bluuebunny/crossref_metadata_2025 huggingface dataset:
Damage Assessment of a Salt Dome in Jizan, Southwestern Saudi Arabia, Using High Spatial Resolution Remote Sensing Data
Authors: Ghrefat Habes , Hakami Ahmed , Ibrahim Elkhedr , Mogren Saad , Qaysi Saleh , Abdelrahman Kamal , Zaidi Faisal K.
Published: July 2021

The salt dome in Jizan, southwestern Saudi Arabia, has caused several problems related to underground dissolution, particularly in the old part of the city. Examples of these problems include surface collapse, building failure, fracturing, tilting, and road cracking. Analysis of the salt dome using X-ray diffraction (XRD) revealed the dominance of gypsum, anhydrite, and halite. This study evaluates the damage assessment using multitemporal high spatial resolution data of the GeoEye-1, and QuickBird-2 sensors. Change detection technique, textural analysis, and visual interpretation were applied to these data. Analysis of the data recorded before and after a particular damage event revealed that three neighborhoods located above the Jizan salt dome—Al-Ashaima, Shamiya, and Aljabal—were affected to the greatest extent. The entire residential neighborhood of Al-Ashaima was evacuated, and the buildings located in it were demolished. Several buildings in the Shamiya and Aljabal neighborhoods were also demolished. Therefore, high spatial remote sensing data are effective in assessing building damage and for anticipating future damage, thus benefiting decision making for the affected cities.
International Research Experiences in the Development of Minority Scientists
Authors: Davis Raeshan D. , Wilson-Kennedy Zakiya S. , Spivak David
Published: July 2021

Undergraduate research and international experiences are often described as high-impact educational practices beneficial for undergraduate student success and for supporting the development of science identity and intercultural competencies. While several studies have investigated the impact of undergraduate research on students from minoritized groups, fewer studies have focused on their engagement in global experiences, and fewer still have explored their engagement in international research experiences. Drawing on the theoretical frameworks of Science Identity, Social Cognitive Career Theory, and the Intercultural Competence Model, this present study explores the benefits of participating in an international research experience for minority undergraduate scientists. Using a qualitative case study methodology, we examined the evolution of students’ science identity, research competencies, and intercultural competence after engaging in a three-month international research opportunity in France and Belgium. We found that after participating in international research, minority undergraduate scientists had: 1) Increased confidence in their science identity and abilities; 2) Gained and strengthened skills necessary to be a successful researcher, 3) Recognized the influence of international exposure on their growth personally and professionally, 4) Expressed how monumental this research opportunity is for all minority students to experience. Our findings suggest substantial benefits from an international research experience on the development of minority undergraduate scientists.
Impact of Thyroid Autoimmunity on In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes and Fetal Weight
Authors: Huang Ning , Chen Lixue , Lian Ying , Wang Haining , Li Rong , Qiao Jie , Chi Hongbin
Published: July 2021

Several studies have reported the association between thyroid autoimmunity (TAI) and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes. However, the findings remain controversial. We performed a large-scale retrospective cohort study to verify the effect of the presence of thyroid antibodies on IVF/ICSI outcomes and fetal growth and to evaluate the association between the types and titers of thyroid antibodies and adverse IVF/ICSI outcomes. A total of 16481 patients with infertility were referred to the Reproductive Center of Peking University Third Hospital for their first IVF/ICSI treatment between January 2018 and June 2019.Patients who sought IVF/ICSI treatment due to tubal or male factors infertility and who achieved fresh embryo transfer were included in our study. Finally, 778 patients with thyroid antibody positivity were selected as the TAI group, and 778 age-matched patients were included in the control group. The number of oocytes retrieved and high-graded embryos and the rates of clinical pregnancy, miscarriage, live birth, and preterm delivery were compared between the TAI and control groups. In addition, subgroup analysis was performed to demonstrate whether different types and titers of thyroid antibodies had different effects on IVF/ICSI outcomes. After adjusting for thyroid function, anti-Müllerian hormone levels, basal follicle stimulating hormone levels, basal estradiol levels and antral follicle count, the number of oocytes retrieved in the TAI group was significantly lower than that in the control group. No significant differences were observed between the two groups in the rates of clinical pregnancy, miscarriage, preterm delivery, live birth, and birth weight in singletons; however, the birth weight in twin pregnancy was significantly lower in the TAI group than in the control group. Subgroup analysis showed no association between the types or titers of thyroid antibodies and adverse IVF/ICSI outcomes. In conclusion, the presence of TAI in patients with infertility did not impair embryo quality or affect pregnancy outcomes, including clinical pregnancy, miscarriage, preterm delivery, and live birth. However, it decreased the number of oocytes retrieved and birth weight in twin pregnancy.
Toward Human-Centered Design of Automated Vehicles: A Naturalistic Brake Policy
Authors: Rahmati Yalda , Samimi Abianeh Arezoo , Tabesh Mahmood , Talebpour Alireza
Published: July 2021

While safety is the ultimate goal in designing Connected and Automated Vehicles (CAVs), current automotive safety standards fail to explicitly define rules and regulations that ensure the safety of CAVs or those interacting with such vehicles. This study investigates CAV safety in mixed traffic environments with both human-driven and automated vehicles, focusing particularly on rear-end collisions at intersections. The central hypothesis is that the primary reason behind these crashes is the potential mismatch between CAVs’ braking decisions and human drivers’ expectations. To test this hypothesis, various Artificial Intelligence (AI) techniques, along with specialized statistical methods are adopted to learn and model the braking behavior of human drivers at intersections and compare the results to that of CAVs. Findings suggest systematical differences in CAVs’ and humans’ braking trajectories, revealing a mismatch between their braking patterns. Accordingly, a Markovian decision modeling framework is adopted to design a novel CAV braking profile that ensures 1) compatibility with human expectation, and 2) safe and comfortable maneuvers by CAVs in mixed driving environments. The findings of this study are expected to facilitate the development of higher levels of vehicle automation by providing guidelines to prevent rear-end collisions caused by existing differences in CAVs’ and humans’ braking strategies.
Creation and Worldwide Utilisation of New COVID-19 Online Information Hub for Genetics Health Professionals, Patients and Families
Authors: Tobias Adam P. , Berg Jonathan , Cetnarskyj Roseanne , Miedzybrodzka Zosia , Porteous Mary E. , Tobias Edward S.
Published: July 2021

The current COVID-19 pandemic has unfortunately resulted in many significant concerns for individuals with genetic disorders and their relatives, regarding the viral infection and, particularly, its specific implications and additional advisable precautions for individuals affected by genetic disorders. To address this, the resulting requirement for guidance and information for the public and for genetics professionals was discussed among colleagues nationally, on the ScotGEN Steering Committee, and internationally on the Education Committee of the European Society of Human Genetics (ESHG). It was agreed that the creation of an online hub of genetics-related COVID-19 information resources would be particularly helpful. The proposed content, divided into a web page for professionals and a page for patients, was discussed with, and approved by, genetics professionals. The hub was created and provided online at www.scotgen.org.uk and linked from the ESHG’s educational website for genetics and genomics, at www.eurogems.org. The new hub provides links, summary information and representative illustrations for a wide range of selected international resources. The resources for professionals include: COVID-19 research related hubs provided by Nature, Science, Frontiers, and PubMed; clinical guidelines; the European Centre for Disease Prevention and Control; the World Health Organisation; and molecular data sources including coronavirus 3D protein structures. The resources for patients and families include links to many accessible sources of support and relevant information. Since the launch of the pages, the website has received visits from over 50 countries worldwide. Several genetics consultants have commented on usefulness, clarity, readability, and ease of navigation. Visits have originated most frequently in the United Kingdom, Kuwait, Hong Kong, Moldova, United States, Philippines, France, and Qatar. More links have been added since the launch of the hub to include additional international public health and academic resources. In conclusion, an up-to-date online hub has been created and made freely available for healthcare professionals, patients, relatives and the public, providing categorised easily navigated links to a range of worldwide resources related to COVID-19. These pages are receiving a rapidly growing number of return visits and the authors continue to maintain and update the pages’ content, incorporating new developments in this field of enormous worldwide importance.
Analysis of DNA Methylation Profiles in Mandibular Condyle of Chicks With Crossed Beaks Using Whole-Genome Bisulfite Sequencing
Authors: Shi Lei , Bai Hao , Li Yunlei , Yuan Jingwei , Wang Panlin , Wang Yuanmei , Ni Aixin , Jiang Linlin , Ge Pingzhuang , Bian Shixiong , Zong Yunhe , Isa Adamu Mani , Tesfay Hailai Hagos , Yang Fujian , Ma Hui , Sun Yanyan , Chen Jilan
Published: July 2021

Crossed beaks have been observed in at least 12 chicken strains around the world, which severely impairs their growth and welfare. To explore the intrinsic factor causing crossed beaks, this study measured the length of bilateral mandibular ramus of affected birds, and investigated the genome-wide DNA methylation profiles of normal and affected sides of mandibular condyle. Results showed that the trait was caused by impaired development of unilateral mandibular ramus, which is extended through calcification of mandibular condyle. The methylation levels in the CG contexts were higher than that of CHG and CHH, with the highest methylation level of gene body region, followed by transcription termination sites and downstream. Subsequently, we identified 1,568 differentially methylated regions and 1,317 differentially methylated genes in CG contexts. Functional annotation analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed that these genes were involved in bone mineralization and bone morphogenesis. Furthermore, by combining the WGBS and previous RNA-Seq data, 11 overlapped genes were regulated by both long non-coding RNA and DNA methylation. Among them, FIGNL1 is an important gene in calcification of mandibular condyle. Generally, because the affected genes play key roles in maintaining mandibular calcification, these changes may be pivotal factors of crossed beaks.
Modulation of Host Immune Response Is an Alternative Strategy to Combat SARS-CoV-2 Pathogenesis
Authors: Singh Lakhveer , Bajaj Sakshi , Gadewar Manoj , Verma Nitin , Ansari Mohd Nazam , Saeedan Abdulaziz S. , Kaithwas Gaurav , Singh Manjari
Published: July 2021

The novel SARS-CoV-2virus that caused the disease COVID-19 is currently a pandemic worldwide. The virus requires an alveolar type-2 pneumocyte in the host to initiate its life cycle. The viral S1 spike protein helps in the attachment of the virus on toACE-2 receptors present on type-2 pneumocytes, and the S2 spike protein helps in the fusion of the viral membrane with the host membrane. Fusion of the SARS-CoV-2virus and host membrane is followed by entry of viral RNA into the host cells which is directly translated into the replicase-transcriptase complex (RTC) following viral RNA and structural protein syntheses. As the virus replicates within type-2 pneumocytes, the host immune system is activated and alveolar macrophages start secreting cytokines and chemokines, acting as an inflammatory mediator, and chemotactic neutrophils, monocytes, natural NK cells, and CD8+ T cells initiate the local phagocytosis of infected cells. It is not the virus that kills COVID-19 patients; instead, the aberrant host immune response kills them. Modifying the response from the host immune system could reduce the high mortality due to SARS-CoV-2 infection. The present study examines the viral life cycle intype-2 pneumocytes and resultant host immune response along with possible therapeutic targets.
Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen
Authors: Su Chinh Tran-To , Lua Wai-Heng , Poh Jun-Jie , Ling Wei-Li , Yeo Joshua Yi , Gan Samuel Ken-En
Published: July 2021

The binding of nickel by immune proteins can manifest as Type IV contact dermatitis (Ni-specific T cells mediated) and less frequently as Type I hypersensitivity with both mechanisms remaining unknown to date. Since there are reports of patients co-manifesting the two hypersensitivities, a common mechanism may underlie both the TCR and IgE nickel binding. Focusing on Trastuzumab and Pertuzumab IgE variants as serendipitous investigation models, we found Ni-NTA interactions independent of Her2 binding to be due to glutamine stretches. These stretches are both Ni-inducible and in fixed pockets at the antibody complementarity-determining regions (CDRs) and framework regions (FWRs) of both the antibody heavy and light chains with influence from the heavy chain constant region. Comparisons with TCRs structures revealed similar interactions, demonstrating the possible underlying mechanism in selecting for Ni-binding IgEs and TCRs respectively. With the elucidation of the interaction, future therapeutic antibodies could also be sagaciously engineered to utilize such nickel binding for biotechnological purposes.
Prognostic Impact of Sarcopenia and Radiotherapy in Patients With Advanced Gastric Cancer Treated With Anti-PD-1 Antibody
Authors: Kim Nalee , Yu Jeong Il , Lim Do Hoon , Lee Jeeyun , Kim Seung Tae , Hong Jung Yong , Kang Won Ki , Jeong Woo Kyoung , Kim Kyoung-Mee
Published: July 2021

Background

We explored the combined effects of sarcopenia (SAR) and radiotherapy (RT) on outcomes in patients with advanced gastric cancer (AGC) treated with immune-checkpoint blockade (ICB).

Methods

Among 185 patients with AGC treated with ICB, we defined SAR as skeletal muscle index <49 cm2/m2 for men and <31 cm2/m2 for women; 93 patients met criteria. We defined high neutrophil-to-lymphocyte ratio (hNLR) as NLR≥3. Palliative RT was performed in 37 patients (20%) before ICB.

Results

We frequently observed hNLR in patients with SAR (53% vs. 35%, p = 0.02). The median overall survival (OS) for the entire cohort was 5 months. Stratification by risk factors of SAR or hNLR revealed a significant difference in median OS (0 [N = 60] vs. 1 [N = 76] vs. 2 [N = 49]: 7.6 vs. 6.4 vs. 2.2 months, p < 0.001). Patients with microsatellite instability-high (MSI-H, N = 19) or Epstein-Barr virus (EBV)-positive tumors (N = 13) showed favorable outcomes compared to those with microsatellite stable (MSS, N = 142) tumors (median OS, not reached vs. 16.8 vs. 3.8 months, respectively). The benefit of RT was evident in patients with both SAR and hNLR (median OS, 3.1 vs. 1.3 months, p = 0.02) and MSS/EBV-negative tumor (median OS, 6.5 vs. 3.5 months, p = 0.03), but outcomes after RT in MSI-H tumor were not significantly different. In multivariable analysis, SAR/hNLR, molecular subtypes, and a history of RT were associated with OS (all p < 0.05).

Conclusions

We demonstrated the negative predictive value of SAR/hNLR on outcomes after ICB for AGC, and the history of RT could overcome the negative impact of SAR/hNLR and the MSS/EBV-negative subtype.
Protein Kinase R in Bacterial Infections: Friend or Foe?
Authors: Smyth Robin , Sun Jim
Published: July 2021

The global antimicrobial resistance crisis poses a significant threat to humankind in the coming decades. Challenges associated with the development of novel antibiotics underscore the urgent need to develop alternative treatment strategies to combat bacterial infections. Host-directed therapy is a promising new therapeutic strategy that aims to boost the host immune response to bacteria rather than target the pathogen itself, thereby circumventing the development of antibiotic resistance. However, host-directed therapy depends on the identification of druggable host targets or proteins with key functions in antibacterial defense. Protein Kinase R (PKR) is a well-characterized human kinase with established roles in cancer, metabolic disorders, neurodegeneration, and antiviral defense. However, its role in antibacterial defense has been surprisingly underappreciated. Although the canonical role of PKR is to inhibit protein translation during viral infection, this kinase senses and responds to multiple types of cellular stress by regulating cell-signaling pathways involved in inflammation, cell death, and autophagy – mechanisms that are all critical for a protective host response against bacterial pathogens. Indeed, there is accumulating evidence to demonstrate that PKR contributes significantly to the immune response to a variety of bacterial pathogens. Importantly, there are existing pharmacological modulators of PKR that are well-tolerated in animals, indicating that PKR is a feasible target for host-directed therapy. In this review, we provide an overview of immune cell functions regulated by PKR and summarize the current knowledge on the role and functions of PKR in bacterial infections. We also review the non-canonical activators of PKR and speculate on the potential mechanisms that trigger activation of PKR during bacterial infection. Finally, we provide an overview of existing pharmacological modulators of PKR that could be explored as novel treatment strategies for bacterial infections.
Modeling Small Scale Impacts of Multi-Purpose Platforms: An Ecosystem Approach
Authors: Serpetti Natalia , Benjamins Steven , Brain Stevie , Collu Maurizio , Harvey Bethany J. , Heymans Johanna J. , Hughes Adam D. , Risch Denise , Rosinski Sophia , Waggitt James J. , Wilson Ben
Published: July 2021

Aquaculture and marine renewable energy are two expanding sectors of the Blue Economy in Europe. Assessing the long-term environmental impacts in terms of eutrophication and noise is a priority for both the EU Water Framework Directive and the Marine Strategy Framework Directive, and cumulative impacts will be important for the Maritime Spatial Planning under the Integrated Maritime Policy. With the constant expansion of aquaculture production, it is expected that farms might be established further offshore in more remote areas, as high-energy conditions offer an opportunity to generate more power locally using Marine Renewable Energy (MRE) devices. A proposed solution is the co-location of MRE devices and aquaculture systems using Multi-Purpose Platforms (MPPs) comprising offshore wind turbines (OWTs) that will provide energy for farm operations as well as potentially shelter the farm. Disentangling the impacts, conflicts and synergies of MPP elements on the surrounding marine ecosystem is challenging. Here we created a high-resolution spatiotemporal Ecospace model of the West of Scotland, in order to assess impacts of a simple MPP configuration on the surrounding ecosystem and how these impacts can cascade through the food web. The model evaluated the following specific ecosystem responses: (i) top-down control pathways due to distribution changes among top-predators (harbor porpoise, gadoids and seabirds) driven by attraction to the farming sites and/or repulsion/killing due to OWT operations; (ii) bottom-up control pathways due to salmon farm activity providing increasing benthic enrichment predicated by a fish farm particle dispersal model, and sediment nutrient fluxes to the water column by early diagenesis of organic matter (recycled production). Weak responses of the food-web were found for top-down changes, whilst the results showed high sensitivity to increasing changes of bottom-up drivers that cascaded through the food-web from primary producers and detritus to pelagic and benthic consumers, respectively. We assessed the sensitivity of the model to each of these impacts and the cumulative effects on the ecosystem, discuss the capabilities and limitations of the Ecospace modeling approach as a potential tool for marine spatial planning and the impact that these results could have for the Blue Economy and the EU’s New Green Deal.
Non-Linear Processes in the Gironde River Plume (North-East Atlantic): Instabilities and Mixing
Authors: Ayouche Adam , Charria Guillaume , Carton Xavier , Ayoub Nadia , Theetten Sébastien
Published: July 2021

Instability and mixing are ubiquitous processes in river plumes but their small spatial and temporal scales often limit their observation and analysis. We investigate flow instability and mixing processes in the Gironde river plume (Bay of Biscay, North-East Atlantic ocean) in response to air-sea fluxes, tidal currents, and winds. High-resolution numerical simulations are conducted in March (average river discharge) and in August (low discharge) to explore such processes. Two areas of the Gironde river plume (the bulge and the coastal current) experience different instabilities: barotropic, baroclinic, symmetric, and/or vertical shear instabilities. Energy conversion terms reveal the coexistence of barotropic and baroclinic instabilities in the bulge and in the coastal current during both months. These instabilities are intensified over the whole domain in August and over the inner-shelf in March. The Hoskins criterion indicates that symmetric instability exists in most parts of the plume during both periods. The evolution of the Gironde plume with the summer stratification, tidal currents and winds favors its development. During both seasons, ageostrophic flow and large Rossby numbers characterize rapidly-growing and small-scale frontal baroclinic and symmetric instabilities. The transition between these instabilities is investigated with an EKE decomposition on the modes of instability. In the frontal region of the plume, during both months, symmetric instabilities grow first followed by baroclinic and mixed ones, during wind bursts and/or high discharge events. In contrast, when the wind is weak or relaxing, baroclinic instabilities grow first followed by symmetric and then mixed ones. Their growth periods range from a few hours to a few days. Mixing at the ocean surface is analyzed via Potential Vorticity (PV) fluxes. The net injection of PV at the ocean surface occurs at submesoscale buoyant fronts of the Gironde plume during both months. Vertical mixing at these fronts has similar magnitude as the wind-driven and surface buoyancy fluxes. During both months, the frontal region of the plume is restratified during wind relaxation events and/or high river discharge events through frontogenetic processes. Conversely, wind bursts destratify the frontal plume interior through non-conservative PV fluxes.
Digital Technologies and Data Science as Health Enablers: An Outline of Appealing Promises and Compelling Ethical, Legal, and Social Challenges
Authors: Cordeiro João V.
Published: July 2021

Digital technologies and data science have laid down the promise to revolutionize healthcare by transforming the way health and disease are analyzed and managed in the future. Digital health applications in healthcare include telemedicine, electronic health records, wearable, implantable, injectable and ingestible digital medical devices, health mobile apps as well as the application of artificial intelligence and machine learning algorithms to medical and public health prognosis and decision-making. As is often the case with technological advancement, progress in digital health raises compelling ethical, legal, and social implications (ELSI). This article aims to succinctly map relevant ELSI of the digital health field. The issues of patient autonomy; assessment, value attribution, and validation of health innovation; equity and trustworthiness in healthcare; professional roles and skills and data protection and security are highlighted against the backdrop of the risks of dehumanization of care, the limitations of machine learning-based decision-making and, ultimately, the future contours of human interaction in medicine and public health. The running theme to this article is the underlying tension between the promises of digital health and its many challenges, which is heightened by the contrasting pace of scientific progress and the timed responses provided by law and ethics. Digital applications can prove to be valuable allies for human skills in medicine and public health. Similarly, ethics and the law can be interpreted and perceived as more than obstacles, but also promoters of fairness, inclusiveness, creativity and innovation in health.
Empty Sella Syndrome as a Window Into the Neuroprotective Effects of Prolactin
Authors: Paul David A. , Strawderman Emma , Rodriguez Alejandra , Hoang Ricky , Schneider Colleen L. , Haber Sam , Chernoff Benjamin L. , Shafiq Ismat , Williams Zoë R. , Vates G. Edward , Mahon Bradford Z.
Published: July 2021

Background: The goal of this study was to relate diffusion MR measures of white matter integrity of the retinofugal visual pathway with prolactin levels in a patient with downward herniation of the optic chiasm secondary to medical treatment of a prolactinoma.

Methods: A 36-year-old woman with a prolactinoma presented with progressive bilateral visual field defects 9 years after initial diagnosis and medical treatment. She was diagnosed with empty-sella syndrome and instructed to stop cabergoline. Hormone testing was conducted in tandem with routine clinical evaluations over 1 year and the patient was followed with diffusion magnetic resonance imaging (dMRI), optical coherence tomography (OCT), and automated perimetry at three time points. Five healthy controls underwent a complementary battery of clinical and neuroimaging tests at a single time point.

Results: Shortly after discontinuing cabergoline, diffusion metrics in the optic tracts were within the range of values observed in healthy controls. However, following a brief period where the patient resumed cabergoline (of her own volition), there was a decrease in serum prolactin with a corresponding decrease in visual ability and increase in radial diffusivity (p < 0.001). Those measures again returned to their baseline ranges after discontinuing cabergoline a second time.

Conclusions: These results demonstrate the sensitivity of dMRI to detect rapid and functionally significant microstructural changes in white matter tracts secondary to alterations in serum prolactin levels. The inverse relations between prolactin and measures of white matter integrity and visual function are consistent with the hypothesis that prolactin can play a neuroprotective role in the injured nervous system.
Case Report: Human Umbilical Cord Mesenchymal Stem Cells as a Therapeutic Intervention for a Critically Ill COVID-19 Patient
Authors: Zhang Quan , Huang Kang , Lv Jianlei , Fang Xiang , He Jun , Lv Ailian , Sun Xuan , Cheng Lamei , Zhong Yanjun , Wu Shangjie , Dai Yao
Published: July 2021

Here we report a critically ill patient who was cured of SARS-CoV-2 infection in Changsha, China. A 66-year-old Chinese woman, with no significant past medical history, developed severe pneumonia-like symptoms and later diagnosed as severe COVID-19 pneumonia. Within 2 months of hospitalization, the patient deteriorated to ARDS including pulmonary edema and SIRS with septic shock. When treatment schemes such as antibiotics plus corticosteroids showed diminished therapeutic value, hUCMSC therapy was compassionately prescribed under the patient's consent of participation. After treatment, there was significant improvement in disease inflammation-related indicators such as IL-4, IL-6, and IL-10. Eventually, it confirmed the therapeutic value that hUCMSCs could dampen the cytokine storm in the critically ill COVID-19 patient and modulated the NK cells. In the continued hUCMSC treatment, gratifying results were achieved in the follow-up of the patient. The data we acquired anticipate a significant therapeutic value of MSC treatment in severe and critically ill patients with COVID-19, while further studies are needed.
Suboptimal Response to Tenofovir Alafenamide in Two Patients With HBeAg-Positive Hepatitis B: A Case Report
Authors: Chen Ruochan , Pei Siya , Chen Yayu , Tan Linxia , Xue Ying , Liu Shao , Huang Yan , Fan Xuegong
Published: July 2021

Tenofovir alafenamide (TAF) is one of the most potent first-line nucleot(s)ide analogs for treating chronic hepatitis B virus (HBV) infections. To date, no cases of TAF drug resistance and/or suboptimal response have been reported. To our knowledge, this is the first report of two adult male patients presenting a suboptimal response response to TAF monotherapy. Our study indicates long-term observations and extensive data are needed to further evaluate the efficacy and safety of TAF, and highlights the need for the development of robust novel direct-acting antivirals and immune therapies for HBV.
Change of Retinal Vessels in Different Sectors of the Parapapillary Area in Primary Open-Angle Glaucoma
Authors: Cheng Jingyi , Zhao Hongmei , Jiang Chunhui , Kong Xiangmei , Sun Xinghuai
Published: July 2021

Purpose: To investigate the changes in the retinal vessels (RVs) in different sectors in patients with primary open-angle glaucoma (POAG), and their possible correlations with retinal nerve fiber layer thickness (RNFLT) and visual-field defects in the temporal parapapillary region.

Methods: The RV diameters, RNFLTs, and visual-field parameters were measured. The temporal parapapillary region was divided into the temporal (T, 315°-45°), temporal superior (TS, 45°-90°), and temporal inferior sectors (TI, 270°-315°). The changes in the RV diameters in each sector were determined, and their relationships with RNFLT, the mean deviation (MD), and visual field sensitivity (VFS) were examined.

Results: Fifty POAG patients (50 eyes) and 50 healthy subjects (50 eyes) were included. Compared with the healthy subjects, the POAG group had a significantly smaller accumulated parapapillary RV diameter (P < 0.001), which was positively correlated with the MD and RNFLT. When the different temporal sectors were examined, the accumulated RV diameters were significantly smaller in the POAG group than in the healthy controls in the TI and T sectors, but not in the TS sector. The accumulated diameters in the TI and T sectors were correlated with the corresponding RNFLTs (all P < 0.05), but only the accumulated diameter in the TI sector was correlated with the VFS.

Conclusions: In POAG, the changes in the RVs differed between different temporal sectors, with the most prominent changes occurring in the TI and T sectors.
Description of Microbial Communities of Phosphate Mine Wastes in Morocco, a Semi-Arid Climate, Using High-Throughput Sequencing and Functional Prediction
Authors: Mghazli Najoua , Sbabou Laila , Hakkou Rachid , Ouhammou Ahmed , El Adnani Mariam , Bruneel Odile
Published: July 2021

Soil microbiota are vital for successful revegetation, as they play a critical role in nutrient cycles, soil functions, and plant growth and health. A rehabilitation scenario of the abandoned Kettara mine (Morocco) includes covering acidic tailings with alkaline phosphate mine wastes to limit water infiltration and hence acid mine drainage. Revegetation of phosphate wastes is the final step to this rehabilitation plan. However, revegetation is hard on this type of waste in semi-arid areas and only a few plants managed to grow naturally after 5 years on the store-and-release cover. As we know that belowground biodiversity is a key component for aboveground functioning, we sought to know if any structural problem in phosphate waste communities could explain the almost absence of plants. To test this hypothesis, bacterial and archaeal communities present in these wastes were assessed by 16S rRNA metabarcoding. Exploration of taxonomic composition revealed a quite diversified community assigned to 19 Bacterial and two Archaeal phyla, similar to other studies, that do not appear to raise any particular issues of structural problems. The dominant sequences belonged to Proteobacteria, Bacteroidetes, Actinobacteria, and Gemmatimonadetes and to the genera Massilia, Sphingomonas, and Adhaeribacter. LEfSe analysis identified 19 key genera, and metagenomic functional prediction revealed a broader phylogenetic range of taxa than expected, with all identified genera possessing at least one plant growth-promoting trait. Around 47% of the sequences were also related to genera possessing strains that facilitate plant development under biotic and environmental stress conditions, such as drought and heat.
The Effect of Radiation on the Gut Bacteriome of Aedes albopictus
Authors: Zhang Dongjing , Chen Shi , Abd-Alla Adly M. M. , Bourtzis Kostas
Published: July 2021

The sterile insect technique (SIT) has been developed as a component of area-wide integrated pest management approaches to control the populations of Aedes albopictus, a mosquito vector capable of transmission of dengue, Zika and chikungunya viruses. One of the key factors for the success of SIT is the requirement of high biological quality sterile males, which upon their release would be able to compete with wild males for matings with wild females in the field. In insects, gut bacteriome have played a catalytic role during evolution significantly affecting several aspects of their biology and ecology. Given the importance of gut-associated bacterial species for the overall ecological fitness and biological quality of their hosts, it is of interest to understand the effects of radiation on the gut-associated bacteriome of Ae. albopictus. In this study, the effect of radiation on the composition and density levels of the gut-associated bacterial species at the pupal stage as well as at 1- and 4-day-old males and females was studied using 16S rRNA gene-based next generation sequencing (NGS) and quantitative PCR (qPCR) approaches. Age, diet, sex, and radiation were shown to affect the gut-associated bacterial communities, with age having the highest impact triggering significant changes on bacterial diversity and clustering among pupae, 1- and 4-day-old adult samples. qPCR analysis revealed that the relative density levels of Aeromonas are higher in male samples compared to all other samples and that the irradiation triggers an increase in the density levels of both Aeromonas and Elizabethkingia in the mosquito gut at specific stages. Our results suggest that Aeromonas could potentially be used as probiotics to enhance protandry and sex separation in support of SIT applications against Ae. albopictus, while the functional role of Elizabethkingia in respect to oxidative stress and damage in irradiated mosquitoes needs further investigation.
Inhibition of SARS CoV Envelope Protein by Flavonoids and Classical Viroporin Inhibitors
Authors: Breitinger Ulrike , Ali Nourhan K. M. , Sticht Heinrich , Breitinger Hans-Georg
Published: July 2021

Severe acute respiratory syndrome coronavirus (SARS-CoV), an enveloped single-stranded positive-sense RNA virus, is a member of the genusBetacoronavirus, family Coronaviridae. The SARS-CoV envelope protein E is a small (∼8.4 kDa) channel-forming membrane protein whose sequence is highly conserved between SARS-CoV and SARS-CoV-2. As a viroporin, it is involved in various aspects of the virus life cycle including assembly, budding, envelope formation, virus release, and inflammasome activation. Here, SARS-CoV E protein was recombinantly expressed in HEK293 cells and channel activity and the effects of viroporin inhibitors studied using patch-clamp electrophysiology and a cell viability assay. We introduced a membrane-directing signal peptide to ensure transfer of recombinant E protein to the plasma membrane. E protein expression induced transmembrane currents that were blocked by various inhibitors. In an ion-reduced buffer system, currents were proton-dependent and blocked by viroporin inhibitors rimantadine and amantadine. I-V relationships of recombinant E protein were not pH-dependent in a classical buffer system with high extracellular Na+and high intracellular K+. E-protein mediated currents were inhibited by amantadine and rimantadine, as well as 5-(N,N-hexamethylene)amiloride (HMA). We tested a total of 10 flavonoids, finding inhibitory activity of varying potency. Epigallocatechin and quercetin were most effective, with IC50values of 1.5 ± 0.1 and 3.7 ± 0.2 nM, respectively, similar to the potency of rimantadine (IC50= 1.7 ± 0.6 nM). Patch-clamp results were independently verified using a modified cell viability assay for viroporin inhibitors. These results contribute to the development of novel antiviral drugs that suppress virus activity and proliferation.
Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori
Authors: Wen Junjie , Chen Chuxi , Luo Meiqun , Liu Xiaocong , Guo Jiading , Wei Tingting , Gu Xinyi , Gu Sinan , Ning Yunshan , Li Yan
Published: July 2021

Helicobacter pylori (H. pylori) is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating H. pylori. Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against H. pylori remains unclear. In the present study, in the co-culture model of macrophages with H. pylori, the inhibition of Notch signaling using γ-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to H. pylori. Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by H. pylori. Clinical specimens showed that the number of Jagged1+ macrophages in the stomach mucosa from H. pylori-infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against H. pylori and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against H. pylori, but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against H. pylori, which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of H. pylori infection.
Nitrogen Supply and Host-Plant Genotype Modulate the Transcriptomic Profile of Plasmodiophora brassicae
Authors: Gazengel Kévin , Aigu Yoann , Lariagon Christine , Humeau Mathilde , Gravot Antoine , Manzanares-Dauleux Maria J. , Daval Stéphanie
Published: July 2021

Nitrogen fertilization can affect the susceptibility of Brassica napus to the telluric pathogen Plasmodiophora brassicae. Our previous works highlighted that the influence of nitrogen can strongly vary regarding plant cultivar/pathogen strain combinations, but the underlying mechanisms are unknown. The present work aims to explore how nitrogen supply can affect the molecular physiology of P. brassicae through its life epidemiological cycle. A time-course transcriptome experiment was conducted to study the interaction, under two conditions of nitrogen supply, between isolate eH and two B. napus genotypes (Yudal and HD-018), harboring (or not harboring) low nitrogen-conditional resistance toward this isolate (respectively). P. brassicae transcriptional patterns were modulated by nitrogen supply, these modulations being dependent on both host-plant genotype and kinetic time. Functional analysis allowed the identification of P. brassicae genes expressed during the secondary phase of infection, which may play a role in the reduction of Yudal disease symptoms in low-nitrogen conditions. Candidate genes included pathogenicity-related genes (“NUDIX,” “carboxypeptidase,” and “NEP-proteins”) and genes associated to obligate biotrophic functions of P. brassicae. This work illustrates the importance of considering pathogen’s physiological responses to get a better understanding of the influence of abiotic factors on clubroot resistance/susceptibility.
The Role of TRPC6 in Renal Ischemia/Reperfusion and Cellular Hypoxia/Reoxygenation Injuries
Authors: Hou Xin , Huang Mengjun , Zeng Xixi , Zhang Yanhong , Sun Anbang , Wu Qifang , Zhu Lin , Zhao Hu , Liao Yanhong
Published: July 2021

Renal ischemia/reperfusion (I/R), a major cause of acute kidney injury (AKI), is a serious clinical event in patients during post-renal transplantation. I/R is associated with renal dysfunction and tubular apoptosis, and calcium (Ca2+) overload has been reported to be a crucial factor on tubular apoptosis in I/R injury (IRI). The canonical transient receptor potential channel 6 (TRPC6), a type of non-selective Ca2+ channel, is involved in many renal diseases. Our earlier study identified that TRPC6-mediated Ca2+ influx plays a novel role in suppressing cytoprotective autophagy triggered by oxidative stress in primary tubular epithelial cells (TECs). This study explored the potential beneficial impact of TRPC6 knockout (TRPC6−/−) and the relevant cellular mechanisms against I/R-induced AKI in mice. Measuring changes of renal function, apoptotic index, and autophagy in mouse kidneys that suffered 24 h reperfusion after 40 min ischemia and working in vitro with TECs that suffered 24 h reoxygenation after 24 h hypoxia, we found that 1) IRI tissues had increased TRPC6 expression and TRPC6 knockout significantly ameliorated renal damage induced by IRI; 2) TRPC6 knockout enhanced the level of autophagy and alleviated the depolarization of mitochondrial membrane potential (ψm, MMP) and apoptotic changes upon IRI; and 3) IRI tissues had increased p-AKT and p-ERK1/2 expressions, while TRPC6 knockout could markedly reduce the phosphorylation of AKT and ERK1/2. These discoveries suggest that, by reducing Ca2+ overload, the underlying protective mechanism of TRPC6−/− may be involved in down-regulation of PI3K/AKT and ERK signaling, which is likely to provide a new avenue for future AKI therapies.
The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment
Authors: Lv Tao , Zhao Bing , Hu Qin , Zhang Xiaohua
Published: July 2021

The glymphatic system (GS) is a novel defined brain-wide perivascular transit network between cerebrospinal fluid (CSF) and interstitial solutes that facilitates the clearance of brain metabolic wastes. The complicated network of the GS consists of the periarterial CSF influx pathway, astrocytes-mediated convective transport of fluid and solutes supported by AQP4 water channels, and perivenous efflux pathway. Recent researches indicate that the GS dysfunction is associated with various neurological disorders, including traumatic brain injury, hydrocephalus, epilepsy, migraine, and Alzheimer’s disease (AD). Meanwhile, the GS also plays a pivotal role in the pathophysiological process of stroke, including brain edema, blood–brain barrier (BBB) disruption, immune cell infiltration, neuroinflammation, and neuronal apoptosis. In this review, we illustrated the key anatomical structures of the GS, the relationship between the GS and the meningeal lymphatic system, the interaction between the GS and the BBB, and the crosstalk between astrocytes and other GS cellular components. In addition, we contributed to the current knowledge about the role of the GS in the pathology of stroke and the role of AQP4 in stroke. We further discussed the potential use of the GS in early risk assessment, diagnostics, prognostics, and therapeutics of stroke.
Discrete Dynamics of Dynamic Neural Fields
Authors: Kwessi Eddy
Published: July 2021

Large and small cortexes of the brain are known to contain vast amounts of neurons that interact with one another. They thus form a continuum of active neural networks whose dynamics are yet to be fully understood. One way to model these activities is to use dynamic neural fields which are mathematical models that approximately describe the behavior of these congregations of neurons. These models have been used in neuroinformatics, neuroscience, robotics, and network analysis to understand not only brain functions or brain diseases, but also learning and brain plasticity. In their theoretical forms, they are given as ordinary or partial differential equations with or without diffusion. Many of their mathematical properties are still under-studied. In this paper, we propose to analyze discrete versions dynamic neural fields based on nearly exact discretization schemes techniques. In particular, we will discuss conditions for the stability of nontrivial solutions of these models, based on various types of kernels and corresponding parameters. Monte Carlo simulations are given for illustration.
Mind Causality: A Computational Neuroscience Approach
Authors: Rolls Edmund T.
Published: July 2021

A neuroscience-based approach has recently been proposed for the relation between the mind and the brain. The proposal is that events at the sub-neuronal, neuronal, and neuronal network levels take place simultaneously to perform a computation that can be described at a high level as a mental state, with content about the world. It is argued that as the processes at the different levels of explanation take place at the same time, they are linked by a non-causal supervenient relationship: causality can best be described in brains as operating within but not between levels. This mind-brain theory allows mental events to be different in kind from the mechanistic events that underlie them; but does not lead one to argue that mental events cause brain events, or vice versa: they are different levels of explanation of the operation of the computational system. Here, some implications are developed. It is proposed that causality, at least as it applies to the brain, should satisfy three conditions. First, interventionist tests for causality must be satisfied. Second, the causally related events should be at the same level of explanation. Third, a temporal order condition must be satisfied, with a suitable time scale in the order of 10 ms (to exclude application to quantum physics; and a cause cannot follow an effect). Next, although it may be useful for different purposes to describe causality involving the mind and brain at the mental level, or at the brain level, it is argued that the brain level may sometimes be more accurate, for sometimes causal accounts at the mental level may arise from confabulation by the mentalee, whereas understanding exactly what computations have occurred in the brain that result in a choice or action will provide the correct causal account for why a choice or action was made. Next, it is argued that possible cases of “downward causation” can be accounted for by a within-levels-of-explanation account of causality. This computational neuroscience approach provides an opportunity to proceed beyond Cartesian dualism and physical reductionism in considering the relations between the mind and the brain.