bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and risk factors of gestational diabetes in the health region of Lleida: a retrospective observational cohort study
Authors: Orós M. , Perejón D. , Serna M. C. , Siscart J. , Leon J. , Ortega M. , Salinas-Roca B.
Published: June 2023

Background

Diabetes is a very common metabolic condition during pregnancy. The number of cases increases with age and obesity. The prevalence of pre-gestational diabetes and gestational diabetes (GD) differs between different ethnic groups.

Objective

The aim of the study was to analyse the prevalence of pre-gestational diabetes and GD in the health region of Lleida. We also studied the GD risk factors during pregnancy according to the country of origin of the pregnant woman.

Methods

We performed a retrospective observational cohort study among pregnant women between 2012 and 2018 in the health region of Lleida. A multivariate model was performed with the different variables analysed by calculating the regression coefficient and its 95% confidence interval (CI).

Results

In our sample of 17,177 pregnant women, we observed a prevalence of pre-gestational diabetes and GD of 8.2% and 6.5%, respectively. We found a relationship of gestational diabetes with different factors: age, with 6.8% in 30–34 year-old women and 11.3% in women over 35 (OR 1.78 and 3.29, respectively); overweight, with 8.29% (OR 1.89); and obesity, with 12.9% (OR 3.15). Finally, women from Asia and the Middle East and the Maghreb had a higher risk of diabetes, with 12.2% (OR 2.1) and 9.91% (OR 1.3), respectively, and Sub-Saharan women had a lower risk of it 6.07% (OR 0.71).

Conclusions

GD has different risk factors, such as age, overweight, and obesity. Non-related conditions include hypothyroidism, arterial hypertension, and dyslipidaemia. Finally, pregnant women from the Maghreb, and Asia and the Middle East, are at higher risk of developing diabetes during pregnancy; meanwhile, Sub-Saharan origin is protector factor.
Storage of High-Strength Steel Flux-Cored Welding Wires in Urbanized Areas
Authors: Wolski Adrian , Świerczyńska Aleksandra , Lentka Grzegorz , Fydrych Dariusz
Published: June 2023

The condition of the consumables is a key factor determining the waste reduction in the welding processes and the quality of the welded joint. The paper presents the results of tests of four types of flux-cored wires dedicated for welding high-strength steels, stored for 1 month and 6 months in Poland in two urbanized areas: in a large seaside city (Gdańsk) and in Warsaw, located in the center of the country. The wires were subjected to macroscopic and microscopic (stereoscopic, SEM) observations, EDS analysis, technological tests assessing elastic properties and targetability. The degree of degradation of the wires was also tested using resistance measurements. In order to assess the effect of storing wires on the weldability of steel, the diffusible hydrogen content in deposited metal was determined by high-temperature extraction. It was found that the storage caused changes in the surface condition of the wires, affected their elasticity and electrical properties, which affects the behavior of the wires during welding. A significant influence of storage conditions on the hydrogenation of deposited metal was found: in the case of three types of wires, the level of low hydrogen processes was exceeded and the maximum result was 15.18 ml/100 g of deposited metal. It was also found that copper-plated wire showed a significantly increased resistance to storage conditions compared to non-copper-plated wires.
Inequalities for the Coefficients of Schwarz Functions
Authors: Zaprawa Paweł
Published: June 2023

The relation between a considered family of analytic functions and the class $${\mathcal {P}}$$
P
of functions with a positive real part is one of the main tools used in solving various extremal problems, among others coefficient problems. Another approach can be useful in solving such tasks. This approach is to exploit the correspondence between a considered family and the family $${\mathcal {B}}_0$$

B
0

of bounded analytic functions $$\omega $$
ω
such that $$\omega (0)=0$$

ω
(
0
)
=
0

. Such functions appear in the well-known Schwarz lemma, so they are called Schwarz functions. In the literature, there are numerous coefficient functionals discussed for functions in $${\mathcal {P}}$$
P
. On the other hand, relative functionals for functions in $${\mathcal {B}}_0$$

B
0

are not so commonly studied. Consequently, we do not know so much about coefficient inequalities for Schwarz functions. We shall fill the gap to some extent considering two types of functionals. The first one is a Zalcman-type functional $$c_{n}-c_{k}c_{n-k}$$

c
n

-

c
k

c

n
-
k

; the other one is the Hankel determinant $$c_{n-1}c_{n+1}-c_{n}{}^2$$

c

n
-
1

c

n
+
1

-

c
n

2

. For these functionals, bounds with respect to a fixed first coefficient $$c_1$$

c
1

(or a few initial coefficients) are obtained. Some generalizations of these functionals are also given. All results are sharp.
Desiderata for Intelligent Maps: A Multiperspective Compilation
Authors: Degbelo Auriol , Schmidt Benno , Henzen Christin , Lechler Sarah , Lubahn Birgitta , Zander Franziska
Published: June 2023

Interactive digital maps are useful for illustrating and analyzing geographic data and are used for diverse purposes (e.g., wayfinding, data journalism, data analysis, and citizen engagement). This article discusses the requirements of intelligent maps from three perspectives: the literature, a user survey, and a reverse-brainstorming workshop. The ideas brought forth are relevant to researchers and designers of digital maps as they incorporate innovative features and strive for a good user experience.
Maniera Greca in Europe's Catholic East
Authors: Mickunaite Giedré
Published: June 2023

How and why does vernacular art become foreign? What does 'Greek manner' mean in regions far beyond the Mediterranean? What stories do images need? How do narratives shape pictures? The study addresses these questions in Byzantine paintings from the former Grand Duchy of Lithuania, contextualized with evidence from Poland, Serbia, Russia, and Italy. The research follows developments in artistic practices and the reception of these images, as well as distinguishing between the Greek manner - based on visual qualities - and the style favoured by the devout, sustained by cults and altered through stories. Following the reception of Byzantine and pseudo-Byzantine art in Lithuania and Poland from the late fourteenth through the early eighteenth centuries, Maniera Greca in Europe's Catholic East argues that tradition is repetitive order achieved through reduction and oblivion, and concludes that the sole persistent understanding of the Greek image has been stereotyped as the icon of the Mother of God.
Evolution of Microstructural Heterogeneity in the Deep Arc Lithosphere During Delamination
Authors: Gruber Benjamin , Chin Emily J. , Le Roux Veronique
Published: June 2023

The microstructural properties of deep arc cumulates (arclogites) are poorly understood, but are essential in gaining a comprehensive picture of the rheology of continental lithosphere. Here, we analyze 16 arclogite xenoliths, comprising a low MgO and a high MgO suite, from Arizona, USA using electron backscatter diffraction to map microstructures, clinopyroxene shape preferred orientations (SPO), and clinopyroxene crystallographic preferred orientations (CPO). The lower pressure (∼1 GPa) low MgO arclogites show a variety of different clinopyroxene fabrics (S, L, and LS‐type), whereas the high pressure (>2 GPa) high MgO arclogites show predominantly LS‐type fabrics. Furthermore, clinopyroxenes in low MgO arclogites all show a pronounced correspondence between the long axis of their grain shape ellipsoids with the [001] crystal direction, indicating an SPO control on the CPO. In contrast, high MgO arclogite clinopyroxenes lack such a correspondence. We propose that both arclogite types originated as igneous cumulates, consistent with previous studies, but that the high MgO suite experienced substantial recrystallization which diminished the original igneous SPO‐induced CPO. Using strain rates appropriate for arc settings, we calculate a strength profile for the lithosphere and argue that the deepest arclogite textures are consistent with lithospheric foundering through ductile deformation under high shear strain (10−14–10−12 s−1). Our study shows that there is a high degree of shear strain localization in deep arc roots while shallower portions are relatively undeformed.
A Slab Window Beneath North Sumatra Revealed by P‐Wave Mantle Tomography
Authors: Hu Hao , Zhao Dapeng , Lin Jian , Pilia Simone
Published: June 2023

Passive seismic studies have suggested that slab tearing occurs beneath North Sumatra, albeit the slab morphology is somewhat poorly constrained. The lack of resolution on the slab means that the presence of a tear has not been validated, and that the main factors responsible for slab tearing are hard to discern. We use a large seismic data set to determine a new 3‐D high‐resolution tomographic model of the crust and upper mantle beneath North Sumatra, which reveals a well‐defined low‐velocity channel that cuts across the subducting slab through a cavity. This feature cannot be reconciled with a tear in the slab, as previously suggested. Our relocated earthquakes exhibit a protruding cluster of seismicity along the subducted Investigator Fracture Zone, indicating that the high reliefs of the Investigator Fracture Zone possibly enhance the coupling between the subducted slab and the overriding plate. Shear stress resulting from the differential coupling in the slab may have created an area of mechanical weakness in correspondence of the fossil‐spreading ridges, which eventually led to the formation of a slab window. This window allows the exchange of mantle material from the subslab region up to the Toba volcano. We propose that the previously damaged parts (e.g., fracture zones and spreading centers) of the oceanic plate could help promote the growth of a slab window.
The Influence of Mesoscale Atmospheric Convection on Local Infrasound Propagation
Authors: Alter Ross E. , Swearingen Michelle E. , McKenna Taylor Mihan H.
Published: June 2023

Infrasound—that is, acoustic waves with frequencies below the threshold of human hearing—has historically been used to detect and locate distant explosive events over global ranges (≥1,000 km). Simulations over these ranges have traditionally relied on large‐scale, synoptic meteorological information. However, infrasound propagation over shorter, local ranges (0–100 km) may be affected by smaller, mesoscale meteorological features. To identify the effects of these mesoscale meteorological features on local infrasound propagation, simulations were conducted using the Weather Research and Forecasting (WRF) meteorological model to approximate the meteorological conditions associated with a series of historical, small‐scale explosive test events that occurred at the Big Black Test Site in Bovina, Mississippi. These meteorological conditions were then incorporated into a full‐wave acoustic model to generate meteorology‐informed predictions of infrasound propagation. A series of WRF simulations was conducted with varying degrees of horizontal resolution—1, 3, and 15 km—to investigate the spatial sensitivity of these infrasound predictions. The results illustrate that convective precipitation events demonstrate potentially observable effects on local infrasound propagation due to strong, heterogeneous gradients in temperature and wind associated with the convective events themselves. Therefore, to accurately predict infrasound propagation on local scales, it may be necessary to use convection‐permitting meteorological models with a horizontal resolution ≤4 km at locations and times that support mesoscale convective activity.
Dynamical Heating in the Martian Thermosphere
Authors: Pilinski M. D. , Roeten K. J. , Bougher S. W. , Benna M.
Published: June 2023

Dynamical heating and cooling are prominent features of planetary atmospheres resulting in thermospheric structures on Venus, Earth and Mars. The purpose of this study is to determine the location and amplitude of localized heating regions in the Martian thermosphere, confirm that they occur in regions of wind convergence and compare the observed dynamical heating with that predicted by a global thermospheric model. This investigation uses several years of data from the NASA Mars Atmosphere and Volatile EvolutioN (MAVEN) mission including observations made by the Neutral Gas and Ion Mass Spectrometer (NGIMS) as well as the Extreme Ultraviolet Monitor (EUVM). Specifically, the analysis focuses on several years of horizontal wind, temperature, and composition data. EUVM measurements provide a solar forcing context for the neutral thermosphere data sets and aid in the statistical analysis. Statistical results are compared with two versions of the Mars Global Ionosphere Thermosphere (M‐GITM) global circulation model: one that includes gravity wave parametrization and a version without gravity wave effects. Data analysis indicates that heating features exist around 2–3 and 17–18 local solar time. These locations coincide with regions of converging winds and are in better agreement with M‐GITM when a gravity wave parametrization is included in the model. An oscillation in the observed wind field also results in convergence and a density enhancement near 15 local time. While a similar oscillation is reproduced by the model, the amplitude is much lower than observed and may be a result of modeled zonal winds that are too low.
Fully Coupled Photochemistry of the Deuterated Ionosphere of Mars and Its Effects on Escape of H and D
Authors: Cangi Eryn , Chaffin Michael , Yelle Roger , Gregory Bethan , Deighan Justin
Published: June 2023

Although deuterium (D) on Mars has received substantial attention, the deuterated ionosphere remains relatively unstudied. This means that we also know very little about non‐thermal D escape from Mars, since it is primarily driven by excess energy imparted to atoms produced in ion‐neutral reactions. Most D escape from Mars is expected to be non‐thermal, highlighting a gap in our understanding of water loss from Mars. In this work, we set out to fill this knowledge gap. To accomplish our goals, we use an upgraded 1D photochemical model that fully couples ions and neutrals and does not assume photochemical equilibrium. To our knowledge, such a model has not been applied to Mars previously. We model the atmosphere during solar minimum, mean, and maximum, and find that the deuterated ionosphere behaves similarly to the H‐bearing ionosphere, but that non‐thermal escape on the order of 8,000–9,000 cm−2 s−1 dominates atomic D loss under all solar conditions. The total fractionation factor, f, is f = 0.04–0.07, and integrated water loss is 147–158 m global equivalent layer. This is still less than geomorphological estimates. Deuterated ions at Mars are likely difficult to measure with current techniques due to low densities and mass degeneracies with more abundant H ions. Future missions wishing to measure the deuterated ionosphere in situ will need to develop innovative techniques to do so.
Extensive Lunar Surface Disturbance at the Chang'e‐5 Mission Landing Site: Implications for Future Lunar Base Design and Construction
Authors: Qiao Le , Hess Marcel , Xu Luyuan , Wöhler Christian , Head James W. , Chen Jian , Wang Yiran , Bugiolacchi Roberto , Xiao Ayang , Zhang Feng , Ling Zongcheng
Published: June 2023

Lunar surface disturbances by spacecraft engine jets are of particular concern in the current new phase of lunar exploration, when dozens of landing missions and permanent bases are being planned. Some of these exploration efforts will involve multiple landings and liftoffs around the same lunar site; thus, it is essential to evaluate their effect on astronauts and assets on the lunar surface. Here, we assess the surface disturbances during the Chang'e‐5 landing and liftoff procedures through the photometric analysis of high‐resolution multi‐temporal surface and orbital images. Centimeter‐scale surface images reveal a four‐stage evolution of the landing plume impingement over a period of ∼50 s, which involves phenomena such as dust devils and streaks, and displacement of cobbles. Temporal‐ratio calculation of orbital images (including one acquired between landing and liftoff) enables the first direct observation of ascent plume effects. The ascent blast zone consists of two separated sub‐areas (∼3,400 m2 in total), which is nearly twice larger than that of the landing blast zone. The final disturbed surface is characterized by a central main zone (∼2,300 m2) surrounded by a marginal diffuse zone (∼15,300 m2). Phase‐ratio analyses suggest that plume impingement destroys the micro‐porous structure of the uppermost regolith. We estimate that future lunar landers (e.g., SpaceX's Starship) may cause significant lunar surface disturbances over an area of square kilometers. Our results provide unique insights into Chang'e‐5 mission activities, and instructive references for the planning of future lunar endeavors, including the design and construction of surface experiment packages and permanent lunar bases.
Disentangling Shallow Subsidence Sources by Data Assimilation in a Reclaimed Urbanized Coastal Plain, South Flevoland Polder, the Netherlands
Authors: Verberne Manon , Koster Kay , Lourens Aris , Gunnink Jan , Candela Thibault , Fokker Peter A.
Published: June 2023

This research targets disentangling shallow causes of anthropogenically induced subsidence in a reclaimed and urbanized coastal plain. The study area is the city of Almere, in the South Flevoland polder, the Netherlands, which is among the countries' fastest subsiding areas. The procedure consists of integrating Interferometric Synthetic Aperture Radar (InSAR) data with high‐resolution phreatic groundwater and lithoclass models, and a database containing construction details. The InSAR data were derived from Sentinel‐1, one ascending and one descending track, over a period from March 2015 until June 2020. The two main parts of the workflow are isolation of the InSAR points of structures without a pile foundation and a data assimilation procedure. The shrinkage of surficial clay beds by phreatic groundwater level lowering is identified as the main cause of subsidence in the area, with an average contribution of 6 mm per year. The history‐matched physics‐based model predicts that 1 m drop in phreatic groundwater level now translates into 10 mm of subsidence in the next 5 years. Additionally, a groundwater deficiency due to severe dry periods should be considered as an accelerator of subsidence. To ensure a robust network to estimate subsidence, we recommend a consistent monitoring strategy of the phreatic groundwater level.
Where Does Fire Retardant Fall in a Forest? Ask a Satellite
Authors: Duncombe Jenessa
Published: June 2023

Knowing where fire retardant lands once it's dropped from a plane is hard to pin down. A new remote sensing approach offers clues.
Nonlinear Equilibrium Structure of Super Thin Current Sheets: Influence of Quasi‐Adiabatic Electron Population
Authors: Tsareva Olga O. , Leonenko Makar V. , Grigorenko Elena E. , Malova Helmi V. , Popov Victor Yu. , Zelenyi Lev M.
Published: June 2023

Recent MMS observations confirmed the existence of the quasi‐stationary electron‐scale super‐thin current sheets (STCSs) with a half‐thickness of few electron gyroradii. STCSs contain the electron population consisting of magnetized and demagnetized particles. To study the role of the demagnetized electrons, we developed a self‐consistent combined model of a STCS in which the dynamics of a part of the electron population is described by the quasi‐adiabatic approximation, while the motion of the other part is described by the guiding center approximation. Demagnetized ion population can be described in a frame of quasi‐adiabatic approach. In the presented model we introduced the weight coefficient of the demagnetized electron plasma density χ depending on the magnetic field normal component Bn/B0 and compared the characteristic profiles of two STCSs differing by the presence (χ ≠ 0) and absence (χ = 0) of demagnetized electrons. It is shown that the presence of demagnetized electrons makes the current density profile of STCS significantly more intense and narrower. The thickness and intensity of STCS depend on the anisotropy coefficient of magnetized electrons and the incoming drift velocity of demagnetized electrons. The maximum current density continuously increases with the growth of the demagnetized electron population and is controlled by the ratio of the thermal to the incoming drift electron velocities. Thus intense current sheets can be formed even in the absence of strong electron anisotropy, which is confirmed by MMS observations.
Rayleigh‐Taylor Instability Observed at the Dayside Magnetopause Under Northward Interplanetary Magnetic Field
Authors: Yan G. Q. , Parks G. K. , Mozer F. S. , Goldstein M. L. , Chen T. , Liu Y.
Published: June 2023

Under northward interplanetary magnetic field, periodical fluctuations with the period of 85 s have been observed by one of the Time History of Events and Macroscale Interactions during Substorms spacecraft at the dayside magnetopause when the solar wind dynamic pressure suddenly dropped. The observed magnetic field distortions, characterized by the compression of the main component as well as the flapping of the perpendicular components, are in line with the theoretical predictions of the Rayleigh‐Taylor (R‐T) instability excited at the magnetopause. With the convective electric field and the mean electric field removed, the perturbations in the electric field are identified as typical two sinusoidal signals with a 90° phase difference, consistent with previous prediction of the attendant electrostatic field arising from the R‐T instability. The transverse motions of the plasmas resulting from the electric drifting driven by the electrostatic field are observed both in pitch‐angle distributions and in distribution functions. The growth rate of the R‐T instability is about 43 s, implying that the instability has time to grow during the disturbances. Using the Gauss theorem, the calculated net charge density based on the electric field observation is one part of 27 compared to the totally observed plasma density, indicating that only a tiny fraction of the charge separates to set up the electrostatic field, which is due to a collective effect in the plasma.
Epigenetic reprogramming of cell cycle genes by ACK1 promotes breast cancer resistance to CDK4/6 inhibitor
Authors: Sawant Mithila , Wilson Audrey , Sridaran Dhivya , Mahajan Kiran , O’Conor Christopher J. , Hagemann Ian S. , Luo Jingqin , Weimholt Cody , Li Tiandao , Roa Juan Carlos , Pandey Akhilesh , Wu Xinyan , Mahajan Nupam P.
Published: June 2023

Hormone receptor-positive, HER2-negative advanced breast cancers exhibit high sensitivity to CDK4/6 inhibitors such as palbociclib. However, most patients inevitably develop resistance, thus identification of new actionable therapeutic targets to overcome the recurrent disease is an urgent need. Immunohistochemical studies of tissue microarray revealed increased activation of non-receptor tyrosine kinase, ACK1 (also known as TNK2) in most of the breast cancer subtypes, independent of their hormone receptor status. Chromatin immunoprecipitation studies demonstrated that the nuclear target of activated ACK1, pY88-H4 epigenetic marks, were deposited at cell cycle genes,CCNB1, CCNB2andCDC20, which in turn initiated their efficient transcription. Pharmacological inhibition of ACK1 using its inhibitor, (R)-9bdampenedCCNB1, CCNB2andCDC20expression, caused G2/M arrest, culminating in regression of palbociclib-resistant breast tumor growth. Further, (R)-9bsuppressed expression of CXCR4 receptor, which resulted in significant impairment of metastasis of breast cancer cells to lung. Overall, our pre-clinical data identifies activated ACK1 as an oncogene that epigenetically controls the cell cycle genes governing the G2/M transition in breast cancer cells. ACK1 inhibitor, (R)-9bcould be a novel therapeutic option for the breast cancer patients that have developed resistance to CDK4/6 inhibitors.
Differences in white blood cell proportions between schizophrenia cases and controls are influenced by medication and variations in time of day
Authors: Villar Jonelle D. , Stavrum Anne-Kristin , Spindola Leticia M. , Torsvik Anja , Bjella Thomas , Steen Niels Eiel , Djurovic Srdjan , Andreassen Ole A. , Steen Vidar M. , Le Hellard Stephanie
Published: June 2023

Cases with schizophrenia (SCZ) and healthy controls show differences in white blood cell (WBC) counts and blood inflammation markers. Here, we investigate whether time of blood draw and treatment with psychiatric medications are related to differences in estimated WBC proportions between SCZ cases and controls. DNA methylation data from whole blood was used to estimate proportions of six subtypes of WBCs in SCZ patients (n = 333) and healthy controls (n = 396). We tested the association of case-control status with estimated cell-type proportions and the neutrophil-to-lymphocyte ratio (NLR) in 4 models: with/without adjusting for time of blood draw, and then compared results from blood samples drawn during a 12-h (07:00–19:00) or 7-h (07:00-14:00) period. We also investigated WBC proportions in a subgroup of medication-free patients (n = 51). Neutrophil proportions were significantly higher in SCZ cases (mean=54.1%) vs. controls (mean=51.1%; p = <0.001), and CD8+T lymphocyte proportions were lower in SCZ cases (mean=12.1%) vs. controls (mean=13.2%; p = 0.001). The effect sizes in the 12-h sample (07:00–19:00) showed a significant difference between SCZ vs. controls for neutrophils, CD4+T, CD8+T, and B-cells, which remained significant after adjusting for time of blood draw. In the samples matched for time of blood draw during 07.00–14.00, we also observed an association with neutrophils, CD4+T, CD8+T, and B-cells that was unaffected by further adjustment for time of blood draw. In the medication-free patients, we observed differences that remained significant in neutrophils (p = 0.01) and CD4+T (p = 0.01) after adjusting for time of day. The association of SCZ with NLR was significant in all models (range: p < 0.001 to p = 0.03) in both medicated and unmedicated patients. In conclusion, controlling for pharmacological treatment and circadian cycling of WBC is necessary for unbiased estimates in case-control studies. Nevertheless, the association of WBC with SCZ remains, even after adjusting for the time of day.
Epigenetically modified AP-2α by DNA methyltransferase facilitates glioma immune evasion by upregulating PD-L1 expression
Authors: Long Shengwen , Huang Guixiang , Ouyang Mi , Xiao Kai , Zhou Hao , Hou Anyi , Li Zhiwei , Zhong Zhe , Zhong Dongmei , Wang Qinghao , Xiang Shuanglin , Ding Xiaofeng
Published: June 2023

Programmed death-ligand 1 (PD-L1) ensures that tumor cells escape T-cell-mediated tumor immune surveillance. However, gliomas are characteristic of the low immune response and high-resistance therapy, it is necessary to understand molecular regulatory mechanisms in glioblastoma, especially the limited regulation of PD-L1 expression. Herein, we show that low expression of AP-2α is correlated with high expression of PD-L1 in high-grade glioma tissues. AP-2α binds directly to the promoter of the CD274 gene, not only inhibits the transcriptional activity of PD-L1 but enhances endocytosis and degradation of PD-L1 proteins. Overexpression of AP-2α in gliomas enhances CD8+ T cell-mediated proliferation, effector cytokine secretion, and cytotoxicity in vitro. Tfap2a could increase the cytotoxic effect of Cd8+ T cells in CT26, B16F10, and GL261 tumor-immune models, improve anti-tumor immunity, and promote the efficacy of anti-PD-1 therapy. Finally, the EZH2/H3K27Me3/DNMT1 complex mediates the methylation modification of AP-2α gene and maintains low expression of AP-2α in gliomas. 5-Aza-dC (Decitabine) treatment combines with anti-PD-1 immunotherapy to efficiently suppress the progression of GL261 gliomas. Overall, these data support a mechanism of epigenetic modification of AP-2α that contributes to tumor immune evasion, and reactivation of AP-2α synergizes with anti-PD-1 antibodies to increase antitumor efficacy, which may be a broadly applicable strategy in solid tumors.
Cathepsin K inhibition induces Raptor destabilization and mitochondrial dysfunction via Syk/SHP2/Src/OTUB1 axis-mediated signaling
Authors: Seo Seung Un , Woo Seon Min , Kwon Taeg Kyu
Published: June 2023

The Raptor signaling pathway is a critical point of intervention in the invasion and progression of cancer. The non-receptor tyrosine kinase Src-mediated phosphorylation of OTUB1-Y26 plays a critical role in Raptor stabilization, whereas cathepsin K inhibitor (odanacatib; ODN) and knockdown (siRNA) induce Raptor destabilization. However, the mechanisms involved in cathepsin K inhibition-induced OTUB1-Y26 phosphorylation in Raptor stabilization have not been yet elucidated. This study showed that cathepsin K inhibition activates SHP2, a tyrosine phosphatase, that dephosphorylates OTUB1 and destabilizes Raptor, whereas SHP2 deletion and pharmacological inhibition increase OTUB1-Y26 phosphorylation and Raptor expression. SHP2 deletion also led to the inhibition of ODN-induced mitochondrial ROS, fusion, and dysfunction. Furthermore, cathepsin K inhibition phosphorylated spleen tyrosine kinase (Syk) at Y525 and Y526, resulting in the SHP2-mediated dephosphorylation of OTUB1-Y26. Collectively, our findings identified Syk not only as an upstream tyrosine kinase required for SHP2 activation but also showed a critical mechanism that regulates ODN-induced Raptor downregulation and mitochondrial dysfunction. In conclusion, Syk/SHP2/Src/OTUB1 axis-mediated signaling can act as a therapeutic target in cancer management.
A data-driven approach for predicting the impact of drugs on the human microbiome
Authors: Algavi Yadid M. , Borenstein Elhanan
Published: June 2023

Many medications can negatively impact the bacteria residing in our gut, depleting beneficial species, and causing adverse effects. To guide personalized pharmaceutical treatment, a comprehensive understanding of the impact of various drugs on the gut microbiome is needed, yet, to date, experimentally challenging to obtain. Towards this end, we develop a data-driven approach, integrating information about the chemical properties of each drug and the genomic content of each microbe, to systematically predict drug-microbiome interactions. We show that this framework successfully predicts outcomes of in-vitro pairwise drug-microbe experiments, as well as drug-induced microbiome dysbiosis in both animal models and clinical trials. Applying this methodology, we systematically map a large array of interactions between pharmaceuticals and human gut bacteria and demonstrate that medications’ anti-microbial properties are tightly linked to their adverse effects. This computational framework has the potential to unlock the development of personalized medicine and microbiome-based therapeutic approaches, improving outcomes and minimizing side effects.
Cannabidiol inhibits Nav channels through two distinct binding sites
Authors: Huang Jian , Fan Xiao , Jin Xueqin , Jo Sooyeon , Zhang Hanxiong Bear , Fujita Akie , Bean Bruce P. , Yan Nieng
Published: June 2023

Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of proteins, but which targets are most relevant for clinical actions is still unclear. Here we show that CBD interacts with Nav1.7 channels at sub-micromolar concentrations in a state-dependent manner. Electrophysiological experiments show that CBD binds to the inactivated state of Nav1.7 channels with a dissociation constant of about 50 nM. The cryo-EM structure of CBD bound to Nav1.7 channels reveals two distinct binding sites. One is in the IV-I fenestration near the upper pore. The other binding site is directly next to the inactivated “wedged” position of the Ile/Phe/Met (IFM) motif on the short linker between repeats III and IV, which mediates fast inactivation. Consistent with producing a direct stabilization of the inactivated state, mutating residues in this binding site greatly reduced state-dependent binding of CBD. The identification of this binding site may enable design of compounds with improved properties compared to CBD itself.
Optically induced electrothermal microfluidic tweezers in bio-relevant media
Authors: Gupta Kshitiz , Moon Hye-Ran , Chen Zhengwei , Han Bumsoo , Green Nicolas G. , Wereley Steven T.
Published: June 2023

Non-contact micro-manipulation tools have enabled invasion-free studies of fragile synthetic particles and biological cells. Rapid electrokinetic patterning (REP) traps target particles/cells, suspended in an electrolyte, on an electrode surface. This entrapment is electrokinetic in nature and thus depends strongly on the suspension medium’s properties. REP has been well characterized for manipulating synthetic particles suspended in low concentration salt solutions (~ 2 mS/m). However, it is not studied as extensively for manipulating biological cells, which introduces an additional level of complexity due to their limited viability in hypotonic media. In this work, we discuss challenges posed by isotonic electrolytes and suggest solutions to enable REP manipulation in bio-relevant media. Various formulations of isotonic media (salt and sugar-based) are tested for their compatibility with REP. REP manipulation is observed in low concentration salt-based media such as 0.1× phosphate buffered saline (PBS) when the device electrodes are passivated with a dielectric layer. We also show manipulation of murine pancreatic cancer cells suspended in a sugar-based (8.5% w/v sucrose and 0.3% w/v dextrose) isotonic medium. The ability to trap mammalian cells and deposit them in custom patterns enables high-impact applications such as determining their biomechanical properties and 3D bioprinting for tissue scaffolding.
Red narrow-linewidth lasing and frequency comb from gain-switched self-injection-locked Fabry–Pérot laser diode
Authors: Shitikov Artem E. , Galiev Ramzil R. , Min’kov Kirill N. , Kondratiev Nikita M. , Cordette Steevy J. , Lobanov Valery E. , Bilenko Igor A.
Published: June 2023

Narrow-linewidth lasers are in extensive demand for numerous cutting-edge applications. Such lasers operating at the visible range are of particular interest. Self-injection locking of a laser diode frequency to a high-Q whispering gallery mode is an effective and universal way to achieve superior laser performance. We demonstrate ultranarrow lasing with less than 10 Hz instantaneous linewidth for 20 $$\mu$$
μ
s averaging time at 638 nm using a Fabry–Pérot laser diode locked to a crystalline MgF$$_2$$

2

microresonator. The linewidth measured with a $$\beta$$
β
-separation line technique that characterizes 10 ms stability is as low as 1.4 kHz. Output power exceeds 80 mW. Demonstrated results are among the best for visible-range lasers in terms of linewidth combined with solid output power. We additionally report the first demonstration of a gain-switched regime for such stabilized Fabry–Pérot laser diode showing a high-contrast visible frequency comb generation. Tunable linespacing from 10 MHz to 3.8 GHz is observed. We demonstrated that the beatnote between the lines has sub-Hz linewidth and experiences spectral purification in the self-injection locking regime. This result might be of special importance for spectroscopy in the visible range.
Predicting outcomes of acute kidney injury in critically ill patients using machine learning
Authors: Nateghi Haredasht Fateme , Viaene Liesbeth , Pottel Hans , De Corte Wouter , Vens Celine
Published: June 2023

Acute Kidney Injury (AKI) is a sudden episode of kidney failure that is frequently seen in critically ill patients. AKI has been linked to chronic kidney disease (CKD) and mortality. We developed machine learning-based prediction models to predict outcomes following AKI stage 3 events in the intensive care unit. We conducted a prospective observational study that used the medical records of ICU patients diagnosed with AKI stage 3. A random forest algorithm was used to develop two models that can predict patients who will progress to CKD after three and six months of experiencing AKI stage 3. To predict mortality, two survival prediction models have been presented using random survival forests and survival XGBoost. We evaluated established CKD prediction models using AUCROC, and AUPR curves and compared them with the baseline logistic regression models. The mortality prediction models were evaluated with an external test set, and the C-indices were compared to baseline COXPH. We included 101 critically ill patients who experienced AKI stage 3. To increase the training set for the mortality prediction task, an unlabeled dataset has been added. The RF (AUPR: 0.895 and 0.848) and XGBoost (c-index: 0.8248) models have a better performance than the baseline models in predicting CKD and mortality, respectively Machine learning-based models can assist clinicians in making clinical decisions regarding critically ill patients with severe AKI who are likely to develop CKD following discharge. Additionally, we have shown better performance when unlabeled data are incorporated into the survival analysis task.
Preceding and trailing role-taking in dyad synchronization using finger tapping
Authors: Kimura Kazuto , Tanaka Yuki , Ogata Taiki , Miyake Yoshihiro
Published: June 2023

In ensembles, people synchronize the timings of their movements with those of others. Players sometimes take on preceding and trailing roles, whereby one’s beat is either slightly earlier or slightly later than that of another. In this study, we aimed to clarify whether the division of preceding and trailing roles occurs in simple rhythmic coordination among non-musicians. Additionally, we investigated the temporal dependencies between these roles. We conducted a synchronous-continuous tapping task involving pairs of people, whereby pairs of participants first tapped to synchronize with a metronome. After the metronome stopped, the participants synchronized their taps to their partners’ tap timings, which were presented as auditory stimuli. Except in one trial, the pairs involved participants taking on preceding and trailing roles. Compared to the participants taking on the trailing role, those taking on the preceding role demonstrated enhanced phase-correction responses, while those taking on the trailing role significantly adapted their tempos to match those of their partners. As a result, people spontaneously divided into preceding and trailing roles. The preceding participants tended to reduce asynchronies, while the trailing participants tended to match their tempo to their partners’.
Entropy optimization and response surface methodology of blood hybrid nanofluid flow through composite stenosis artery with magnetized nanoparticles (Au-Ta) for drug delivery application
Authors: Algehyne Ebrahem A. , Ahammad N. Ameer , Elnair Mohamed E. , Zidan Mohamed , Alhusayni Yasir Y. , El-Bashir B. O. , Saeed Anwar , Alshomrani Ali Saleh , Alzahrani Faris
Published: June 2023

Entropy creation by a blood-hybrid nanofluid flow with gold-tantalum nanoparticles in a tilted cylindrical artery with composite stenosis under the influence of Joule heating, body acceleration, and thermal radiation is the focus of this research. Using the Sisko fluid model, the non-Newtonian behaviour of blood is investigated. The finite difference (FD) approach is used to solve the equations of motion and entropy for a system subject to certain constraints. The optimal heat transfer rate with respect to radiation, Hartmann number, and nanoparticle volume fraction is calculated using a response surface technique and sensitivity analysis. The impacts of significant parameters such as Hartmann number, angle parameter, nanoparticle volume fraction, body acceleration amplitude, radiation, and Reynolds number on the velocity, temperature, entropy generation, flow rate, shear stress of wall, and heat transfer rate are exhibited via the graphs and tables. Present results disclose that the flow rate profile increase by improving the Womersley number and the opposite nature is noticed in nanoparticle volume fraction. The total entropy generation reduces by improving radiation. The Hartmann number expose a positive sensitivity for all level of nanoparticle volume fraction. The sensitivity analysis revealed that the radiation and nanoparticle volume fraction showed a negative sensitivity for all magnetic field levels. It is seen that the presence of hybrid nanoparticles in the bloodstream leads to a more substantial reduction in the axial velocity of blood compared to Sisko blood. An increase in the volume fraction results in a noticeable decrease in the volumetric flow rate in the axial direction, while higher values of infinite shear rate viscosity lead to a significant reduction in the magnitude of the blood flow pattern. The blood temperature exhibits a linear increase with respect to the volume fraction of hybrid nanoparticles. Specifically, utilizing a hybrid nanofluid with a volume fraction of 3% leads to a 2.01316% higher temperature compared to the base fluid (blood). Similarly, a 5% volume fraction corresponds to a temperature increase of 3.45093%.
Research on the establishment of NDVI long-term data set based on a novel method
Authors: Fan Dongliang
Published: June 2023

This study compares the relationship between different NDVI (Normalized Difference Vegetation Index), the NDVI of AVHRR (Advanced Very High Resolution Radiometer) (NDVIa), the NDVI of MODIS (Moderate Resolution Imaging Spectrometer) (NDVIm), and the NDVI of VIRR (Visible and Infrared Radiometer) (NDVIv), and found that there is a significant correlation between the NDVIa and the NDVIm, and between the NDVIv and the NDVIa, the relationship between the three is NDVIv < NDVIa < NDVIm. Machine learning is an important method in artificial intelligence. It can solve some complex problems through algorithms. This research uses linear regression algorithm in machine learning to construct the Fengyun Satellite NDVI correction method. By constructing a linear regression model, the NDVI value of Fengyun Satellite VIRR is corrected to a level that is basically the same as NDVIm. The corrected correlation coefficients (R2) were significantly improved, and the corrected correlation coefficients were significantly improved, and the confidence levels were all significant correlations less than 0.01. It is proved that the corrected normalized vegetation index of Fengyun Satellite has significantly improved accuracy and product quality compared with the normalized vegetation index of MODIS.
The role of asymmetric dimethylarginine (ADMA) in COVID-19: association with respiratory failure and predictive role for outcome
Authors: Sozio Emanuela , Hannemann Juliane , Fabris Martina , Cifù Adriana , Ripoli Andrea , Sbrana Francesco , Cescutti Demetrio , Vetrugno Luigi , Fapranzi Stefano , Bassi Flavio , Sponza Massimo , Curcio Francesco , Tascini Carlo , Böger Rainer
Published: June 2023

We aimed to assess the potential role of Asymmetric dimethylarginine (ADMA) in conditioning respiratory function and pulmonary vasoregulation during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Within 72 h from admission, samples from 90 COVID-19 patients were assessed for ADMA, SDMA, L-arginine concentrations. In addition to classical statistics, patients were also clustered by a machine learning approach according to similar features. Multivariable analysis showed that C-reactive protein (OR 1.012), serum ADMA (OR 4.652), white blood cells (OR = 1.118) and SOFA (OR = 1.495) were significantly associated with negative outcomes. Machine learning-based clustering showed three distinct clusters: (1) patients with low severity not requiring invasive mechanical ventilation (IMV), (2) patients with moderate severity and respiratory failure whilst not requiring IMV, and (3) patients with highest severity requiring IMV. Serum ADMA concentration was significantly associated with disease severity and need for IMV although less pulmonary vasodilation was observed by CT scan. High serum levels of ADMA are indicative of high disease severity and requirement of mechanical ventilation. Serum ADMA at the time of hospital admission may therefore help to identify COVID-19 patients at high risk of deterioration and negative outcome.
Spectroscopic investigations to reveal synergy between polystyrene waste and paraffin wax in super-hydrophobic sand
Authors: Al-Mokhalelati K. , Karabet F. , Allaf A. W. , Naddaf M. , Al Lafi A. G.
Published: June 2023

Sand based superhydrophobic materials, such as paraffin-coated sand, are the focus of global research to fight land desertification. The present work investigates the development of paraffin-coated sand with extending service life as well as improving and stabilizing hydrophobic property by adding plastic waste. While the addition of polyethylene (PE) did not improve the hydrophobic property of paraffin coated sand, incorporating 4.5% of polystyrene (PS) in the composition of coated sand increased the contact angle. Fourier Transform Infrared spectroscopy (FTIR), X-ray diffraction patterns (XRD) and two-dimensional correlation spectroscopy (2D-COS) indicated that PS increased the molecular orientation of sand and reduced the thickness of the paraffin coating. Paraffin on the other hand improved the distribution of PS and prevented aggregation with sand. Both FTIR bands at 1085 cm−1 and 462 cm−1 were more sensitive to change in PS contents, while other bands at 780 cm−1 and 798 cm−1 were more sensitive to change in paraffin contents. Moreover, the XRD patterns of sand were split into two components by the addition of PS indicating the transformation of morphology to less ordered or more distorted form. 2D-COS is a powerful tool to reveal harmony of components in mixtures, extract information related to the role of each of them, and help in decision-making process regarding choosing the appropriate recipes.
Single-cell transcriptomic profiling of microvascular endothelial cell heterogeneity in congenital diaphragmatic hernia
Authors: Robertson Jason O. , Bazeley Peter , Erzurum Serpil C. , Asosingh Kewal
Published: June 2023

Congenital diaphragmatic hernia (CDH) is a neonatal anomaly that includes pulmonary hypoplasia and hypertension. We hypothesized that microvascular endothelial cell (EC) heterogeneity is different in CDH lungs and related to lung underdevelopment and remodeling. To test this, we evaluated rat fetuses at E21.5 in a nitrofen model of CDH to compare lung transcriptomes among healthy controls (2HC), nitrofen-exposed controls (NC) and nitrofen-exposed subjects with CDH. Single-cell RNA sequencing with unbiased clustering revealed 3 distinct microvascular EC clusters: a general population (mvEC), a proliferative population and a population high in hemoglobin. Only the CDH mvEC cluster had a distinct inflammatory transcriptomic signature as compared to the 2HC and NC endothelial cells, e.g. greater activation and adhesion of inflammatory cells and production of reactive oxygen species. Furthermore, CDH mvECs had downregulated Ca4, Apln and Ednrb gene expression. Those genes are markers for ECs important to lung development, gas exchange and alveolar repair (mvCa4+). mvCa4+ ECs were reduced in CDH (2HC [22.6%], NC [13.1%] and CDH [5.3%], p < 0.0001). Overall, these findings identify transcriptionally distinct microvascular endothelial cell clusters in CDH, including the distinctly inflammatory mvEC cluster and the depleted group of mvCa4+ ECs, which together may contribute to pathogenesis.