Loughry Gillian , Meachair Aisling O. , Galea Sarah , Shorten George
Published: July 2024

Background

Psychological factors such as anxiety and mood appear to influence acute postoperative pain; however, there is conflicting evidence on the relationship between preoperative psychological parameters and the severity of postoperative pain. In the context of the stressful setting of initial surgery for breast cancer, we conducted a prospective observational study of patients who were scheduled to undergo initial breast cancer surgery.

Methods

The objectives were to examine the potential associations between predefined preoperative psychological parameters and (i) Self-reported pain scores at discharge from the postoperative acute care unit, (ii) Cumulative perioperative opioid consumption at four hours postoperatively and (iii) Self-reported pain as measured during the first seven days after surgery. Patients completed the following questionnaires during the three hours prior to surgery: the Spielberger State Trait Anxiety Inventory (STAI State and Trait), the Pain Catastrophizing Scale (PCS), the Cohen Stress Questionnaire (CSQ), the Hospital Anxiety and Depression Scale (HADS A and D), and the short-form McGill Pain Questionnaire. Postoperative pain experience was assessed using patient self-reports of pain (SF Magill Pain questionnaire on discharge from the postanaesthesia care unit and a pain diary for seven days postoperatively) and records of analgesic consumption.

Results

Pre- to postoperative self-reported pain was significantly different with respect to the STAI State, Cohen score and PCS for both low and high values (p < 0.001), but only patients categorized as having low STAI Trait, HADS A, and HADS D values achieved significant differences (p < 0.001). A significant positive correlation was demonstrated between preoperative state anxiety (STAI) and the most severe pain reported during the first seven days postoperatively (r = 0.271, p = 0.013). Patients who were categorized preoperatively as having a “high value” for each of the psychological parameters studied (HADS A and D, STAI State and Trait and PCS) tended to have greater perioperative opioid consumption (up to four hours postoperatively); this trend was statistically significant for HADS D and HADS A only. Using a linear regression model, state anxiety was found to be a significant predictor of postoperative pain based on self-reports during the first seven postoperative days (standardized β = 0.271, t = 2.286, p = 0.025).

Conclusion

Preoperative state anxiety, in particular, is associated with the severity of postoperative pain experienced by women undergoing initial breast cancer surgery. Formal preoperative assessment of anxiety may be warranted in this setting with a view to optimize perioperative analgesia and wellbeing.
M1 macrophage-derived exosomes inhibit cardiomyocyte proliferation through delivering miR-155
Authors: He Xiaoqing , Liu Shan , Zhang Zhanyu , Liu Qirui , Dong Juan , Lin Zhifeng , Chen Junhao , Li Lihuan , Liu Weihua , Liu Shaojun , Liu Shiming
Published: July 2024

Background

M1 macrophages are closely associated with cardiac injury after myocardial infarction (MI). Increasing evidence shows that exosomes play a key role in pathophysiological regulation after MI, but the role of M1 macrophage-derived exosomes (M1-Exos) in myocardial regeneration remains unclear. In this study, we explored the impact of M1 macrophage-derived exosomes on cardiomyocytes regeneration in vitro and in vivo.

Methods

M0 macrophages were induced to differentiate into M1 macrophages with GM-CSF (50 ng/mL) and IFN-γ (20 ng/mL). Then M1-Exos were isolated and co-incubated with cardiomyocytes. Cardiomyocyte proliferation was detected by pH3 or ki67 staining. Quantitative real-time PCR (qPCR) was used to test the level of miR-155 in macrophages, macrophage-derived exosomes and exosome-treated cardiomyocytes. MI model was constructed and LV-miR-155 was injected around the infarct area, the proliferation of cardiomyocytes was counted by pH3 or ki67 staining. The downstream gene and pathway of miR-155 were predicted and verified by dual-luciferase reporter gene assay, qPCR and immunoblotting analysis. IL-6 (50 ng/mL) was added to cardiomyocytes transfected with miR-155 mimics, and the proliferation of cardiomyocytes was calculated by immunofluorescence. The protein expressions of IL-6R, p-JAK2 and p-STAT3 were detected by Western blot.

Results

The results showed that M1-Exos suppressed cardiomyocytes proliferation. Meanwhile, miR-155 was highly expressed in M1-Exos and transferred to cardiomyocytes. miR-155 inhibited the proliferation of cardiomyocytes and antagonized the pro-proliferation effect of interleukin 6 (IL-6). Furthermore, miR-155 targeted gene IL-6 receptor (IL-6R) and inhibited the Janus kinase 2(JAK)/Signal transducer and activator of transcription (STAT3) signaling pathway.

Conclusion

M1-Exos inhibited cardiomyocyte proliferation by delivering miR-155 and inhibiting the IL-6R/JAK/STAT3 signaling pathway. This study provided new insight and potential treatment strategy for the regulation of myocardial regeneration and cardiac repair by macrophages.
Gender differences in presentation, management, and outcomes among Egyptian patients with acute coronary syndrome: a single-centre registry
Authors: Elbarbary Mohammed , Shalaby Hazem K. , Elshokafy Salma M. , Khalil Mohamed A.
Published: July 2024

Background

Despite a significant rise in cardiovascular disease (CVD)-related mortality in low- and middle-income countries (LMICs), data are scarce regarding the quality of care provided, particularly for women.

Methods

This is a prospective observational, cross-sectional study. Acute coronary syndrome (ACS) patients presented to the Cardiology Department at Tanta University, Egypt, between September 1, 2023, and December 31, 2023, were enrolled. The study assessed gender disparities by comparing men and women regarding presentation, management, and major adverse cardiovascular events (MACE) occurrence during hospitalization and 30 days after discharge.

Results

A total of 400 ACS patients were included, with 29.5% being women. Women were comparatively older (59 ± 9 years vs. 55 ± 13 years), with a significantly higher prevalence of hypertension (70.3% vs. 47.5%) and diabetes (55% vs. 36.8%). Non-ST-segment elevation myocardial infarction (Non-STEMI) was more common in women (35.29% vs. 21%). Dyspnea was expressed by 34.4% of women (vs. 21.35% of men). Women were hospitalized later (9.29 h vs. 6.74 h). In-hospital outcomes were poorer for women with worse NYHA classes III and IV. Additionally, the odds ratio (OR) for in-hospital cardiac mortality was 0.303 (95% CI 0.103–0.893) for women compared to men. However, a one-month follow-up for MACE post-hospital discharge did not indicate significant gender differences.

Conclusions

The current study suggests that women with ACS in Egypt exhibit a higher risk profile for CVD compared to men and tend to present later with atypical symptoms. Women additionally experience poorer in-hospital MACE and higher cardiac mortality. Therefore, increasing awareness about ACS syndrome and eliminating obstacles that delay hospital admission are imperative.