bluuebunny/crossref_metadata_2025 huggingface dataset:
Diverse Effects of Exosomes on COVID-19: A Perspective of Progress From Transmission to Therapeutic Developments
Authors: Gurunathan Sangiliyandi , Kang Min Hee , Kim Jin-Hoi
Published: July 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus and the causative agent of the current global pandemic of coronavirus disease 2019 (COVID-19). There are currently no FDA-approved antiviral drugs for COVID-19 and there is an urgent need to develop treatment strategies that can effectively suppress SARS-CoV-2 infection. Numerous approaches have been researched so far, with one of them being the emerging exosome-based therapies. Exosomes are nano-sized, lipid bilayer-enclosed structures, share structural similarities with viruses secreted from all types of cells, including those lining the respiratory tract. Importantly, the interplay between exosomes and viruses could be potentially exploited for antiviral drug and vaccine development. Exosomes are produced by virus-infected cells and play crucial roles in mediating communication between infected and uninfected cells. SARS-CoV-2 modulates the production and composition of exosomes, and can exploit exosome formation, secretion, and release pathways to promote infection, transmission, and intercellular spread. Exosomes have been exploited for therapeutic benefits in patients afflicted with various diseases including COVID-19. Furthermore, the administration of exosomes loaded with immunomodulatory cargo in combination with antiviral drugs represents a novel intervention for the treatment of diseases such as COVID-19. In particular, exosomes derived from mesenchymal stem cells (MSCs) are used as cell-free therapeutic agents. Mesenchymal stem cell derived exosomes reduces the cytokine storm and reverse the inhibition of host anti-viral defenses associated with COVID-19 and also enhances mitochondrial function repair lung injuries. We discuss the role of exosomes in relation to transmission, infection, diagnosis, treatment, therapeutics, drug delivery, and vaccines, and present some future perspectives regarding their use for combating COVID-19.
Satellite Tracking Reveals Nesting Patterns, Site Fidelity, and Potential Impacts of Warming on Major Green Turtle Rookeries in the Red Sea
Authors: Shimada Takahiro , Duarte Carlos M. , Al-Suwailem Abdulaziz M. , Tanabe Lyndsey K. , Meekan Mark G.
Published: July 2021

Major aggregations of nesting green turtles (Chelonia mydas) occur in the northern Red Sea, although little is known about the reproductive ecology of this endangered species in the region. To address this issue, we satellite-tracked 30 female green turtles to document their movements and to identify factors driving habitat use at two major rookeries in the Red Sea, Jazirat Mashabah (Mashabah Island) and Ras Al Baridi in Saudi Arabia. Between successive nesting events, turtles displayed high fidelity to nesting beaches and adjacent in-water habitats (inter-nesting habitats). Using generalized linear mixed models, we estimated the mean probability of nesting per beach emergence (nesting success rate) to be 0.628, and the mean duration between a successful nesting event and the successive emergence onto the beach (re-nesting interval) to be 10.8 days at each site. The nesting success rate was relatively high (>0.8) when the preceding daytime land surface temperature (LST) was lower than 37°C but decreased with elevated daytime LST (<0.4 when >47°C). Re-nesting interval was longer at lower water temperatures and towards the end of the nesting season of individuals. Our study improves the robustness of abundance estimates from census data (e.g., track counts) and shows that the protection of nesting and inter-nesting habitats during a breeding season would be an effective conservation strategy for the species. We discuss how global warming could increase energy expenditure due to lowered nesting success, ultimately compromising the reproductive fitness of these populations.
Co-governance, Transregional Maritime Conventions, and Indigenous Customary Practices Among Subsistence Fishermen in Ende, Indonesia
Authors: Ramenzoni Victoria C.
Published: July 2021

This article presents a case study of a fishery in the port-town community of Ende, Flores, a former littoral hub located at the periphery of major commercial systems in the Indo-Pacific region. The article argues that more attention be paid to the role of transregional maritime networks, nautical conventions, and navigational practices embedded within local tenure systems to understand the apparent absence of formal control of marine and coastal resources. Through ethnographic and archival research, this study identifies the presence of indigenous institutions for fishing grounds regulation and documents the existence of broader transregional norms dictating proper fishing and navigation. Exploring the interactions between more pluralistic customary systems that exist in port-towns such as Ende and recent fishery development policies, the article discusses some of the obstacles to implementing sustainable co-management strategies. While the Indonesian central government is strongly promoting co-governance approaches for resource management, these institutional models are based on geographically narrow definitions of tradition and customary law which can lead to management failures, such as elite capture and local fishers’ disenfranchisement. In this case, policies emphasize the formation of cooperative groups without considering transregional beliefs about independence and pre-established systems of obligations. As a result, disputes among the fishermen, conflicts with local fishery officers, and the use of non-sustainable practices continue. For example, embodying predominant Southeast Asian beliefs, Endenese are known for their entrepreneurial nature and strong self-sufficiency ethos. Yet, these notions are ignored by local government agencies that view the fishermen as selfish and disorganized. In order to formulate true participatory solutions, a careful assessment of the role played by transregional perspectives that go beyond geographically localized understandings of customary practices is needed. The article concludes with a consideration of the role played by decentralization processes, subsidies, and aid programs in entrenching poverty and inequality among local communities.
Diazotroph-Derived Nitrogen Assimilation Strategies Differ by Scleractinian Coral Species
Authors: Meunier Valentine , Bonnet Sophie , Benavides Mar , Ravache Andreas , Grosso Olivier , Lambert Christophe , Houlbrèque Fanny
Published: July 2021

Reef-building corals generally thrive in nutrient-poor tropical waters, where among other elements, nitrogen (N) availability often limits primary productivity. In addition to their close association with endosymbiotic dinoflagellates of the family Symbiodiniaceae, enabling an effective use and retention of dissolved inorganic nitrogen (DIN), scleractinian corals have developed strategies to acquire new N: (1) They can ingest N-rich sediment particles and preys (from picoplankton to macro-zooplankton) via heterotrophy, including diazotrophs [plankton fixing dinitrogen (N2) and releasing part of this nitrogen—Diazotroph-Derived N (DDN)—in seawater], a pathway called “heterotrophic nutrition on diazotrophs”; (2) Symbiotic diazotrophs located in the coral holobiont have the molecular machinery to fix N2, a pathway called “symbiotic N2 fixation”. Here we used the 15N2 isotopic labeling in a series of incubations to investigate the relative contribution of each of these DDN transfer pathways in three worldwide distributed coral species: Acropora muricata, Galaxea fascicularis, and Pocillopora damicornis. We show that N provision via “symbiotic N2 fixation” is negligible compared to that obtained via “heterotrophic nutrition on diazotrophs,” with DDN assimilation rates about a thousand times lower for P. damicornis and G. fascicularis, or assimilation rates via “symbiotic N2 fixation” almost nil for A. muricata. Through heterotrophic feeding on planktonic diazotrophs, only G. fascicularis and P. damicornis can successfully obtain N and fulfill a large part of their N requirements (DDN asimilation rates: 0.111 ± 0.056 and 0.517 ± 0.070 μg N cm–2 h–1 in their Symbiodiniaceae, respectively). Whereas this contribution is again negligible for A. muricata. They also largely consume the picoplankton that likely benefit from this DDN (Prochlorococcus and Synechococcus cells; respectively, 2.56 ± 1.57 104 and 2.70 ± 1.66 104 cell h–1 cm–2 for G. fascicularis; 3.02 ± 0.19 105 and 1.14 ± 0.79 104 cell h–1 cm–2 for P. damicornis). The present study confirms the different dependencies of the three tested species regarding heterotrophy, with P. damicornis and G. fascicularis appearing highly efficient at capturing plankton, while A. muricata, considered as mainly autotroph, does not rely on these food resources to meet its N and energy needs.
Impact of Meteorological Factors and Southern Oscillation Index on Scrub Typhus Incidence in Guangzhou, Southern China, 2006–2018
Authors: Lu Jianyun , Liu Yanhui , Ma Xiaowei , Li Meixia , Yang Zhicong
Published: July 2021

Background: Scrub typhus was epidemic in the western Pacific Ocean area and East Asia, scrub typhus epidemic in densely populated areas in southern China. To better understand the association between meteorological variables, Southern Oscillation Index (SOI), and scrub typhus incidence in Guangzhou was benefit to the control and prevention.

Methodology/Principal Findings: We collected weekly data for scrub typhus cases and meteorological variables in Guangzhou, and Southern Oscillation Index from 2006 to 2018, and used the distributed lag non-linear models to evaluate the relationships between meteorological variables, SOI and scrub typhus. The median value of each variable was set as the reference. The high-risk occupations were farmer (51.10%), house worker (17.51%), and retiree (6.29%). The non-linear relationships were observed with different lag weeks. For example, when the mean temperature was 27.7°C with1-week lag, the relative risk (RR) was highest as 1.08 (95% CI: 1.01–1.17). The risk was the highest when the relative humidity was 92.0% with 9-week lag, with the RR of 1.10 (95% CI: 1.02–1.19). For aggregate rainfall, the highest RR was 1.06 (95% CI: 1.03–1.11), when it was 83.0 mm with 4-week lag. When the SOI was 19 with 11-week lag, the highest RR was 1.06 (95% CI: 1.01–1.12). Most of the extreme effects of SOI and meteorological factors on scrub typical cases were statistically significant.

Conclusion/Significance: The high-risk occupations of scrub typhus in Guangzhou were farmer, house worker, and retiree. Meteorological factors and SOI played an important role in scrub typhus occurrence in Guangzhou. Non-linear relationships were observed in almost all the variables in our study. Approximately, mean temperature, and relative humidity positively correlated to the incidence of scrub typhus, on the contrary to atmospheric pressure and weekly temperature range (WTR). Aggregate rainfall and wind velocity showed an inverse-U curve, whereas the SOI appeared the bimodal distribution. These findings can be helpful to facilitate the development of the early warning system to prevent the scrub typhus.
Effects of Lipotoxicity in Brain Microvascular Endothelial Cells During Sirt3 Deficiency-Potential Role in Comorbid Alzheimer’s Disease
Authors: Tyagi Alpna , Mirita Carol , Shah Iman , Reddy P. Hemachandra , Pugazhenthi Subbiah
Published: July 2021

Silence information regulator 3 (SIRT3) is an NAD+ dependent deacetylase enzyme that enhances the function of key mitochondrial proteins. We have earlier demonstrated that deletion of Sirt3 gene leads to downregulation of metabolic enzymes, mitochondrial dysfunction and neuroinflammation in the brain, the major causes of Alzheimer’s disease (AD). We also reported recently that Sirt3 gene deletion in Alzheimer’s transgenic mice leads to exacerbation of neuroinflammation, amyloid plaque deposition and microglial activation. AD often coexists with other brain lesions caused by comorbidities which can exert their deleterious effects through the neurovascular unit. This unit consists of brain microvascular endothelial cells (BMECs), end feet of astrocytes, and pericytes. BMECs are uniquely different from other vascular endothelial cells because they are glued together by tight-junction proteins. BMECs are in constant contact with circulating factors as they line the luminal side. Therefore, we hypothesized that vascular endothelial injury caused by comorbidities plays a significant role in neuroinflammation. Herein, we investigated the effects of lipotoxicity in BMECs and how Sirt3 deficiency facilitate the deleterious effects of lipotoxicity on them using in vivo and in vitro models. We observed decreases in the levels of SIRT3 and tight junction proteins in the brain samples of western diet-fed APP/PS1 mice. Similar observations were obtained with Alzheimer’s post-mortem samples. Exposure of BEND3 cells, mouse brain-derived Endothelial cells3, to a combination of high glucose and palmitic acid resulted in significant (P < 0.01-P < 0.001) decreases in the levels of SIRT3, claudin-5 and ZO-1. Induction of inflammatory mediators, including Cox-2, CXCL1, RANTES, and GADD45β was also observed in these treated cells. Interestingly, the induction was more with Sirt3-silenced BEND3 cells, suggesting that Sirt3 deficiency exacerbates inflammatory response. Palmitic acid was more potent in inducing the inflammatory mediators. Significant cytotoxicity and changes in microglial morphology were observed when cocultures of Sirt3-silenced BEND3 and Sirt3-silenced BV2 cells were exposed to palmitic acid. Transendothelial electrical resistance measurement with these cocultures suggested decreased barrier integrity. The findings of this study suggest that hyperlipidemia in comorbidities can compromise blood brain barrier integrity by inducing inflammatory mediators and decreasing tight junction proteins in the vascular endothelial cells of the AD brain, leading to activation of microglia.
Acupuncture Treatment for Social Defeat Stress
Authors: Kawanokuchi Jun , Takagi Ken , Tanahashi Nobuyuki , Yamamoto Teruhisa , Nagaoka Nobuyuki , Ishida Torao , Ma Ning
Published: July 2021

Depression is a mood disorder characterized by disordered affect, thoughts, cognition, and behavior. Antidepressant therapy is often the primary treatment for depression. However, antidepressant therapy may cause unwanted side effects, and its effects are slow. Therefore, some patients are seeking alternative treatments for depression, such as acupuncture. However, there are many unclear points regarding the mechanism of the effect of acupuncture on depression. In recent years, we have reported that acupuncture improves the symptoms of mild depression induced by water-immersion stress in a rat model and depression induced by forced swimming in a mouse model. In this study, we examined the effect of acupuncture on the symptoms of social defeat stress (SDS)-induced depression in mice that most closely resemble human symptoms. In this study, we investigated the preventive and therapeutic effects of acupuncture as part of GV20 “Bai-Hui” and Ex-HN3 “Yintang” on model mice with depression induced by SDS. To examine the mechanism of the preventive and therapeutic effects of acupuncture on depression model mice, we examined the expression of neurotrophic factors in the brains of SDS mice. Two weeks of simultaneous acupuncture stimulation as part of GV20 and Ex-HN3 restored SDS-reduced brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3, and NT-4/5 expression, which was not observed with antidepressants. In contrast, acupuncture stimulation suppressed nerve growth factor (NGF) expression induced by SDS. These results suggest that acupuncture treatment could be effective in correcting the imbalance in the expression of neurotrophic factors. Furthermore, the effects of acupuncture on the expression of neurotrophic factors appear earlier than those of antidepressants, suggesting that it may be a useful treatment for depression.
Targeting Paretic Propulsion and Walking Speed With a Soft Robotic Exosuit: A Consideration-of-Concept Trial
Authors: Porciuncula Franchino , Baker Teresa C. , Arumukhom Revi Dheepak , Bae Jaehyun , Sloutsky Regina , Ellis Terry D. , Walsh Conor J. , Awad Louis N.
Published: July 2021

Background: Soft robotic exosuits can facilitate immediate increases in short- and long-distance walking speeds in people with post-stroke hemiparesis. We sought to assess the feasibility and rehabilitative potential of applying propulsion-augmenting exosuits as part of an individualized and progressive training program to retrain faster walking and the underlying propulsive strategy.

Methods: A 54-yr old male with chronic hemiparesis completed five daily sessions of Robotic Exosuit Augmented Locomotion (REAL) gait training. REAL training consists of high-intensity, task-specific, and progressively challenging walking practice augmented by a soft robotic exosuit and is designed to facilitate faster walking by way of increased paretic propulsion. Repeated baseline assessments of comfortable walking speed over a 2-year period provided a stable baseline from which the effects of REAL training could be elucidated. Additional outcomes included paretic propulsion, maximum walking speed, and 6-minute walk test distance.

Results: Comfortable walking speed was stable at 0.96 m/s prior to training and increased by 0.30 m/s after training. Clinically meaningful increases in maximum walking speed (Δ: 0.30 m/s) and 6-minute walk test distance (Δ: 59 m) were similarly observed. Improvements in paretic peak propulsion (Δ: 2.80 %BW), propulsive power (Δ: 0.41 W/kg), and trailing limb angle (Δ: 6.2 degrees) were observed at comfortable walking speed (p's < 0.05). Likewise, improvements in paretic peak propulsion (Δ: 4.63 %BW) and trailing limb angle (Δ: 4.30 degrees) were observed at maximum walking speed (p's < 0.05).

Conclusions: The REAL training program is feasible to implement after stroke and capable of facilitating rapid and meaningful improvements in paretic propulsion, walking speed, and walking distance.
Subclinical Carotid Artery Atherosclerosis and Cognitive Function: A Mini-Review
Authors: Ihle-Hansen Håkon , Ihle-Hansen Hege , Sandset Else Charlotte , Hagberg Guri
Published: July 2021

Carotid artery atherosclerosis, the result of a multitude of vascular risk factors, is a promising marker for use in risk stratification. Recent evidence suggests that carotid artery atherosclerosis affects cognitive function and is an independent risk factor for the development of cognitive impairment. Both atherosclerosis and cognitive impairment develop over a prolonged period (years), and due to the aging population, markers to identify persons at risk are needed. Carotid artery atherosclerosis can easily be visualized using non-invasive ultrasound, potentially enabling early and intensified risk factor management to preserve cognitive function or delay further decline. However, the burden of atherosclerosis and temporal exposure required to pose a risk of cognitive impairment is unclear. This mini-review aims to explore the available evidence on the association between carotid atherosclerosis and cognition, and furthermore identify the remaining gaps in knowledge.
Magnitudes of Anemia and Its Determinant Factors Among Lactating Mothers in East African Countries: Using the Generalized Mixed-Effect Model
Authors: Tusa Biruk Shalmeno , Weldesenbet Adisu Birhanu , Bahiru Nebiyu , Enyew Daniel Berhanie
Published: July 2021

Background: The number of studies on the magnitude of anemia and its determinant factors among lactating mothers is limited in East African countries regardless of its multivariate consequences. Even though few studies were conducted on the magnitude of anemia and its determinants, most of them focused on the country level and different parts of countries. Therefore, the current study is aimed to determine the magnitude of anemia and determinant factors among lactating mothers in East African countries.

Methods: From nine East African countries, a total weighted sample of 25,425 lactating mothers was included in the study. Determinate factors of anemia were identified using generalized linear mixed models (GLMM). Variables with a p < 0.05 in the final GLMM model were stated to confirm significant association with anemia.

Result: The magnitude of anemia in East African countries was found to be 36.5% [95% confidence interval (CI): 35.55%, 36.75%]. Besides, as for the generalized linear mixed-effect model, age, educational status, working status, country of residence, wealth index, antenatal care service, place of delivery, history of using family planning in a health facility, current pregnancy, and visited by fieldworker in the last 12 months were factors that have a significant association with anemia in lactating mothers.

Conclusion: In East Africa, more than one-third of lactating mothers have anemia. The odds of anemia were significantly low among young mothers (15–34), who had primary education, were working, country of residence, and higher wealth index (middle and high). In addition, the likelihood of anemia was also low among lactating mothers who had antenatal care, used family planning, delivered at a health facility, were pregnant during the survey, and visited by fieldworkers. Therefore, promoting maternal care services (family planning, Antenatal Care (ANC), and delivery at health facilities) and a field visit by health extension workers are strongly recommended.
Broccoli Florets Supplementation Improves Insulin Sensitivity and Alters Gut Microbiome Population—A Steatosis Mice Model Induced by High-Fat Diet
Authors: Zandani Gil , Anavi-Cohen Sarit , Tsybina-Shimshilashvili Nina , Sela Noa , Nyska Abraham , Madar Zecharia
Published: July 2021

Nonalcoholic fatty liver disease (NAFLD) is linked to obesity, type 2 diabetes, hyperlipidemia, and gut dysbiosis. Gut microbiota profoundly affects the host energy homeostasis, which, in turn, is affected by a high-fat diet (HFD) through the liver-gut axis, among others. Broccoli contains beneficial bioactive compounds and may protect against several diseases. This study aimed to determine the effects of broccoli supplementation to an HFD on metabolic parameters and gut microbiome in mice. Male (7–8 weeks old) C57BL/J6 mice were divided into four groups: normal diet (ND), high-fat diet (HFD), high-fat diet+10% broccoli florets (HFD + F), and high-fat diet + 10% broccoli stalks (HFD + S). Liver histology and serum biochemical factors were evaluated. Alterations in protein and gene expression of the key players in lipid and carbohydrate metabolism as well as in gut microbiota alterations were also investigated. Broccoli florets addition to the HFD significantly reduced serum insulin levels, HOMA-IR index, and upregulated adiponectin receptor expression. Conversely, no significant difference was found in the group supplemented with broccoli stalks. Both broccoli stalks and florets did not affect fat accumulation, carbohydrate, or lipid metabolism-related parameters. Modifications in diversity and in microbial structure of proteobacteria strains, Akermansia muciniphila and Mucispirillum schaedleri were observed in the broccoli-supplemented HFD-fed mice. The present study suggests that dietary broccoli alters parameters related to insulin sensitivity and modulates the intestinal environment. More studies are needed to confirm the results of this study and to investigate the mechanisms underlying these beneficial effects.
Computed Tomography-Based Evaluation of Volume and Position Changes of the Target Region and Organs at Risk During Radiotherapy for Esophageal Cancer: A Pilot Study
Authors: Liu Yi-mei , Peng Ying-lin , Li Qi-wen , Shen Guanzhu , Ma Ya-ru , Chen Mei-ning , Zhang Jun , Fu Li-rong , Qiu Bo , Liu Hui , Deng Xiao-wu
Published: July 2021

Objective

To analyze changes in volume and position of target regions and organs at risk (OARs) during radiotherapy for esophageal cancer patients.

Methods

Overall, 16 esophageal cancer patients who underwent radiotherapy, including 10 cases of intensity-modulated radiation therapy (IMRT) and six of three-dimensional conformal radiotherapy (3D-CRT), were enrolled. The prescription doses for the planning target volumes (PTVs) were as follows: PTV1, 64 Gy/32 fractions; and PTV2, 46 Gy/23 fractions. Repeat computed tomography (CT) was performed for patients after the 5th, 10th, 15th, 20th, and 25th fractions. Delineation of the gross tumor volume (GTV) and OAR volume was determined using five repeat CTs performed by the same physician. The target and OAR volumes and centroid positions were recorded and used to analyze volume change ratio (VCR), center displacement (ΔD), and changes in the distance from the OAR centroid positions to the planned radiotherapy isocenter (distance to isocenter, DTI) during treatment.

Results

No patient showed significant changes in target volume (TV) after the first week of radiotherapy (five fractions). However, TV gradually decreased over the following weeks, with the rate slowing after the fourth week (40 Gy). The comparison of TV from baseline to 40 Gy (20 fractions) showed that average GTVs decreased from 130.7 ± 63.1 cc to 92.1 ± 47.2 cc, with a VCR of −29.21 ± 13.96% (p<0.01), while the clinical target volume (CTV1) decreased from 276.7 ± 98.2 cc to 246.7 ± 87.2 cc, with a VCR of −10.34 ± 7.58% (p<0.01). As TVs decreased, ΔD increased and DTI decreased. After the fourth week of radiotherapy (40 Gy), centroids of GTV, CTV1, and prophylactic CTV (CTV2) showed average deviations in ΔD of 7.6 ± 4.0, 6.9 ± 3.4, and 6.0 ± 3.0 mm, respectively. The average DTI of the heart decreased by 4.53 mm (from 15.61 ± 2.96 cm to 15.16 ± 2.27 cm).

Conclusion

During radiotherapy for esophageal cancer, Targets and OARs change significantly in volume and position during the 2nd–4th weeks. Image-guidance and evaluation of dosimetric changes are recommended for these fractions of treatment to appropriate adjust treatment plans.
Leukemia With TCF3-ZNF384 Rearrangement as a Distinct Subtype of Disease With Distinct Treatments: Perspectives From A Case Report and Literature Review
Authors: Lin Na , Yan Xiaojing , Cai Dali , Wang Lei
Published: July 2021

Background

ZNF384 rearrangements are found in 5-10% of B-cell acute lymphoblastic leukemia (B-ALL) and 48% of B cell/myeloid mixed phenotype acute leukemia (B/M MPAL). ZNF384-rearranged B-ALL is prone to lineage conversion after chemotherapy. TCF3 is the second most common rearrangement partner of ZNF384 in B-ALL (27.5%) and the most common partner in B/M MPAL (53.3%). TCF3-ZNF384 fusion is related to a poor steroid response and a high frequency of relapse. It is mostly reported in children and adolescents but rarely seen in adults.

Patients and Methods

Here, we report a rare case of adult common B-ALL with TCF3-ZNF384 fusion in which the patient relapsed after one cycle of consolidation chemotherapy. Relapsed leukemia cells from the bone marrow were cultured for 72 hours ex vivo, and a panel of 156 kinds of cytotoxic drugs, targeted therapy drugs, combination chemotherapy drugs, etc., was used for sensitivity screening. The literature on TCF3-ZNF384 fusion was reviewed, and reported cases with TCF3-ZNF384 fusion were summarized. Clinical characteristics were compared between B-ALL and MPAL with TCF3-ZNF384 fusion.

Results

The relapsed lymphoblasts showed moderate sensitivity to both acute myelocytic leukemia (AML) - and acute lymphoblastic leukemia (ALL)-directed combination chemotherapy schemes, as well as to multiple targeted therapeutic drugs. The hyper-CVAD (B) scheme showed synergistic effects with multiple targeted compounds and had the highest sensitivity. The patient chose the hyper-CVAD (B) scheme combined with sorafenib and achieved complete remission (CR), then consolidated with myeloid-directed homoharringtonine+cytarabine+daunorubicin (HAD) scheme and gained molecular CR. By reviewing the literature, we found that both the genomic landscapes and gene expression profiles of ZNF384-rearranged B-ALL and MPAL are similar and that both diseases have lineage plasticity. The gene expression profile in TCF3-ZNF384-positive patients shows enrichment of hematopoietic stem cell features. No significant differences in clinical characteristics were found between TCF3-ZNF384-positive ALL and MPAL.

Conclusion

TCF3-ZNF384-positive leukemia may be a distinct subtype of leukemia regardless of immunophenotype. Considering the frequent lineage switches and sensitivity to both ALL- and AML-directed schemes, a uniform strategy directed at both lymphoid and myeloid lineages or at hematopoietic stem cells may be better for TCF3-ZNF384-positive leukemia. Small molecule targeted therapies may be promising treatment options and deserve further investigation.
Expert-Augmented Computational Drug Repurposing Identified Baricitinib as a Treatment for COVID-19
Authors: Smith Daniel P. , Oechsle Olly , Rawling Michael J. , Savory Ed , Lacoste Alix M.B. , Richardson Peter John
Published: July 2021

The onset of the 2019 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitated the identification of approved drugs to treat the disease, before the development, approval and widespread administration of suitable vaccines. To identify such a drug, we used a visual analytics workflow where computational tools applied over an AI-enhanced biomedical knowledge graph were combined with human expertise. The workflow comprised rapid augmentation of knowledge graph information from recent literature using machine learning (ML) based extraction, with human-guided iterative queries of the graph. Using this workflow, we identified the rheumatoid arthritis drug baricitinib as both an antiviral and anti-inflammatory therapy. The effectiveness of baricitinib was substantiated by the recent publication of the data from the ACTT-2 randomised Phase 3 trial, followed by emergency approval for use by the FDA, and a report from the CoV-BARRIER trial confirming significant reductions in mortality with baricitinib compared to standard of care. Such methods that iteratively combine computational tools with human expertise hold promise for the identification of treatments for rare and neglected diseases and, beyond drug repurposing, in areas of biological research where relevant data may be lacking or hidden in the mass of available biomedical literature.
The Potential of Lisosan G as a Possible Treatment for Glaucoma
Authors: Amato Rosario , Rossino Maria Grazia , Cammalleri Maurizio , Timperio Anna Maria , Fanelli Giuseppina , Dal Monte Massimo , Pucci Laura , Casini Giovanni
Published: July 2021

Lisosan G (LG), a fermented powder obtained from whole grains, is a nutritional supplement containing a variety of metabolites with documented antioxidant properties. We have recently demonstrated that orally administered LG protects diabetic rodent retinas from oxidative stress, inflammation, apoptosis, blood-retinal barrier disruption, and functional damage. Here, we investigated whether LG may exert protective effects in a model of glaucoma and measured the amounts of selected LG components that reach the retina after oral LG administration. Six-month-old DBA/2J mice were given an aqueous LG solution in place of drinking water for 2 mo. During the 2 mo of treatment with LG, the intraocular pressure (IOP) was monitored and the retinal ganglion cell (RGC) functional activity was recorded with pattern-electroretinography (PERG). At the end of the 2-mo period, the expression of oxidative stress and inflammatory markers was measured with qPCR, and RGC survival or macroglial activation were assessed with immunofluorescence. Alternatively, LG was administered by gavage and the concentrations of four of the main LG components (nicotinamide, gallic acid, 4-hydroxybenzoic acid, and quercetin) were measured in the retinas in the following 24 h using mass spectrometry. LG treatment in DBA/2J mice did not influence IOP, but it affected RGC function since PERG amplitude was increased and PERG latency was decreased with respect to untreated DBA/2J mice. This improvement of RGC function was concomitant with a significant decrease of both oxidative stress and inflammation marker expression, of RGC loss, and of macroglial activation. All four LG metabolites were found in the retina, although with different proportions with respect to the amount in the dose of administered LG, and with different temporal profiles in the 24 h following administration. These findings are consistent with neuroenhancing and neuroprotective effects of LG in glaucoma that are likely to derive from its powerful antioxidant properties. The co-occurrence of different metabolites in LG may provide an added value to their beneficial effects and indicate LG as a basis for the potential treatment of a variety of retinal pathologies.
NLRP3 Overexpression Associated With Poor Prognosis and Presented as an Effective Therapeutic Target in Osteosarcoma
Authors: Huang Zhen , Chen Hui , Wang Shenglin , Wei Hongxiang , Wang Xinwen , Shen Rongkai , Wang Yunqing , Lin Rongjin , Lin Jianhua
Published: July 2021

Despite the development of diagnostic and treatment strategies, the survival outcome of patients with osteosarcoma remains poor. Nod-like receptor protein 3 (NLRP3) plays a crucial role in the inflammasome pathway, which is related to the progression of various tumors. However, the effect of NLRP3 on osteosarcoma has not yet been well explored. Our study aimed to investigate the role of NLRP3 in the malignant biological behavior of osteosarcoma as well as its therapeutic value. Immunohistochemistry was applied to investigate the NLRP3 expression in osteosarcoma and osteochondroma specimens. Cell Counting Kit-8, colony formation, wound healing, transwell, and flow cytometry assays were used to explore the contribution of NLRP3 to the proliferation, migration, invasion, apoptosis and cell cycle distribution of osteosarcoma cells in vitro. Western blot was performed to evaluate the expression of NLRP3 and the related proteins in osteosarcoma cell lines after the blockade of NLRP3 using CY-09 and lentivirus intervention. Furthermore, tumor formation assay was used to analyze the effect of NLRP3 on the growth of osteosarcoma in vivo. The results showed that the NLRP3 protein was overexpressed in osteosarcoma, which was independently correlated with the poor prognosis of patients. Moreover, NLRP3 suppression by the inhibitor of CY-09 or lentivirus-induced gene knockdown inhibited the cell proliferation, migration, invasion and promoted the cell apoptosis and G1 cell cycle arrest in osteosarcoma via targeting the inflammasome pathway. Our in vivo results confirmed that the inhibition of NLRP3 suppressed the tumor formation of osteosarcoma. In conclusion, NLRP3 may be regarded as an independent prognostic biomarker and a potential therapeutic target for osteosarcoma.
Control of Néel-type Magnetic Kinks Confined in a Square Nanostructure by Spin-Polarized Currents
Authors: Chen Ji-Pei , Lin Jia-Qiang , Song Xiao , Chen Yuan , Chen Zhi-Feng , Li Wen-An , Qin Ming-Hui , Hou Zhi-Peng , Gao Xing-Sen , Liu Jun-Ming
Published: July 2021

Magnetic skyrmion in chiral magnet exhibits a variety of unique topological properties associated with its innate topological structure. This inspires a number of ongoing searching for new topological magnetic textures. In this work, we used micromagnetic simulations and Monte Carlo simulations to investigate an exotic Néel-type magnetic kinks in square-shaped nanostructures of chiral magnets, which performs rather stably in the absence of magnetic field. The individual magnetic kink can reside in one of the four possible corners, and carry possibly upward or downward core polarity, constituting eight degenerate states. In addition, these kinks also exhibit unique behaviors of generation, stability and dynamics, as revealed by micromagnetic simulations. It was found that such kinks can be created, annihilated, displaced, and polarity-reversed on demand by applying a spin-polarized current pulse, and are easily switchable among the eight degenerate states. In particularly, the kinks can be switched toward the ferromagnetic-like states and backward reversibly by applying two successive current pulses, indicating the capability of writing and deleting the kink structures. These findings predict the existence of Néel-type magnetic kinks in the square-shaped nanostructures, as well as provide us a promising approach to tailor the kinks by utilizing the corners of the nanostructures, and control these states by spin-polarized currents. The present work also suggests a theoretical guide to explore other chiral magnetic textures in nanostructures of polygon geometries.
Identification, Characterization, and Expression Analysis Reveal Diverse Regulated Roles of Three MAPK Genes in Chlamys farreri Under Heat Stress
Authors: Liu Zhi , Huang Xiaoting , Yang Zujing , Peng Cheng , Yu Haitao , Cui Chang , Hu Yuqing , Wang Xuefeng , Xing Qiang , Hu Jingjie , Bao Zhenmin
Published: July 2021

Mitogen-activated protein kinase (MAPK) cascades are fundamental signal transduction modules in all eukaryotic organisms, participating growth and development, as well as stress response. In the present study, three MAPK genes were successfully identified from the genome of Chlamys farreri, respectively, named CfERK1/2, CfJNK, and Cfp38, and only one copy of ERK, JNK, and p38 were detected. Domain analysis indicated that CfMAPKs possessed the typical domains, including S_TKc, Pkinase, and PKc_like domain. Phylogenetic analysis showed that three CfMAPKs of MAPK subfamilies exists in the common ancestor of vertebrates and invertebrates. All CfMAPKs specifically expressed during larval development and in adult tissues, and the expression level of CfERK1/2 and Cfp38 was apparently higher than that of CfJNK. Under heat stress, the expression of CfERK1/2 and Cfp38 were significantly downregulated and then upregulated in four tissues, while the expression of CfJNK increased in all tissues; these different expression patterns suggested a different molecular mechanism of CfMAPKs for bivalves to adapt to temperature changes. The diversity of CfMAPKs and their specific expression patterns provide valuable information for better understanding of the functions of MAPK cascades in bivalves.
Comprehensive in silico Characterization of Universal Stress Proteins in Rice (Oryza sativa L.) With Insight Into Their Stress-Specific Transcriptional Modulation
Authors: Arabia Shatil , Sami Asif Ahmed , Akhter Saima , Sarker Rakha Hari , Islam Tahmina
Published: July 2021

In a world where climate change is real and its consequences are unprecedented, understanding of the plant adaptive capacity and native stress-responsive machinery is crucial. In recent years, universal stress proteins (USPs) have received much attention in the field of plant science due to their stress-specific transcriptional regulation. This study focuses on the extensive characterization of the USP gene family members in the monocot crop rice (Oryza sativa L. var. japonica). Here, we report a total of 44 USP genes in the rice genome. In silico characterization of these genes showed that domain architecture played a major role in the functional diversification of the USP gene family which holds for all plant USPs. On top of that, a higher conservation of OsUSP members has been exhibited with a monocot genome (Zea mays L.) as compared to a dicot genome (Arabidopsis thaliana L.). Expression profiling of the identified genes led to the discovery of multiple OsUSP genes that showed pronounced transcript alteration under various abiotic stress conditions, indicating their potential role as multi-functional stress-specific modules. Furthermore, expression validation of OsUSP genes using qRT-PCR provided a strong evidence for the utility OsUSP genes in building multi-stress tolerant plants. Altogether, this study provides leads to suitable USP candidates that could be targeted for plant breeding and genetic engineering experiments to develop stress resilient crop species.
Measurement Invariance of Liberal and Authoritarian Notions of Democracy: Evidence From the World Values Survey and Additional Methodological Considerations
Authors: Sokolov Boris
Published: July 2021

This article offers a gentle introduction to the measurement invariance (MI) literature with a focus on its relevance to comparative political research. It reviews 1) the conceptual foundations of MI; 2) standard procedures of testing for MI in practical applications within the multiple-group confirmatory factor analysis (MGCFA) paradigm; and 3) two novel approaches to MI, Bayesian approximate measurement invariance, and MGCFA alignment optimization, which are especially suitable for dealing with extremely heterogeneous data from large-scale comparative surveys typical for modern political science. It then provides an empirical illustration of the key concepts and methods from the MGCFA-MI literature by applying them to testing for MI of two recently introduced measures of democracy attitudes, so-called liberal and authoritarian notions of democracy, across 60 countries in the sixth round of the World Values Survey. These analyses show that both measures can be considered reliable comparative measures of democratic attitudes, although for different reasons. Finally, this study emphasizes that some survey-based constructs, e.g., authoritarian notions of democracy, do not follow the reflective (correlation-based) logic of construct development. These alternative measures, known as formative measures, do not assume strong correlations between their indicators, for which reason it is inappropriate to test their comparability using the reflective MGCFA approach. Instead, their comparability can be tied to their correlations with theoretically relevant external variables.
Exploring the Entrepreneurial Intention-Competency Model for Nascent Entrepreneurs: Insights From a Developing Country Context
Authors: Botha Melodi , Taljaard Amorie
Published: July 2021

Several previous scholars have investigated the relationship between entrepreneurial intention (EI) and entrepreneurial competencies (ECs), yet categorising individual ECs in relation to higher-order competence constructs has not been explored. Based on the previous literature studies, four higher-order constructs are identified, namely cognitive, functional, social/personal and meta-competence. Investigating which ECs are categorised according to the four higher-order constructs in this relationship with EI is important as it contributes to the development and training of these antecedents of entrepreneurial behaviour. Data are collected from 203 nascent entrepreneurs in South Africa and analysed by using structural equation modelling. In this developing country context, only two higher-order constructs, cognitive/functional competence and social/personal competence, fit the data in relationship with EI. The strongest positive relationships were found between the cognitive and functional higher-order construct, opportunity recognition and opportunity assessment, conveying a compelling vision and creative problem-solving. The cognitive and functional higher-order competence construct also showed a strong positive relationship with EI. To improve pedagogical interventions and enhance EI, educators and policymakers can use these findings in entrepreneurship programmes to ensure that this higher-order competence construct with the individual ECs in this category are developed simultaneously rather than individually. Research efforts and support programmes that include cognitive and functional higher-order competence constructs for nascent entrepreneurs should therefore not be neglected. Such efforts and programmes can encourage EI, which in turn can enhance entrepreneurial behaviour, thereby potentially contributes to economic growth and employment creation.
The Impact of Switching Intention of Telelearning in COVID-19 Epidemic's Era: The Perspective of Push-Pull-Mooring Theory
Authors: Lin Xin , Chien Shih-Wen , Hung Chung-Wen , Chen Shih-Chih , Ruangkanjanases Athapol
Published: July 2021

Under the impact of COVID-19, medical telelearning education is increasingly becoming urgent to resolve the contradiction between the physical isolation of medical students and the need for on-site clinical teaching. In this study, the push-pull-mooring (PPM) theory is integrated into a comprehensive model as a conceptual PPM framework: push factors (information system quality and perceived risk), pull factors [telepresence (TP), trust, etc.], mooring factors (switching costs), and switching intention. The results show that most hypotheses were positive, but perceived risk did not influence user satisfaction significantly, and switching costs did not provide the impact on switching intention. This study provides a comprehensive empirical analysis of key factors influencing the choice of distance education by medical students through the integrated multi-model framework.
Subjective Impact of the COVID-19 Pandemic on Schizotypy and General Mental Health in Germany and the United Kingdom, for Independent Samples in May and in October 2020
Authors: Daimer Sarah , Mihatsch Lorenz , Ronan Lisa , Murray Graham K. , Knolle Franziska
Published: July 2021

Studies reported a strong impact on mental health during the first wave of the COVID-19 pandemic in March–June, 2020. In this study, we assessed the impact of the pandemic on mental health in general and on schizotypal traits in two independent general population samples of the United Kingdom (May sample N: 239, October sample N: 126; participation at both timepoints: 21) and in two independent general population samples of Germany (May sample N: 543, October sample N: 401; participation at both timepoints: 100) using online surveys. Whereas general psychological symptoms (global symptom index, GSI) and percentage of responders above clinical cut-off for further psychological investigation were higher in the May sample compared to the October sample, schizotypy scores (Schizotypal Personality Questionnaire) were higher in the October sample. We investigated potential associations, using general linear regression models (GLM). For schizotypy scores, we found that loneliness, use of drugs, and financial burden were more strongly corrected with schizotypy in the October compared to the May sample. We identified similar associations for GSI, as for schizotypy scores, in the May and October samples. We furthermore found that living in the United Kingdom was related to higher schizotypal scores or GSI. However, individual estimates of the GLM are highly comparable between the two countries. In conclusion, this study shows that while the general psychological impact is lower in the October than the May sample, potentially showing a normative response to an exceptional situation; schizotypy scores are higher at the second timepoint, which may be due to a stronger impact of estimates of loneliness, drug use, and financial burden. The ongoing, exceptional circumstances within this pandemic might increase the risk for developing psychosis in some individuals. The development of general psychological symptoms and schizotypy scores over time requires further attention and investigation.