bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of contrast medium volume for abdominal CT in oncologic patients: prospective comparison between fixed and lean body weight-adapted dosing protocols
Authors: Caruso Damiano , Rosati Elisa , Panvini Nicola , Rengo Marco , Bellini Davide , Moltoni Giulia , Bracci Benedetta , Lucertini Elena , Zerunian Marta , Polici Michela , De Santis Domenico , Iannicelli Elsa , Anibaldi Paolo , Carbone Iacopo , Laghi Andrea 
Published: March 2021

Abstract
Background
Patient body size represents the main determinant of parenchymal enhancement and by adjusting the contrast media (CM) dose to patient weight may be a more appropriate approach to avoid a patient over dosage of CM. To compare the performance of fixed-dose and lean body weight (LBW)-adapted contrast media dosing protocols, in terms of image quality and parenchymal enhancement.

Results
One-hundred cancer patients undergoing multiphasic abdominal CT were prospectively enrolled in this multicentric study and randomly divided in two groups: patients in fixed-dose group (n = 50) received 120 mL of CM while in LBW group (n = 50) the amount of CM was computed according to the patient’s LBW. LBW protocol group received a significantly lower amount of CM (103.47 ± 17.65 mL vs. 120.00 ± 0.00 mL, p < 0.001). Arterial kidney signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) and pancreatic CNR were significantly higher in LBW group (all p ≤ 0.004). LBW group provided significantly higher arterial liver, kidney, and pancreatic contrast enhancement index (CEI) and portal venous phase kidney CEI (all p ≤ 0.002). Significantly lower portal vein SNR and CNR were observed in LBW-Group (all p ≤ 0.020).

Conclusions
LBW-adapted CM administration for abdominal CT reduces the volume of injected CM and improves both image quality and parenchymal enhancement.
Chitosan hydrogel-loaded MSC-derived extracellular vesicles promote skin rejuvenation by ameliorating the senescence of dermal fibroblasts
Authors: Zhao Xiangnan , Liu Yue , Jia Pingping , Cheng Hui , Wang Chen , Chen Shang , Huang Haoyan , Han Zhibo , Han Zhong-Chao , Marycz Krzysztof , Chen Xiaoniao , Li Zongjin 
Published: March 2021

Abstract
Background
The senescence of dermal fibroblasts (DFLs) leads to an imbalance in the synthesis and degradation of extracellular matrix (ECM) proteins, presenting so-called senescence-associated secretory phenotype (SASP), which ultimately leads to skin aging. Recently, mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been recognized as a promising cell-free therapy for degenerative diseases, which opens a new avenue for skin aging treatment.

Methods
In this study, we utilized chitosan (CS) hydrogel for effective loading and sustained release of EVs. In vitro, we explored the rejuvenation effects of CS hydrogel-incorporated EVs (CS-EVs) on replicative senescence DFLs through a series of experiments such as senescence-associated β-galactosidase (SA-β-gal) staining, RT-PCR, and Western blot analysis. Besides, we employed local multi-site subcutaneous injection to treat skin aging of naturally aged mice with CS-EVs and DiI fluorescent dye was used to label EVs to achieve in vivo real-time tracking.

Results
CS-EVs can significantly improve the biological functions of senescent fibroblasts, including promoting their proliferation, enhancing the synthesis of ECM proteins, and inhibiting the overexpression of matrix metalloproteinases (MMPs). Moreover, CS hydrogel could prolong the release of EVs and significantly increase the retention of EVs in vivo. After CS-EVs subcutaneous injection treatment, the aging skin tissues showed a rejuvenation state, manifested explicitly as the enhanced expression of collagen, the decreased expression of SASP-related factors, and the restoration of tissue structures.

Conclusions
CS hydrogel-encapsulated EVs could delay the skin aging processes by ameliorating the function of aging DFLs. Our results also highlight the potential of CS hydrogel-encapsulated EVs as a novel therapeutic strategy for improving aging skin to rejuvenation.
Human placental mesenchymal stem cells ameliorate chemotherapy-induced damage in the testis by reducing apoptosis/oxidative stress and promoting autophagy
Authors: Lu Jiafeng , Liu Zhenxing , Shu Mingkai , Zhang Liya , Xia Wenjuan , Tang Liuna , Li Jincheng , Huang Boxian , Li Hong 
Published: March 2021

Abstract
Background
The side effects of busulfan on male reproduction are serious, so fertility preservation in children undergoing busulfan treatment is a major worldwide concern. Human placental mesenchymal stem cells (hPMSCs) have advantages such as stable proliferation and lower immunogenicity that make them an ideal material for stimulating tissue repair, especially restoring spermatogenesis. The protective effects of hPMSCs in busulfan-induced Sertoli cells and in busulfan-treated mouse testes have not been determined. Our study aimed to elaborate the protective effect and potential mechanisms of hPMSCs in busulfan-treated testes and Sertoli cells.

Methods
First, we developed a mouse model of busulfan-induced testicular toxicity in vivo and a mouse Sertoli cell line treated with busulfan in vitro to assess the protective effect and mechanisms of hPMSC treatment on spermatogenesis. Then, the length, width, and weight of the testes were monitored using Vernier calipers. Furthermore, at 1 week and 4 weeks after the transplantation of hPMSCs, histological sections of testes were stained with hematoxylin-eosin, and the seminiferous tubules with fluid-filled cavities were counted. Through ELISA analysis, testosterone levels and MDA, SOD, LDH, and CAT activities, which are associated with ROS, were detected. Markers of ROS, proliferation (Ki67), and apoptosis (Annexin V) were evaluated by FACS. Next, the fluorescence intensity of proliferation markers (BrdU and SCP3), an antioxidant marker (SIRT1), a spermatogenesis marker (PLZF), and autophagy-related genes (P62 and LC3AB) were detected by fluorescence microscopy. The mRNA expression of γ-H2AX, BRCA1, PARP1, PCNA, Ki67, P62, and LC3 was determined by qRT-PCR.

Results
hPMSCs restored disrupted spermatogenesis, promoted improved semen parameters, and increased testosterone levels, testis size, and autophagy in the testis toxicity mouse model induced by busulfan. hPMSCs suppressed the apoptosis of Sertoli cells and enhanced their rate of proliferation in vitro. Additionally, hPMSCs protected against oxidative stress and decreased oxidative damage in the testis toxicity mouse model induced by busulfan. Furthermore, hPMSCs increased the expression of proliferation genes (PCNA and KI67) and decreased the mRNA levels of apoptotic genes such as γ-H2AX, BRCA1, and PARP1.

Conclusions
This research showed that hPMSC injection ameliorated busulfan-induced damage in the testis by reducing apoptosis/oxidative stress and promoting autophagy. The present study offers an idea for a new method for clinical treatment of chemotherapy-induced spermatogenesis.
Molecular optimization by capturing chemist’s intuition using deep neural networks
Authors: He Jiazhen , You Huifang , Sandström Emil , Nittinger Eva , Bjerrum Esben Jannik , Tyrchan Christian , Czechtizky Werngard , Engkvist Ola 
Published: March 2021

AbstractA main challenge in drug discovery is finding molecules with a desirable balance of multiple properties. Here, we focus on the task of molecular optimization, where the goal is to optimize a given starting molecule towards desirable properties. This task can be framed as a machine translation problem in natural language processing, where in our case, a molecule is translated into a molecule with optimized properties based on the SMILES representation. Typically, chemists would use their intuition to suggest chemical transformations for the starting molecule being optimized. A widely used strategy is the concept of matched molecular pairs where two molecules differ by a single transformation. We seek to capture the chemist’s intuition from matched molecular pairs using machine translation models. Specifically, the sequence-to-sequence model with attention mechanism, and the Transformer model are employed to generate molecules with desirable properties. As a proof of concept, three ADMET properties are optimized simultaneously:logD,solubility, andclearance, which are important properties of a drug. Since desirable properties often vary from project to project, the user-specified desirable property changes are incorporated into the input as an additional condition together with the starting molecules being optimized. Thus, the models can be guided to generate molecules satisfying the desirable properties. Additionally, we compare the two machine translation models based on the SMILES representation, with a graph-to-graph translation model HierG2G, which has shown the state-of-the-art performance in molecular optimization. Our results show that the Transformer can generate more molecules with desirable properties by making small modifications to the given starting molecules, which can be intuitive to chemists. A further enrichment of diverse molecules can be achieved by using an ensemble of models.
Cooperative treatment effectiveness of ATR and HSP90 inhibition in Ewing’s sarcoma cells
Authors: Marx Christian , Schaarschmidt Marc U. , Kirkpatrick Joanna , Marx-Blümel Lisa , Halilovic Melisa , Westermann Martin , Hoelzer Doerte , Meyer Felix B. , Geng Yibo , Buder Katrin , Schadwinkel Hauke M. , Siniuk Kanstantsin , Becker Sabine , Thierbach René , Beck James F. , Sonnemann Jürgen , Wang Zhao-Qi 
Published: March 2021

Abstract
Introduction
Ewing's sarcoma is an aggressive childhood malignancy whose outcome has not substantially improved over the last two decades. In this study, combination treatments of the HSP90 inhibitor AUY922 with either the ATR inhibitor VE821 or the ATM inhibitor KU55933 were investigated for their effectiveness in Ewing's sarcoma cells.

Methods
Effects were determined in p53 wild-type and p53 null Ewing's sarcoma cell lines by flow cytometric analyses of cell death, mitochondrial depolarization and cell-cycle distribution as well as fluorescence and transmission electron microscopy. They were molecularly characterized by gene and protein expression profiling, and by quantitative whole proteome analysis.

Results
AUY922 alone induced DNA damage, apoptosis and ER stress, while reducing the abundance of DNA repair proteins. The combination of AUY922 with VE821 led to strong apoptosis induction independent of the cellular p53 status, yet based on different molecular mechanisms. p53 wild-type cells activated pro-apoptotic gene transcription and underwent mitochondria-mediated apoptosis, while p53 null cells accumulated higher levels of DNA damage, ER stress and autophagy, eventually leading to apoptosis. Impaired PI3K/AKT/mTOR signaling further contributed to the antineoplastic combination effects of AUY922 and VE821. In contrast, the combination of AUY922 with KU55933 did not produce a cooperative effect.

Conclusion
Our study reveals that HSP90 and ATR inhibitor combination treatment may be an effective therapeutic approach for Ewing's sarcoma irrespective of the p53 status.
Community-based educational interventions for prevention of type II diabetes: a global systematic review and meta-analysis
Authors: Shirvani Tayebeh , Javadivala Zeinab , Azimi Somayeh , Shaghaghi Abdolreza , Fathifar Zahra , Devender Bhalla H. D. R. , Abdekhoda Mohammadhiwa , Nadrian Haidar 
Published: March 2021

Abstract
Purpose
Our objective was to estimate the change in community-based education interventions throughout the world that may effectuate in risk parameters of type II diabetes (T2D), including the diabetes incidence rate, fasting blood glucose, hemoglobin A1C, body mass index, waist circumference, and systolic and diastolic blood pressure.

Methods
A comprehensive search for globally eligible studies was conducted on PubMed, Embase, ProQuest, CINAHL nursing & allied health source, Cochrane Library, Google Scholar, conference proceedings, and reference lists. Data were extracted using JBI standardized data extraction tool. The primary outcome variables were diabetes incidence rate, fasting blood sugar (FBS), hemoglobin A1c (HbAlc), body mass index (BMI), waist circumference (WC), systolic/diastolic blood pressure (s/d BP). Random-effects meta-analysis and sub-group analyses were conducted.

Results
Nineteen interventional studies were included in the review, and ten studies were pooled in the meta-analysis (n = 16,106, mean age = 41.5 years). The incidence rate of T2D was reported in three trials, within which the risk of developing T2D was reduced by 54.0% in favor of community-based educational interventions, (RR = 0.54, 95% CI = 0.38–0.75; p < 0.001). In eleven (n = 11,587) and six (n = 6416) studies, the pooled mean differences were − 0.33 (95% CI: − 0.45 to − 0.20, p < 0.0001) and − 0.15 (95% CI: − 0.28 to − 0.03, p < 0.0001) for FBS and HbA1c levels, respectively. Positive significant effects were observed on reducing BMI [pooled mean difference = − 0.47 (95% CI: − 0.66 to − 0.28), I2 = 95.7%, p < 0.0001] and WC [pooled mean difference = − 0.66 (95% CI: − 0.89 to − 0.43), I2 = 97.3%, p < 0.0001]. The use of theoretical frameworks was found to provide a 48.0% change in fasting blood sugar.

Conclusions
Based on a comprehensive data collection of about 16,106 participants and reasonable analyses, we conclude that educational interventions may reduce diabetes incidence by 54.0%, particularly through reductions in fasting blood glucose, body mass index, and waist circumference. The diabetes risk parameters may favorably improve irrespective of the duration of intervention, at as low as 6 months. The application of theoretical frameworks while designing educational interventions is also encouraged.

Systematic review registration
PROSPERO CRD42018115877
Optimal harvesting strategies of a stochastic competitive model with S-type distributed time delays and Lévy jumps
Authors: Qiu Hong , Deng Wenmin , Xiang Mingqi 
Published: March 2021

AbstractThe aim of this paper is to investigate the optimal harvesting strategies of a stochastic competitive Lotka–Volterra model with S-type distributed time delays and Lévy jumps by using ergodic method. Firstly, the sufficient conditions for extinction and stable in the time average of each species are established under some suitable assumptions. Secondly, under a technical assumption, the stability in distribution of this model is proved. Then the sufficient and necessary criteria for the existence of optimal harvesting policy are established under the condition that all species are persistent. Moreover, the explicit expression of the optimal harvesting effort and the maximum of sustainable yield are given.
Central versus wellhead power plants in geothermal grid electricity generation
Authors: Kabeyi Moses Jeremiah Barasa , Olanrewaju Oludolapo A. 
Published: March 2021

AbstractThe long gestation period, high upfront costs and the risks in the development of central geothermal power plants are the main reasons for the slow rate of geothermal electricity growth and its contribution to the global electricity mix. The overall objective of this study was to make a comparison between central geothermal power plants and wellhead power plants in the delivery of geothermal electricity projects. The study showed that wellhead power plants are generally less efficient compared to central power plants because of higher specific steam consumption, but are financially attractive because of the quicker return on investment, early electricity generation and the lower financial risks. The study showed that permanent wellhead power plants are a better option for geothermal wells with too low or too high steam pressure compared to others in the steam field. Temporary use of wellhead power plants as opposed to their permanent use is preferred when only limited time is available between the commissioning of a wellhead plant and the commissioning of a central power plant in the same steam field. Technical, operational and environmental challenges, including higher specific steam consumption and lower efficiency than central power plants as well as absence of geothermal fluid reinjection system make wellhead plants less economical and less sustainable in resource use. It can thus be concluded that wellhead power plants can reduce the long wait to generate geothermal electricity and make an early return on investment for investors. Both central and wellhead power plants have relatively higher capacity factor than many other power plants and so can be used to supply base load electricity for the grid or off-grid power supply. This study is a review of the central and wellhead power plants and additionally provides policy guidelines in the execution of geothermal electricity projects either as central or wellhead power plants for grid electricity generation.
PR interval as a predictor of syncope in tilt-up testing in adolescents and young adults
Authors: Jug Juraj , Bradić Lada , Levicki Rea , Benčić Martina Lovrić 
Published: March 2021

Abstract
Background
Syncope, as the most frequent consciousness disorder, is very common in young individuals. The aim of this study was to analyze ECG parameters and clinical properties obtained during tilt-up testing in 12 to 30-year-old subjects. We enrolled a total of 142 patients from our outpatient clinic (39 males, 103 females) with a true positive tilt-up test and analyzed ECG records obtained during tilt-testing. Data were stratified according to the age, gender, and type of syncope.

Results
PR interval shortening preceding syncope was found in all syncope types, irrespective of the gender. All types of syncope were more frequent in women (72.5%). Mixed syncope type was found to be the most common (47.18%). Male and female subjects differed in initial heart rate (71.56 vs 76.23/min, p=0.05), as well as heart rate dynamics during tilt-up testing. A gender difference was also found in systolic blood pressure (116.92 vs 110.44 mmHg, p<0.01), time to syncope onset (20.77 vs. 16.44 min, p=0.03), and the total number of syncopal episodes in patient history (2.79 vs. 4.62, p<0.05). Subjects with cardioinhibitory syncope had the longest PR interval (average 154.3 ms). PR interval prolongation and loss of variability during tilt-up testing positively correlated with aging (r=0.22, p<0.05). Nodal rhythm was found in 8 patients.

Conclusion
PR interval shortening on ECG tracings during a tilt-up test can be found in all subtypes of vasovagal syncope, thereby contrasting previous reports that these changes are a hallmark of the cardioinhibitory type of syncope. PR shortening, if observed during ECG monitoring, could be a potential predictor of syncope.
Impurity effects in a two-dimensional nonsymmorphic Dirac semimetal
Authors: He Chaocheng 
Published: March 2021

Abstract
We theoretically study the impurity-induced states in a two-dimensional nonsymmorphic Dirac semimetal based on the T-matrix method. For calculating the local density of states, we find that for a Dirac system with two symmetry-inequivalent Dirac points the impurity states are similar to those in an ordinary two-dimensional Dirac sysytem. Whereas for the situation of two symmetry-equivalent Dirac points, the impurity states exhibit many distinct features, which are attributed to the spin-sublattice correlation associated with nonsymmorphic symmetry. In particular, these features are robust for the presence of the chiral symmetry-breaking term. Furthermore the impurity states in a Weyl semimetal and topological insulator with nonsymmorphic symmetries are derived and discussed. Thus the impurity effects of a two-dimensional nonsymmorphic Dirac semimetal can be used to probe the various topological nontrivial phases.
Symmetry and fluctuation of cell movements in neural crest-derived facial mesenchyme
Authors: Danescu Adrian , Rens Elisabeth G. , Rehki Jaspreet , Woo Johnathan , Akazawa Takashi , Fu Katherine , Edelstein-Keshet Leah , Richman Joy M. 
Published: March 2021

ABSTRACT
In the face, symmetry is established when bilateral streams of neural crest cells leave the neural tube at the same time, follow identical migration routes and then give rise to the facial prominences. However, developmental instability exists, particularly surrounding the steps of lip fusion. The causes of instability are unknown but inability to cope with developmental fluctuations are a likely cause of congenital malformations, such as non-syndromic orofacial clefts. Here, we tracked cell movements over time in the frontonasal mass, which forms the facial midline and participates in lip fusion, using live-cell imaging of chick embryos. Our mathematical examination of cell velocity vectors uncovered temporal fluctuations in several parameters, including order/disorder, symmetry/asymmetry and divergence/convergence. We found that treatment with a Rho GTPase inhibitor completely disrupted the temporal fluctuations in all measures and blocked morphogenesis. Thus, we discovered that genetic control of symmetry extends to mesenchymal cell movements and that these movements are of the type that could be perturbed in asymmetrical malformations, such as non-syndromic cleft lip.
This article has an associated ‘The people behind the papers’ interview.
Murine intestinal stem cells are highly sensitive to modulation of the T3/TRα1-dependent pathway
Authors: Godart Matthias , Frau Carla , Farhat Diana , Giolito Maria Virginia , Jamard Catherine , Le Nevé Clementine , Freund Jean-Noel , Penalva Luiz O. , Sirakov Maria , Plateroti Michelina 
Published: March 2021

ABSTRACT
The thyroid hormone T3 and its nuclear receptor TRα1 control gut development and homeostasis through the modulation of intestinal crypt cell proliferation. Despite increasing data, in-depth analysis on their specific action on intestinal stem cells is lacking. By using ex vivo 3D organoid cultures and molecular approaches, we observed early responses to T3 involving the T3-metabolizing enzyme Dio1 and the transporter Mct10, accompanied by a complex response of stem cell- and progenitor-enriched genes. Interestingly, specific TRα1 loss-of-function (inducible or constitutive) was responsible for low ex vivo organoid development and impaired stem cell activity. T3 treatment of animals in vivo not only confirmed the positive action of this hormone on crypt cell proliferation but also demonstrated its key action in modulating the number of stem cells, the expression of their specific markers and the commitment of progenitors into lineage-specific differentiation. In conclusion, T3 treatment or TRα1 modulation has a rapid and strong effect on intestinal stem cells, broadening our perspectives in the study of T3/TRα1-dependent signaling in these cells.
The RAC1 activator Tiam1 regulates centriole duplication through controlling PLK4 levels
Authors: Porter Andrew P. , Reed Hannah , White Gavin R. M. , Ogg Erinn-Lee , Whalley Helen J. , Malliri Angeliki 
Published: March 2021

ABSTRACT
Centriole duplication is tightly controlled to maintain correct centriole number through the cell cycle. Key to this is the regulated degradation of PLK4, the master regulator of centriole duplication. Here, we show that the Rac1 guanine nucleotide exchange factor (GEF) Tiam1 localises to centrosomes during S-phase, where it is required for the maintenance of normal centriole number. Depletion of Tiam1 leads to an increase in centrosomal PLK4 and centriole overduplication, whereas overexpression of Tiam1 can restrict centriole overduplication. Ultimately, Tiam1 depletion leads to lagging chromosomes at anaphase and aneuploidy, which are potential drivers of malignant progression. The effects of Tiam1 depletion on centrosomal PLK4 levels and centriole overduplication can be rescued by re-expression of both wild-type Tiam1 and catalytically inactive (GEF*) Tiam1, but not by Tiam1 mutants unable to bind to the F-box protein βTRCP (also known as F-box/WD repeat-containing protein 1A) implying that Tiam1 regulates PLK4 levels through promoting βTRCP-mediated degradation independently of Rac1 activation.