bluuebunny/crossref_metadata_2025 huggingface dataset:
RIG-I acts as a tumor suppressor in melanoma via regulating the activation of the MKK/p38MAPK signaling pathway
Authors: Guo Rui , Lu Shun-Yuan , Ma Jin-Xia , Wang Qian-Lan , Zhang Lu , Tang Ling-Yun , Shen Yan , Shen Chun-Ling , Wang Jin-Jin , Lu Li-Ming , Wang Zhu-Gang , Zhang Hong-Xin
Published: April 2022

Studies have indicated that RIG-I may act as a tumor suppressor and participate in the tumorigenesis of some malignant diseases. However, RIG-I induces distinct cellular responses via different downstream signaling pathways depending on the cell type. To investigate the biological function and underlying molecular mechanism of RIG-I in the tumorigenesis of melanoma, we constructed RIG-I knockout, RIG-I-overexpressing B16-F10 and RIG-I knockdown A375 melanoma cell lines, and analyzed the RIG-I-mediated change in the biological behavior of tumor cells in spontaneous and poly (I:C)-induced RIG-I activation. Cell proliferation, cell cycling, apoptosis and migration were detected by CCK-8 assay, BrdU incorporation assay, Annexin V–PI staining assay and Transwell assay, respectively. In vivo tumorigenicity was evaluated by tumor xenograft growth in nude mice and subsequently by Ki67 staining and TUNEL assays. Furthermore, Western blotting was utilized to explore the underlying mechanism of RIG-I in melanoma cells. Our data showed that RIG-I promotes apoptosis and inhibits proliferation by G1 phase cell cycle arrest in the melanoma cell lines. Mechanistically, RIG-I induced the phosphorylation of p38 MAPK and MAPK kinases MKK3 and MKK4. In conclusion, the current study demonstrated that RIG-I suppressed the development of melanoma by regulating the activity of the MKK/p38 MAPK signaling pathway, which is relevant to research on novel therapeutic targets for this malignant disease.
Solid-State Hydrogen Storage Properties of Ti–V–Nb–Cr High-Entropy Alloys and the Associated Effects of Transitional Metals (M = Mn, Fe, Ni)
Authors: Cheng Bo , Li Yunkai , Li Xiaoxi , Ke Huibin , Wang Liang , Cao Tangqing , Wan Di , Wang Benpeng , Xue Yunfei
Published: April 2022

Recently, high-entropy alloys (HEAs) designed by the concepts of unique entropy-stabilized mechanisms, started to attract widespread interests for their hydrogen storage properties. HEAs with body-centered cubic (BCC) structures present a high potential for hydrogen storage due to the high hydrogen-to-metal ratio (up to H/M = 2) and vastness of compositions. Although many studies reported rapid absorption kinetics, the investigation of hydrogen desorption is missing, especially in BCC HEAs. We have investigated the crystal structure, microstructure and hydrogen storage performance of a series of HEAs in the Ti–V–Nb–Cr system. Three types of TiVCrNb HEAs (Ti4V3NbCr2, Ti3V3Nb2Cr2, Ti2V3Nb3Cr2) with close atomic radii and different valence electron concentrations (VECs) were designed with single BCC phase by CALPHAD method. The three alloys with fast hydrogen absorption kinetics reach the H/M ratio up to 2. Particularly, Ti4V3NbCr2 alloy shows the hydrogen storage capacity of 3.7 wt%, higher than other HEAs ever reported. The dehydrogenation activation energy of HEAs’ hydride has been proved to decrease with decreasing VEC, which may be due to the weakening of alloy atom and H atom. Moreover, Ti4V3NbCr2M (M = Mn, Fe, Ni) alloys were also synthesized to destabilize hydrides. The addition of Mn, Fe and Ni lead to precipitation of Laves phase, however, the kinetics did not improve further because of their own excellent hydrogen absorption. With increasing the content of Laves phase, there appear more pathways for hydrogen desorption so that the hydrides are more easily dissociated, which may provide new insights into how to achieve hydrogen desorption in BCC HEAs at room temperature.
The Co-evolution of the Regional Logistics Network in the Chengdu–Chongqing Region Based on Node Attraction
Authors: Mu Nengye , Wang Yuanshun , Wang Min , Han Shijiao , Chen Zhen-Song
Published: April 2022

With the formation of urban agglomerations, economic zones, and metropolitan areas, the supporting role of the regional logistics industry in economic development is becoming increasingly prominent. It is of great significance to study the spatiotemporal evolution and the coordinated development of regional logistics networks to realize regional integration. In this paper, we propose the weighted co-evolution model of regional logistics networks based on node attraction by introducing concepts such as logistics attractiveness, geographic space distance, and logistics node level, and we integrate the true regional situation into the evolution model. Taking the Chengdu–Chongqing region as an example, we analyze the co-evolution simulation of the area’s regional logistics network. The results show that (1) there are three node connections between new and original nodes, and 50 nodes are added per time interval, which is an ideal situation for studying the evolution of a regional logistics network; (2) the future evolution of the regional logistics network in the Chengdu–Chongqing region can be divided into three stages: the initial construction period from the initial state to the T2 stage, the slow maturity period from T2 to T3, and the coordinated development period from T3 to T4. This research serves as a reference for government managers to formulate logistics development plans.
Generalized Frequency Distributions for Environmental and Water Engineering
Authors: Singh Vijay P. , Zhang Lan
Published: April 2022

A multitude of processes in hydrology and environmental engineering are either random or entail random components which are characterized by random variables. These variables are described by frequency distributions. This book provides an overview of different systems of frequency distributions, their properties, and applications to the fields of water resources and environmental engineering. A variety of systems are covered, including the Pearson system, Burr system, and systems commonly applied in economics, such as the D'Addario, Dagum, Stoppa, and Esteban systems. The latter chapters focus on the Singh system and the frequency distributions deduced from Bessel functions, maximum entropy theory, and the transformations of random variables. The final chapter introduces the genetic theory of frequency distributions. Using real-world data, this book provides a valuable reference for researchers, graduate students, and professionals interested in frequency analysis.
L’histoire intellectuelle de l’Europe après le tournant global
Authors: Moyn Samuel
Published: April 2022

L’histoire intellectuelle de l’Europe après le tournant global

La globalisation de l’histoire intellectuelle de l’Europe moderne et contemporaine est attendue depuis longtemps ; elle en est également encore à ses débuts. Cet essai distingue quatre pistes suivies jusqu’à présent par les historiens. La première correspond à une tentative de retrouver les sources et les contextes mondiaux du canon de la « pensée européenne ». Une deuxième approche consiste à redonner vie aux imaginaires globaux des penseurs européens modernes. Une troisième possibilité, plus difficile à envisager, revient à retracer la circulation des traditions de pensée et des concepts européens à travers la planète en analysant leur réception et leur refaçonnage au cours de ces voyages, tandis que des réseaux de rétroaction complexes brouillaient les démarcations entre l’européen et le non-européen. Une quatrième et dernière voie, plus controversée, insiste sur l’importance capitale du canon de pensée européen dans la compréhension des interactions mondiales passées et présentes, en soulignant qu’une partie de la valeur de ce canon réside dans le fait qu’il peut aider à corriger les points aveugles que ses propres historiens lui ont imposés en représentant, à tort, la pensée européenne comme un isolat coupé du reste du monde.
L’histoire globale de l’Europe à l’aune de la religion
Authors: Green Abigail
Published: April 2022

L’histoire globale de l’Europe à l’aune de la religion

L’histoire européenne en tant que champ a été construite autour d’une idée de l’Europe – de ses frontières, de ses valeurs, de sa civilisation et de ses nationalités – structurée par le christianisme et ses héritages séculiers. Plutôt que de chercher à globaliser l’histoire de l’Europe en considérant l’influence de la chrétienté sur d’autres parties du monde, et vice versa, cet article remet en question ce récit dominant. Il se demande comment l’historiographie de l’Europe peut intégrer les historiographies des populations non chrétiennes de l’Europe, à savoir les juifs et les musulmans. Ces historiographies possèdent leurs rythmes propres, ainsi que des cadres conceptuels et des géographies spécifiques, dans lesquels l’Europe revêt des connotations très différentes ; elles déplacent notre attention du Nord et de l’Ouest vers le Sud et l’Est, nous enjoignant de penser différemment l’Europe et la diversité qui a toujours existé en son sein. Séparément, ces historiographies parlent d’expériences très différentes. Prises ensemble, elles nous aident à penser d’une autre manière l’interface entre l’Europe et le monde, et à écrire l’histoire de l’Europe elle-même à contre-courant.
Investigating the Preparedness of Iranian Families in the Face of Disasters
Authors: Karimi Kivi Hamid , Peyravi Mahmoudreza , Ahmadi Marzaleh Milad
Published: April 2022

Objective:

Preparedness in different sections of a society can improve the reactions of individuals at the time of disasters and strengthen the cooperation and coordination between people and organizations. The present study aimed to investigate the preparedness of households in Ardabil Province of Iran in the face of disasters in 2020.

Methods:

This descriptive, cross-sectional study was conducted in Ardabil Province in Iran in 2020. The target population included the households living in Ardabil Province. The study was conducted on 10 502 participants. The data were collected using a questionnaire completed by trained questioners by referring to the participants’ houses. It should be noted that the questionnaires were completed by one of the household parents. The questionnaire contained 15 questions related to taking and not taking disaster preparedness measures at specific times. EXCEL 2016 (Microsoft, Redmond, WA) and SPSS 23 software (IBM Corp, Armonk, NY) were used for data analysis.

Results:

Considering the score of 1 for each action, the mean score of households’ disaster preparedness in Ardabil Province was 31.09%. The preparedness level of 51.4%, 42.31%, and 6.29% of the households in the province against disasters was at low, moderate, and good levels, respectively. Among the items of preparedness in the face of disasters, the highest value was related to the familiarity of family members with the initial warnings of significant hazards (5162 households, 49.15%) followed by planning for coping with disasters (43.12%) and assessing the non-structural vulnerability (38.93%). Furthermore, the results showed that the level of household preparedness was higher in the center of the province compared to other cities.

Conclusion:

Evaluating the level of preparedness of different societies in the face of disasters can be very useful in identifying the challenges to improve preparedness and, consequently, achieving sustainable development. This assessment can be considered a resource for provincial policy-making and planning to achieve the priorities set out in the Sendai framework. However, such assessments should be performed periodically, for example, annually, to reflect the effectiveness of the interventional measures in improving preparedness. Considering the low level of households’ preparedness in the present study, there is a gap between what people know and what they do, and comprehensive studies are needed on various factors that encourage people to take preparedness measures.
Evolution of machine learning in environmental science—A perspective
Authors: Hsieh William W.
Published: April 2022

The growth of machine learning (ML) in environmental science can be divided into a slow phase lasting till the mid-2010s and a fast phase thereafter. The rapid transition was brought about by the emergence of powerful new ML methods, allowing ML to successfully tackle many problems where numerical models and statistical models have been hampered. Deep convolutional neural network models greatly advanced the use of ML on 2D or 3D data. Transfer learning has allowed ML to progress in climate science, where data records are generally short for ML. ML and physics are also merging in new areas, for example: (a) using ML for general circulation model parametrization, (b) adding physics constraints in ML models, and (c) using ML in data assimilation.
PaleoRec: A sequential recommender system for the annotation of paleoclimate datasets
Authors: Manety Shravya , Khider Deborah , Heiser Christopher , McKay Nicholas , Emile-Geay Julien , Routson Cody
Published: April 2022

Studying past climate variability is fundamental to our understanding of current changes. In the era of Big Data, the value of paleoclimate information critically depends on our ability to analyze large volume of data, which itself hinges on standardization. Standardization also ensures that these datasets are more Findable, Accessible, Interoperable, and Reusable. Building upon efforts from the paleoclimate community to standardize the format, terminology, and reporting of paleoclimate data, this article describes PaleoRec, a recommender system for the annotation of such datasets. The goal is to assist scientists in the annotation task by reducing and ranking relevant entries in a drop-down menu. Scientists can either choose the best option for their metadata or enter the appropriate information manually. PaleoRec aims to reduce the time to science while ensuring adherence to community standards. PaleoRec is a type of sequential recommender system based on a recurrent neural network that takes into consideration the short-term interest of a user in a particular dataset. The model was developed using 1996 expert-annotated datasets, resulting in 6,512 sequences. The performance of the algorithm, as measured by the Hit Ratio, varies between 0.7 and 1.0. PaleoRec is currently deployed on a web interface used for the annotation of paleoclimate datasets using emerging community standards.
Why we need to focus on developing ethical, responsible, and trustworthy artificial intelligence approaches for environmental science
Authors: McGovern Amy , Ebert-Uphoff Imme , Gagne David John , Bostrom Ann
Published: April 2022

Given the growing use of Artificial intelligence (AI) and machine learning (ML) methods across all aspects of environmental sciences, it is imperative that we initiate a discussion about the ethical and responsible use of AI. In fact, much can be learned from other domains where AI was introduced, often with the best of intentions, yet often led to unintended societal consequences, such as hard coding racial bias in the criminal justice system or increasing economic inequality through the financial system. A common misconception is that the environmental sciences are immune to such unintended consequences when AI is being used, as most data come from observations, and AI algorithms are based on mathematical formulas, which are often seen as objective. In this article, we argue the opposite can be the case. Using specific examples, we demonstrate many ways in which the use of AI can introduce similar consequences in the environmental sciences. This article will stimulate discussion and research efforts in this direction. As a community, we should avoid repeating any foreseeable mistakes made in other domains through the introduction of AI. In fact, with proper precautions, AI can be a great tool to help reduce climate and environmental injustice. We primarily focus on weather and climate examples but the conclusions apply broadly across the environmental sciences.
GAMES CHARACTERIZING LIMSUP FUNCTIONS AND BAIRE CLASS 1 FUNCTIONS
Authors: ELEKES MÁRTON , FLESCH JÁNOS , KISS VIKTOR , NAGY DONÁT , POÓR MÁRK , PREDTETCHINSKI ARKADI
Published: April 2022

We consider a real-valued function f defined on the set of infinite branches X of a countably branching pruned tree T. The function f is said to be a limsup function if there is a function
$u \colon T \to \mathbb {R}$
such that
$f(x) = \limsup _{t \to \infty } u(x_{0},\dots ,x_{t})$
for each
$x \in X$
. We study a game characterization of limsup functions, as well as a novel game characterization of functions of Baire class 1.
Increased energy and/or protein intake improves anthropometry and muscle strength in chronic obstructive pulmonary disease patients: a systematic review with meta-analysis on randomised controlled clinical trials
Authors: Bernardes Simone , Eckert Igor da Conceição , Burgel Camila Ferri , Teixeira Paulo José Zimermann , Silva Flávia Moraes
Published: April 2022

Compromised nutritional status is associated with a poor prognosis in chronic obstructive pulmonary disease (COPD) patients. However, the impact of nutritional support in this group of patients is controversial. The present study systematically reviewed the effect of energy and or protein supplements or food fortification on anthropometry and muscle strength of COPD patients. We searched MEDLINE (PubMed), EMBASE, Cochrane Library and Scopus for all published randomised clinical trials without language restriction up to May 2021. Three reviewers performed study selection and data extraction independently. We judged the risk of bias by RoB 2 and the certainty of evidence by the GRADE approach. We included thirty-two randomised controlled trials and compiled thirty-one of them (1414 participants) in the random-effects model meta-analyses. Interventions were energy and/or protein oral nutritional supplements or food fortification added to the diet for at least one week. Pooled analysis revealed that nutritional interventions increased body weight (muscle circumference (MD) = 1·44 kg, 95 % CI 0·81, 2·08, I2 = 73 %), lean body mass (standardised mean difference (SMD) = 0·37; 95 % CI 0·15, 0·59, I2 = 46 %), midarm muscle circumference (MD = 0·29 mm2, 95 % CI 0·02, 0·57, I2 = 0 %), triceps skinfold (MD = 1·09 mm, 95 % CI 0·01, 2·16, I2 = 0 %) and handgrip strength (SMD = 0·39, 95 % CI 0·07, 0·71, I2 = 62 %) compared with control diets. Certainty of evidence ranged from very low to low, and most studies were judged with some concerns or at high risk of bias. This meta-analysis revealed, with limited evidence, that increased protein and/or energy intake positively impacts anthropometric measures and handgrip strength of COPD patients.
Comparative analysis of five correction methods for thyroid volume by ultrasound and their recommended reference values in Chinese children aged 8–10 years
Authors: Liu Lanchun , Qian Tingting , Sun Rong , Du Yang , Li Ming , Liu Lixiang , Liu Peng , Fan Lijun , Meng Fangang
Published: April 2022

Considering the influence of body’s growth and development on thyroid volume (TVOL), whether five existed corrected methods could be applied to correct TVOL remains unclear, in terms of Chinese children’s increased growth and development trends. This study aimed to compare the applicability of five correction methods: Body Surface Area corrected Volume (BSAV), Body Mass Indicator corrected Volume (BMIV), Weight and Height corrected Volume Indicator (WHVI), Height corrected Volume Indicator 1 (HVI1) and Height corrected Volume Indicator 2 (HVI2) and to establish the reference values for correction methods. The data of Iodine Nutrition and Thyroid Function Survey were used to analyse the differences in TVOL between normal and abnormal thyroid function children. Data of National Iodine Deficiency Disorders Survey were used to compare five correction methods and to establish their reference values. The median urinary iodine concentrations of children surveyed were 256·1 μg/l in 2009 and 192·6 μg/l in 2019. No significant difference was found in TVOL and thyroid goitre rate between children with normal and abnormal thyroid function. In the determination of goitre, HVI1, HVI2, BSAV and BMIV all showed high agreement with TVOL, while the area under the receiver operating characteristic curve (AUC) of WHVI was relatively low for children aged 8 (AUC = 0·8993) and 9 (AUC = 0·8866) years. Most differences of TVOL between light and heavy weight, short and tall height children can be eliminated by BSAV. BSAV was the best corrected method in this research. Reference values were established for corrected TVOL in Chinese children aged 8–10 years by sex.
Implementation of an AI chatbot as an English conversation partner in EFL speaking classes
Authors: Yang Hyejin , Kim Heyoung , Lee Jang Ho , Shin Dongkwang
Published: April 2022

With the growth of chatbots, concerns about implementing artificial intelligence (AI) chatbots in educational settings have consistently arisen, especially for the purpose of language learning. This study introduced a task-based voice chatbot called “Ellie”, newly developed by the researchers, and examined the appropriateness of its task design and performance as an English conversation partner and students’ perceptions on using it in EFL class. Korean EFL learners (N = 314) aged 10–15 years performed three speaking tasks with Ellie in their school classroom. The participants took 9.63 turns per session on average using the first 1,000-word band, indicating that the chatbot highly encouraged students to engage in conversation, which rarely occurs in general EFL classes in Korea. The high task success rates (88.3%) showed the design appropriateness of both L2 tasks and operational intents in terms of users’ successful understanding and completeness of the given chatbot tasks. The participants’ responses to the survey not only supported the positive potential of the chatbot in EFL settings but also revealed limitations to be resolved. Future suggestions for advancing and implementing AI chatbots in EFL classrooms are discussed.
Participation in cost-offset community-supported agriculture by low-income households in the USA is associated with community characteristics and operational practices
Authors: Hanson Karla L , Xu Lynn , Marshall Grace A , Sitaker Marilyn , Jilcott Pitts Stephanie B , Kolodinsky Jane , Bennett April , Carriker Salem , Smith Diane , Ammerman Alice S , Seguin-Fowler Rebecca A
Published: April 2022

Objective:

Subsidised or cost-offset community-supported agriculture (CO-CSA) connects farms directly to low-income households and can improve fruit and vegetable intake. This analysis identifies factors associated with participation in CO-CSA.

Design:

Farm Fresh Foods for Healthy Kids (F3HK) provided a half-price, summer CO-CSA plus healthy eating classes to low-income households with children. Community characteristics (population, socio-demographics and health statistics) and CO-CSA operational practices (share sizes, pick up sites, payment options and produce selection) are described and associations with participation levels are examined.

Setting:

Ten communities in New York (NY), North Carolina (NC), Vermont and Washington states in USA.

Participants:

Caregiver–child dyads enrolled in spring 2016 or 2017.

Results:

Residents of micropolitan communities had more education and less poverty than in small towns. The one rural location (NC2) had the fewest college graduates (10 %) and most poverty (23 %) and poor health statistics. Most F3HK participants were white, except in NC where 45·2 % were African American. CO-CSA participation varied significantly across communities from 33 % (NC2) to 89 % (NY1) of weeks picked up. Most CO-CSA farms offered multiple share sizes (69·2 %) and participation was higher than when not offered (76·8 % v. 57·7 % of weeks); whereas 53·8 % offered a community pick up location, and participation in these communities was lower than elsewhere (64·7 % v. 78·2 % of weeks).

Conclusion:

CO-CSA programmes should consider offering a choice of share sizes and innovate to address potential barriers such as rural location and limited education and income among residents. Future research is needed to better understand barriers to participation, particularly among participants utilising community pick up locations.
Why communities hosting internally displaced persons in the Sahel need stronger and more effective legal protection
Authors: Fomekong Steve Tiwa
Published: April 2022

In the Sahel, host communities are among those most affected by recurrent internal displacement, but they are often ignored in responses to displacement. Furthermore, their situation has attracted little attention from researchers or other observers. The present article will argue that it is essential to provide these communities with adequate protection, especially as they play a leading role in providing humanitarian protection and assistance to internally displaced persons (IDPs). The article begins by examining the legal instruments that protect populations affected by forced displacement, in order to identify and present the legal protection they offer to IDP host communities. The article will then analyze and highlight the advantages of fully applying this protection. It will show that the recurrent violence and breaches of the law that these communities suffer are impeding the full realization of those advantages. Finally, the article shall propose solutions that would overcome the deficiencies noted and hence ensure enhanced protection for IDP host communities in Burkina Faso, Mali and Niger.
“Reason to know” in the international law of command responsibility
Authors: Fellmeth Aaron , Crawford Emily
Published: April 2022

A recent report by the Australian Defence Force arrived at a conclusion that further investigation was not warranted of commanders regarding their responsibility for failing to investigate suspicious behaviour of subordinates in Afghanistan, who were accused of violations of international humanitarian law. This troubling conclusion calls for a better analysis and understanding of command responsibility in international law and gaps in the law of command responsibility. This article identifies the conflicting precedents and scholarship regarding the law of command responsibility, which create uncertainty, and proposes a clarification of that law, with a special focus on the “reason to know” standard that triggers responsibility for failing to prevent or punish war crimes. It refutes the popular claim that commanders must act wilfully, and it rejects the common dichotomy between a commander who orders or otherwise directly participates in the war crimes of subordinates and one who unwittingly fails to prevent or punish such crimes. Using the empirical psychological literature, the article further explains how commanders can insidiously signal toleration of war crimes without giving direct orders. Finally, the article argues that international law, by absolving commanders who fail to properly train their subordinates to respect the law of armed conflict, misses a rare opportunity to deter war crimes, and offers some suggestions to fill this gap in the law.
High expression level of ROR1 and ROR1-signaling associates with venetoclax resistance in chronic lymphocytic leukemia
Authors: Ghia Emanuela M. , Rassenti Laura Z. , Choi Michael Y. , Quijada-Álamo Miguel , Chu Elvin , Widhopf George F. , Kipps Thomas J.
Published: April 2022

Although the BH3-mimetic venetoclax is highly cytotoxic for chronic lymphocytic leukemia (CLL) cells, some patients with CLL fail to clear minimal residual disease (MRD). We examined the CLL cells of seven such patients (CLL1-7) and found each had high-level expression of ROR1. By examining the CLL cells from such patients prior to therapy at SC1 and then more than 1 year later (Sample Collection 2 (SC2)), when they had progressive increases in MRD despite continued venetoclax therapy, we found the levels of ROR1 expressed on CLL cells at SC2 were significantly higher than that on CLL cells collected at SC1. At SC2, we also observed upregulation of genes induced by Wnt5a-induced ROR1 signaling, including BCL2L1. Transduction of the CLL-cell-line MEC1 to express ROR1 enhanced expression of target genes induced by ROR1-signaling, increased expression of BCL-XL, and enhanced resistance to venetoclax, even in MEC1 made to express mutant forms of BCL2, which are associated with venetoclax resistance. Treatment of primary CLL cells with Wnt5a also increased their resistance to venetoclax, an effect that could be inhibited by the anti-ROR1 mAb (UC-961, zilovertamab). Collectively, these studies indicate that Wnt5a-induced ROR1-signaling can enhance resistance to venetoclax therapy.
Difference in clinical features of SARS-CoV-2 in pediatric patients before and after emergence of P.1
Authors: Leung Char , Khong Ka-Wah , Chan Kwok-Hung , Lacerda Marcus Vinicius Guimarães , Frank Carlos Henrique Michiles
Published: April 2022

Background

The P.1 variant is a Variant of Concern announced by the WHO. The present work aimed to characterize the clinical features of pediatric patients with SARS-CoV-2 before and after the emergence of P.1.

Methods

This is a cohort study. Data of symptomatic patients younger than 18 years diagnosed with COVID-19 by PCR tests registered in Painel COVID-19 Amazonas were analyzed.

Results

A total of 4080 symptomatic pediatric patients were identified in the database between March 2020 and July 2021, of which 1654 were categorized as pre-P.1 and 978 as P.1-dominant cases, based on the prevalence of P.1 of >90% in the North Region, Brazil. Lower case-fatality rate was observed in non-infants infected during the P.1-dominant period (0.9% vs. 2.2%). In general, patients infected during the P.1-dominant period had less fever (70.8% vs. 74.2%) and less lower respiratory tract symptoms (respiratory distress: 11.8% vs. 18.9%, dyspnea: 27.9% vs. 34.5%) yet higher prevalence of neurological symptoms, headache for example (42.8% vs. 5.9%).

Conclusions

The prevalence of symptoms of COVID-19 can differ across different periods of variant dominance. Lower prevalence of fever during the P.1-dominant period may reduce the effectiveness of symptom-based screening in public premises where laboratory diagnostic tests are not available.

Impact

The prevalence rate of symptoms of SARS-CoV-2 infection can differ among different variants.

The present work documents the difference in the clinical features of SARS-CoV-2 in patients aged below 18 years before and after the emergence of P.1, the first study of its kind.

Unlike previous studies that focus solely on hospitalized cases, the present work considers both mild and severe cases.

While non-infants had a lower fatality rate, lower prevalence of fever associated with the emergence of P.1 may reduce the effectiveness of symptom-based screening in public premises where laboratory diagnostic tests are not available.
Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS production
Authors: Wu Qipeng , Li Le , Miao Chunmeng , Hasnat Muhammad , Sun Lixin , Jiang Zhenzhou , Zhang Luyong
Published: April 2022

Osteopontin (OPN) is a multifunctional cytokine that can impact cancer progression. Therefore, it is crucial to determine the key factors involved in the biological role of OPN for the development of treatment. Here, we investigated that OPN promoted hepatocellular carcinoma (HCC) cell proliferation and migration by increasing Reactive oxygen species (ROS) production and disclosed the underlying mechanism. Knockdown of OPN suppressed ROS production in vitro and in vivo, whereas treatment with human recombinant OPN produced the opposite effect. N-Acetyl-L-cysteine (NAC, ROS scavenger) partially blocked HCC cell proliferation and migration induced by OPN. Mechanistically, OPN induced ROS production in HCC cells by upregulating the expression of NADPH oxidase 1 (NOX1). NOX1 knockdown in HCC cells partially abrogated the cell proliferation and migration induced by OPN. Moreover, inhibition of JAK2/STAT3 phosphorylation effectively decreased the transcription of NOX1, upregulated by OPN. In addition, NOX1 overexpression increased JAK2 and STAT3 phosphorylation by increasing ROS production, creating a positive feedback loop for stimulating JAK2/STAT3 signaling induced by OPN. This study for the first time demonstrated that HCC cells utilized OPN to generate ROS for tumor progression, and disruption of OPN/NOX1 axis might be a promising therapeutic strategy for HCC.
Dislocation avalanches are like earthquakes on the micron scale
Authors: Ispánovity Péter Dusán , Ugi Dávid , Péterffy Gábor , Knapek Michal , Kalácska Szilvia , Tüzes Dániel , Dankházi Zoltán , Máthis Kristián , Chmelík František , Groma István
Published: April 2022

Compression experiments on micron-scale specimens and acoustic emission (AE) measurements on bulk samples revealed that the dislocation motion resembles a stick-slip process – a series of unpredictable local strain bursts with a scale-free size distribution. Here we present a unique experimental set-up, which detects weak AE waves of dislocation slip during the compression of Zn micropillars. Profound correlation is observed between the energies of deformation events and the emitted AE signals that, as we conclude, are induced by the collective dissipative motion of dislocations. The AE data also reveal a two-level structure of plastic events, which otherwise appear as a single stress drop. Hence, our experiments and simulations unravel the missing relationship between the properties of acoustic signals and the corresponding local deformation events. We further show by statistical analyses that despite fundamental differences in deformation mechanism and involved length- and time-scales, dislocation avalanches and earthquakes are essentially alike.
Genomic evidence for homoploid hybrid speciation between ancestors of two different genera
Authors: Wang Zefu , Kang Minghui , Li Jialiang , Zhang Zhiyang , Wang Yufei , Chen Chunlin , Yang Yongzhi , Liu Jianquan
Published: April 2022

Homoploid hybrid speciation (HHS) has been increasingly recognized as occurring widely during species diversification of both plants and animals. However, previous studies on HHS have mostly focused on closely-related species while it has been rarely reported or tested between ancestors of different genera. Here, we explore the likely HHS origin of Carpinus sect. Distegocarpus between sect. Carpinus and Ostrya in the family Betulaceae. We generate a chromosome-level reference genome for C. viminea of sect. Carpinus and re-sequence genomes of 44 individuals from the genera Carpinus and Ostrya. Our integrated analyses of all genomic data suggest that sect. Distegocarpus, which has three species, likely originates through HHS during the early divergence between Carpinus and Ostrya. Our study highlights the likelihood of an HHS event between ancestors of the extant genera during their initial divergences, which may have led to reticulate phylogenies at higher taxonomic levels.
Synchronizing rock clocks in the late Cambrian
Authors: Zhao Zhengfu , Thibault Nicolas R. , Dahl Tais W. , Schovsbo Niels H. , Sørensen Aske L. , Rasmussen Christian M. Ø. , Nielsen Arne T.
Published: April 2022

The Cambrian is the most poorly dated period of the past 541 million years. This hampers analysis of profound environmental and biological changes that took place during this period. Astronomically forced climate cycles recognized in sediments and anchored to radioisotopic ages provide a powerful geochronometer that has fundamentally refined Mesozoic–Cenozoic time scales but not yet the Palaeozoic. Here we report a continuous astronomical signal detected as geochemical variations (1 mm resolution) in the late Cambrian Alum Shale Formation that is used to establish a 16-Myr-long astronomical time scale, anchored by radioisotopic dates. The resulting time scale is biostratigraphically well-constrained, allowing correlation of the late Cambrian global stage boundaries with the 405-kyr astrochronological framework. This enables a first assessment, in numerical time, of the evolution of major biotic and abiotic changes, including the end-Marjuman extinctions and the Steptoean Positive Carbon Isotope Excursion, that characterized the late Cambrian Earth.
FAIR Genomes metadata schema promoting Next Generation Sequencing data reuse in Dutch healthcare and research
Authors: van der Velde K. Joeri , Singh Gurnoor , Kaliyaperumal Rajaram , Liao XiaoFeng , de Ridder Sander , Rebers Susanne , Kerstens Hindrik H. D. , de Andrade Fernanda , van Reeuwijk Jeroen , De Gruyter Fini E. , Hiltemann Saskia , Ligtvoet Maarten , Weiss Marjan M. , van Deutekom Hanneke W. M. , Jansen Anne M. L. , Stubbs Andrew P. , Vissers Lisenka E. L. M. , Laros Jeroen F. J. , van Enckevort Esther , Stemkens Daphne , ‘t Hoen Peter A. C. , Beliën Jeroen A. M. , van Gijn Mariëlle E. , Swertz Morris A.
Published: April 2022

The genomes of thousands of individuals are profiled within Dutch healthcare and research each year. However, this valuable genomic data, associated clinical data and consent are captured in different ways and stored across many systems and organizations. This makes it difficult to discover rare disease patients, reuse data for personalized medicine and establish research cohorts based on specific parameters. FAIR Genomes aims to enable NGS data reuse by developing metadata standards for the data descriptions needed to FAIRify genomic data while also addressing ELSI issues. We developed a semantic schema of essential data elements harmonized with international FAIR initiatives. The FAIR Genomes schema v1.1 contains 110 elements in 9 modules. It reuses common ontologies such as NCIT, DUO and EDAM, only introducing new terms when necessary. The schema is represented by a YAML file that can be transformed into templates for data entry software (EDC) and programmatic interfaces (JSON, RDF) to ease genomic data sharing in research and healthcare. The schema, documentation and MOLGENIS reference implementation are available at https://fairgenomes.org.
Multi-beam X-ray ptychography using coded probes for rapid non-destructive high resolution imaging of extended samples
Authors: Lyubomirskiy Mikhail , Wittwer Felix , Kahnt Maik , Koch Frieder , Kubec Adam , Falch Ken Vidar , Garrevoet Jan , Seyrich Martin , David Christian , Schroer Christian G.
Published: April 2022

Imaging large areas of a sample non-destructively and with high resolution is of great interest for both science and industry. For scanning coherent X-ray diffraction microscopy, i. e., ptychography, the achievable scan area at a given spatial resolution is limited by the coherent photon flux of modern X-ray sources. Multibeam X-ray ptychography can improve the scanning speed by scanning the sample with several parallel mutually incoherent beams, e. g., generated by illuminating multiple focusing optics in parallel by a partially coherent beam. The main difficulty with this scheme is the robust separation of the superimposed signals from the different beams, especially when the beams and the illuminated sample areas are quite similar. We overcome this difficulty by encoding each of the probing beams with its own X-ray phase plate. This helps the algorithm to robustly reconstruct the multibeam data. We compare the coded multibeam scans to uncoded multibeam and single beam scans, demonstrating the enhanced performance on a microchip sample with regular and repeating structures.
Circuit network theory of n-horizontal bridge structure
Authors: Fang Xin-Yu , Tan Zhi-Zhong
Published: April 2022

This research investigates a complex n order cascading circuit network with embedded horizontal bridge circuits with the N-RT method. The contents of the study include equivalent resistance analytical formula and complex impedance characteristics of the circuit network. The research idea is as follows. Firstly the equivalent model of n-order resistance network is established, and a fractional difference equation model is derived using Kirchhoff’s law. Secondly, the equivalent transformation method is employed to transform the fractional equation into a simple linear difference equation, and its particular solution is computed. Then the solution to the difference equation is used to derive the effective resistance of the resistance network of the embedded horizontal bridge circuit, and various special cases of equivalent resistance formula are analyzed and the correctness of the analysis model gets verified. Finally, as an expanded application, the equivalent complex impedance of LC network is studied, and Matlab drawing tool is employed to offer the equivalent impedance with various variables of the graph. Our results provide new research ideas and theoretical basis for relevant scientific researches and practical applications.
A generative adversarial network for synthetization of regions of interest based on digital mammograms
Authors: Oyelade Olaide N. , Ezugwu Absalom E. , Almutairi Mubarak S. , Saha Apu Kumar , Abualigah Laith , Chiroma Haruna
Published: April 2022

Deep learning (DL) models are becoming pervasive and applicable to computer vision, image processing, and synthesis problems. The performance of these models is often improved through architectural configuration, tweaks, the use of enormous training data, and skillful selection of hyperparameters. The application of deep learning models to medical image processing has yielded interesting performance, capable of correctly detecting abnormalities in medical digital images, making them surpass human physicians. However, advancing research in this domain largely relies on the availability of training datasets. These datasets are sometimes not publicly accessible, insufficient for training, and may also be characterized by a class imbalance among samples. As a result, inadequate training samples and difficulty in accessing new datasets for training deep learning models limit performance and research into new domains. Hence, generative adversarial networks (GANs) have been proposed to mediate this gap by synthesizing data similar to real sample images. However, we observed that benchmark datasets with regions of interest (ROIs) for characterizing abnormalities in breast cancer using digital mammography do not contain sufficient data with a fair distribution of all cases of abnormalities. For instance, the architectural distortion and breast asymmetry in digital mammograms are sparsely distributed across most publicly available datasets. This paper proposes a GAN model, named ROImammoGAN, which synthesizes ROI-based digital mammograms. Our approach involves the design of a GAN model consisting of both a generator and a discriminator to learn a hierarchy of representations for abnormalities in digital mammograms. Attention is given to architectural distortion, asymmetry, mass, and microcalcification abnormalities so that training distinctively learns the features of each abnormality and generates sufficient images for each category. The proposed GAN model was applied to MIAS datasets, and the performance evaluation yielded a competitive accuracy for the synthesized samples. In addition, the quality of the images generated was also evaluated using PSNR, SSIM, FSIM, BRISQUE, PQUE, NIQUE, FID, and geometry scores. The results showed that ROImammoGAN performed competitively with state-of-the-art GANs. The outcome of this study is a model for augmenting CNN models with ROI-centric image samples for the characterization of abnormalities in breast images.
Flow invariants in a channel obstructed by a line of inclined rods
Authors: Herrero V. A. , Ferrari H. , Marino R. , Clausse A.
Published: April 2022

An experiment is conducted in a rectangular channel obstructed by a transverse line of four inclined cylindrical rods. The pressure on the surface of a central rod and the pressure drop through the channel are measured varying the inclination angle of the rods. Three assemblies of rods with different diameters are tested. The measurements were analyzed applying momentum conservation principles and semi-empirical considerations. Several invariant dimensionless groups of parameters relating the pressure at key locations of the system with characteristic dimensions of the rods are produced. It was found that the independence principle holds for most of the Euler numbers characterizing the pressure at different locations, that is, the group is independent of the inclination angle provided that the inlet velocity projection normal to the rods is used to non-dimensionalize the pressure. The resulting semi-empirical correlations can be useful for designing similar hydraulic units.
Clinical and genetic features of a cohort of patients with MFN2-related neuropathy
Authors: Abati Elena , Manini Arianna , Velardo Daniele , Del Bo Roberto , Napoli Laura , Rizzo Federica , Moggio Maurizio , Bresolin Nereo , Bellone Emilia , Bassi Maria Teresa , D’Angelo Maria Grazia , Comi Giacomo Pietro , Corti Stefania
Published: April 2022

Charcot–Marie–Tooth disease type 2A (CMT2A) is a rare inherited axonal neuropathy caused by mutations in MFN2 gene, which encodes Mitofusin 2, a transmembrane protein of the outer mitochondrial membrane. We performed a cross-sectional analysis on thirteen patients carrying mutations in MFN2, from ten families, describing their clinical and genetic characteristics. Evaluated patients presented a variable age of onset and a wide phenotypic spectrum, with most patients presenting a severe phenotype. A novel heterozygous missense variant was detected, p.K357E. It is located at a highly conserved position and predicted as pathogenic by in silico tools. At a clinical level, the p.K357E carrier shows a severe sensorimotor axonal neuropathy. In conclusion, our work expands the genetic spectrum of CMT2A, disclosing a novel mutation and its related clinical effect, and provides a detailed description of the clinical features of a cohort of patients with MFN2 mutations. Obtaining a precise genetic diagnosis in affected families is crucial both for family planning and prenatal diagnosis, and in a therapeutic perspective, as we are entering the era of personalized therapy for genetic diseases.
Vero cells gain renal tubule markers in low-calcium and magnesium chemically defined media
Authors: Logan Megan , Rinas Karsten , McConkey Brendan , Aucoin Marc G.
Published: April 2022

In this study, a chemically defined, animal component-free media was developed to promote Vero growth in suspension. Key media compounds were screened using Plackett–Burman styled experiments to create a media formulation to support suspension growth. Vero cells remained viable in suspension, but their growth rate was extremely low, conversely, other cell types such as CHO-K1, MDCK and HEK293T were able to grow in single cell suspension in the same media. To investigate the slow growth of Vero cells, RNA-seq analysis was conducted. Vero cells were cultured in three different conditions: adherently in serum-containing medium, adherently in in-house medium, and in suspension in low calcium and magnesium in-house medium. This study illustrates that adherent cells maintain similar gene expression, while the suspension phenotype tends to overexpress genes related to renal tubules.