bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between race and prostate cancer treatment benefit in the Veterans Health Administration
Authors: Rude Temitope , Walter Dawn , Ciprut Shannon , Kelly Matthew D. , Wang Chan , Fagerlin Angela , Langford Aisha T. , Lepor Herbert , Becker Daniel J. , Li Huilin , Loeb Stacy , Ravenell Joseph , Leppert John T. , Makarov Danil V.
Published: June 2021

Background

Studies have demonstrated that Black men may undergo definitive prostate cancer (CaP) treatment less often than men of other races, but it is unclear whether they are avoiding overtreatment of low‐risk disease or experiencing a reduction in appropriate care. The authors' aim was to assess the role of race as it relates to treatment benefit in access to CaP treatment in a single‐payer population.

Methods

The authors used the Veterans Health Administration (VHA) Corporate Data Warehouse to perform a retrospective cohort study of veterans diagnosed with low‐ or intermediate‐risk CaP between 2011 and 2017.

Results

The authors identified 35,427 men with incident low‐ or intermediate‐risk CaP. When they controlled for covariates, Black men had 1.05 times the odds of receiving treatment in comparison with non‐Black men (P < .001), and high‐treatment‐benefit men had 1.4 times the odds of receiving treatment in comparison with those in the low‐treatment‐benefit group (P < .001). The interaction of race and treatment benefit was significant, with Black men in the high‐treatment‐benefit category less likely to receive treatment than non‐Black men in the same treatment category (odds ratio, 0.89; P < .001).

Conclusions

Although race does appear to influence the receipt of definitive treatment in the VHA, this relationship varies in the context of the patient's treatment benefit, with Black men receiving less definitive treatment in high‐benefit situations. The influence of patient race at high treatment benefit levels invites further investigation into the driving forces behind this persistent disparity in this consequential group.
Retracted: An integrated framework for COVID‐19 classification based on classical and quantum transfer learning from a chest radiograph
Authors: Umer Muhammad Junaid , Amin Javeria , Sharif Muhammad , Anjum Muhammad Almas , Azam Faisal , Shah Jamal Hussain
Published: June 2021

COVID‐19 is a quickly spreading over 10 million persons globally. The overall number of infected patients worldwide is estimated to be around 133,381,413 people. Infection rate is being increased on daily basis. It has also caused a devastating effect on the world economy and public health. Early stage detection of this disease is mandatory to reduce the mortality rate. Artificial intelligence performs a vital role for COVID‐19 detection at an initial stage using chest radiographs. The proposed methods comprise of the two phases. Deep features (DFs) are derived from its last fully connected layers of pre‐trained models like AlexNet and MobileNet in phase‐I. Later these feature vectors are fused serially. Best features are selected through feature selection method of PCA and passed to the SVM and KNN for classification. In phase‐II, quantum transfer learning model is utilized, in which a pre‐trained ResNet‐18 model is applied for DF collection and then these features are supplied as an input to the 4‐qubit quantum circuit for model training with the tuned hyperparameters. The proposed technique is evaluated on two publicly available x‐ray imaging datasets. The proposed methodology achieved an accuracy index of 99.0% with three classes including corona virus‐positive images, normal images, and pneumonia radiographs. In comparison to other recently published work, the experimental findings show that the proposed approach outperforms it.
Photoactivatable Small‐Molecule Inhibitors for Light‐Controlled TAM Kinase Activity
Authors: Le Bescont Julie , Mouawad Liliane , Boddaert Thomas , Bombard Sophie , Piguel Sandrine
Published: June 2021

The TAM kinase family arises as a promising therapeutic target for cancer therapy, as well as auto‐immune and viral diseases. In this study, we report the first photoactivatable caged inhibitors of Tyro3 and Mer. This strategy enables spatial and temporal control of the biological activity of the inhibitor upon irradiation with UV light. We describe the design, synthesis, photocleavage properties, and inhibitory activities of four Tyro3 and Mer photoactivatable small molecules. The proof of concept on the TAM kinase family was achieved in vitro, since irradiation by UV light restored the full inhibitory activity of two prodrugs.
Role of microRNAs in oncogenesis: Insights from computational and systems‐level modeling approaches
Authors: Govindaraj Vinodhini , Kar Sandip
Published: June 2021

MicroRNAs (miRNAs) often govern the cell fate decision‐making events associated with oncogenesis. miRNAs repress the target genes either by degrading the target mRNA or inhibiting the process of translation. However, mathematical and computational modeling of miRNA‐mediated target gene regulation in various cellular network motifs indicates that miRNAs play a much more complex role in cellular decision‐making events. In this review, we give an overview of the quantitative insights obtained from mathematical modeling of miRNA‐mediated gene regulations by highlighting the various factors associated with it that are pivotal in diversifying the cell fate decisions related to oncogenesis. Intriguingly, recent experiments suggest that under certain circumstances, miRNAs can lead to more complex gene regulatory dynamics by causing target gene upregulation. We discuss these modeling approaches that can help in understanding the subtleties of miRNA effects in oncogenesis.
Bactericidal fully human single‐chain fragment variable antibodies protect mice against methicillin‐resistant Staphylococcusaureus bacteraemia
Authors: Soltanmohammadi Behnoush , Piri‐Gavgani Somayeh , Basardeh Eilnaz , Ghanei Mostafa , Azizi Masoumeh , Khaksar Zabihollah , Sharifzadeh Zahra , Badmasti Farzad , Soezi Mahdieh , Fateh Abolfazl , Azimi Parisa , Siadat Seyed Davar , Shooraj Fahimeh , Bouzari Saeid , Omrani Mir Davood , Rahimi‐Jamnani Fatemeh
Published: June 2021

Objectives

The increasing prevalence of antibiotic‐resistant Staphylococcus aureus, besides the inadequate numbers of effective antibiotics, emphasises the need to find new therapeutic agents against this lethal pathogen.

Methods

In this study, to obtain antibody fragments against S. aureus, a human single‐chain fragment variable (scFv) library was enriched against living methicillin‐resistant S. aureus (MRSA) cells, grown in three different conditions, that is human peripheral blood mononuclear cells with plasma, whole blood and biofilm. The antibacterial activity of scFvs was evaluated by the growth inhibition assay in vitro. Furthermore, the therapeutic efficacy of anti‐S. aureus scFvs was appraised in a mouse model of bacteraemia.

Results

Three scFv antibodies, that is MEH63, MEH158 and MEH183, with unique sequences, were found, which exhibited significant binding to S. aureus and reduced the viability of S. aureus in in vitro inhibition assays. Based on the results, MEH63, MEH158 and MEH183, in addition to their combination, could prolong the survival rate, reduce the bacterial burden in the blood and prevent inflammation and tissue destruction in the kidneys and spleen of mice with MRSA bacteraemia compared with the vehicle group (treated with normal saline).

Conclusion

The combination therapy with anti‐S. aureus scFvs and conventional antibiotics might shed light on the treatment of patients with S. aureus infections.
Fluoxetine results in misleading conclusions on fish behavior
Authors: Grzesiuk Malgorzata , Pawelec Alicja
Published: June 2021

Fluoxetine is an antidepressant medicine causing relaxation and mood improvement in people, with silencing certain personality traits in some cases. The question arise if such phenomena can be observed in nontarget organisms such as fish. Fluoxetine affects fishes behavior; however, it is not known if the medicine affects its “personality.” This study aimed to evaluate the reaction of the invasive Neogobius fluviatilis and native Gobio gobio individuals to fluoxetine at environmental concentration of 360 ng/L. We prepared three variants of the experiments: (a) behavioral trials with unexposed fishes, (b) behavioral trials with the same fishes after 21 days of fluoxetine exposure, and (c) behavioral trials with the same fishes after 21‐day depuration period, that is, without fluoxetine. The fishes reaction time (RT), that is, difference in time spent on reaching food with and without the necessity of overcoming the obstacle, was analyzed. Additionally, the personality, bold or shy, traits of each fish individual, was assigned. The results indicated that environmental concentrations of the antidepressant influenced RT. The average RT of the fishes cultured with fluoxetine was by 7‐min shorter in comparison with the nonexposed control. Share of individuals exposed to fluoxetine assigned as bold raised to 71.4% in comparison with 46.4% in nonexposed control. This sheds new light on wild fishes behavior caught from freshwater. Environmental concentrations of the antidepressant influenced the time of fishes reaction and share individuals assigned as bold. Moreover, 21‐day recovery lasting might be not enough to get fluoxetine effect on fishes.
Incongruent long‐term trends of a marine consumer and primary producers in a habitat affected by nutrient pollution
Authors: Long Christopher A. , Chabot Ryan M. , El‐Khazen Mia N. , Kelley Jake R. , Mollet‐Saint Benoît Céline , Mansfield Katherine L.
Published: June 2021

Nutrient pollution, defined as excess nitrogen and phosphorus related to human activities, is a widespread anthropogenic impact that decreases water quality and limits light penetration in estuarine habitats. These factors can lead to shifts in primary producer communities, but the association between these changes and marine consumer patterns of abundance and growth is relatively unknown. Understanding these relationships is necessary for herbivorous species of conservation concern like the green turtle (Chelonia mydas). We used generalized additive models to analyze concurrent 18‐yr data sets of seagrass cover, drift macroalgae cover, juvenile green turtle abundance, and growth to (1) evaluate long‐term trends in primary producer cover and green turtle demographics; and (2) gain insights into their interrelatedness at a study site known to be affected by nutrient pollution throughout the study period. We found that seagrass cover sharply declined during our study period while macroalgae cover was more resilient with trends varying over time. Juvenile green turtle abundance slowly declined throughout the study period with altered intra‐annual trends, while growth rates remained relatively stable. The incongruence of these trends suggests that relationships between marine consumers and nutrient pollution are more complex than effects on food availability alone. Our results focus on the green turtle but highlight the need for greater understanding of relationships between marine consumer species and nutrient pollution at both local and regional scales.
Multiparameter diagnostic sensor measurements in heart failure patients presenting with SARS‐CoV‐2 infection
Authors: Gardner Roy S. , Capodilupo Robert C. , Ahmed Rezwan , Stolen Craig M. , An Qi , Averina Viktoria , Hernandez Adrian F. , Boehmer John P.
Published: June 2021

Aims

Implantable device‐based sensor measurements including heart sounds, markers of ventilation, and thoracic impedance have been shown to predict heart failure (HF) hospitalizations. We sought to assess how these parameters changed prior to COVID‐19 (Cov‐19) and how these compared with those presenting with decompensated HF or pneumonia.

Methods and results

This retrospective analysis explores patterns of changes in daily measurements by implantable sensors in 10 patients with Cov‐19 and compares these findings with those observed prior to HF (n = 88) and pneumonia (n = 12) hospitalizations from the MultiSENSE, PREEMPT‐HF, and MANAGE‐HF trials. The earliest sensor changes prior to Cov‐19 were observed in respiratory rate (6 days) and temperature (5 days). There was a three‐fold to four‐fold greater increase in respiratory rate, rapid shallow breathing index, and night heart rate compared with those presenting with HF or pneumonia. Furthermore, activity levels fell more in those presenting with Cov‐19, a change that was often sustained for some time. In contrast, there were no significant changes in 1st or 3rd heart sound (S1 and S3) amplitude in those presenting with Cov‐19 or pneumonia compared with the known changes that occur in HF decompensation.

Conclusions

Multi‐sensor device diagnostics may provide early detection of Cov‐19, distinguishable from worsening HF by an extreme and fast rise in respiratory rate along with no changes in S3.
Perfluorooctane Sulfonate in US Ambient Surface Waters: A Review of Occurrence in Aquatic Environments and Comparison to Global Concentrations
Authors: Jarvis Amanda L. , Justice James R. , Elias Michael C. , Schnitker Brian , Gallagher Kathryn
Published: June 2021

Perfluorooctane sulfonate (PFOS) is one of the dominant perfluoroalkyl substances (PFAS) detected in aquatic ecosystems. It has been used in a wide range of industrial and consumer products for decades. The unique properties of PFOS, including its stability and resistance to degradation, have made it highly persistent in the aquatic environment. Because of its persistence, potential toxicity, and occurrence in aquatic ecosystems, interest in PFOS has increased in recent decades. Despite this interest, current information on the environmental distribution of PFOS in ambient surface waters of the United States is fairly limited. This critical review summarizes the currently available literature on PFOS occurrence in surface waters across the United States and highlights existing data gaps. Available data are largely from a handful of study areas with known PFAS manufacturing or industrial uses, with much of the data collected from freshwater systems in eastern states and the upper Midwest. Measured PFOS concentrations in surface waters vary widely, over 8 orders of magnitude, with the highest concentrations occurring downstream from manufacturing and industrial use plants, areas near aqueous film-forming foam–use sites, and sites where PFOS precursors were used in textile treatment. Non–point source–related occurrences are highest near urbanized areas with high population densities. Current data illustrate the occurrence of PFOS in surface waters across multiple US states. Additional data are needed to better understand PFOS occurrence in US aquatic ecosystems, particularly in estuarine and marine systems and where monitoring data are not available (e.g., southwestern, central, and western United States). Additional PFOS occurrence data would provide valuable information on potential spatial and temporal variability in surface waters and possible risks posed to aquatic ecosystems. Environ Toxicol Chem 2021;40:2425–2442. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.
A fog‐based fault‐tolerant and QoE‐aware service composition in smart cities
Authors: Hosseini Bidi Arshia , Movahedi Zahra , Movahedi Zeinab
Published: June 2021

Nowadays, the smart city trend has attracted an important number of municipalities, enabling to control and manage smartly the city environment and provide the citizens with value‐added urban services. In this regard, Internet of Things and fog computing play a key role in providing smart city services, simplifying the decision making for city authorities and improving the quality of experience (QoE) for citizens. In this article, we address the problem of selecting appropriate urban service providers and their sequencing given the citizen request for a set of urban services (eg, banks, laundries, carwashes, gas stations, bakeries) considering a number of quality metrics. This latter can be translated into a service composition problem with the aim of optimizing the QoE of citizens, the load of service providers and the roads traffic. In such a context, the first contribution of this article consists of proposing a fog‐based fault‐tolerant architecture capable to address the scalability and reliability issues of smart cities, while processing efficiently and reactively the service composition requests of citizens. In addition, we map the QoE‐aware service composition problem in smart cities to a generalized traveling salesman problem and propose three metaheuristics based on genetic algorithms, particle swarm optimization, and artificial bee colony to solve this problem in a timely manner. The results obtained based on the developed prototype of our proposal demonstrate the superiority of our proposed approach compared with other existing service composition alternatives.
Can fire cause the collapse of Plasco Building: A numerical investigation
Authors: Khan Mustesin Ali , Khan Aatif Ali , Usmani Asif Sohail , Huang Xinyan
Published: June 2021

Since the tragic event of the World Trade Centre (WTC), efforts to understand realistic fire behaviour in tall buildings are accelerated. It is critical to understand the fire dynamics involved in a compartment fire before performing a forensic investigation of a fire accident. In this paper, various fire scenarios are considered to simulate the behaviour of fire in a high‐rise building and demonstrated the case of the Plasco Building using computationally fluid dynamics (CFD). Two fuel distribution patterns are assumed with different packing densities as clothes placed throughout the compartment in a scattered form (similar as in racks) and densely packed as stacked (stored in cartons). It is observed that the distribution of the fuel highly influences the duration of the fire, peak temperatures, and the severity of the fire. The fuel distribution also affects the spread of the fire in both horizontal and vertical directions, which helps in understanding probable fire scenario responsible for the collapse of a building. A case of subsequent heat transfer analysis in an OpenSEES FE model is conducted to represent the extent of temperature reaching the structural elements where temperature data from FDS are used as thermal boundary conditions. Large variations in the temperature of the structural members have been observed between two fuel distributions, which can be a governing factor while analysing structural behaviour in fire conditions. This paper provides insight into performing a forensic investigation of fire collapsed high‐rise buildings based on visual evidence.
Hypoglycemic effect of camel milk powder in type 2 diabetic patients: A randomized, double‐blind, placebo‐controlled trial
Authors: Zheng Yajie , Wu Fang , Zhang Ming , Fang Bing , Zhao Liang , Dong Lijie , Zhou Xiaojuan , Ge Shaoyang
Published: June 2021

Fresh camel milk was widely accepted to help to prevent and control of diabetes, especially in Africa, Middle East, and cooler dry areas of Asia. In this study, type 2 diabetic patients were enrolled to supplement with 10 g of camel milk powder twice a day for 4 weeks (n = 14), cow milk powder served as the placebo (n = 13). It was found that camel milk supplement decreased fasting blood glucose, 2‐hr postprandial blood glucose, serum content of total cholesterol, resistin, and lipocalin‐2. There was also a significant increase in serum content of osteocrin, amylin, and GLP‐1in camel milk group, indicating an improvement on adipose tissue and skeletal muscle. Camel milk powder supplement significantly enriched the relative abundance ofClostridium_sensu_stricto_1and[Eubacterium]_eligens_groupcompared with cow milk after the 4‐week intervention. This study suggested that camel milk powder can be used as a functional food help to treat type 2 diabetes.
Novel fusion genes in spindle cell rhabdomyosarcoma: The spectrum broadens
Authors: Montoya‐Cerrillo Diego M. , Diaz‐Perez Julio A. , Velez‐Torres Jaylou M. , Montgomery Elizabeth A , Rosenberg Andrew E.
Published: June 2021

Rhabdomyosarcoma (RMS) encompasses a heterogeneous group of tumors with striated muscle differentiation. RMSs are classified as alveolar, embryonal, spindle cell/sclerosing, and pleomorphic types and molecular analysis of these tumors has identified aberrations that are useful in their further subclassification. Spindle cell rhabdomyosarcoma (SpRMS) is uncommon and has been described withVGLL2fusions,EWSR1/FUS‐TFCP2rearrangements, andmyoD1mutations—the mutations are associated with significantly different prognoses. In addition, theNCOA2‐MEIS1fusion gene was recently described in two primary intraosseous RMS that contained spindle cell components. Herein, we report three cases of SpRMS harboring different novel fusion genes, one possessingEP300‐VGLL3, a second withNCOA2‐MEIS1andCAV1‐MET, and the third case hadHMGA2‐NEGR1and multiple amplified genes.
Larger benthic and planktonic biostratigraphy and facies of Albian sediments in Coastal Fars Zone (Zagros area, south‐west Iran)
Authors: Keshavarzi Mojtaba , Afghah Massih , Asadi Abdolmajid , Parvaneh Nejad Shirazi Mahnaz
Published: June 2021

A total of 64 samples were collected from the Kazhdumi Formation (Albian) of south Zagros Basin (Coastal Fars Zone) in order to study the biostratigraphy and analyse the lithofacies. Stratigraphic distribution of identified larger benthic and planktonic foraminifers has confirmed the presence of three successive biozones: Mesorbitolina subconcava‐Orbitolina discoidea Zone, Favusella washitensis Zone followed by an upper Conicorbitolina conica‐Mesorbitolina parva Zone. Generally, orbitolinids are well developed in the Albian succession in the studied section, whereas the stratigraphic distribution of planktonic foraminifers is more restricted, dominating the Favusella washitensis Zone. Nevertheless, microscopic investigation recognizes five microfacies consisting of extraclast‐foraminifer packstone, peloid‐intraclast Orbitolina wackestone, foraminiferal plankton wackestone, intraclast‐Orbitolina grainstone, and coral‐rudist wackestone, which indicated a shallow water carbonates palaeoenvironment (intertidal, lagoon, bar) and open marine. The alternation of both planktic and benthic foraminifera through the Kazhdumi Formation confirms a rapid transgression and regression in the studied section during Albian time, which is attributed to Kazerun basement fault behaviour in the mentioned time interval.
Ore‐forming mafic plutons emplaced at syn‐collisional compressive setting in Kalatongke Ni–Cu sulphide district, Southern Altay, CAOB: New evidence from the Late Carboniferous granitic porphyries
Authors: Wang Xue‐Hai , Xu Xing‐Wang , Zhang Bao‐Lin , Niu Lei
Published: June 2021

The Kalatongke deposit is the largest Ni–Cu sulphide deposit in the Central Asian Orogenic Belt (CAOB) in northern Xinjiang. The tectonic setting of the Kalatongke deposit and the collision period of the Altai and East Junggar terranes remain controversial. This study involves petrological, geochemical, and geochronological evaluations of granitic porphyries in the Kalatongke. The granitic porphyries are divided into three types according to the characteristics of petrology and geochemistry, dated at ~339, ~325, and ~310 Ma. Type‐1 granitic porphyry exhibits evident syn‐collisional characteristics, with plagioclase phenocrysts extending in one direction. This type is metaluminous (A/CNK <1.1), characterized by low SiO2 and K2O contents, and depleted in Nb, Ta, P, and Ti. Type‐2 granitic porphyry is strongly peraluminous (A/CNK >1.1) and characterized by high SiO2 and Al2O3 but low Sr contents. Type‐3 granitic porphyry is also metaluminous (A/CNK <1.1) and has high SiO2 and K2O contents. The estimated crustal thickness of the Kalatongke area increased from 40 to 55 km from 339 to 310 Ma, thereby indicating that its existence within the collisional orogeny period. According to the estimated emplacement depth of the granitic and mafic intrusions, the crust had been thickening since then. During the late collision period, lithospheric detachment caused by terrane collision resulted in asthenospheric mantle upwelling and formed regional mafic intrusions along the Irtysh fault.
Nonlinear manifold learning in functional magnetic resonance imaging uncovers a low‐dimensional space of brain dynamics
Authors: Gao Siyuan , Mishne Gal , Scheinost Dustin
Published: June 2021

Large‐scale brain dynamics are believed to lie in a latent, low‐dimensional space. Typically, the embeddings of brain scans are derived independently from different cognitive tasks or resting‐state data, ignoring a potentially large—and shared—portion of this space. Here, we establish that a shared, robust, and interpretable low‐dimensional space of brain dynamics can be recovered from a rich repertoire of task‐based functional magnetic resonance imaging (fMRI) data. This occurs when relying on nonlinear approaches as opposed to traditional linear methods. The embedding maintains proper temporal progression of the tasks, revealing brain states and the dynamics of network integration. We demonstrate that resting‐state data embeds fully onto the same task embedding, indicating similar brain states are present in both task and resting‐state data. Our findings suggest analysis of fMRI data from multiple cognitive tasks in a low‐dimensional space is possible and desirable.
Catastrophic health expenditures for children with disabilities in Iran: A national survey
Authors: Moradi Ghobad , Bolbanabad Amjad Mohamadi , Abdullah Farman Zahir , Safari Hossein , Rezaei Satar , Aghaei Abbas , Hematpour Siros , Farshadi Salahaddin , Naleini Nima , Piroozi Bakhtiar
Published: June 2021

Objective

The aim of this study was to investigate the percentage of households with disabled children aged 0–8 years who had faced catastrophic health expenditures (CHEs) due to the health costs of these children in Iran.

Methods

This cross‐sectional study was carried out on 2000 households with disabled children aged 0–8 years in five provinces of Iran in 2020. Data were collected using the World Health Survey questionnaire and face‐to‐face interview. Determinants of CHE were identified using logistic regression.

Results

32.7% of households with disabled children had faced CHE. Head of household being female (Adjusted OR = 18.89, 95%CI: 10.88–29.42), poor economic status of the household (Q1: Adjusted OR = 20.26, 95% CI, 11.42–35.94; Q2: Adjusted OR = 8.27, 95%CI, 4.45–15.36; Q3: Adjusted OR = 13.88, 95%CI, 7.89–24.41), lack of supplementary insurance by a child with disabilities (Adjusted OR = 6.13, 95%CI, 3.39–11.26), having a child with mental disability (Adjusted OR = 2.71, 95%CI, 1.60–4.69), and type of basic health insurance (having Iranian Health Insurance: Adjusted OR = 2.20, 95%CI, 1.38–3.49; having Social security insurance: Adjusted OR = 1.66, 95%CI, 1.06–2.61) significantly increased the chances of facing CHE.

Conclusion

A significant percentage of households with disabled children had faced CHE because of their disabled child's health costs. The key determinants of CHE should be considered by health policy‐makers in order to more financial protection of these households.
Canopy structure metrics governing stemflow funnelling differ between leafed and leafless states: Insights from a large‐scale rainfall simulator
Authors: Iida Shin'ichi , Wheeler Kathryn I. , Nanko Kazuki , Shinohara Yoshinori , Sun Xinchao , Sakai Naoki , Levia Delphis F.
Published: June 2021

An increasing number of studies have examined the effects of various biotic and abiotic factors on stemflow production. Of those that have ascribed the importance of canopy structure to stemflow production, there has been a bias towards field studies. Coupling Bayesian inference with the NIED (National Research Institute for Earth Science and Disaster Resilience, Tsukuba, Japan) large‐scale rainfall simulator, this study leveraged a unique opportunity to control rainfall amounts and intensities to pinpoint the canopy structural metrics that differentially influence stemflow funnelling ratios for three common tree species between leafed and leafless canopy states. For the first time, we examined whether canopy structure metrics exert a static control on stemflow funnelling ratios or whether different elements of canopy structure are more or less important under leafed or leafless states, thereby allowing us to determine if tacit assumptions about the static influence of canopy structure on stemflow production (and funnelling) are valid (or not). Rainfall simulations were conducted at 15, 20, 30, 40, 50, and 100 mm h−1 under both leafed and leafless tree conditions (12 simulations in total) to detect any differential effects on the presence or absence of foliage on stemflow funnelling ratios. For leafed conditions, the highest percentages of best‐fitting models (ΔDIC ≤2) indicated that stemflow funnelling ratios were mainly controlled by total dry aboveground biomass (Ball), diameter at breast height (DBH), total dry foliar biomass (Bf), tree height (H), and woody to foliar dry biomass ratio (BR). Whilst for the leafless state, the highest percentages of best‐fitting models (ΔDIC ≤2) indicated that total dry branch biomass (Bbr) was relatively dominant as was the interaction effects between crown projection area and species (CPA:species). These results compel us to reject any assumption of a static effect of different elements of canopy structure on stemflow funnelling.
Assessing soil quality changes after 10 years of agricultural activities in eastern Hungary*
Authors: Takács István , Amiri Mahdis , Károly Kith , Mohammed Safwan
Published: June 2021

In Hungary, soil plays a fundamental role in agricultural production. The main aim of this research was to track the spatial–temporal variations in certain soil properties (soil organic carbon [So], pH, NO3−, P, K, Mn, Zn and Cu) between 2000 and 2010 in 55 different farms in the eastern part of Hungary (Hajdú‐Bihar region). Soil data were collected from the Soil Conservation Information and Monitoring System. After 10 years of agricultural activities results reveal that the means of pH, So, NO3−, and Zn were higher in 2010 than in 2000. Indeed, of nine studied soil characteristics only two (So%, NO3−) showed a significant change according to the WilcoxonT‐test. The average pH_H2O increased by 0.13 and reached 7.31 ± 0.12 in 2010. The average NO3−(ppm) increased by 4.75 ppm and reached 19.9 ppm in 2010. For other soil nutrients, available P, K and Mg decreased slightly, while Mn decreased from 269 ± 25 ppm to 236 ± 21 ppm in 2010. Interestingly, Zn and Cu showed no change between 2000 and 2010. However, the inverse distance weighting (IDW) showed that the central part of the study area is more prone to changes due to intensive agricultural activities. The output of this research could assist decision makers when making soil conservation plans within the study area.
Providing a safer passage: Perceptions about a neighborhood intervention program for disadvantaged youth
Authors: George Molly , Twyford Jennifer M.
Published: June 2021

“Safe Passage” is an after‐school intervention program for disadvantaged youth in a medium‐sized city in southern California. Led by local law enforcement, as well as the city's recreation and park department, the program's goal is to combine community policing with after‐school care and tutoring to support children living in a large apartment complex with the highest rates of gang membership and crime in the city. This is an exploratory study that examines the perspectives of various stakeholders in the intervention program, including the community members, the local police, and Safe Passage staff members. Survey data from the community residents, program staff and law enforcement were collected. Findings indicate that there was some consensus across the various subpopulations on the challenges that have had the largest negative influence on youth in the community. The local police and the community members surveyed were also in agreement that police/community relations were largely positive. All stakeholders surveyed felt generally positive about the intervention program, but the community members were more skeptical of the program's ability to deter their children from trouble. Implications of our findings for the program and for future studies are discussed.
The European Medicines Agency Experience With Pediatric Dose Selection
Authors: Manolis Efthymios , Musuamba Flora T. , Karlsson Kristin E.
Published: June 2021

Getting the right dose regimen for children and adolescents is important but poses great scientific, practical, and ethical challenges. At the same time, the availability of data in adults is a huge advantage and needs to be used optimally when designing studies in children and analyzing pediatric data. Furthermore, the processes of maturation and growth are always key when selecting doses for children. All the above make study adaptations and model‐informed approaches imperative for dose exposure‐response characterization and dose selection in children. This article summarizes the experience gained in the European Medicines Agency on this topic and proposes some general guiding principles for defining objectives, study designs, and methodology tools for pediatric dose selection.
Prevalence of clinically relevant liver fibrosis due to nonalcoholic fatty liver disease in Indian individuals with type 2 diabetes
Authors: Kuchay Mohammad Shafi , Choudhary Narendra Singh , Mishra Sunil Kumar , Bano Tarannum , Gagneja Sakshi , Mathew Anu , Singh Manish Kumar , Kaur Parjeet , Gill Harmandeep Kaur , Wasir Jasjeet Singh , Sud Randhir , Mithal Ambrish
Published: June 2021

Background and Aim

Type 2 diabetes (T2D) in associated with higher prevalence and worse outcomes of nonalcoholic fatty liver disease (NAFLD). However, data regarding the prevalence of clinically relevant liver fibrosis (CRLF) in Indian individuals with T2D are scarce. We investigated the prevalence of, and factors associated with, CRLF in Indians with T2D.

Methods

We conducted a prospective study of 601 consecutive adults with T2D. Steatosis was diagnosed using ultrasonography. Liver stiffness measurement (LSM) by transient elastography of ≥8.0 kPa was taken as cutoff suggesting CRLF. Individuals with LSM > 13.0 kPa underwent dynamic magnetic resonance imaging (MRI) of liver for detecting changes consistent with cirrhosis.

Results

The prevalence of steatosis was 84.2%. Higher body mass index (BMI, P = 0.022), alanine aminotransferase (ALT; P = 0.001), and lower high‐density lipoprotein (HDL; P = 0.002) were independent factors associated with steatosis. The prevalence of CRLF was 28.2%. Higher BMI (P = 0.001), aspartate aminotransferase (AST; P < 0.0001), gamma‐glutamyl transpeptidase (GGT; P < 0.0001), and concomitant hypertension (P = 0.03) were independent factors associated with CRLF. Elevated ALT and AST (≥40 units/L) levels were present in 70.6 and 51.6% individuals with CRLF, respectively. Thirty‐one (7.2%) individuals had LSM > 13.0 kPa. Among them, 25 individuals underwent dynamic MRI of liver, which revealed features consistent with cirrhosis in 18 patients.

Conclusion

CRLF, an established risk factor for cirrhosis and overall mortality, affects at least one out of four (25%) Indians with T2D. These results support screening of all patients with T2D and NAFLD for liver fibrosis.
Sustained calcium ion release from bioceramics promotes CaSR-mediated M2 macrophage polarization for osteoinduction
Authors: Zhang Jinglun , Wu Qian , Yin Chengcheng , Jia Xiaoshi , Zhao Zifan , Zhang Xiaoxin , Yuan Guohua , Hu Hao , Zhao Qin
Published: June 2021

Innate immune cells, especially macrophages, play a dual role in tissue repair and the defense against foreign bodies. Although biphasic calcium phosphate (BCP) ceramics have been confirmed as an excellent osteoimmunoregulatory biomaterial, it is unclear whether the ions release of BCP directly affects macrophage polarization and the mechanism by which the ions release is involved in osteoimmunomodulation. Herein, we verified the superior osteoinductive capacity of BCP in wild-type mice and showed its inability to promote this process in macrophage-deficient (LysM−/−) mice. Moreover, scanning electron microscopy, ion release curve, and calcein AM-staining results confirmed that BCP-released Ca2+ in a sustained manner, thereby maintaining the long-term induction of M2 macrophage polarization and promoting the differentiation of mesenchymal stem cells into osteoblasts during osteogenesis. Furthermore, Ca2+ targeted the Wnt/β-catenin signaling pathway and activated Arg1 and IL-10 (M2 marker genes) transcription through the calcium-sensing receptor (CaSR) in macrophages. Under treatment with a CaSR antagonist, macrophages cultured with the BCP fluid extract exhibited lower Ca2+ intake and weaker M2 macrophage polarization. These findings underscore the critical role of macrophages in bone regeneration and clarify the molecular mechanisms of Ca2+-mediated osteoinduction by biomaterials, which is of great significance for the future design of biomaterial-oriented tissue regeneration engineering.
High prolactin levels in dihydropteridine reductase deficiency: A sign of therapy failure or additional pathology?
Authors: Vitturi Nicola , Lenzini Livia , Luisi Concetta , Carecchio Miryam , Gugelmo Giorgia , Francini‐Pesenti Francesco , Avogaro Angelo
Published: June 2021

We report the case of a 22‐year‐old man with a diagnosis of dihydropteridine reductase (DHPR) deficiency who progressively developed movement disorders and epilepsy. Despite L‐Dopa supplementation the patient continued to show high prolactin levels, with a discrepancy between the neurological clinical picture and the hormonal biochemical levels. For this reason, other potential causes were ruled out by performing a cerebral magnetic resonance imaging, which demonstrated a solid lesion in the pituitary gland strongly suggestive of a prolactinoma. As the association between metabolic disorders affecting biogenic amine synthesis and prolactinoma has not been previously reported in humans, this report suggests that a critical evaluation of the use of prolactin as a guide for therapy dosage should be made in patients with DHPR deficiency disorders.
Noninvasive Evaluation of Renal Hypoxia by Multiparametric Functional MRI in Early Diabetic Kidney Disease
Authors: Wang Rui , Lin Zhiyong , Yang Xuedong , Zhao Kai , Wang Suxia , Sui Xueqing , Su Tao , Wang Xiaoying
Published: June 2021

Background

Renal hypoxia, which caused by a mismatch between oxygen delivery and oxygen demand, may be the primary pathophysiological pathway driving diabetic kidney disease (DKD). Blood oxygenation level‐dependent (BOLD) magnetic resonance imaging (MRI) could detect hypoxia, but can be limited in distinguishing increased oxygen consumption or decreased blood supply.

Purpose

To explore multiparametric functional MRI in evaluating mechanism of the hypoxia changes in early stage of DKD.

Study Type

Prospective.

Animal Model

Thirty‐five New Zealand White rabbits were divided into control group (n = 5) and alloxan‐induced diabetes mellitus (DM) groups (DM3 group: n = 15, DM7 group: n = 15).

Field Strength/Sequence

3 T MRI/BOLD, arterial spin labeling (ASL), and asymmetric spin‐echo (ASE).

Assessment

The renal oxygenation level (R2*), renal blood flow (RBF), and oxygen extraction fraction (OEF) were evaluated by BOLD, ASL, and ASE MRI, respectively. The regions of interest were manually drawn including cortex, outer stripes of outer medulla (OS), and inner stripes of outer medulla (IS).

Statistical Tests

Analysis of variance, independent‐sample t‐test, and paired‐sample t‐test were applied for comparisons among groups, between groups, and within the same group. P < 0.05 was considered statistically significant.

Results

All renal regions of DM3 group at Day 3 after DM induction showed significantly higher R2* and OEF values compared to baseline. The RBF values showed no statistically significant difference (P = 0.62, 0.76, 0.09 in cortex, OS, and IS, respectively). For DM7 group at Day 7, R2*, OEF, and RBF values showed no statistically significant difference compared to baseline (P = 0.06, 0.05, 0.06 of R2*; 0.70, 0.64, 0.68 of OEF; and 0.33, 0.58, 0.48 of RBF in cortex, OS, and IS, respectively).

Data Conclusion

BOLD MRI could detect renal hypoxia in early stage of DKD rabbit model, which was mainly revealed by increased oxygen consumption, but not affected by renal blood flow change.

Level of Evidence: 2

Technical Efficacy Stage: 1
Hepatitis C virus genotype 4: A poorly characterized endemic genotype
Authors: Leumi Steve , El Kassas Mohamed , Zhong Jin
Published: June 2021

Globally, 13% of all hepatitis C virus (HCV) infections are caused by genotype 4 (GT4), which consists of 17 subtypes with various levels of susceptibility to anti‐HCV therapy. This genotype is endemic in the Middle East and Africa and has considerably spread to Europe lately. The molecular features of HCV‐GT4 infection, as well as its appropriate therapeutics, are poorly characterized as it has not been the subject of widespread basic research. As such, in this review, we aim to gather the current state of knowledge of this genotype with a particular emphasis on its heterogeneity, sequence signatures, resistance‐associated substitutions, and available in vivo and in vitro models used for its study. We urge developing more cell‐culture models based on different GT4 subtypes to better understand the virology and therapeutic response of this particular genotype. This review may raise more awareness about this genotype and trigger more basic research work to develop its research tools. This will be critical to design better therapeutics and help to provide adequate guidelines for physicians working with HCV‐GT4 patients.
Remember as we empathize. Do brain mechanisms engaged in autobiographical memory retrieval causally affect empathy awareness? A combined TMS and EEG registered report
Authors: Meconi Federica , Hodsoll John , Smullen Daniel , Degano Giulio , Di Lello Nicolò , Miniussi Carlo , Avenanti Alessio , Mevorach Carmel
Published: June 2021

Social interactions are partly driven by our ability to empathize—the capacity to share and understand others’ inner states. While a growing body of evidence suggests a link between past experiences and empathy, to what degree empathy is dependent on our own previous experiences (autobiographical memories, AMs) is still unclear. Whereas neuroimaging studies have shown wide overlapping brain networks underpinning AM and empathic processes, studies on clinical populations with memory loss have not always shown empathy is impaired. The current transcranial magnetic stimulation (TMS) and electroencephalography study will seek to shed light on this neuropsychological puzzle by testing whether self‐perceived empathy is causally linked to AM retrieval. Cortical activity, together with self‐rating of empathy, will be recorded for scenarios that echo personal experiences while a brain region critical for AM retrieval will be transiently inhibited using TMS before task performance.
MuRF1 deficiency prevents age‐related fat weight gain, possibly through accumulation of PDK4 in skeletal muscle mitochondria in older mice
Authors: Sugiura Kosuke , Hirasaka Katsuya , Maeda Tasuku , Uchida Takayuki , Kishimoto Koji , Oarada Motoko , Labeit Siegfried , Ulla Anayt , Sakakibara Iori , Nakao Reiko , Sairyo Koichi , Nikawa Takeshi
Published: June 2021

Recent studies show that muscle mass and metabolic function are interlinked. Muscle RING finger 1 (MuRF1) is a critical muscle‐specific ubiquitin ligase associated with muscle atrophy. Yet, the molecular target of MuRF1 in atrophy and aging remains unclear. We examined the role of MuRF1 in aging, using MuRF1‐deficient (MuRF1–/–) mice in vivo, and MuRF1‐overexpressing cell in vitro. MuRF1 deficiency partially prevents age‐induced skeletal muscle loss in mice. Interestingly, body weight and fat mass of more than 7‐month‐old MuRF1–/– mice were lower than in MuRF1+/+ mice. Serum and muscle metabolic parameters and results of indirect calorimetry suggest significantly higher energy expenditure and enhanced lipid metabolism in 3‐month‐old MuRF1–/– mice than in MuRF1+/+ mice, resulting in suppressed adipose tissue gain during aging. Pyruvate dehydrogenase kinase 4 (PDK4) is crucial for a switch from glucose to lipid metabolism, and the interaction between MuRF1 and PDK4 was examined. PDK4 protein levels were elevated in mitochondria from the skeletal muscle in MuRF1–/– mice. In vitro, MuRF1 interacted with PDK4 but did not induce degradation through ubiquitination. Instead, SUMO posttranscriptional modification (SUMOylation) of PDK4 was detected in MuRF1‐overexpressing cells, in contrast to cells without the RING domain of MuRF1. MuRF1 deficiency enhances lipid metabolism possibly by upregulating PDK4 localization into mitochondrial through prevention of SUMOylation. Inhibition of MuRF1‐mediated PDK4 SUMOylation is a potential therapeutic target for age‐related dysfunction of lipid metabolism and muscle atrophy.
Urinary metabolomics analysis of the protective effects of Daming capsule on hyperlipidemia rats using ultra‐high‐performance liquid chromatography coupled to quadrupole time‐of‐flight mass spectrometry
Authors: Zhao Wenting , An Ran , Liu Fangtong , Gu Jintao , Sun Yue , Xu Silun , Pan Yumiao , Gao Zhiyuan , Ji Hongyu , Du Zhimin
Published: June 2021

Hyperlipidemia is recognized as one of the most important risk factors for morbidity and mortality due to cardiovascular diseases. Daming capsule, a Chinese patent medicine, has shown definitive efficacy in patients with hyperlipidemia. In this study, serum biochemistry and histopathology assessment were used to investigate the lipid‐lowering effect of Daming capsule. Furthermore, urinary metabolomics based on ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry was conducted to identify the urinary biomarkers associated with hyperlipidemia and discover the underlying mechanisms of the antihyperlipidemic action of Daming capsule. After 10 weeks of treatment, Daming capsule significantly lowered serum lipid levels and ameliorated hepatic steatosis induced by a high‐fat diet. A total of 33 potential biomarkers associated with hyperlipidemia were identified, among which 26 were robustly restored to normal levels after administration of Daming capsule. Pathway analysis revealed that the lipid‐lowering effect of Daming capsule is related to the regulation of multiple metabolic pathways including vitamin B and amino acid metabolism, tricarboxylic acid cycle, and pentose phosphate pathway. Notably, the study demonstrates that metabolomics is a powerful tool to elucidate the multitarget mechanism of traditional Chinese medicines, thereby promoting their research and development.