bluuebunny/crossref_metadata_2025 huggingface dataset:
Human alveolar macrophage response to Mycobacterium tuberculosis: immune characteristics underlying large inter-individual variability
Authors: Sadee Wolfgang , Cheeseman Ian H. , Papp Audrey , Pietrzak Maciej , Seweryn Michal , Zhou Xiaofei , Lin Shili , Williams Amanda M. , Wewers Mark D. , Curry Heather M. , Zhang Hao , Cai Hong , Kunsevi-Kilola Carine , Tshivhula Happy , Walzl Gerhard , Restrepo Blanca I. , Kleynhans Léanie , Ronacher Katharina , Wang Yufeng , Arnett Eusondia , Azad Abul K. , Schlesinger Larry S.
Published: June 2023

Background: Mycobacterium tuberculosis (M.tb), the causative bacterium of tuberculosis (TB), establishes residence and grows in human alveolar macrophages (AMs). Inter-individual variation in M.tb-human AM interactions can indicate TB risk and the efficacy of therapies and vaccines; however, we currently lack an understanding of the gene and protein expression programs that dictate this variation in the lungs.
Results: Herein, we systematically analyze interactions of a virulent M.tb strain H37Rv with freshly isolated human AMs from 28 healthy adult donors, measuring host RNA expression and secreted candidate proteins associated with TB pathogenesis over 72h. A large set of genes possessing highly variable inter-individual expression levels are differentially expressed in response to M.tb infection. Eigengene modules link M.tb growth rate with host transcriptional and protein profiles at 24 and 72h. Systems analysis of differential RNA and protein expression identifies a robust network with IL1B, STAT1, and IDO1 as hub genes associated with M.tb growth. RNA time profiles document stimulation towards an M1-type macrophage gene expression followed by emergence of an M2-type profile. Finally, we replicate these results in a cohort from a TB-endemic region, finding a substantial portion of significant differentially expressed genes overlapping between studies.
Conclusions: We observe large inter-individual differences in bacterial uptake and growth, with tenfold variation in M.tb load by 72h.The fine-scale resolution of this work enables the identification of genes and gene networks associated with early M.tb growth dynamics in defined donor clusters, an important step in developing potential biological indicators of individual susceptibility to M.tb infection and response to therapies.
Loss of mitochondrial adaptation associates with deterioration of mitochondrial turnover and structure in obesity-related fatty liver disease
Authors: Sarabhai Theresia , Kahl Sabine , Gancheva Sofiya , Mastrototaro Lucia , Dewidar Bedair , Pesta Dominik , Ratter-Rieck Jacqueline M. , Bobrov Pavel , Jeruschke Kay , Schlensak Matthias , Roden Michael
Published: June 2023

Background Obesity and type 2 diabetes feature higher prevalence of non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH). In obesity-related insulin resistance, the liver may adapt its oxidative capacity, but the role of mitochondrial turnover in progressive NAFL/NASH remains uncertain.
Methods This cross-sectional study compared individuals with class III obesity (n=8/group) and with NAFL (OBE NAFL, NAFLD activity score: 2.3±0.4), NASH (OBE NASH, 5.3±0.3, p<0.05 vs. both other groups) or without fatty liver (control, OBE CON; 0.4±0.1). Hepatic mitochondrial ultrastructure was assessed by transmission electron microscopy, mitochondrial respiration by high-resolution respirometry and biomarkers of mitochondrial quality control by protein expression.
Results Mitochondrial oxidative capacity was 31% higher in OBE NAFL, but 25% lower in OBE NASH (both p<0.05 vs. OBE CON). Conversely, OBE NASH showed ~1.5fold lower mitochondrial number, but ~1.2-1.5fold higher mitochondrial diameter and area (p<0.001 vs. both other groups). Biomarkers of autophagy (p62), mitophagy (PINK1, PARKIN), fission (DRP-1, FIS1) and fusion (MFN1/2, OPA1) were reduced in OBE NASH (p<0.05 vs. OBE NAFL). Selected biomarkers (p62, p-PARKIN/PARKIN, p-DRP-1) were lower in OBE NAFL (p<0.05 vs. OBE CON). Mitochondrial diameter associated inversely with fusion and fission biomarkers and with oxidative capacity, but positively with H2O2.
Conclusion Humans with NAFL exhibit impaired mitochondrial turnover, despite upregulated oxidative capacity. In NASH, oxidative stress likely mediates the progressive decline of mitochondrial turnover along with impaired mitochondrial ultrastructure and respiration. Thus, mitochondrial quality control is key for hepatic energy metabolism and may have potential for targeting obesity-related NASH.
Research on surface plasmon resonance Sensing of metal nano hollow elliptic cylinder
Authors: Zhu Dandan , kang lixixn , Tong Kai , Yu Shancheng , Chai JinGuo , Wang Zhengtai , Xu LuLu , Ren Yuxuan
Published: June 2023

In this article, a new three-dimensional multi-layered nanoscale elliptical cylinder structure-based surface plasmon resonance sensor is designed, which utilizes the finite difference time domain method and FDTD simulation software for numerical simulation. The top of the structure is an elliptical cylinder array attached to a gold film with nanoholes. The middle layer is a dielectric layer, which can restrict the electromagnetic field. The bottom layer is an Au film and Si substrate. Surface plasmon resonance is excited by a vertically incident plane wave structure, and the incident electromagnetic wave is coupled to local surface plasmon through gold nanoscale elliptical cylinders. By adjusting the relevant structural parameters, the structure's resonance wavelength and resonance depth can be well adjusted. The optimized sensing structure has a smaller half-width than the traditional solid elliptical cylinder, higher sensitivity, and a larger quality factor. This structure can detect refractive indices in both gaseous and liquid environments, overcome the disadvantage of only being able to sense in a single environment, and provide a new approach for surface plasmon resonance sensing in biology and chemistry.
Brazilian pine seeds (Araucaria angustifolia): a source of oligosaccharides and resistant starch
Authors: de Godoy Rossana Catie Bueno , Nadolny Jaqueline Moura , Ferreira Celia Lucia de Luces Fortes , Leonel Magali
Published: June 2023

The authors have requested that this preprint be removed from Research Square.
Advancing Precipitation across the United States through Multi-decadal Convection-Permitting Simulations
Authors: Akinsanola Afolayan Akinsanola , Jung Chunyong , Wang Jiali , Kotamarthi Veerabhadra Rao
Published: June 2023

Climate simulations at convection-permitting (CP) spatial resolution could offer an improved representation of precipitation. To fully assess the benefits of CP simulations, we need multi-decadal simulations at global and regional scales. This first-in-class study presents results from 20-year simulations using the Weather Research and Forecasting model at the CP scale (ADDA_V2), covering a large domain covering North America and up to Puerto Rico. We evaluated ADDA_V2’s performance in capturing mean and extreme precipitation across the contiguous United States (CONUS). ADDA_V2 can capture the spatial variability and statistics of the mean and extreme precipitation over most of the CONUS. Particularly compared with the reanalysis data, ADDA_V2 exhibits superior performance in orographic-induced (mesoscale-convection-induced) winter (summer) precipitation, adding significant value to more than 40% of the grids in the CONUS. ADDA_V2 clearly improves the representation of diurnal precipitation patterns, the 95th percentile of daily precipitation, consecutive dry days, maximum 5-day precipitation, and very heavy precipitation across all seasons due to improved representation of orographic effects east of the Rocky Mountains and tropical systems in the Southeast. These results provide an incentive for using these simulations for robust assessments of future climate change impacts at regional and local scales.
Decreased Local Specialization of Brain Structural Networks Associated with Cognitive Dysfuntion Revealed by Probabilistic Diffusion Tractography for Different Cerebral Small Vessel Disease Burdens
Authors: Feng Mengmeng , Hongwei Hongwei , Haotian Xin , Wang Shengpei , Gao Yian , Sui Chaofan , Liang Changhu , Guo Lingfei
Published: June 2023

Objective To reveal the network-level structural disruptions associated with cognitive dysfunctions in different cerebral small vessel disease (CSVD) burdens. Materials and Methods Probabilistic diffusion tractography and graph theory were used to investigate the brain network topology in 67 patients with a severe CSVD burden (CSVD-s), 133 patients with a mild CSVD burden (CSVD-m) and 89 healthy controls. We used one-way analysis of covariance to assess the altered topological measures between groups, and then evaluated their Pearson correlation with cognitive parameters. Results Both the CSVD and control groups showed efficient small-world organization in white matter (WM) networks. However, compared with CSVD-m patients and controls, CSVD-s patients exhibited significantly decreased local efficiency, with partially reorganized hub distributions. For regional topology, CSVD-s patients showed significantly decreased nodal efficiency in the bilateral anterior cingulate gyrus, caudate nucleus, right opercular inferior frontal gyrus (IFGoperc), supplementary motor area (SMA), insula and left orbital superior frontal gyrus and angular gyrus. Intriguingly, global/local efficiency and nodal efficiency of the bilateral caudate nucleus, right IFGoperc, SMA and left angular gyrus showed significant correlations with cognitive parameters in the CSVD-s group, while only the left pallidum showed significant correlations with cognitive metrics in the CSVD-m group. Conclusions The decreased local specialization of brain structural networks in patients with different CSVD burdens provides novel insights into understanding the brain structural alterations in relation to CSVD severity. Cognitive correlations with brain structural network efficiency suggest their potential use as neuroimaging biomarkers to assess the severity of CSVD.
Effects of green light-emitting diode irradiation on hepatic differentiation of hepatocyte-like cells generated from human adipose-derived mesenchymal cells
Authors: Waki Yuhei , Saito Yu , Chen Shuhai , Ikemoto Tetsuya , Noma Takayuki , Teraoku Hiroki , Yamada Shinichiro , Morine Yuji , Shimada Mitsuo
Published: June 2023

Background
Light-emitting diode (LED) irradiation has been used in the differentiation of mesenchymal stem cells into a variety of cell types. This study investigated the effect of green LED (GLED) irradiation on the differentiation of adipocyte-derived mesenchymal cells into hepatocyte-like cells (HLCs) and the mechanism of its action.
Methods
HLCs in the hepatocyte maturation phase were irradiated with GLED (520 nm, 21 W/m2, 5 min/day for 10 days). The cells were then assessed for expression of hepatocyte maturity genes and opsin 3 (OPN3), hepatocyte function, viability, apoptosis, and levels of reactive oxygen species (ROS), intracellular adenosine triphosphate (ATP) and calcium ions (Ca2+).
Results
GLED irradiation increased Alpha-1 antitrypsin and Ornithine transcarbamylase gene expression, promoted Cytochrome P450 3A4 activity and urea synthesis, and elevated intracellular ROS, ATP and Ca2+ levels. OPN3 expression was significantly more upregulated in GLED-irradiated HLCs than in the non-irradiated HLCs. No significant difference in cell viability or apoptosis was observed between GLED-irradiated and non-irradiated HLCs.
Conclusions
GLED irradiation can promote hepatocyte maturation and functions through OPN3. GLED irradiation also stimulated mitochondrial function via Ca2+/ATP/ROS activation. GLED irradiation has potential to support cell-based transplantation in patients.
Sex-specific effects of obesity on aortic inflammation and dysfunction
Authors: Tran Vivian , Brettle Holly , Diep Henry , Dinh Quynh Nhu , O’Keeffe Maeve , Fanson Kerry V , Sobey Christopher G , Lim Kyungjoon , Drummond Grant R , Vinh Antony , Jelinic Maria
Published: June 2023

Obesity and vascular dysfunction are independent and sexually dimorphic risk factors for cardiovascular disease. Sex-specific changes in aortic immune cell profile and vascular function were characterized in a high fat diet (HFD)-induced model of early obesity. Six-week-old male and female C57BL/6 mice were fed a normal chow diet (NCD) or HFD for ten weeks. Metabolic parameters were measured weekly and fortnightly. At end point, aortic immune cell populations and endothelial function were characterized using flow cytometry and wire myography. HFD-male mice had higher bodyweight, blood cholesterol, fasting blood glucose and plasma insulin levels than NCD mice (P < 0.05). HFD did not alter systolic blood pressure (SBP), glycated hemoglobin or blood triglycerides in either sex. HFD-females had delayed onset of obesity with a transient increase in fasting blood glucose at week 8 (P < 0.05). Flow cytometry revealed fewer proinflammatory aortic monocytes in females fed a HFD compared to NCD. HFD did not affect aortic leukocyte populations in males. Conversely, HFD impaired endothelium-dependent vasorelaxation, but only in males. Overall, this highlights biological sex as a key factor determining vascular disease severity in early obesity.
Photodynamic therapy using metal-conjugated novel photosensitizer with the expectation of heavy atom effects
Authors: Sasaki Makiko , Tanaka Mamoru , Kojima Yuki , Nomoto Akihiro , Shimmasu Ayako , Watada Tomohiro , Narumi Atsushi , Yano Shigenobu , Ozeki Keiji , Shimura Takaya , Kubota Eiji , Kataoka Hiromi
Published: June 2023

Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light, causing a photochemical reaction that releases free radicals, thereby inducing tumor cell necrosis via oxidative stress. The oxygen molecule reaches the singlet excited state through efficient energy transfer from an excited triplet state of the photosensitizer. Heavy atoms are frequently introduced in photosensitizers for efficiently generating reactive oxygen species (ROS) in PDT, known as the heavy atom effect. However, metal-complexed photosensitizers often show low water-solubility. Here, we established maltotriose (Mal3)-conjugation with heavy metallochlorins (M (Mal3-chlorin), M = Pt or Pd)) to improve its solubility and evaluated its anti-tumor effect. M (Mal3-chlorin) showed effective ROS production and singlet oxygen induction as a result of the heavy-atom effect. Consequently, these cytotoxic factors caused effective anti-tumor effects and induced morphological changes, followed by cell death in vitro. In a xenograft tumor mouse model, PDT with M (Mal3-chlorin) showed tumor growth suppression. Thereby, M (Mal3-Chlorin) might be an excellent glucose-conjugated chlorin because of its strong anti-tumor PDT effect.
Title: Regular physical activity can contribute to preventing cardiovascular risk factors in adolescents with ACE gene polymorphism
Authors: JUNIOR NIVALDO Soares , Senna Carlan , Dias-Filho Carlos , Rodrigues Bruno , Irigoyen Maria , Mendes Vinícius , Ferreira Andressa , Dias Carlos José , Mostarda Cristiano
Published: June 2023

Background
The article aims to analyze the influence of the level of physical activity and the polymorphism in the ACE gene on cardiac autonomic modulation and the chance of cardiovascular risk in adolescents.
Methods
One hundred thirty-six adolescents, 14 years old (11 to 18), divided into active (AG) and sedentary (SG) groups. Blood pressure, body composition, physical activity level, and sexual maturation were assessed to characterize the groups. Afterward, an electrocardiogram was performed, and oral mucosal cells were collected to analyze heart rate variability and genotypic research of angiotensin-converting enzyme.
Results
Distribution frequency of D and I alleles, and time-domain variables of heart rate variability were similar between AG and SG subjects. AG presented lower systolic blood pressure and sympathetic modulation when compared to the SG DD. Additionally, the odds ratio for the cardiovascular events was increased in the SG DD compared with that in AG with DD allele (AG DD) adolescents, as verified for the autonomic variables LF%, HF%, LF/HF, and SBP.
Conclusions
Regular physical activity in adolescents can contribute to the maintenance of blood pressure levels, preventing autonomic imbalance and cardiovascular risk factors in adolescents with ACE gene polymorphism.
Association Between Immediate Oxygenation Response and Survival in Preterm Infants Receiving Rescue Inhaled Nitric Oxide Therapy for Hypoxemia from Pulmonary Hypertension: A Systematic Review and Meta-analysis
Authors: Baczynski Michelle , Jasani Bonny , De Castro Charmaine , Dani Carlo , Subhedar Nimish V. , Chandrasekharan Praveen , Lakshminrusimha Satyan , McNamara Patrick J , Bischoff Adrianne R , Jain Amish
Published: June 2023

Purpose To investigate whether immediate response to inhaled nitric oxide (iNO) therapy is associated with reduced mortality in preterm infants with hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH). Methods A systematic review and meta-analysis were conducted to examine the association between immediate response (improved oxygenation within ≤ 6h) compared to non-response, and all-cause mortality among preterm infants < 34 weeks gestational age without congenital anomalies or genetic disorders who received iNO treatment. Adjusted and unadjusted odds ratio, were pooled using a random effects meta-analysis Hartung-Knapp-Sidik-Jonkman approach. Subgroup analyses were planned for infants with preterm premature rupture of membranes (PPROM) and those treated within 72 hours after birth. Results The primary analysis included 5 eligible studies, a total of 400 infants (196 responders; 204 non-responders). The studies were rated as low to moderate risk of bias based on the Quality in Prognostic Studies tool. Immediate iNO responsiveness was associated with reduced odds of mortality [odds ratio (OR) 0.22, 95% confidence interval (95% CI) (0.10–0.49)]. Although there was insufficient data for a subgroup analysis of infants with PPROM, infants treated with iNO within 72 hours demonstrated consistent findings of reduced mortality [OR 0.21 95% CI (0.13–0.36)]. Based on the GRADE approach, considering the risk of bias of included studies, the overall strength of evidence was rated as moderate. Conclusion There is evidence to suggest that immediate improvement in oxygenation following iNO therapy is associated with reduced odds of mortality before discharge in preterm infants with HRF and clinically suspected or confirmed PH.
Large spread in interannual Variance of atmospheric CO2 concentration across CMIP6 Earth System Models
Authors: Martin-Gomez Veronica , Ruprich-Robert Yohan , Tourigny Etienne , Bernardello Raffaele , Cabré Margarida Samsó , Donat Markus , Ortega Pablo
Published: June 2023

Numerical Earth System Models (ESMs) are our best tool to predict the evolution of atmospheric CO2 concentration and its effect on Global temperature. However, large uncertainties exist among ESMs in the year-to-year variations of atmospheric CO2 concentration. This prevents us from precisely understanding its past evolution and from accurately estimating its future evolution. Here we analyze various ESMs simulations from the 6th Coupled Model Intercomparison Projects (CMIP6) to understand the origins of the inter-model uncertainty in the interannual variability of the atmospheric CO2 concentration. We show that most of this uncertainty is coming from the simulation of the land CO2 flux internal variability. Although models agree that those variations are driven by El Niño Southern Oscillation (ENSO), similar ENSO-related surface temperature and precipitation teleconnections across models drive different land CO2 fluxes, pointing to the land vegetation models as the dominant source of the inter-model uncertainty.
Validation of self-reported cardiovascular problems in childhood cancer survivors by contacting general practitioners: feasibility and results
Authors: Hau Eva-Maria , Sláma Tomáš , Essig Stefan , Michel Gisela , Wengenroth Laura , Bergstraesser Eva , Weid Nicolas Xavier von der , Schindera Christina , Kuehni Claudia Elisabeth
Published: June 2023

Background

Epidemiological studies often rely on self-reported health problems and validation greatly improves study quality. In a study of late effects after childhood cancer, we validated self-reported cardiovascular problems by contacting general practitioners (GPs). This paper describes: a) the feasibility of this approach; and b) the agreement between survivor-reports and reports from their GP.

Methods

The Swiss Childhood Cancer Survivor Study (SCCSS) contacts all childhood cancer survivors registered in the Swiss Childhood Cancer Registry since 1976 who survived at least 5 years from cancer diagnosis. We validated answers of all survivors who reported a cardiovascular problem in the questionnaire. Reported cardiovascular problems were hypertension, arrhythmia, congestive heart failure, myocardial infarction, angina pectoris, stroke, thrombosis, and valvular problems. In the questionnaire, we further asked survivors to provide a valid address of their GP and a consent for contact. We sent case-report forms to survivors’ GPs and requested information on cardiovascular diagnoses of their patients. To determine agreement between information reported by survivors and GPs, we calculated Cohen’s kappa (k) coefficients for each category of cardiovascular problems.

Results

We used questionnaires from 2172 respondents of the SCCSS. Of 290 survivors (13% of 2172) who reported cardiovascular problems, 166 gave consent to contact their GP and provided a valid address. Of those, 135 GPs (81%) replied, and 128 returned the completed case-report form. Survivor-reports were confirmed by 54/128 GPs (42%). Of the 54 GPs, 36 (28% of 128) confirmed the problems as reported by the survivors; 11 (9% of 128) confirmed the reported problem(s) and gave additional information on more cardiovascular outcomes; and seven GPs (5% of 128) confirmed some, but not all cardiovascular problems. Agreement between GPs and survivors was good for stroke (κ=0.79), moderate for hypertension (κ=0.51), arrhythmias (κ=0.41), valvular problems (κ=0.41) and thrombosis (κ=0.56), and poor for coronary heart disease (κ=0.15) and heart failure (κ=0.32).

Conclusions

Despite excellent GP compliance, it was found unfeasible to validate self-reported cardiovascular problems via GPs because they do not serve as gatekeepers in the Swiss health care system. It is thus necessary to develop other validation methods to improve the quality of patient-reported outcomes.
Exploration of Urban Ecological Recreation Space——Taking Nanjing Commercial Buildings as an Example
Authors: jiang xintong
Published: June 2023

As urbanization accelerates and the built-up area continues to expand, people's opportunities for outdoor activities are decreasing. In addition, the pressure of survival brought on by epidemic prevention and control is forcing more and more people to choose outdoor recreational facilities to get close to nature and relax. Most people believe that low density should correspond to comfortable space, while high density corresponds to oppression and compactness. However, high-density space often brings a stronger sense of vitality, convenient living conditions, efficient and resourceful centralization, and rich living levels. I am also transforming the existing urban passive space into active space, starting with the physical and psychological needs of residents and intervening new forces into the existing urban space or architectural space to find a super-density symbiotic recreation space between people and buildings and buildings and architecture. The main content of this design is as follows: first, review the existing literature and related urban open space planning; synthesize and analyze the existing urban open space structure and typical open space functional area research results; and make an objective analysis. Secondly, to explore the recreation demand of urban commercial buildings, to explore the ideal urban recreation space structure pattern and composition elements, and to reflect on their own design. Then, we analyze the hierarchical structure of ecological open space in commercial buildings through the distribution of open space in Nanjing and propose the overall design idea of ecological open space. Finally, we summarize the shortcomings and outlook.
The friction-reduction and anti-wear mechanism of AISI321 stainless steel treated by surface nanocrystallization assisted sulfurization
Authors: ding lifen , Li You
Published: June 2023

Through compound treatment of surface nanocrystallization and low-temperature ion sulfurization, the compound-modified layer (nanocrystalline/FeS film) with excellent friction-reduction and anti-wear properties was fabricated on the surface of AISI321 stainless steel. A comparative study is conducted on the element distribution, microstructure, and vacuum tribology properties (1 × 10‒4 Pa) of compound-treated samples, single-related samples (surface nanocrystallization or low-temperature ion sulfurization), and original substrate samples. The nanocrystallization treatment formed the high hardness, high activity nanocrystalline structure on the surface of AISI321, which results in significantly refined microstructure, increased thickness and concentration of S element in the compound-sulfurized layer compared to the single-sulfurized layer on the substrate. Tribological tests reveal that both the original AISI321 substrate and the single-sulfurizing treated samples are subject to severe abrasion. Single nanocrystallization treatment can improve the wear resistance of AISI321, while the compound treatment can obviously improve the comprehensive tribological properties with milder wear and lower friction of coefficient. The good tribological properties of the compound-modified layer are related to the enhancement of substrate hardness and the increase of the thickness, density, and homogeneity of the sulfurized layer. Furthermore, a physical model is developed for the vacuum tribological behavior of the samples after different treatments. This model provides a reference for revealing the tribological mechanism of the compound-modified layer treated by surface nanocrystallization assisted chemical heat treatment.
Behavioral and metabolic and effects of ABCG4 KO in the APPswe,Ind (J9) mouse model of Alzheimer’s disease
Authors: Fong Vincent , Kanuri Babunageswararao , Traubert Owen , Lui Min , Patel Shailendra B.
Published: June 2023

The pathogenesis of Alzheimer’s disease (AD) is complex and involves an imbalance between production and clearance of amyloid-ß peptides (Aß), resulting in accumulation of Aß in senile plaques. Hypercholesterolemia is a major risk factor for developing AD, with cholesterol shown to accumulate in senile plaques and increase production of Aß. ABCG4 is a member of the ATP-binding cassette transporters predominantly expressed in the CNS, and has been suggested to play a role in cholesterol and Aß efflux from the brain. In this study, we bred Abcg4 knockout (KO) with the APPSwe,Ind (J9) mouse model of AD to test the hypothesis that loss of Abcg4 would exacerbate the AD phenotype. Unexpectedly, no differences were observed in Novel object recognition (NOR) and Novel object placement (NOP) behavioral tests, or on histologic examinations of brain tissues for senile plaque numbers. Furthermore, clearance of radiolabeled Aß from the brains did not differ between Abcg4 KO and control mice. Metabolic testing by indirect calorimetry, glucose tolerance test (GTT) and insulin tolerance test (ITT), were also mostly similar between groups with only a few mild metabolic differences noted. Overall these data suggest that the loss of ABCG4 did not exacerbate the AD phenotype.
A Smart IDS in IoT System to Detect Zero-Day Intrusions Using Automated Signature Update
Authors: Mahmood Mutahher , Shafi Qaisar
Published: June 2023

Protecting industry infrastructure from cyber-attacks is the necessity of time. We heard of zero-day attacks, and now every industry is facing them. The death of the Perimeter term in cybersecurity defines that we can't make our infrastructure 100\% secure. We are using Firewalls, Anti-viruses, IPS (Intrusion Prevention Systems) and IDS (Intrusion Detection Systems), etc., to make industry perimeter secure. But we are still facing zero-day attacks, and we can't prevent them. There is a need for smart IDS that can detect intrusion in networks and systems, and prevent them as well. Some previous work is already been done to detect zero-day attacks in networks, and they are using different approaches based on anomaly detection using Machine Learning algorithms. Machine Learning provides many benefits including and not limited to zero-day attacks by analyzing previously learned and trained datasets. But the only problem that remains is the accuracy of ML algorithms. Our approach is using old-fashioned signature-based detection, which guarantees 100\% accuracy but is limited to zero-day attacks. To deal with zero-day attacks, we're using our approach with the ML algorithms and a multi-classifier to detect zero-day intrusion in a network and update their signatures automatically. Our approach will guarantee prevention from known threats using signatures and more accuracy in the detection of zero-day attacks by using ML algorithms with a multi-classifier.
Unveiling Spatial Associations Between COVID-19 Severe Health Index, Racial/Ethnic Composition, And Community Factors
Authors: juboori Ruaa Al , Subramaniam Divya S. , Hinyard Leslie , Sandoval Ness
Published: June 2023

Limited efforts have been made to incorporate various predisposing factors, including racial/ethnic composition, into prediction models exploring the spatial distribution of COVID-19 Severe Health Risk Index (SHRI). This study examines county-level data from 3,107 US counties, utilizing publicly available datasets. Spatial and non-spatial regression models were constructed, adjusting for rurality, socio-demographic factors, physical health, smoking, sleep, health insurance, healthcare providers, hospitalizations, and environmental risks. Findings reveal spatial models effectively explain geospatial disparities of COVID-19 SHRI. White, Hispanic, and other racial/ethnic majority counties exhibit lower burdens compared to majority Black counties. Older population, lower income, smoking, insufficient sleep, and preventable hospitalizations are associated with higher burdens. Counties with better health access and internet coverage experience lower burdens. This study provides insights into at-risk populations, guiding resource allocation. Racial/ethnic inequalities play a significant role in driving disparities. Addressing these factors reduces health outcome disparities. This work establishes a baseline typology for exploring social, health, economic, and political factors contributing to different health outcomes.
Clinical characteristics and prediction of neurodevelopmental outcomes of infants with ventriculomegaly in utero: A prospective observational study
Authors: Zhou Faliang , Li Chen , Huo Yixuan , Sun Guoyu , Lin Yan , Chen Junya , Hou Xinlin , Liu Lili
Published: June 2023

Background: To evaluate the clinical features and neurodevelopmental outcomes of infants with fetal ventriculomegaly (VM) and determine prognostic factors.
Methods: We studied 167 VM fetuses, assessed the perinatal outcome and the neurodevelopmental outcome at age of 18 months by Bayley Scales of Infant Development. We assessed the association of clinical features and characteristics of VM with Mental Development Index (MDI) and Psychomotor Development Index (PDI).
Results: Among the 167 VM fetuses, 23 underwent induced abortion or were stillborn, and 130 completed a thorough VM evaluation and postnatal follow-up. Of 130 cases, 47% (61/130) showed isolated VM and 53% (69/130) non-isolated VM. Non-isolated VM cases had a higher rate of bilateral (52% vs.25%), severe (12% vs.2%), and progressive (16% vs.10%) VM compared with isolated VM. Neurodevelopmental outcome differed between the isolated and non-isolated VM groups, and the mild and severe VM groups. Progressive VM cases had lower PDI (p=0.006). Anomalies in the CNS, urogenital system, and gastrointestinal tract were associated with lower MDI (ORCNS 4.19,95%CI 1.56-11.28;ORUrogenity 7.00,95%CI 1.81-27.07) or PDI (ORCNS 4.61,95%CI 1.79-11.85;ORGastrointestine 7.88,95%CI 1.24-50.18). Cases with lower MDI or PDI were more likely to have multiple anomalies (both CNS and non-CNS anomalies) (MDI: OR 5.78,95%CI 1.57-21.30,p=0.004, PDI: OR 7.20,95%CI 1.98-26.24,p=0.001).
Conclusions: The neurodevelopmental outcomes in a fetus with VM were poor when VM was severe or progressive VM, or accompanied by structural anomalies. Cerebral, urogenital, and gastrointestinal structural anomalies contribute to poor neurodevelopmental outcomes.
Mental Health and the Youth Athlete: An Analysis of the HeartBytes Database
Authors: Vyas Arthraj J. , Sun Mengyi , Farber Jason , Dikdan Sean J. , Ruge Max , Corgan Sondra , Johnson Drew , Shipon David
Published: June 2023

Background
There is a high rate of mental health conditions among the youth athlete population; however, there is limited information about the impact mental health disorders can have on their overall health and athletic performance.
Methods
Data was collected by Simon’s Heart, a nonprofit organization that coordinates pre-participation examinations (PPE) for adolescents. Multivariable logistic regression adjusting for age, gender, race, BMI, asthma, anemia, and participation in sports was performed to assess the relationship between mental health disorders and each outcome.
Results
The HeartBytes dataset is composed of screening data from 7425 patients ranging from 12 to 20 years old. We identified 565 patients (7.6%) diagnosed with ADHD and 370 patients (5.0%) diagnosed with anxiety/depression. Screened participants without a diagnosis of ADHD, anxiety, or depression were significantly more likely to play sports compared to those with these conditions (75.4% vs 59.4%, P < 0.001 for ADHD; 89.4% vs 72.4%, P < 0.001 for anxiety/depression). Those with anxiety/depression not on an antidepressant (OR: 2.09, CI: 1.31–3.19, P < 0.01), but not those on an antidepressant (OR: 1.87, CI: 0.96–3.33, P = 0.05), were more likely to report chest pain or dyspnea with exercise. Those with ADHD not on a stimulant (aOR 1.91, CI 1.22–2.89, p < 0.01), but not those on a stimulant (aOR 1.40, CI 0.82–2.24, p = 0.19) were more likely to report palpitations. ECG abnormalities were not more prevalent regardless of anxiety/depression, ADHD, or medical therapy with an antidepressant or a stimulant.
Conclusion
Young athletes with anxiety/depression were less likely to participate in sports than healthy individuals. This may be due to deterrence as a result of the symptoms, such as dyspnea or chest pain, they experience during exercise. However, those taking antidepressants had fewer symptoms during exercise. Given that exercise has been shown to improve depression/anxiety, increasing the rate of antidepressant use may lead to less symptoms, more exercise, and an overall improvement in the mental health conditions in this population.
UAV based smart grazing：A prototype and test bed for space-air- ground integrated IoT networks in Qinghai-Tibet plateau
Authors: Li Ji , Ling Min , Huang Shijie , Dong Yugang , Fu Bin , Wang Kun , Gou Biao , Wu Yanshuang
Published: June 2023

Smart grazing is a relatively difficult field of digital agriculture. Restricted by the geographical conditions of pastures, poor network infrastructure and low economic output, relevant applications have been difficult to achieve. In this paper, we propose the SAG-GIoT system based on the background of yak grazing production in the Qinghai Tibet Plateau, and define three intelligent grazing management application scenarios: daily grazing supervision, UAV grazing and searching for yaks. To this end, we have designed the three-tier technical architecture of SAG-GIoT, and developed collar, base station and grazing management system. We designed the all-terrain network service scheme with BDS-BSS and SBSs, and verified the daily grazing supervision test in long-term. UAV grazing test was carried out in pasture, and a flexible communication networking was realized through the UAV-BS. With the guidance of UAV searching and APP positioning, taking HBSs in hand, we quickly and accurately find the lost yaks. SAG-GIoT system is characterized as low cost, flexible deployment and global service, and has broad application prospects.
Using physiological and morphological methods for comparison: is mixed Phyllostachys edulis and Carya illinoinensis a reasonable mixed forest model?
Authors: Lu Qifan , Zhang Xu , Yu Qunfen , Liu Shenghui , Zhou Zhou , Wang Anke , Du Xuhua , Wang Zijie , Zhong Hao , Ning Yilin , Lan Lan , Bi Yufang
Published: June 2023

The purpose of this study was to investigate whether thePhyllostachys edulis-Carya illinoinensisco-plantation is a feasible forest model. Two treatments and one control were evaluated. The control was a low-densityC. illinoinensisforest (CK), and the treatments were a high-densityC. illinoinensis forest(DF), and aC. illinoinensis-P. edulisco-plantation forest (MF). Gas exchange and chlorophyll fluorescence parameters, leaf physiology, macromorphology, and anatomical structure ofC. illinoinensiswere measured and principal component analysis (PCA) was used to evaluate treatment effects. The highest net photosynthetic rate (Pn), which was 13.72 .µmol CO2·m-2·s-1, was recorded forC. illinoinensisunder the CK treatment, while the corresponding values for MF and DF treatments were 8.98 and 5.25 µmol CO2·m-2·s-1, respectively. The JIP test revealed that plastoquinone libraries were inhibited under both MF and DF, particularly in the latter. Compared with CK, antioxidant substances in MF and DF leaves increased to a certain extent, again, particularly in the latter. Leaf macromorphology and anatomical structures under the different treatments also changed to acclimated to different environments. The leaf area of MF became lower, and the vascular tissue of DF petiole became larger. Finally, based on the main data, the order of the PCA scores was CK > MF > DF. The results indicated that both co-plantation and high-density planting caused both interspecific and intraspecific competition. Photosynthesis was inhibited inC. illinoinensisto varying degrees under both cultivation models. Nonetheless, the stress levels inC. illinoinensiswere significantly lower under the co-plantation forest than under high-density planting. These findings indicate thatC. illinoinensisgrowth was not severely inhibited by co-plantation withP. edulis, as it still developed well. Hence, co-plantation ofP. edulisandC. illinoinensisis a promising mixed-forest model.
Characterization of Dropouts in Crowdsourcing Markets
Authors: Bhattacharya Bijoly Saha , Biswas Arindam , Bhattacharyya Malay
Published: June 2023

There have been limited attempts toward the characterization of dropouts in crowdsourcing markets arguably due to the disagreement in defining a dropout. In this paper, we evaluate three different approaches of designating a crowd dropout and demonstrate that a prolonged interruption is enough to characterize a dropout. Our analyses on the crowdsourcing platform Flightfox reflect that the persistence of crowd workers depends on the remuneration and nature of task in addition to the previously reported success rate. Based on this, we show that it is possible to predict the dropouts in a crowdsourcing market with a very high (more than 90%) accuracy, as demonstrated both on cross-validation and independent test sets, with appropriate selection of features. A comprehensive analysis across different machine learning algorithms and feature selection approaches demonstrate that a graph-based robust feature selection performs the best with a boot-strap aggregation approach. It also highlights the importance of having effective communication among the crowd workers who tend to be dropout, a hitherto untold fact. The overall investigation not only provides new perspectives toward designating a dropout but also ensures their effective recognition. Moreover, it highlights the significance of incorporating feedback mechanism in crowdsourcing environments.
The tyrosine kinase inhibitor Dasatinib reduces cardiac steatosis and fibrosis in obese, type 2 diabetic mice
Authors: Gu Yue , Avolio Elisa , Alvino Valeria V , Thomas Anita C , Herman Andrew , Miller Poppy J , Sullivan Niall , Faulkner Ashton , Madeddu Paolo
Published: June 2023

Background Cardiac steatosis is an early yet overlooked feature of diabetic cardiomyopathy. There is no available therapy to treat this condition. Tyrosine kinase inhibitors (TKIs), clinically used as an anti-cancer treatment, influence glucose and lipid metabolism, leading to improved glycemic control and allowing insulin discontinuation in cancer patients with diabetes mellitus. The present study aimed to determine the therapeutic effect of the second-generation TKI Dasatinib on lipid accumulation and cardiac function in obese, type 2 diabetic mice. We also assessed if the drug impacts extra-cardiac fat tissue depots.Methods Two studies on 21-week-old male obese leptin receptor mutant BKS.Cg-+Leprdb/+Leprdb/OlaHsd (db/db) mice compared the effect of Dasatinib (5 mg/kg) and vehicle (10% DMSO + 90% PEG-300) given via gavage once every three days for a week or once every week for four weeks. Functional and volumetric indices were studied using echocardiography. Post-mortem analyses included the assessment of fat deposits and fibrosis using histology, and senescence using immunohistochemistry and flow cytometry. The anti-adipogenic action of Dasatinib was investigated on human bone marrow (BM)-derived mesenchymal stem cells (MSCs). Two-tailed independent samples t-tests and one-way analysis of variance were used as appropriate.Results Dasatinib reduced steatosis and fibrosis in the heart of diabetic mice. The drug also reduced BM adiposity but did not affect other fat depots. These structural changes were associated with an improvement in the diastolic index E/A. Moreover, Dasatinib-treated mice had lower levels of p16 in the heart and BM, and lower circulating PAI-1, compared with vehicle-treated controls, suggesting an inhibitory impact of the drug on the senescence signalling pathway. In vitro, Dasatinib inhibited human BM-MSC viability and adipogenesis commitment.Conclusions Our findings suggest that Dasatinib opposes heart and BM adiposity and cardiac fibrosis. In the heart, this was associated with favourable functional consequences, namely improvement in an index of diastolic function. Repurposing TKI for cardiac benefit could address the unmet need of diabetic cardiac steatosis.
Machine Learning in Heart Failure Research: A Bibliometric Analysis from 2003 to 2023
Authors: Yu Deshuai , Yang Shuangjie , Wang Ruiting , Wang Kai , Han Wenbo , Wu Huanlin , Wang Wei , Wang Xian
Published: June 2023

Background
Heart failure (HF) is a global public health problem with high morbidity and mortality. While machine learning (ML) has been perceived as a promising tool for HF research, a bibliometric analysis of this application is still lacking. This study aims to analyze the relevant papers from 2003 to 2023 and provide a comprehensive overview of this field in a visual way.
Methods
We systematically searched Web of Science Core Collection, PubMed, and preprint servers (arXiv, BioRxiv, and MedRxiv) to identify records from 2003 to 2023 on ML in HF research. After manual data cleansing, a Python approach based on the regular expression matching algorithm was used to automate text annotations, while three bibliometric analysis tools (CiteSpace, VOSviewer, and Bibliometrix) were used for the visualization of research trends, collaboration networks, and research hotspots.
Results
We analyzed 6,115 records (including 1,797 published papers) and observed a steady increase in annual publication rates since 2015, with a significant uptick after 2020. We identified 23 core journals in the field according to Bradford's law, and presented the top 10 journals with the highest citations, h-index, g-index, or m-index. The United States was the most productive country, followed by China and the United Kingdom. The most prolific institutions were Harvard Medical School and Mayo Clinic. Using text annotations, we identified 1,257 ML-related original HF research. In these studies, the main data modalities were ultrasound, electronic health records, and electrocardiograms. The most frequently applied ML methods were neural networks, followed by linear models and ensembles. The most common clinical goals were diagnosis, prediction, and classification. The main research topics included the classification of HF, AI-assisted medical diagnostic technologies, HF-related clinical prediction models, and HF-related bioinformatics research.
Conclusions
This bibliometric analysis revealed a significant growth in the application of ML in HF research over the past two decades. The current research landscape encompasses a wide range of ML techniques and applications, focusing on improving diagnosis, prognosis, classification, and precision treatment for HF patients.
Pro-inflammatory response of monocytes in systemic sclerosis
Authors: Kirichenko Tatiana V. , Markin Alexander M. , Gerasimova Elena V. , Popkova Tatiana V. , Markina Yuliya V. , Tolstik Taisiya V. , Bogatyreva Anastasia I. , Orekhov Alexander N.
Published: June 2023

Objective.
The investigation of inflammatory response of immune cells is one of the most actual trends in research of autoimmune disorders including SSc. This study was aimed to investigate the inflammatory cytokines secretion and to evaluate the pro-inflammatory status of blood-derived monocytes in SSc.
Methods.
The study included 35 SSc and 25 heathy participants. Secretion of inflammatory cytokines TNF-α a, IL1β, CCL2 and IL8 was measured by ELISA in primary culture of monocytes/macrophages after stimulation with LPS on day 1 and 6 of incubation to assess the pro-inflammatory activation and immune tolerance of monocytes. Impaired tolerance of immune response is characterized by increased secretion of inflammatory mediators in response to re-stimulation.
Results.
Basal secretion of TNF-α, IL1β, CCL2 and IL8 was significantly higher in SSc patients than in healthy subjects. After the first LPS-stimulation secretion of TNF-α and IL1β, but not CCL2 and IL8 was also higher in SSc group. In 24 hours after re-stimulation, the secretion of IL1β, CCL2 and IL8, but not TNF-α increased significantly in SSc group compared to healthy control. CCL2 secretion by re-stimulated monocytes was 1.8-fold higher than in cells without re-stimulation in SSc group, that was significantly different from healthy subjects.
Conclusion.
The study results demonstrate pro-inflammatory activation and impaired immune tolerance of monocytes in SSc. The violation of immune response in terms of CCL2 may be an important factor of the chronification of inflammation in SSc. Thus, CCL2 should be considered as therapeutic target for the development of immunomodulatory strategies for SSc treatment.
Stability estimates for the expected utility in Bayesian optimal experimental design
Authors: Duong Duc-Lam , Helin Tapio , Rojo-Garcia Jose Rodrigo
Published: June 2023

We study stability properties of the expected utility function in Bayesian optimal experimental design. We provide a framework for this problem in a non-parametric setting and prove a convergence rate of the expected utility with respect to a likelihood perturbation. This rate is uniform over the design space and its sharpness in the general setting is demonstrated by proving a lower bound in a special case. To make the problem more concrete we proceed by considering non-linear Bayesian inverse problems with Gaussian likelihood and prove that the assumptions set out for the general case are satisfied and regain the stability of the expected utility with respect to perturbations to the observation map. Theoretical convergence rates are demonstrated numerically in three different examples.