bluuebunny/crossref_metadata_2025_split huggingface dataset:
Segmented intravaginal ring for the combination delivery of hydroxychloroquine and anti-CCR5 siRNA nanoparticles as a potential strategy for preventing HIV infection
Authors: Traore Yannick L. , Chen Yufei , Padilla Fernanda , Ho Emmanuel A. 
Published: April 2021

Abstract
Vaginal drug delivery has been shown to be a promising strategy for the prevention of sexually transmitted infections. Therapy delivered at the site of infection has many advantages including improved therapeutic efficacy, reduction in systemic toxicity, and reduced potential for development of drug resistance. We developed a “smart” combination intravaginal ring (IVR) that will (1) provide continuous release of hydroxychloroquine (HCQ) to induce T cell immune quiescence as the first-line of defense and (2) release nanoparticles containing anti-CCR5 siRNA only during sexual intercourse when triggered by the presence of seminal fluid as the second-line of defense. The IVR was capable of releasing HCQ over 25 days with a mean daily release of 31.17 ± 3.06 µg/mL. In the presence of vaginal fluid simulant plus seminal fluid simulant, over 12 × more nanoparticles (5.12 ± 0.9 mg) were released over a 4-h period in comparison to IVR segments that were incubated in the presence of vaginal fluid simulant alone (0.42 ± 0.19 mg). Anti-CCR5 siRNA nanoparticles were able to knockdown 83 ± 5.1% of CCR5 gene expression in vitro in the CD4+ T cell line Sup-T1. The IVR system also demonstrated to be non-cytotoxic to VK2/E6E7 vaginal epithelial cells.

Graphical abstract
Prognostic role of proliferating CD8+ cytotoxic Tcells in human cancers
Authors: Blessin Niclas C. , Li Wenchao , Mandelkow Tim , Jansen Hannah L. , Yang Cheng , Raedler Jonas B. , Simon Ronald , Büscheck Franziska , Dum David , Luebke Andreas M. , Hinsch Andrea , Möller Katharina , Menz Anne , Bernreuther Christian , Lebok Patrick , Clauditz Till , Sauter Guido , Marx Andreas , Uhlig Ria , Wilczak Waldemar , Minner Sarah , Krech Till , Fraune Christoph , Höflmayer Doris , Burandt Eike , Steurer Stefan 
Published: April 2021

Abstract
Purpose
Expansion of CD8+ cytotoxic Tlymphocytes is a prerequisite for anti-cancer immune activity and has gained interest in the era of immune checkpoint therapy.

Methods
To understand the CD8+ T cell dynamics in the tumor microenvironment, we used multiplex fluorescence immunohistochemistry to quantitate CD8+ proliferation (Ki67 co-expression) in tissue microarrays from 1107 colorectal, 642 renal cell, 1066 breast, 375 ovarian, 451 pancreatic and 347 gastric cancer samples.

Results
The density and the percentage of proliferating (Ki67+) CD8+ T cells were both highly variable between tumor types as well as between patients with the same tumor type. Elevated density and percentage of proliferating CD8+ cytotoxic T cells were significantly associated with favorable tumor parameters such as low tumor stage, negative nodal stage (p ≤ 0.0041 each), prolonged overall survival (p ≤ 0.0028 each) and an inflamed immune phenotype (p = 0.0025) in colorectal cancer and, in contrast, linked to high tumor stage, advanced ISUP/Fuhrman/Thoenes grading (each p ≤ 0.003), shorter overall survival (p ≤ 0.0330 each) and an immune inflamed phenotype (p = 0.0094) in renal cell cancer. In breast, ovarian, pancreatic and gastric cancer the role of (Ki67+)CD8+ Tcells was not linked to clinicopathological data.

Conclusion
Our data demonstrate a tumor type dependent prognostic impact of proliferating (Ki67+)CD8+ Tcells and an inverse impact in colorectal and renal cell cancer.
Biopsy findings after detection of de novo donor-specific antibodies in renal transplant recipients: a single center experience
Authors: Waldecker Christoph B. , Zgoura Panagiota , Seibert Felix S. , Gall Sabina , Schenker Peter , Bauer Frederic , Rohn Benjamin , Viebahn Richard , Babel Nina , Westhoff Timm H. 
Published: April 2021

Abstract
Background
De novo donor-specific antibodies (DSA) are associated with an increased risk of antibody-mediated rejection and a substantial reduction of allograft survival. We hypothesized that detection of DSA should prompt a biopsy even in the absence of proteinuria and loss of estimated glomerular filtration rate (eGFR). However, data on a population without proteinuria or loss of kidney function is scant, and this is the main novelty of our study design.

Methods
Single center retrospective analysis on biopsy findings after detection of de novo DSA. One-hundred-thirty-two kidney and pancreas-kidney transplant recipients were included. Eighty-four of these patients (63.6%) underwent allograft biopsy. At the time of biopsy n = 50 (59.5%) had a protein/creatinine ratio (PCR) > 300 mg/g creatinine and/or a loss of eGFR ≥ 10 ml/min in the previous 12 months, whereas 40.5% did not. Diagnosis of rejection was performed according to Banff criteria.

Results
Seventy-seven (91.7%) of the biopsies had signs of rejection (47.6% antibody mediated rejection (ABMR), 13.1% cellular, 20.2% combined, 10.7% borderline). Among subjects without proteinuria or loss of eGFR ≥ 10 ml/min/a (n = 34), 29 patients (85.3%) showed signs of rejection (44.1% antibody mediated (ABMR), 14.7% cellular, 11.8% combined, 14.7% borderline).

Conclusion
The majority of subjects with de novo DSA have histological signs of rejection, even in the absence of proteinuria and deterioration of graft function. Thus, it appears reasonable to routinely perform an allograft biopsy after the detection of de novo DSA.

Graphic abstract
Diabetes classification application with efficient missing and outliers data handling algorithms
Authors: Torkey Hanaa , Ibrahim Elhossiny , Hemdan EZZ El-Din , El-Sayed Ayman , Shouman Marwa A. 
Published: April 2021

AbstractCommunication between sensors spread everywhere in healthcare systems may cause some missing in the transferred features. Repairing the data problems of sensing devices by artificial intelligence technologies have facilitated the Medical Internet of Things (MIoT) and its emerging applications in Healthcare. MIoT has great potential to affect the patient's life. Data collected from smart wearable devices size dramatically increases with data collected from millions of patients who are suffering from diseases such as diabetes. However, sensors or human errors lead to missing some values of the data. The major challenge of this problem is how to predict this value to maintain the data analysis model performance within a good range. In this paper, a complete healthcare system for diabetics has been used, as well as two new algorithms are developed to handle the crucial problem of missed data from MIoT wearable sensors. The proposed work is based on the integration of Random Forest, mean, class' mean, interquartile range (IQR), and Deep Learning to produce a clean and complete dataset. Which can enhance any machine learning model performance. Moreover, the outliers repair technique is proposed based on dataset class detection, then repair it by Deep Learning (DL). The final model accuracy with the two steps of imputation and outliers repair is 97.41% and 99.71% Area Under Curve (AUC). The used healthcare system is a web-based diabetes classification application using flask to be used in hospitals and healthcare centers for the patient diagnosed with an effective fashion.
Abrasion Resistance of Ultra-High-Performance Concrete for Railway Sleepers
Authors: Hasnat Ariful , Ghafoori Nader 
Published: April 2021

AbstractThis study aimed to determine the abrasion resistance of ultra-high-performance concretes (UHPCs) for railway sleepers. Test samples were made with different cementitious material combinations and varying steel fiber contents and shapes, using conventional fine aggregate. A total of 25 UHPCs and two high-strength concretes (HSCs) were selected to evaluate their depth of wear and bulk properties. The results of the coefficient of variation (CV), relative gain in abrasion, and abrasion index of the studied UHPCs were also obtained and discussed. Furthermore, a comparison was made on the resistance to wear of the selected UHPCs with those of the HSCs typically used for prestressed concrete sleepers. The outcomes of this study revealed that UHPCs displayed excellent resistance against abrasion, well above that of HSCs. Amongst the utilized cementitious material combinations, UHPCs made with silica fume as a partial replacement of cement performed best against abrasion, whereas mixtures containing fly ash showed the highest depth of wear. The addition of steel fibers had a more positive influence on the abrasion resistance than it did on compressive strength of the studied UHPCs.
Structure, phase transformation, and hardness of NiTiHfNd alloys
Authors: Zhao Chunwang , Zhao Shilei 
Published: April 2021

AbstractNi50Ti29Hf21−xNdx (x = 0, 1, 2 at.%) and Ni50Ti29−xHf21Ndx (x = 1, 2 at.%) alloys were fabricated via arc melting. For the first time, the influence of Nd addition on structure, phase transformation, and hardness of NiTiHf alloy was investigated experimentally. It is found that the NiTiHfNd alloys consist of NiTiHf matrix and Nd-rich precipitates. Ni50Ti29Hf21 alloy demonstrates a martensitic transformation temperature as high as 314.1 °C, a thermal hysteresis as narrow as 37.7 °C, and a Vickers hardness as high as 500 HV. Nd addition obviously decreases the martensitic transformation temperature of NiTiHf alloys but still maintains a relatively narrow thermal hysteresis and a relatively high Vickers hardness compared with most other components of NiTiHf-based alloys.
Green synthesis of single phase hausmannite Mn3O4 nanoparticles via Aspalathus linearis natural extract
Authors: Diallo A. , Tandjigora N. , Ndiaye S. , Jan Tariq , Ahmad I. , Maaza M. 
Published: April 2021

Abstract
Nowadays, green synthesis of nanoparticles using plant precursors has been extensively studied. However, less attention has been given to Mn3O4. This contribution validates the synthesis of single-phase Hausmannite Mn3O4 nanoparticles by a green approach without using any standard acid/base compounds, surfactants, and organic/inorganic dissolving agents. The chemical chelation of the Mn precursor was performed via bioactive compounds of the Aspalathus Linearis’ extract, an African indigenous plant. Annealing at 400 °C for ~ 1 h was required to crystallize the small amorphous nanoparticles with an initial bimodal size distribution peaking at $$\left\langle {\phi_{1} } \right\rangle$$

ϕ
1

~ 4.21 nm and $$\left\langle {\phi_{2} } \right\rangle$$

ϕ
2

~ 8.51 nm respectively. Such annealing lead to increase in the diameter of the nanoparticles from 17 to 28 nm.The morphological, structural, vibrational, surface, and photoluminescence properties of the single-phase Hausmannite nanoparticles were comprehensively investigated by High Resolution Transmission Electron Microscopy(HRTEM),Energy Dispersive X-ray Spectroscopy (EDS), X-ray Diffraction (XRD), Raman and X-rays Photoelectron Spectroscopy (XPS), spectroscopy as well as room temperature photoluminescence. Structural and morphological investigations revealed the formation of quasi-spherical nanoparticles having a single phase Hausmannite Mn3O4 crystal structure. XPS results also validated the XRD results about the formation of Hausmannite Mn3O4 nanoparticles. Raman investigations allowed a crystal-clear distinction between the Mn3O4 nature of the nanoparticles from the potential γ -Mn2O3 phase as both phases belong to the same space group and both assume tetragonally-distorted cubic lattices of nearly similar dimensions. The optical studies of the single phase Hausmannite crystalline nanoparticles exhibited a broad photoluminescence in the spectral range of 300–700 nm, which is ideal for emission devices.

Graphic abstract
A novel sensitive based approach to ATC enhancement in wind power integrated transmission system
Authors: Narain Aishvarya , Srivastava S. K. , Singh S. N. 
Published: April 2021

Abstract
Available transfer capability (ATC) plays an important role for both buyers and suppliers in the deregulated power system. As the integration of renewable energy sources is taking place very quickly in the system. It is not suggested to place wind generation (WG) at any point of the system. In this paper, the optimal location of buses for WG using a novel sensitive based formula is proposed. The zones are formed using the transmission congestion distribution factor (TCDF) values. The average transmission congestion distribution factor (ATCDF) is used to locate the optimal point of the system. When the WG is integrated into the system its obvious ATC increases but at which point the ATC values will be more is considered as the main objective. The WG is placed at every bus in the zone created by the TCDF value and the ATC value is calculated. The test is performed on the IEEE-30 bus system in MATLAB coding environment. The comparison result shows the ATC value enhances more when the WG is placed according to the proposed method. The proposed method also helps to find multiple locations for WG installation according to ATCDF value.

Highlights

Average TCDF value is proposed to find the optimal bus location for getting more ATC value.

Integration of WG according to highest ATCDF value in the system.

Comparison of ATC obtain from the integration of WG at different buses in sensitive zones.

Validation of a proposed method by comparing the ATC value obtain from integrating WG at different buses.

The optimal bus location based on the ATCDF value gave enhance ATC value compare to the other bus location.

ATCDF value helps in finding the multiple locations for integration of WG in the system.
The effect of copper source on the stability and activity of α-tocopherol acetate, butylated hydroxytoulene and phytase
Authors: Concarr Michael J. , O’Rourke Rachel , Murphy Richard A. 
Published: April 2021

AbstractThe supplementation of Copper (Cu) is essential for the optimum performance of physiological functions, including growth performance and immune function. Cu is usually formulated into animal premixes in the form of inorganic salts, such as sulphates, or organic minerals. Organic minerals are mineral salts that are either complexed or chelated to organic ligands such as proteins, amino acids, and polysaccharides. Cu is often formulated into premixes alongside other essential components such as vitamins, enzymes and synthetic antioxidants, all of which are susceptible to negative interactions with Cu which can detrimentally effect both their stability and activity. The aim of this study was to determine the effect of five different commercially available Cu sources in relation to their effect on the stability of α-tocopherol acetate and on the activity of Butylated Hydroxytoluene (BHT) and three commercially available phytases in vitro. The results determined that Cu source played a significant role in relation to limiting the interactions between Cu and each of the other components in vitro. There were significant differences (p ≤ 0.05), not only, between the inorganic and organic Cu sources but also between some of the individual organic Cu sources in relation to their effect on α-tocopherol acetate, BHT and phytase.
Role of Atmospheric Indices in Describing Inshore Directional Wave Climate in the United Kingdom and Ireland
Authors: Scott T. , McCarroll R. J. , Masselink G. , Castelle B. , Dodet G. , Saulter A. , Scaife A. A. , Dunstone N. 
Published: April 2021

AbstractImproved understanding of how our coasts will evolve over a range of time scales (years‐decades) is critical for effective and sustainable management of coastal infrastructure. A robust knowledge of the spatial, directional and temporal variability of the inshore wave climate is required to predict future coastal evolution and hence vulnerability. However, the variability of the inshore directional wave climate has received little attention, and an improved understanding could drive development of skillful seasonal or decadal forecasts of coastal response. We examine inshore wave climate at 63 locations throughout the United Kingdom and Ireland (1980–2017) and show that 73% are directionally bimodal. We find that winter‐averaged expressions of six leading atmospheric indices are strongly correlated (r = 0.60–0.87) with both total and directional winter wave power (peak spectral wave direction) at all studied sites. Regional inshore wave climate classification through hierarchical cluster analysis and stepwise multi‐linear regression of directional wave correlations with atmospheric indices defined four spatially coherent regions. We show that combinations of indices have significant skill in predicting directional wave climates (R2 = 0.45–0.8; p < 0.05). We demonstrate for the first time the significant explanatory power of leading winter‐averaged atmospheric indices for directional wave climates, and show that leading seasonal forecasts of the NAO skillfully predict wave climate in some regions.
Increasing Human‐Perceived Heat Stress Risks Exacerbated by Urbanization in China: A Comparative Study Based on Multiple Metrics
Authors: Luo Ming , Lau Ngar‐Cheung 
Published: April 2021

AbstractMore than half of the total population in China are living in cities. Especially, the people in highly developed and spatially integrated city clusters, i.e., urban agglomerations (UAs), are facing increasing human‐perceived heat stress that describes the combined effects of hot temperature, high humidity, and lowered surface wind speed. By analyzing multiple indicators over 20 major UAs across China, we demonstrate that summer heat stress has been significantly intensifying in nearly all UAs during 1971–2014. This intensification is more profound in northern than southern regions and is especially stronger in more urbanized and densely populated areas (e.g., Beijing‐Tianjin‐Hebei and the Yangtze River Delta). Based on a dynamic classification of weather stations using time‐varying land use/land cover maps, we find that urban core areas exhibit distinctly stronger increasing heat stress trends than their surrounding rural areas. On average, urbanization contributes to approximately one‐quarter of the total increase in mean heat stress over urban core areas of UAs and nearly half of the total increase in extreme heat stress events. The urbanization effect is also dependent on the geographical region within China. Urbanization tends to have stronger intensifying effects on heat stress in UAs with higher population density in low‐altitude areas, while it has a relatively weaker intensifying and even weakening effect in some arid and high‐altitude regions. Moreover, as various heat stress metrics may yield different estimations of long‐term trend and urbanization contribution, the particular choice of heat stress indicator is of critical importance for investigations on this subject matter.
From Flood to Drip Irrigation Under Climate Change: Impacts on Evapotranspiration and Groundwater Recharge in the Mediterranean Region of Valencia (Spain)
Authors: Pool S. , Francés F. , Garcia‐Prats A. , Pulido‐Velazquez M. , Sanchis‐Ibor C. , Schirmer M. , Yang H. , Jiménez‐Martínez J. 
Published: April 2021

AbstractAgricultural irrigation is the major water consumer in the Mediterranean region. In response to the growing pressure on freshwater resources, more efficient irrigation technologies have been widely promoted. In this study, we assess the impact of the ongoing transition from flood to drip irrigation on future hydroclimatic regimes under various climate change scenarios, with a particular focus on actual evapotranspiration and groundwater recharge in the Mediterranean region of Valencia, Spain. Hydroclimatic predictions for the near‐term future (2020–2049) and the mid‐term future (2045–2074) were made under two emission scenarios (RCP 4.5 and RCP 8.5) using a hydrological model that was forced with data from five GCM‐RCM combinations and field‐based irrigation volume and frequency observations. Our findings suggest that climate change could lead to statistically significant changes in the regional hydroclimatic regime despite projection uncertainties. Major changes include a statistically significant decrease in mean groundwater recharge of up to −6.6% under flood irrigation and −9.3% under drip irrigation and contrasting changes in mean actual evapotranspiration for flood and drip irrigation in the order of +1% and −2.1%, respectively. Since sustainably available water resources in the Valencia region are entirely allocated, the expected changes and associated uncertainties create a challenging context for future water management. Our simulations further indicate that, rather than climate change, the choice of irrigation technique may have a greater impact on actual evapotranspiration and groundwater recharge. Our findings therefore highlight the importance of considering both climate change and irrigation technique when assessing future water resources in irrigated Mediterranean agriculture.
Spatially Resolved Measurements in Tropical Reservoirs Reveal Elevated Methane Ebullition at River Inflows and at High Productivity
Authors: Linkhorst Annika , Paranaíba José R. , Mendonça Raquel , Rudberg David , DelSontro Tonya , Barros Nathan , Sobek Sebastian 
Published: April 2021

AbstractAn increasing number of rivers is being dammed, particularly in the tropics, and reservoir water surfaces can be a substantial anthropogenic source of greenhouse gases. On average, 80% of the CO2‐equivalent emission of reservoirs globally has been attributed to CH4, which is predominantly emitted via ebullition. Since ebullition is highly variable across space and time, both measuring and upscaling to an entire reservoir is challenging, and estimates of reservoir CH4 emission are therefore not well constrained. We measured CH4 ebullition at high spatial resolution with an echosounder and bubble traps in two reservoirs of different use (water storage and hydropower), size and productivity in the tropical Brazilian Atlantic Rainforest biome. Based on the spatially most well‐resolved whole‐reservoir ebullition measurements in the tropics so far, we found that mean CH4 ebullition was twice as high in river inflow areas as in other parts of the reservoirs, and more than 4 times higher in the eutrophic compared to the oligotrophic reservoir. Using different upscaling approaches rendered similar whole‐reservoir CH4 ebullition estimates, suggesting that highly spatially‐resolved measurements may be more important for constraining reservoir‐wide CH4 estimates than choice of upscaling approach. The minimum sampling effort was high (>250 and >1,700 thirty‐meter segments of hydroacoustic survey to reach within 50% or 80% accuracy, respectively). This suggests that traditional manual bubble‐trap measurements should be abandoned in favor of highly resolved measurements in order to get spatially representative estimates of CH4 ebullition, which accounted for 60% and 99% of total C emission in the two studied reservoirs.