bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms and histopathological impacts of acetamiprid and azoxystrobin in male rats
Authors: EL-Hak Heba Nageh Gad , Al-Eisa Rasha A. , Ryad Lamia , Halawa Ekramy , El-Shenawy Nahla S.
Published: February 2022

Acetamiprid (neonicotinoid insecticide) and azoxystrobin (fungicide) are widespread pesticides used for pest management, but they have the potential for toxicity to mammals. The goal of this study was to look for oxidative stress, metabolic alterations, and reproductive problems in male rats’ serum after 2 months of exposure to sub-lethal dosages of acetamiprid and azoxystrobin. Seven classes of male rats were formed: control, 3 groups of acetamiprid (1/10, 1/20, 1/40 LD50), and 3 groups of azoxystrobin (1/10, 1/20, 1/40 LD50) and were orally daily treated (n = 8/group). Our findings revealed that acetamiprid and azoxystrobin disrupted oxidative and metabolic processes in the examined rats throughout 30 and 60 days of testing. The levels of nitric oxide increased significantly, while catalase, a superoxide dismutase enzyme, and glutathione reductase activity were reduced. Serum levels of sex hormones, calcium, and total protein have all dropped substantially in rats. In comparison to the control group, the testis and liver structure, as well as spermatozoa parameters, had distinct histological characteristics. In conclusion, acetamiprid and azoxystrobin exhibit dose- and time-dependent effects on oxidative parameters that cause testis damage.
Iron Oxide Nanoparticles in Mesenchymal Stem Cell Detection and Therapy
Authors: Mehta Kosha J.
Published: February 2022

Mesenchymal stem cells (MSCs) exhibit regenerative and reparative properties. However, most MSC-related studies remain to be translated for regular clinical usage, partly due to challenges in pre-transplantation cell labelling and post-transplantation cell tracking. Amidst this, there are growing concerns over the toxicity of commonly used gadolinium-based contrast agents that mediate in-vivo cell detection via MRI. This urges to search for equally effective but less toxic alternatives that would facilitate and enhance MSC detection post-administration and provide therapeutic benefits in-vivo. MSCs labelled with iron oxide nanoparticles (IONPs) have shown promising results in-vitro and in-vivo. Thus, it would be useful to revisit these studies before inventing new labelling approaches. Aiming to inform regenerative medicine and augment clinical applications of IONP-labelled MSCs, this review collates and critically evaluates the utility of IONPs in enhancing MSC detection and therapeutics. It explains the rationale, principle, and advantages of labelling MSCs with IONPs, and describes IONP-induced intracellular alterations and consequent cellular manifestations. By exemplifying clinical pathologies, it examines contextual in-vitro, animal, and clinical studies that used IONP-labelled bone marrow-, umbilical cord-, adipose tissue- and dental pulp-derived MSCs. It compiles and discusses studies involving MSC-labelling of IONPs in combinations with carbohydrates (Venofer, ferumoxytol, dextran, glucosamine), non-carbohydrate polymers [poly(L-lysine), poly(lactide-co-glycolide), poly(L-lactide), polydopamine], elements (ruthenium, selenium, gold, zinc), compounds/stains (silica, polyethylene glycol, fluorophore, rhodamine B, DAPI, Prussian blue), DNA, Fibroblast growth Factor-2 and the drug doxorubicin. Furthermore, IONP-labelling of MSC exosomes is reviewed. Also, limitations of IONP-labelling are addressed and methods of tackling those challenges are suggested.

Graphical Abstract
Hippocampus and its involvement in Alzheimer’s disease: a review
Authors: Rao Y. Lakshmisha , Ganaraja B. , Murlimanju B. V. , Joy Teresa , Krishnamurthy Ashwin , Agrawal Amit
Published: February 2022

Hippocampus is the significant component of the limbic lobe, which is further subdivided into the dentate gyrus and parts of Cornu Ammonis. It is the crucial region for learning and memory; its sub-regions aid in the generation of episodic memory. However, the hippocampus is one of the brain areas affected by Alzheimer’s (AD). In the early stages of AD, the hippocampus shows rapid loss of its tissue, which is associated with the functional disconnection with other parts of the brain. In the progression of AD, atrophy of medial temporal and hippocampal regions are the structural markers in magnetic resonance imaging (MRI). Lack of sirtuin (SIRT) expression in the hippocampal neurons will impair cognitive function, including recent memory and spatial learning. Proliferation, differentiation, and migrations are the steps involved in adult neurogenesis. The microglia in the hippocampal region are more immunologically active than the other regions of the brain. Intrinsic factors like hormones, glia, and vascular nourishment are instrumental in the neural stem cell (NSC) functions by maintaining the brain’s microenvironment. Along with the intrinsic factors, many extrinsic factors like dietary intake and physical activity may also influence the NSCs. Hence, pro-neurogenic lifestyle could delay neurodegeneration.
Zero-valent iron supported-lemon derived biochar for ultra-fast adsorption of methylene blue
Authors: Abd El-Monaem Eman M. , Omer Ahmed M. , El-Subruiti Gehan M. , Mohy-Eldin Mohamed S. , Eltaweil Abdelazeem S.
Published: February 2022

Green-based materials represent a new promising class of ecofriendly and economic adsorbents. Herein, nano zero-valent iron supported-lemon derived biochar (NZVI-LBC) was prepared for the first time and examined in the adsorptive removal of methylene blue as a model pollutant. Different characterization tools were used to ensure the successful fabrication of the NZVI-LBC composite including FTIR, XRD, TEM, XPS, VSM, BET, and zeta potential analysis. It was found that the fabricated NZVI–supported biochar composite attained the propitious adsorbent criteria since it provided a supreme efficient adsorption process at short  time. The reckoned maximum adsorption capacity of MB onto NZVI-LBC reached 1959.94 mg/g within merely 5 min. The obtained data clarified that the adsorption process of MB onto NZVI-LBC fitted pseudo 2nd order kinetic model and Freundlich isotherm model. Besides, the adsorption process of MB onto NZVI-LBC was found to be endothermic in nature. In addition, NZVI-LBC composite revealed an excellent adsorption behavior even after seven cycles. The concrete results reflect the potentiality of NZVI-LBC composite to be a superb candidate to remove cationic pollutants from their aqueous solutions.

Graphical abstract
Isolation, identification, and statistical optimization of a psychrotolerant Mucor racemosus for sustainable lipid production
Authors: Hashem Amr H. , Abu-Elreesh Gadallah , El-Sheikh Hussein H. , Suleiman Waleed B.
Published: February 2022

Lipid accumulating fungi are promising tools as alternative lipid source with different applications. In this study, seven oleaginous fungal strains were isolated from dung samples from the Egyptian ecosystem which later investigated for lipid accumulation, and Mucor racemosus AH1 represented the highest one. Statistical optimization of M. racemosus AH1 for lipid production was carried out using Taguchi design. Accordingly, dry biomass, total lipids, and lipid content were 3.72 gL−1, 1.21 gL−1, and 32.4%, respectively. Fatty acid profile of the produced lipids at different temperatures from 5 to 35 °C was investigated using gas chromatography mass spectroscopy GC–MS. Results revealed that the best temperature range for unsaturated fatty acids production particularly polyunsaturated fatty acids (PUFAs) was between 10 and 20 °C in which unsaturated fatty acids (USFAs) were higher than saturated fatty acids (SFAs); 54.47% and 43.67%, respectively. In conclusion, a promising lipid accumulating and cold-adapted M. racemosus MG547571 are considered as hopeful source of USFAs particularly oleic and linoleic acids which can be recruited for pharmaceutical applications, additionally, the high lipid yield could be exploited for biodiesel production.
Unmasking Antenatal Tuberous Sclerosis and 13 Years Retrospective Review of Its Diverse Presentations, Clinical-Imaging Follow Up and Learning the Latest Advances in Management
Authors: Chaudhuri Maitri , Tomar Munesh , Gaonkar Seema , Shankar BalaSubramanyam , Shenoi Arvind
Published: February 2022

A 27 year old multigravida, presented with giant left ventricular cardiac rhabdomyoma at the 23rd gestational week. A previous bad obstetric history prompted amniocentesis. A heterozygous, pathogenic, missense variant in exon 40 of the Tuberous Sclerosis (TSC 2) gene with autosomal dominant inheritance was extracted from fetal DNA by targeted gene capture. Sanger’s sequencing confirmed the same. This fetus highlighted the need for genetic assessment in every cardiac rhabdomyoma and a paradigm shift in fetal counseling protocol. We retrospectively reviewed our personal, multi-centric 13 years (2008–2020) database of cardiac rhabdomyomas in the fetal and pediatric cohort. Cardiac rhabdomyoma preceded extra-cardiac manifestations of Tuberous Sclerosis in 87.5% of our cohort. This article underscores this forgotten ominous association. We propose a paradigm shift in fetal counseling in such a scenario, remembering the heterogeneous timing and presentations of this widely variable genetic lesion.
A mathematical framework for the analysis and comparison of contact detection methods for ellipses and ellipsoids
Authors: Kheradmand Elham , Laforest Marc , Prudhomme Serge
Published: February 2022

The purpose of this research is to provide a framework for the analysis and comparison of contact detection algorithms for pairs of ellipses and ellipsoids. This work focuses primarily on the category of algorithms that are the most computationally efficient and can produce estimates of the separation and the penetration distance between ellipses and ellipsoids. Specifically, only analytic representations of the ellipses and ellipsoids are considered and contact detection for moving pairs of ellipsoids is not treated. The first contribution is a mathematical framework for the study of these algorithms, most notably with existence and uniqueness proofs for classes of contact detection algorithms, formal descriptions of the asymptotics of pairs of ellipses in close contact (or overlap), and a global analysis of constraints on the normals. The framework highlights the key role played by the different definitions of contact found in the literature, independent of the numerical strategies deployed to estimate the separation/penetration distance. Specifically, it is shown that all the studied algorithms can be expressed as minimization problems, with or without non-binding constraints on the normal(s) at the contact point(s), and that the constraints can be used to identify the global minima among the critical points in the minimization problem. Another contribution of this research, based on the mathematical framework introduced, is a better classification of the known algorithms. These algorithms are compared on established test problems, and their strengths and weaknesses are highlighted and explained in terms of their classification. Furthermore, this research provides comparisons in speed and stability between the most efficient algorithms in each category over a large sample size of test problems. Among the other contributions, this research describes inexpensive but effective initial estimates of the contact to be used in iterative algorithms. Finally, the usefulness of the new framework is illustrated with the introduction of a fast algorithm combining some new and old ideas.
Conflict and Climate Factors and the Risk of Child Acute Malnutrition Among Children Aged 24–59 Months: A Comparative Analysis of Kenya, Nigeria, and Uganda
Authors: Grace Kathryn , Verdin Andrew , Brown Molly , Bakhtsiyarava Maryia , Backer David , Billing Trey
Published: February 2022

Acute malnutrition affects a sizeable number of young children around the world, with serious repercussions for mortality and morbidity. Among the top priorities in addressing this problem are to anticipate which children tend to be susceptible and where and when crises of high prevalence rates would be likely to arise. In this article, we highlight the potential role of conflict and climate conditions as risk factors for acute malnutrition, while also assessing other vulnerabilities at the individual- and household-levels. Existing research reflects these features selectively, whereas we incorporate all the features into the same study. The empirical analysis relies on integration of health, conflict, and environmental data at multiple scales of observation to focuses on how local conflict and climate factors relate to an individual child’s health. The centerpiece of the analysis is data from the Demographic and Health Surveys conducted in several different cross-sectional waves covering 2003–2016 in Kenya, Nigeria, and Uganda. The results obtained from multi-level statistical models indicate that in Kenya and Nigeria, conflict is associated with lower weight-for-height scores among children, even after accounting for individual-level and climate factors. In Nigeria and Kenya, conflict lagged 1–3 months and occurring within the growing season tends to reduce WHZ scores. In Uganda, however, weight-for-height scores are primarily associated with individual-level and household-level conditions and demonstrate little association with conflict or climate factors. The findings are valuable to guide humanitarian policymakers and practitioners in effective and efficient targeting of attention, interventions, and resources that lessen burdens of acute malnutrition in countries prone to conflict and climate shocks.
Überwachungskapitalistische Biopolitik: Big Tech und die Regierung der Körper
Authors: Maschewski Felix , Nosthoff Anna-Verena
Published: February 2022

Der Artikel analysiert den Einzug Big Techs (der Fokus liegt auf Apple und Alphabet) in den Gesundheitsmarkt und beschreibt in Anlehnung an Michel Foucault und Shoshana Zuboff das Konzept einer „überwachungskapitalistischen Biopolitik“. Ziel ist, die Ausweitung des „Datenextraktivismus“ im Gesundheitswesen und der Gesundheitsforschung machtkritisch einzuordnen und damit einen Trend in der digitalen Gesundheitsfürsorge zu problematisieren, der sich in den letzten Jahren und, wie wir zeigen, besonders während der Coronakrise beschleunigt und ausgefächert hat. Anhand wissenschaftlicher und kommerzieller Projekte sowie Kooperationen im Bereich public health wird deutlich, dass zeitgenössische Formen der Biopolitik keineswegs auf staatliche Regime beschränkt sind. Stattdessen sind sie zunehmend über private Technologieunternehmen vermittelt, die dabei nicht nur intime Verhaltens- und Vitaldaten akkumulieren, sondern – qua proprietärer Algorithmen – auch den Zugang zu diesen kontrollieren und schließlich ihren Einfluss in exklusive Services und Produkte überführen. Ein besonderer Akzent des Artikels liegt zudem auf der voranschreitenden Verbreitung sogenannter Wearable-Technologien (Smartwatches etc.), über die sich nicht nur die herausgehobene Marktposition der Konzerne, sondern – in der Entwicklung von einem „quantifizierten Selbst“ zu einem „quantifizierten Kollektiv“ – auch ihre epistemische bzw. „infrastrukturelle Macht“ konkretisiert. Entgegen einer einseitig repressiven Perspektive auf biopolitische Praxen zeigen wir schließlich Ansätze einer Demokratisierung „überwachungskapitalistischer Biopolitik“ auf. Hierbei heben wir vier Topoi hervor, die von zentraler Bedeutung sind: Privatsphäre bzw. individuelle Souveränität, demokratische Deliberation, Pluralismus und epistemische Gleichheit.
Using Weighted Differences in Hazards as Effect Sizes for Survival Data
Authors: Wang H. , Chen D. , Pan Q. , Hueman M. T.
Published: February 2022

Sensitive to the change in sample sizes, traditional measures such as values of test statistics or p values can fail to quantify the difference in survival between populations for time-to-event data. We thereby propose to use effect sizes defined as the weighted differences in hazards to evaluate the survival difference between two groups. On the basis of the logrank test statistic, Gehan–Wilcoxon test statistic and Prentice–Wilcoxon test statistic, we developed three effect sizes that compare the survival experiences over the time period of investigation. Estimates of these three effect sizes were provided and their large sample behaviors were studied. In light of the Mann–Whitney parameter, we presented an effect size that compares the survival experiences over the entire possible/hypothetical time period. Two estimates of this effect size were constructed. We compared the proposed effect sizes and illuminated their use by theoretical studies, simulations and real cancer data. The effect sizes proposed in this article can help understand the survival difference in populations and are expected to have promising applications in the field of survival analysis.
Lost in Translation: Bilingual Parent Coaches' Experiences Implementing an Un-adapted Early Childhood Intervention with Non-English Speakers
Authors: Sattler Patricia L. , Paceley Meg , Byers Kaela , Mulkey Zoë , Mendenhall Amy
Published: February 2022

When implementing an evidence-based intervention in new contexts and with different populations, evaluation of not only outcomes, but also implementation processes become necessary. The purpose of this study was to explore the experiences of bilingual, bicultural parent coaches delivering Attachment and Biobehavioral Catch-up (ABC), an early childhood evidence-based home visiting intervention (EBI), to Spanish-speaking families in the United States (U.S.). This qualitative study draws on semi-structured interviews completed with four ABC parent coaches in two U.S. states. All participants identify as female and are bicultural, native Spanish speakers. Analyses resulted in six themes organized into two broad categories: (1) challenges to providing ABC to Spanish-speaking families and (2) positive experiences providing ABC to Spanish-speaking families. Results highlight that in-the-field translation and delivery of an empirically supported early intervention that has not been adapted for use with non-English speakers is challenging even for bilingual, bicultural parent coaches. Opportunities for deep-structure adaptations of the ABC intervention are explored. Practice and research implications also are discussed.
Polymethine dyes for PDT: recent advances and perspectives to drive future applications
Authors: Dereje Degnet Melese , Pontremoli Carlotta , Moran Plata Maria Jesus , Visentin Sonja , Barbero Nadia
Published: February 2022

It has been proved that the effectiveness of photodynamic therapy (PDT) is closely related to the intrinsic features of the photosensitizer (PS). Over the recent years, several efforts have been devoted to the discovery of novel and more efficient photosensitizers showing higher efficacy and lower side effects. In this context, squaraine and cyanine dyes have been reported to potentially overcome the drawbacks related to the traditional PSs. In fact, squaraines and cyanines are characterized by sharp and intense absorption bands and narrow emission bands with high extinction coefficients typically in the red and near-infrared region, good photo and thermal stability and a strong fluorescent emission in organic solvents. In addition, biocompatibility and low toxicity make them suitable for biological applications. Despite these interesting intrinsic features, their chemical instability and self-aggregation properties in biological media still limit their use in PDT. To overcome these drawbacks, the self-assembly and incorporation into smart nanoparticle systems are forwarded promising approaches that can control their physicochemical properties, providing rational solutions for the limitation of free dye administration in the PDT application. The present review summarizes the latest advances in squaraine and cyanine dyes for PDT application, analyzing the different strategies, i.e.the self-assembly and the incorporation into nanoparticles, to further enhance their photochemical properties and therapeutic potential. The in vivo assessments are still limited, thus further delaying their effective application in PDT.

Graphical abstract
Social Determinants of the Mental Health of Young	Migrants
Authors: Verelst An , Spaas Caroline , Pfeiffer Elisa , Devlieger Ines , Kankaapää Reeta , Peltonen Kirsi , Vänskä Mervi , Soye Emma , Watters Charles , Osman Fatumo , Durbeej Natalie , Sarkadi Anna , Andersen Arnfinn , Primdahl Nina Langer , Derluyn Ilse
Published: February 2022

Abstract. Background: Young migrants face particular risks to develop mental health problems. Discrimination and social support impact mental health, yet little is known about the differential impact thereof on mental health in newcomers, non-newcomer migrants, and non-migrants. Aim: This study sheds light on mental health (posttraumatic stress, behavioral problems, hyperactivity, emotional distress, peer relationship problems, prosocial behavior) and the overall well-being of newcomers, non-newcomer migrants, and non-migrants. Furthermore, the impact of social support and discrimination on mental health is investigated. Method: Descriptive analysis and Structural Equation Modelling (SEM) were applied to analyze responses of 2,320 adolescents through self-report questionnaires in Finland, Sweden, and the UK. Results: Newcomers, non-newcomer migrants, and non-migrants have different psychological profiles. While newcomers suffer more from posttraumatic stress disorder (PTSD) and peer problems, non-newcomers and non-migrants report more hyperactivity. Discrimination strongly threatens all mental health dimensions, while support from family serves as a protective factor. Support from friends has a positive impact on PTSD among newcomers. Limitations: As this study has a cross-sectional design, conclusions about causality cannot be drawn. In addition, history of traumatic life events or migration trajectory was lacking, while it may impact mental health. Conclusion: Different mental health profiles of newcomers, non-newcomer migrants, and non-migrants point to the need for a tailored and diversified approach. Discrimination remains a risk factor for mental health, while family support is a protective factor for adolescents. Interventions that foster social support from friends would be especially beneficial for newcomers.
Dynamic Rupture Simulation of the 1833 Songming, Yunnan, China,M8.0 Earthquake: Effects From Stepover Location and Overlap Distance
Authors: Yu Houyun , Hu Feng , Xu Jiankuan , Zhang Zhenguo , Chen Xiaofei
Published: February 2022

Stepover structures are widely distributed in natural fault systems. The jump distance is typically easier to identify than both the stepover location and the overlap distance because of the presence of lakes and sedimentary basins around the stepover. Using the curved grid finite‐difference method, we first conducted a 3D spontaneous dynamic rupture simulation of the 1833 Songming earthquake on a continuous model of the western Xiaojiang fault to estimate the regional stress azimuth. Then, we performed rupture process simulations with different stepover structure models on the western Xiaojiang fault to investigate the effects of the stepover location and overlap distance on the dynamic rupture process. In addition, we analyzed the fault strength ratioSand rupture velocity of the preferred fault models and discussed the occurrence of supershear rupture during the Songming event. Finally, we simulated the strong ground motion with the preferred fault models for the 1833 Songming earthquake. Our simulation results suggest that the optimal regional maximum principal stress azimuth during the Songming event was N20°W. Our simulations further reveal that the Qingshuihai stepover is located in the middle of Qingshuihai Lake, and the overlap distance is 6 km; in contrast, the location of the Yangzonghai stepover is located in the southern part of Yangzonghai Lake, and the overlap distance is not constrained. Furthermore, our numerical simulation indicates that the Songming earthquake exhibited supershear rupture; however, this supershear rupture is not sustained and is easily affected by the friction parameters and nucleation location.
Transient Influence of the Reduction of Deepwater Formation on Ocean Heat Uptake and Heat Budgets in the Global Climate System
Authors: Suzuki Tatsuo , Komuro Yoshiki , Kusahara Kazuya , Tatebe Hiroaki
Published: February 2022

The formation and spreading of dense deepwater in the polar regions play a key role in one of the most important climate systems, namely ocean meridional overturning circulation, and the deepwater formation is projected to decrease under the global warming. However, the impact of the reduced deepwater formation on the climate system has not been explored in detail. Here, we performed a series of numerical experiments with a climate model where the downward water mass transport through the bottom boundary layer is artificially reduced to quantitatively evaluate its impacts on the transient ocean and climate responses. It is demonstrated that changes in deepwater formation have non‐negligible impacts on not only ocean heat content but also the Earth's radiation budget at the top of the atmosphere: reduction in deepwater formation in high‐latitude oceans causes warming of bottom water, cooling of the ocean surface, and a subsequent decrease in outgoing longwave radiation.
Improving the Predictability of Two Types of ENSO by the Characteristics of Extratropical Precursors
Authors: Tseng Yu‐heng , Huang Jo‐Hsu , Chen Han‐Ching
Published: February 2022

The Central Pacific (CP) and Eastern Pacific (EP) types of El Niño‐Southern Oscillation events are distinctly different in terms of their forming locations and mechanisms. Using an updated physical‐base statistical forecast model, the forecast of CP indices has overall higher skills than that of EP indices due to the higher persistent forecast skill. At lead time beyond 6‐month, the predictability of CP indices can be greatly enhanced by including the extratropical precursor from the North Pacific, confirming the ocean‐atmosphere interaction associated with North Pacific Oscillation (NPO)/Victoria Mode (VM) evolution. The predictability of EP indices can be moderately enhanced by including the extratropical precursor from the south, resulting from the charging of the equatorial Pacific. We also find that the predictability of CP indices does not significantly decrease after 2000 while the predictability of EP indices drops dramatically, suggesting the strengthening impacts of NPO/VM on the CP‐ENSO in the recent two decades.
Selective inhibition of nuclear export: a promising approach in the shifting treatment paradigms for hematological neoplasms
Authors: Balasubramanian Suresh Kumar , Azmi Asfar S. , Maciejewski Jaroslaw
Published: February 2022

Novel targeted therapeutics alone or in rational combinations are likely to dominate the future management of various hematological neoplasms. However, the challenges currently faced are the molecular heterogeneity in driver lesions and genetic plasticity leading to multiple resistance pathways. Thus, progress has overall been gradual. For example, despite the advent of targeted agents against actionable drivers like FLT3 in acute myeloid leukemia (AML), the prognosis remains suboptimal in newly diagnosed and dismal in the relapsed/refractory (R/R) setting, due to other molecular abnormalities contributing to inherent and acquired treatment resistance. Nuclear export inhibitors are of keen interest because they can inhibit several active tumorigenic processes simultaneously and also synergize with other targeted drugs and chemotherapy. XPO1 (or CRM1, chromosome maintenance region 1) is one of the most studied exportins involved in transporting critical cargoes, including tumor suppressor proteins like p27, p53, and RB1. Apart from the TSP cargo transport and its role in drug resistance, XPO1 inhibition results in retention of master transcription factors essential for cell differentiation, cell survival, and autophagy, rendering cells more susceptible to the effects of other antineoplastic agents, including targeted therapies. This review will dissect the role of XPO1 inhibition in hematological neoplasms, focusing on mechanistic insights gleaned mainly from work with SINE compounds. Future potential combinatorial strategies will be discussed.
C1q deletion exacerbates stress-induced learned helplessness behavior and induces neuroinflammation in mice
Authors: Madeshiya Amit Kumar , Whitehead Carl , Tripathi Ashutosh , Pillai Anilkumar
Published: February 2022

Increased levels of pro-inflammatory cytokines have been reported in postmortem brain samples and in the blood of depressed subjects. However, the inflammatory pathways that lead to depressive-like symptoms are not well understood. Using the learned helplessness (LH) model of depression, we examined the role of C1q, the initiator of classical complement pathway in mediating stress-induced depressive-like behavior in mice. We observed no significant changes in social behavior, despair behavior, spatial memory, and aggressive behavior between the wild type (WT) and C1q knockout (KO) mice. However, C1q deletion exacerbated the inescapable electric foot shock-induced learned helplessness behavior in mice. We found significant reductions in C1q mRNA levels in the prefrontal cortex (PFC) of WT helpless mice as compared to the naïve mice. Increased levels of pro-inflammatory cytokines were found in the PFC of C1q KO mice. These findings suggest that classical complement pathway-mediated learned helplessness behavior is accompanied by neuroinflammatory changes under stressful conditions.
Circulating endocannabinoids and genetic polymorphisms as predictors of posttraumatic stress disorder symptom severity: heterogeneity in a community-based cohort
Authors: deRoon-Cassini Terri A. , Bergner Carisa L. , Chesney Samantha A. , Schumann Nicholas R. , Lee Tara Sander , Brasel Karen J. , Hillard Cecilia J.
Published: February 2022

The endocannabinoid signaling system (ECSS) regulates fear and anxiety. While ECSS hypoactivity can contribute to symptoms of established post-traumatic stress disorder (PTSD), the role of the ECSS in PTSD development following trauma is unknown. A prospective, longitudinal cohort study of 170 individuals (47% non-Hispanic Caucasian and 70% male) treated at a level 1 trauma center for traumatic injury was carried out. PTSD symptom assessments and blood were obtained during hospitalization and at follow-up (6–8 months post injury). Serum concentrations of the endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) were determined at both time points and selected genetic polymorphisms in endocannabinoid genes, including rs324420 in fatty acid amide hydrolase, were assessed. For the entire sample, serum concentrations of AEA at hospitalization were significantly higher in those diagnosed with PTSD at follow-up (p = 0.030). Serum concentrations of 2-AG were significantly, positively correlated with PTSD symptom severity at follow-up only in minorities (p = 0.014). Minority participants (mostly Black/African American) also demonstrated significant, negative correlations between serum AEA concentrations and PTSD symptom severity both measured at hospitalization (p = 0.015). The A/A genotype at rs324420 was associated with significantly higher PTSD symptom severity (p = 0.025) and occurred exclusively in the Black participants. Collectively, these results are contrary to our hypothesis and find positive associations between circulating endocannabinoids and risk for PTSD. Minority status is an important modulator of the association between endocannabinoids and risk for PTSD, suggesting that the ECSS contributes to risk most significantly in these individuals and the contextual factors related to these findings should be further explored.
Efficacy and practice of facemask use in general population: a systematic review and meta-analysis
Authors: Li Hui , Yuan Kai , Sun Yan-Kun , Zheng Yong-Bo , Xu Ying-Ying , Su Si-Zhen , Zhang Yu-Xin , Zhong Yi , Wang Yi-Jie , Tian Shan-Shan , Gong Yi-Miao , Fan Teng-Teng , Lin Xiao , Gobat Nina , Wong Samuel Yeung Shan , Chan Emily Ying Yang , Yan Wei , Sun Si-Wei , Ran Mao-Sheng , Bao Yan-Ping , Shi Jie , Lu Lin
Published: February 2022

In recent decades, respiratory infections, including SARS, HINI and the currently spreading COVID-19, caused by various viruses such as influenza and coronavirus have seriously threatened human health. It has generated inconsistent recommendations on the mandatory use of facemasks across countries on a population level due to insufficient evidence on the efficacy of facemask use among the general population. This meta-analysis aimed to explore (1) the efficacy of facemask use on preventing respiratory infections, and (2) the perceptions, intentions, and practice about facemask use among the general population worldwide. We searched PubMed, MEDLINE, Web of Science, Cochrane, bioRxiv, and medRxiv databases since inception to August 17, 2020. From 21,341 records identified, eight RCTs on facemask in preventing infections and 78 studies on perception, intention, and practice of facemask use among the general population were included in the analysis. The meta-analysis of RCTs found a significant protective effect of facemask intervention (OR = 0.84; 95% CI = 0.71–0.99;I2 = 0%). This protective effect was even more pronounced when the intervention duration was more than two weeks (OR = 0.76; 95% CI = 0.66–0.88;I2 = 0%). The meta-analysis of observational studies on perception, intention, and practice on facemask use showed that 71% of respondents perceived facemasks to be effective for infection prevention, 68% of respondents would wear facemasks, and 54% of respondents wore facemasks for preventing respiratory infections. Differences in perception, intention, and practice behavior of facemask use in different regions may be related to the impact of respiratory infections, regional culture, and policies. The governments and relevant organizations should make effort to reduce the barriers in the use of facemasks.
Determining clinical course of diffuse large B-cell lymphoma using targeted transcriptome and machine learning algorithms
Authors: Albitar Maher , Zhang Hong , Goy Andre , Xu-Monette Zijun Y. , Bhagat Govind , Visco Carlo , Tzankov Alexandar , Fang Xiaosheng , Zhu Feng , Dybkaer Karen , Chiu April , Tam Wayne , Zu Youli , Hsi Eric D. , Hagemeister Fredrick B. , Huh Jooryung , Ponzoni Maurilio , Ferreri Andrés J. M. , Møller Michael B. , Parsons Benjamin M. , van Krieken J. Han , Piris Miguel A. , Winter Jane N. , Li Yong , Xu Bing , Young Ken H.
Published: February 2022

Multiple studies have demonstrated that diffuse large B-cell lymphoma (DLBCL) can be divided into subgroups based on their biology; however, these biological subgroups overlap clinically. Using machine learning, we developed an approach to stratify patients with DLBCL into four subgroups based on survival characteristics. This approach uses data from the targeted transcriptome to predict these survival subgroups. Using the expression levels of 180 genes, our model reliably predicted the four survival subgroups and was validated using independent groups of patients. Multivariate analysis showed that this patient stratification strategy encompasses various biological characteristics of DLBCL, and only TP53 mutations remained an independent prognostic biomarker. This novel approach for stratifying patients with DLBCL, based on the clinical outcome of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, can be used to identify patients who may not respond well to these types of therapy, but would otherwise benefit from alternative therapy and clinical trials.
Myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T): Mayo-Moffitt collaborative study of 158 patients
Authors: Mangaonkar Abhishek A. , Lasho Terra L. , Ketterling Rhett P. , Reichard Kaaren K. , Gangat Naseema , Al-Kali Aref , Begna Kebede H. , Pardanani Animesh , Al Ali Najla H. , Talati Chetasi , Sallman David , Padron Eric , Patnaik Mrinal M. , Tefferi Ayalew , Komrokji Rami
Published: February 2022

The current World Health Organization (WHO) classification of myeloid malignancies includes myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) as a distinct entity. Previous literature on predictors of survival was based on the provisional category of refractory anemia with ring sideroblast and thrombocytosis (RARS-T), which was not subject to MDS/MPN-RS-T exclusionary criteria such as PB blast% ≥1, BM blast% ≥5 or cytogenetic abnormalities such as t(3;3)(q21.2;q26.2), inv(3)(q21.23q26.2) or isolated del(5q). We examined overall (OS) and leukemia-free (LFS) survival and its predictors, among 158 patients with WHO-defined MDS/MPN-RS-T. In univariate analysis, age ≥70 years (P = 0.006), hemoglobin (Hb) ≤10 g/dL (P = 0.03) and abnormal karyotype (excluding -Y, P = 0.008) were associated with shortened OS, which was otherwise not affected by either ASXL1 (P = 0.7), SF3B1 (P = 0.4) or JAK2 V617F (P = 0.7) mutations; in multivariable analysis, Hb ≤ 10 g/dL (P = 0.03) and abnormal karyotype (P = 0.001) remained significant, and thus allowed the development of an operational survival model with low (0 risk factors, median OS 10.5 years), intermediate (1 risk factor, median OS 4.8 years) and high risk (2 risk factors, median OS 1.4 years) categories (P = 0.0009). Comparison of MDS/MPN-RS-T (n = 158) and MDS/MPN-U with BM RS ≥ 15% (MDS/MPN-U-RS; n = 25) did not reveal significant differences in frequency of thrombosis, OS, or LFS, although SF3B1 mutation frequency was higher in the former (93% versus 59%; P = 0.0005). These data suggest limited survival impact for molecular abnormalities and the morphological distinction between MDS/MPN-RS-T and MDS/MPN-U-RS.
Cross-species metabolomic analysis identifies uridine as a potent regeneration promoting factor
Authors: Liu Zunpeng , Li Wei , Geng Lingling , Sun Liang , Wang Qiaoran , Yu Yang , Yan Pengze , Liang Chuqian , Ren Jie , Song Moshi , Zhao Qian , Lei Jinghui , Cai Yusheng , Li Jiaming , Yan Kaowen , Wu Zeming , Chu Qun , Li Jingyi , Wang Si , Li Chunyi , Han Jing-Dong J. , Hernandez-Benitez Reyna , Shyh-Chang Ng , Belmonte Juan Carlos Izpisua , Zhang Weiqi , Qu Jing , Liu Guang-Hui
Published: February 2022

Regenerative capacity declines throughout evolution and with age. In this study, we asked whether metabolic programs underlying regenerative capability might be conserved across species, and if so, whether such metabolic drivers might be harnessed to promote tissue repair. To this end, we conducted metabolomic analyses in two vertebrate organ regeneration models: the axolotl limb blastema and antler stem cells. To further reveal why young individuals have higher regenerative capacity than the elderly, we also constructed metabolic profiles for primate juvenile and aged tissues, as well as young and aged human stem cells. In joint analyses, we uncovered that active pyrimidine metabolism and fatty acid metabolism correlated with higher regenerative capacity. Furthermore, we identified a set of regeneration-related metabolite effectors conserved across species. One such metabolite is uridine, a pyrimidine nucleoside, which can rejuvenate aged human stem cells and promote regeneration of various tissues in vivo. These observations will open new avenues for metabolic intervention in tissue repair and regeneration.
CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity
Authors: Long Yiru , Sun Jianhua , Song Tian-Zhang , Liu Tingting , Tang Feng , Zhang Xinxin , Ding Longfei , Miao Yunqiu , Zhu Weiliang , Pan Xiaoyan , An Qi , Qin Mian , Tong Xiankun , Peng Xionghua , Yu Pan , Zhu Peng , Xu Jianqing , Zhang Xiaoyan , Zhang Yachun , Liu Datao , Chen Ben , Chen Huilin , Zhang Leike , Xiao Gengfu , Zuo Jianping , Tang Wei , Zhou Ji , Li Heng , Xu Zhijian , Zheng Hong-Yi , Long Xin-Yan , Qin Qiuping , Gan Yong , Ren Jin , Huang Wei , Zheng Yong-Tang , Jin Guangyi , Gong Likun
Published: February 2022

Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.
Robust induction of B cell and T cell responses by a third dose of inactivated SARS-CoV-2 vaccine
Authors: Liu Yihao , Zeng Qin , Deng Caiguanxi , Li Mengyuan , Li Liubing , Liu Dayue , Liu Ming , Ruan Xinyuan , Mei Jie , Mo Ruohui , Zhou Qian , Liu Min , Peng Sui , Wang Ji , Zhang Hui , Xiao Haipeng
Published: February 2022

SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a nonrandomized trial among the healthcare workers (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccines and the potential need for a third booster dose. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 29.3 arbitrary units (AU)/mL to 8.8 AU/mL 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 63.6 AU/mL by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to two doses were not truly “non-responders” but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which could be rapidly recalled and further boosted by a third dose.
Multiplexed nanomaterial-assisted laser desorption/ionization for pan-cancer diagnosis and classification
Authors: Zhang Hua , Zhao Lin , Jiang Jingjing , Zheng Jie , Yang Li , Li Yanyan , Zhou Jian , Liu Tianshu , Xu Jianmin , Lou Wenhui , Yang Weige , Tan Lijie , Liu Weiren , Yu Yiyi , Ji Meiling , Xu Yaolin , Lu Yan , Li Xiaomu , Liu Zhen , Tian Rong , Hu Cheng , Zhang Shumang , Hu Qinsheng , Deng Yangdong , Ying Hao , Zhong Sheng , Zhang Xingdong , Wang Yunbing , Wang Hua , Bai Jingwei , Li Xiaoying , Duan Xiangfeng
Published: February 2022

As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis.
Orbital stability analysis and photometric characterization of the second Earth Trojan asteroid 2020 XL5
Authors: Santana-Ros T. , Micheli M. , Faggioli L. , Cennamo R. , Devogèle M. , Alvarez-Candal A. , Oszkiewicz D. , Ramírez O. , Liu P.-Y. , Benavidez P. G. , Campo Bagatin A. , Christensen E. J. , Wainscoat R. J. , Weryk R. , Fraga L. , Briceño C. , Conversi L.
Published: February 2022

Trojan asteroids are small bodies orbiting around the L4 or L5 Lagrangian points of a Sun-planet system. Due to their peculiar orbits, they provide key constraints to the Solar System evolution models. Despite numerous dedicated observational efforts in the last decade, asteroid 2010 TK7 has been the only known Earth Trojan thus far. Here we confirm that the recently discovered 2020 XL5 is the second transient Earth Trojan known. To study its orbit, we used archival data from 2012 to 2019 and observed the object in 2021 from three ground-based observatories. Our study of its orbital stability shows that 2020 XL5 will remain in L4 for at least 4 000 years. With a photometric analysis we estimate its absolute magnitude to be $${H}_{r}=18.5{8}_{-0.15}^{+0.16}$$

H

r

=
18.5

8

−
0.15

+
0.16

, and color indices suggestive of a C-complex taxonomy. Assuming an albedo of 0.06 ± 0.03, we obtain a diameter of 1.18 ± 0.08 km, larger than the first known Earth Trojan asteroid.
Downstream high-speed plasma jet generation as a direct consequence of shock reformation
Authors: Raptis Savvas , Karlsson Tomas , Vaivads Andris , Pollock Craig , Plaschke Ferdinand , Johlander Andreas , Trollvik Henriette , Lindqvist Per-Arne
Published: February 2022

Shocks are one of nature’s most powerful particle accelerators and have been connected to relativistic electron acceleration and cosmic rays. Upstream shock observations include wave generation, wave-particle interactions and magnetic compressive structures, while at the shock and downstream, particle acceleration, magnetic reconnection and plasma jets can be observed. Here, using Magnetospheric Multiscale (MMS) we show in-situ evidence of high-speed downstream flows (jets) generated at the Earth’s bow shock as a direct consequence of shock reformation. Jets are observed downstream due to a combined effect of upstream plasma wave evolution and an ongoing reformation cycle of the bow shock. This generation process can also be applicable to planetary and astrophysical plasmas where collisionless shocks are commonly found.