bluuebunny/crossref_metadata_2025 huggingface dataset:
Approximating Soil Organic Carbon Stock in the Eastern Plains of Colombia
Authors: Rainford Shauna-kay , Martín-López Javier M. , Da Silva Mayesse
Published: July 2021

In Colombia, the rise of agricultural and pastureland expansion continues to exert increasing pressure on the structure and ecological processes of savannahs in the Eastern Plains. However, the effect of land use change on soil properties is often unknown due to poor access to remote areas. Effective management and conservation of soils requires the development spatial approaches that measure and predict dynamic soil properties such as soil organic carbon (SOC). This study estimates the SOC stock in the Eastern Plains of Colombia, with validation and uncertainty analyses, using legacy data of 653 soil samples. A random forest model of nine environmental covariate layers was used to develop predictions of SOC content. Model validation was determined using the Taylor series method, and root-mean-squared error (RMSE) and mean error (ME) were calculated to assess model performance. We found that the model explained 50.28% of the variation within digital SOC content map. Raster layers of SOC content, bulk density, and coarse rock fragment within the Eastern Plains were used to calculate SOC stock within the region. With uncertainty, SOC stock in the topsoil of the Eastern Plains was 1.2 G t ha−1. We found that SOC content contributed nearly all the uncertainty in the SOC stock predictions, although better determinations of SOC stock can be obtained with the use of a more geomorphological diverse dataset. The digital soil maps developed in this study provide predictions of extant SOC content and stock in the topsoil of the Eastern Plains, important soil information that may provide insight into the development of research, regulatory, and legislative initiatives to conserve and manage this evolving ecosystem.
Construction of the Mean Sea Surface Model Combined HY-2A With DTU18 MSS in the Antarctic Ocean
Authors: Sun Weikang , Zhou Xinghua , Yang Lei , Zhou Dongxu , Li Feng
Published: July 2021

A new Mean Sea Surface (MSS) model called Shandong University of Science and Technology Antarctic Mean Sea Surface model (SDUST_ANT MSS) in the Antarctic Ocean is presented and validated in this paper. The SDUST_ANT MSS updates the DTU18 MSS with 6 years of Exact Repeat Mission (ERM) and Geodetic Mission (GM) data from HY-2A. Collinear adjustment was applied to all the ERM data to obtain the along-track mean sea surface height. Oceanic variability has been removed from the GM data. Crossover adjustment was applied to both the ERM and GM data. We constructed the HY-2A_MSS using HY-2A altimetry data based on optimal interpolation method. Several types of errors (such as white noise, residual effect of oceanic variability, and long wavelength bias) have been taken into account for the determination of MSS using optimal interpolation method. The SDUST_ANT MSS was constructed by mapping HY-2A_MSS onto the DTU18 MSS. The SDUST_ANT MSS was compared with DTU18 MSS and CNES_CLS15 MSS. At wavelengths below 150 km, differences between models are consistent with seafloor topographic gradient. At wavelengths above 150 km, differences are affected by the mesoscale activities and the altimetry errors in coastal areas. The errors of the three models, as indicated by their power spectral densities (PSDs), are of similar orders of magnitude. The absolute error is slightly smaller in SDUST_ANT than in CNES_CLS15 or DTU18.
Depletion of Soil Water-Extractable Organic Matter With Long-Term Coverage by Impervious Surfaces
Authors: Wang Yinghui , Zhang Qiang , Majidzadeh Hamed , He Chen , Shi Quan , Kong Sifang , Yang Zhibing , Wang Junjian
Published: July 2021

Water-extractable organic matter (WEOM) in soil is the critical substrate that fuels microbial-driven biogeochemical cycles. However, questions remain regarding whether and how expanding impervious surface area under global urbanization may alter soil WEOM cycling. Based on absorbance and fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), we compared the content and chemical signatures of soil WEOM under impervious surfaces with those in adjoining open areas and evaluated the impacts of types (complete sealing by concrete and partial sealing by house structures) and durations (1.5, 27, and 114 years) of impervious surface coverage. The content of soil WEOM and its chromophoric and fluorescent fractions were not significantly changed (less than 20%) after 1.5 years of coverage by concrete and house structures. However, these parameters decreased by more than 30% with 27 and 114 years of coverage by the residential home structures. The microbial-humic-like and protein-like fluorescent WEOM persisted preferentially over the terrestrial-humic-like and nonfluorescent WEOM. FT-ICR MS results suggest various degrees of depletion of biochemical groups in WEOM. While the water-extractable lipid-like compounds increased with 1.5 years of coverage, all studied biochemical groups were depleted with long-term coverage, which might reduce the microbial processing of suberin-derived compounds. This study highlights the remarkable impacts of soil sealing on reducing substrate availability for microbial carbon processing in urban environments.
Identification of Distinct Molecular Subtypes of Endometrioid Adenocarcinoma
Authors: Lei Jia , Yan Shuping , Guo Xiangqian , Wang Fengling , Zhang Guosen , Kan Quancheng , Guo Ruixia
Published: July 2021

Endometrial carcinoma (EC) is one of the most common gynecological cancers worldwide. Endometrioid adenocarcinoma (EAC) is the major form of EC, accounting for 75–80% of cases. Currently, there is no molecular classification system for EAC, so there are no corresponding targeted treatments. In this study, we identified two distinct molecular subtypes of EAC with different gene expression patterns and clinicopathologic characteristics. Subtype I EAC cases, accounting for the majority of cases (56%), were associated with an earlier stage, a more well-differentiated grade, a lower tumor invasion rate, and a more favorable prognosis, and the median tumor necrosis percent (15%) was also significantly higher in subtype I EAC. In contrast, subtype II EAC represents high-grade EAC, with a higher tumor invasion rate and tumor weight. The up-regulated genes in subtype I EAC were associated with the immune response, defense response, cell motion, and cell motility pathway, whereas the up-regulated genes in subtype II EAC were associated with the cell cycle, DNA replication, and RNA processing pathways. Additionally, we identified three potential subtype-specific biomarkers, comprisingMDM2(MDM2 proto-oncogene) for subtype I, andMSH2(mutS homolog 2) andMSH6(mutS homolog 6) for subtype II.
Circular RNA Circ_0013958 Functions as a Tumor Promoter in Ovarian Cancer by Regulating miR-637/PLXNB2 Axis
Authors: Liang Yanfei , Meng Kaiyi , Qiu Rui
Published: July 2021

Background: Circular RNAs (circRNAs) have emerged as important regulators in diverse human malignancies, including ovarian cancer (OC). This study was performed to explore the function and regulatory mechanism underlying circ_0013958 in OC progression.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay was applied to examine the expression of circ_0013958, microRNA-637 (miR-637), and Plexin B2 (PLXNB2). The target relationship between miR-637 and circ_0013958 or PLXNB2 was verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP) assay. Cell Counting Kit-8 (CCK-8) and colony formation assays were employed to detect cell viability and clonogenicity ability, respectively. Cell migration and invasion were analyzed by Transwell assay. Cell apoptosis was monitored by flow cytometry. The role of circ_0013958 in vivo was determined by xenograft tumor assay.

Results: Circ_0013958 and PLXNB2 were upregulated, while miR-637 was downregulated in OC tissues and cells. Circ_0013958 acted as a sponge for miR-637 to regulate the expression of PLXNB2 in OC cells. The repression effects of circ_0013958 knockdown on cell proliferation, migration, invasion, and apoptosis in OC cells were partly attenuated by the miR-637 inhibitor. And miR-637 targeted PLXNB2 to suppress OC cell proliferation, migration, and invasion. Moreover, circ_0013958 silencing blocked OC tumor growth in vivo.

Conclusion: Circ_0013958 knockdown impeded OC development through modulating the miR-637/PLXNB2 axis, highlighting a therapeutic target for OC.
Identification of Potential Prognostic Biomarkers Associated With Cancerometastasis in Skin Cutaneous Melanoma
Authors: Li Yang , Lyu Shanshan , Gao Zhe , Zha Weifeng , Wang Ping , Shan Yunyun , He Jianzhong , Huang Suyang
Published: July 2021

Skin cutaneous melanoma (SKCM) is a highly aggressive tumor. The mortality and drug resistance among it are high. Thus, exploring predictive biomarkers for prognosis has become a priority. We aimed to find immune cell-based biomarkers for survival prediction. Here 321 genes were differentially expressed in immune-related groups after ESTIMATE analysis and differential analysis. Two hundred nineteen of them were associated with the metastasis of SKCM via weighted gene co-expression network analysis. Twenty-six genes in this module were hub genes. Twelve of the 26 genes were related to overall survival in SKCM patients. After a multivariable Cox regression analysis, we obtained six of these genes (PLA2G2D, IKZF3, MS4A1, ZC3H12D, FCRL3, and P2RY10) that were independent prognostic signatures, and a survival model of them performed excellent predictive efficacy. The results revealed several essential genes that may act as significant prognostic factors of SKCM, which could deepen our understanding of the metastatic mechanisms and improve cancer treatment.
Pandemic State Failure, Hydrocarbon Control, and Indigenous Territorial Counteraction in the Peruvian Amazon
Authors: Watson Ana , Davidsen Conny
Published: July 2021

During the COVID-19 pandemic, the Peruvian government failed to protect its sparsely populated Amazon region. While infections were still rising, resource extraction was quickly approved to continue operations as a declared essential service that permitted an influx of workers into vulnerable indigenous territories despite weak or almost absent local healthcare. This article analyzes territorial counteraction as an indigenous response to pandemic national state failure, highlighted in a case of particularly conflictive stakes of resource control: Peru’s largest liquid natural gas extraction site Camisea in the Upper Amazon, home to several indigenous groups in the Lower Urubamba who engaged in collective action to create their own district. Frustration with the state’s handling of the crisis prompted indigenous counteraction to take COVID-19 measures and territorial control into their own hands. By blocking boat traffic on their main river, they effectively cut off their remote and roadless Amazon district off from the outside world. Local indigenous control had already been on the rise after the region had successfully fought for its own formal subnational administrative jurisdiction in 2016, named Megantoni district. The pandemic then created a moment of full indigenous territorial control that openly declared itself as a response and replacement of a failed national state. Drawing on political ecology, we analyze this as an interesting catalyst moment that elevated long-standing critiques of inequalities, and state neglect into new negotiations of territory and power between the state and indigenous self-determination, with potentially far-reaching implications on state-indigenous power dynamics and territorial control, beyond the pandemic.
Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema
Authors: Santana Kelly Gomes , Righetti Renato Fraga , Breda Cristiane Naffah de Souza , Domínguez-Amorocho Omar Alberto , Ramalho Theresa , Dantas Francisca Elda B. , Nunes Valéria Sutti , Tibério Iolanda de Fátima Lopes Calvo , Soriano Francisco Garcia , Câmara Niels O. S. , Quintão Eder Carlos Rocha , Cazita Patrícia M.
Published: July 2021

Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis. Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related to comorbidities such as chronic obstructive pulmonary disease (COPD). Macrophages are significantly associated with pulmonary emphysema, and depending on the microenvironment, might exhibit an M1 or M2 phenotype. Macrophages derived from the peritoneum and bone marrow reveal CETP that contributes to its plasma concentration. Here, we evaluated the role of CETP in macrophage polarization and elastase-induced pulmonary emphysema (ELA) in human CETP-expressing transgenic (huCETP) (line 5203, C57BL6/J background) male mice and compared it to their wild type littermates. We showed that bone marrow-derived macrophages from huCETP mice reduce polarization toward the M1 phenotype, but with increased IL-10. Compared to WT, huCETP mice exposed to elastase showed worsened lung function with an increased mean linear intercept (Lm), reflecting airspace enlargement resulting from parenchymal destruction with increased expression of arginase-1 and IL-10, which are M2 markers. The cytokine profile revealed increased IL-6 in plasma and TNF, and IL-10 in bronchoalveolar lavage (BAL), corroborating with the lung immunohistochemistry in the huCETP-ELA group compared to WT-ELA. Elastase treatment in the huCETP group increased VLDL-C and reduced HDL-C. Elastase-induced pulmonary emphysema in huCETP mice promotes lung M2-like phenotype with a deleterious effect in experimental COPD, corroborating the in vitro result in which CETP promoted M2 macrophage polarization. Our results suggest that CETP is associated with inflammatory response and influences the role of macrophages in COPD.
Cancer Immunotherapies: From Efficacy to Resistance Mechanisms – Not Only Checkpoint Matters
Authors: Wang Shuyue , Xie Kun , Liu Tengfei
Published: July 2021

The immunotherapeutic treatment of various cancers with an increasing number of immune checkpoint inhibitors (ICIs) has profoundly improved the clinical management of advanced diseases. However, just a fraction of patients clinically responds to and benefits from the mentioned therapies; a large proportion of patients do not respond or quickly become resistant, and hyper- and pseudoprogression occur in certain patient populations. Furthermore, no effective predictive factors have been clearly screened or defined. In this review, we discuss factors underlying the elucidation of potential immunotherapeutic resistance mechanisms and the identification of predictive factors for immunotherapeutic responses. Considering the heterogeneity of tumours and the complex immune microenvironment (composition of various immune cell subtypes, disease processes, and lines of treatment), checkpoint expression levels may not be the only factors underlying immunotherapy difficulty and resistance. Researchers should consider the tumour microenvironment (TME) landscape in greater depth from the aspect of not only immune cells but also the tumour histology, molecular subtype, clonal heterogeneity and evolution as well as micro-changes in the fine structural features of the tumour area, such as myeloid cell polarization, fibroblast clusters and tertiary lymphoid structure formation. A comprehensive analysis of the immune and molecular profiles of tumour lesions is needed to determine the potential predictive value of the immune landscape on immunotherapeutic responses, and precision medicine has become more important.
The Salivary Microbiota of Patients With Primary Biliary Cholangitis Is Distinctive and Pathogenic
Authors: Lv Longxian , Jiang Huiyong , Chen Xiaoxiao , Wang Qiangqiang , Wang Kaicen , Ye Jianzhong , Li Yating , Fang Daiqiong , Lu Yingfeng , Yang Liya , Gu Silan , Chen Jianing , Diao Hongyan , Yan Ren , Li Lanjuan
Published: July 2021

The role of host-microbiota interactions in primary biliary cholangitis (PBC) has received increased attention. However, the impact of PBC on the oral microbiota and contribution of the oral microbiota to PBC are unclear. In this study, thirty-nine PBC patients without other diseases and 37 healthy controls (HCs) were enrolled and tested for liver functions and haematological variables. Saliva specimens were collected before and after brushing, microbiota was determined using 16S rDNA sequencing, metabolomics was profiled using Gas Chromatography-Mass Spectrometer (GC-MS), 80 cytokines were assayed using biochips, and inflammation inducibility was evaluated using OKF6 keratinocytes and THP-1 macrophages. Finally, the effect of ultrasonic scaling on PBC was estimated. Compared with HCs, PBC saliva had enriched taxa such as Bacteroidetes, Campylobacter, Prevotella and Veillonella and depleted taxa such as Enterococcaceae, Granulicatella, Rothia and Streptococcus. PBC saliva also had enriched sCD163, enriched metabolites such as 2-aminomalonic acid and 1-dodecanol, and depleted metabolites such as dodecanoic acid and propylene glycol. sCD163, 4-hydroxybenzeneacetic acid and 2-aminomalonic acid were significantly correlated with salivary cytokines, bacteria and metabolites. Salivary Veillonellaceae members, 2-aminomalonic acid, and sCD163 were positively correlated with liver function indicators such as serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PBC salivary microbes induced more soluble interleukin (IL)-6 receptor α (sIL-6Rα), sIL-6Rβ and tumour necrosis factor ligand superfamily (TNFSF)13B from OKF6 keratinocytes, and PBC salivary supernatant induced more IL-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokine (C-C motif) ligand (CCL)13, C-X-C motif chemokine (CXC)L1 and CXCL16 from THP-1 macrophages. Toothbrushing significantly reduced the expression of inflammatory cytokines such as IL-1β, IL-8 and TNF-α and harmful metabolites such as cadaverine and putrescine in PBC but not HC saliva after P‐value correction. The levels of ALP and bilirubin in PBC serum were decreased after ultrasonic scaling. Together, PBC patients show significant alterations in their salivary microbiota, likely representing one cause and treatment target of oral inflammation and worsening liver functions.
Advanced Remote Data Acquisition Using a Pop-Up Data Shuttle (PDS) to Report Data From Current- and Pressure-Recording Inverted Echo Sounders (CPIES)
Authors: Jeon Chanhyung , Park Jae-Hun , Kennelly Maureen , Sousa Erran , Watts D. Randolph , Lee Eun-Joo , Park Taewook , Peacock Thomas
Published: July 2021

A current- and pressure-recording inverted echo sounder (CPIES) placed on the sea floor monitors aspects of the physical ocean environment for periods of months to years. Until recently, acoustic telemetry of daily-processed data was the existing method for data acquisition from CPIES without full instrument recovery. However, this approach, which requires positioning a ship at the mooring site and operator time, is expensive and time-consuming. Here, we introduce a new method of obtaining data remotely from CPIES using a popup-data-shuttle (PDS), which enables straightforward data acquisition without a ship. The PDS data subsampled from CPIES has 30–60 min temporal resolution. The PDS has a scheduled pop-up-type release system, so each data pod floats to the sea surface at a user-specified date and relays the recorded data via the Iridium satellite system. We demonstrated the capability of an array of PDS-CPIES via two successful field experiments in the Arctic Ocean. The data acquired through the PDS were in agreement with the fully recovered datasets. An example of the data retrieved from the PDS shows that time-varying signals of tides and high-frequency internal waves were well captured. GPS-tracked trajectories of the PDS floating free at the sea surface can provide insights into ice drift or ocean surface currents. This PDS technology provides an alternative method for remote deep-ocean mooring data acquisition.
Combining Imaging Flow Cytometry and Molecular Biological Methods to Reveal Presence of Potentially Toxic Algae at the Ural River in Kazakhstan
Authors: Mirasbekov Yersultan , Abdimanova Aigerim , Sarkytbayev Kuanysh , Samarkhanov Kanat , Abilkas Aidyn , Potashnikova Daria , Arbuz Galina , Issayev Zhanpeis , Vorobjev Ivan A. , Malashenkov Dmitry V. , Barteneva Natasha S.
Published: July 2021

Algal blooms occur in freshwater bodies throughout the world, often leading to fish kills. Cases of these kills along the Ural River were reported in 2018–2019, involving significant amount of sturgeon in fish farming areas. In this study, the analysis of algal samples from the delta of the Ural River up to 100 km inland was carried out from August to December 2019 using imaging flow cytometry (IFC), molecular biological, and microscopic techniques. We identified the filamentous cyanobacteriaCuspidothrix issatschenkoi,Dolichospermumcf.flos-aquae,Dolichospermumcf.macrosporum,Pseudanabaena limnetica, andPlanktothrixspp. as the dominant potentially toxic phytoplankton species, and we also found minor quantities ofCylindrospermopsis raciborskii. For the first time, molecular phylogenetic investigations of field clones of cyanobacteria from Ural River were carried out to establish the taxa of the dominant species and to identify the presence of genes encoding toxins. The complementary analysis with nanopore-based next-generation sequencing overlapped with the results of IFC and was instrumental in revealing minor cyanobacteria taxa. Real-time PCR analysis and sequencing indicated the presence ofMicrocystisand ADA-clade spp. as well as genes associated with the production of microcystin (mcyE) and the algal neurotoxin saxitoxin (sxtA) originating from cyanobacteria. These findings suggest that toxin-producing cyanobacteria could become a threat in the Ural River near Atyrau, which can significantly affect aquaculture in the region.
Unraveling Salinity Extreme Events in Coastal Environments: A Winter Focus on the Bay of Brest
Authors: Poppeschi Coline , Charria Guillaume , Goberville Eric , Rimmelin-Maury Peggy , Barrier Nicolas , Petton Sébastien , Unterberger Maximilian , Grossteffan Emilie , Repecaud Michel , Quéméner Loïc , Theetten Sébastien , Le Roux Jean-François , Tréguer Paul
Published: July 2021

Extreme weather events affect coastal marine ecosystems. The increase in intensity and occurrence of such events drive modifications in coastal hydrology and hydrodynamics. Here, focusing on the winter period (from December to March), we investigated multi-decade (2000–2018) changes in the hydrological properties of the Bay of Brest (French Atlantic coast) as an example of the response of a semi-enclosed bay to extreme weather episodes and large-scale atmospheric circulation patterns. The relationships between extreme weather events and severe low salinity conditions (as a proxy for changes in water density) were investigated using high-frequencyin situobservations and high-resolution numerical simulations. The identification of intense episodes was based on the timing, duration, and annual occurrence of extreme events. By examining the interannual variability of extreme low salinity events, we detect a patent influence of local and regional weather conditions on atmospheric and oceanic circulation patterns, precipitation, and river runoff. We revealed that low salinity events in Brittany were controlled by large-scale forcings: they prevailed during the positive phase of the North Atlantic Oscillation and periods of low occurrences of the Atlantic Ridge weather regime. The increase in severe storms observed in western France since 2010 has led to a doubling of the occurrence and duration of extreme low salinity events in Brittany.
Comparing Multimorbidity Patterns Among Discharged Middle-Aged and Older Inpatients Between Hong Kong and Zurich: A Hierarchical Agglomerative Clustering Analysis of Routine Hospital Records
Authors: Lai Francisco T. T. , Beeler Patrick E. , Yip Benjamin H. K. , Cheetham Marcus , Chau Patsy Y. K. , Chung Roger Y. , Wong Eliza L. Y. , Yeoh Eng-Kiong , Battegay Edouard , Wong Samuel Y. S.
Published: July 2021

Background: Multimorbidity, defined as the co-occurrence of ≥2 chronic conditions, is clinically diverse. Such complexity hinders the development of integrated/collaborative care for multimorbid patients. In addition, the universality of multimorbidity patterns is unclear given scarce research comparing multimorbidity profiles across populations. This study aims to derive and compare multimorbidity profiles in Hong Kong (HK, PRC) and Zurich (ZH, Switzerland).

Methods: Stratified by sites, hierarchical agglomerative clustering analysis (dissimilarity measured by Jaccard index) was conducted with the objective of grouping inpatients into clinically meaningful clusters based on age, sex, and 30 chronic conditions among 20,000 randomly selected discharged multimorbid inpatients (10,000 from each site) aged ≥ 45 years. The elbow point method based on average within-cluster dissimilarity, complemented with a qualitative clinical examination of disease prevalence, was used to determine the number of clusters.

Results: Nine clusters were derived for each site. Both similarities and dissimilarities of multimorbidity patterns were observed. There was one stroke-oriented cluster (3.9% in HK; 6.5% in ZH) and one chronic kidney disease-oriented cluster (13.1% in HK; 11.5% ZH) in each site. Examples of site-specific multimorbidity patterns, on the other hand, included a myocardial infarction-oriented cluster in ZH (2.3%) and several clusters in HK with high prevalence of heart failure (>65%) and chronic pain (>20%).

Conclusion: This is the first study using hierarchical agglomerative clustering analysis to profile multimorbid inpatients from two different populations to identify universalities and differences of multimorbidity patterns. Our findings may inform the coordination of integrated/collaborative healthcare services.
Innovative Diagnostic Endoscopy in Inflammatory Bowel Diseases: From High-Definition to Molecular Endoscopy
Authors: Bojarski Christian , Waldner Maximilian , Rath Timo , Schürmann Sebastian , Neurath Markus F. , Atreya Raja , Siegmund Britta
Published: July 2021

High-definition endoscopy is one essential step in the initial diagnosis of inflammatory bowel disease (IBD) characterizing the extent and severity of inflammation, as well as discriminating ulcerative colitis (UC) from Crohn's disease (CD). Following general recommendations and national guidelines, individual risk stratification should define the appropriate surveillance strategy, biopsy protocol and frequency of endoscopies. Beside high-definition videoendoscopy the application of dyes applied via a spraying catheter is of additional diagnostic value with a higher detection rate of intraepithelial neoplasia (IEN). Virtual chromoendoscopy techniques (NBI, FICE, I-scan, BLI) should not be recommended as a single surveillance strategy in IBD, although newer data suggest a higher comparability to dye-based chromoendoscopy than previously assumed. First results of oral methylene blue formulation are promising for improving the acceptance rate of classical chromoendoscopy. Confocal laser endomicroscopy (CLE) is still an experimental but highly innovative endoscopic procedure with the potential to contribute to the detection of dysplastic lesions. Molecular endoscopy in IBD has taken application of CLE to a higher level and allows topical application of labeled probes, mainly antibodies, against specific target structures expressed in the tissue to predict response or failure to biological therapies. First pre-clinical and in vivo data from label-free multiphoton microscopy (MPM) are now available to characterize mucosal and submucosal inflammation on endoscopy in more detail. These new techniques now have opened the door to individualized and highly specific molecular imaging in IBD in the future and pave the path to personalized medicine approaches. The quality of evidence was stated according to the Oxford Center of evidence-based medicine (March 2009). For this review a Medline search up to January 2021 was performed using the words “inflammatory bowel disease,” “ulcerative colitis,” “crohn's disease,” “chromoendoscopy,” “high-definition endoscopy,” “confocal laser endomicroscopy,” “confocal laser microscopy,” “molecular imaging,” “multiphoton microscopy.”
Diagnosing Diabetic Retinopathy With Artificial Intelligence: What Information Should Be Included to Ensure Ethical Informed Consent?
Authors: Ursin Frank , Timmermann Cristian , Orzechowski Marcin , Steger Florian
Published: July 2021

Purpose: The method of diagnosing diabetic retinopathy (DR) through artificial intelligence (AI)-based systems has been commercially available since 2018. This introduces new ethical challenges with regard to obtaining informed consent from patients. The purpose of this work is to develop a checklist of items to be disclosed when diagnosing DR with AI systems in a primary care setting.

Methods: Two systematic literature searches were conducted in PubMed and Web of Science databases: a narrow search focusing on DR and a broad search on general issues of AI-based diagnosis. An ethics content analysis was conducted inductively to extract two features of included publications: (1) novel information content for AI-aided diagnosis and (2) the ethical justification for its disclosure.

Results: The narrow search yielded n = 537 records of which n = 4 met the inclusion criteria. The information process was scarcely addressed for primary care setting. The broad search yielded n = 60 records of which n = 11 were included. In total, eight novel elements were identified to be included in the information process for ethical reasons, all of which stem from the technical specifics of medical AI.

Conclusions: Implications for the general practitioner are two-fold: First, doctors need to be better informed about the ethical implications of novel technologies and must understand them to properly inform patients. Second, patient's overconfidence or fears can be countered by communicating the risks, limitations, and potential benefits of diagnostic AI systems. If patients accept and are aware of the limitations of AI-aided diagnosis, they increase their chances of being diagnosed and treated in time.
Assembling the Current Pieces: The Puzzle of RNA-Mediated Regulation in Staphylococcus aureus
Authors: Barrientos Laura , Mercier Noémie , Lalaouna David , Caldelari Isabelle
Published: July 2021

The success of the major opportunistic human Staphylococcus aureus relies on the production of numerous virulence factors, which allow rapid colonization and dissemination in any tissues. Indeed, regulation of its virulence is multifactorial, and based on the production of transcriptional factors, two-component systems (TCS) and small regulatory RNAs (sRNAs). Advances in high-throughput sequencing technologies have unveiled the existence of hundreds of potential RNAs with regulatory functions, but only a fraction of which have been validated in vivo. These discoveries have modified our thinking and understanding of bacterial physiology and virulence fitness by placing sRNAs, alongside transcriptional regulators, at the center of complex and intertwined regulatory networks that allow S. aureus to rapidly adapt to the environmental cues present at infection sites. In this review, we describe the recently acquired knowledge of characterized regulatory RNAs in S. aureus that are associated with metal starvation, nutrient availability, stress responses and virulence. These findings highlight the importance of sRNAs for the comprehension of S. aureus infection processes while raising questions about the interplay between these key regulators and the pathways they control.
Development of a Hyperosmotic Stress Inducible Gene Expression System by Engineering the MtrA/MtrB-Dependent NCgl1418 Promoter in Corynebacterium glutamicum
Authors: Huang Jingwen , Chen Jiuzhou , Wang Yu , Shi Tuo , Ni Xiaomeng , Pu Wei , Liu Jiao , Zhou Yingyu , Cai Ningyun , Han Shuangyan , Zheng Ping , Sun Jibin
Published: July 2021

Corynebacterium glutamicum is an important workhorse for industrial production of diversiform bioproducts. Precise regulation of gene expression is crucial for metabolic balance and enhancing production of target molecules. Auto-inducible promoters, which can be activated without expensive inducers, are ideal regulatory tools for industrial-scale application. However, few auto-inducible promoters have been identified and applied in C. glutamicum. Here, a hyperosmotic stress inducible gene expression system was developed and used for metabolic engineering of C. glutamicum. The promoter of NCgl1418 (PNCgl1418) that was activated by the two-component signal transduction system MtrA/MtrB was found to exhibit a high inducibility under hyperosmotic stress conditions. A synthetic promoter library was then constructed by randomizing the flanking and space regions of PNCgl1418, and mutant promoters exhibiting high strength were isolated via fluorescence activated cell sorting (FACS)-based high-throughput screening. The hyperosmotic stress inducible gene expression system was applied to regulate the expression of lysE encoding a lysine exporter and repress four genes involved in lysine biosynthesis (gltA, pck, pgi, and hom) by CRISPR interference, which increased the lysine titer by 64.7% (from 17.0 to 28.0 g/L) in bioreactors. The hyperosmotic stress inducible gene expression system developed here is a simple and effective tool for gene auto-regulation in C. glutamicum and holds promise for metabolic engineering of C. glutamicum to produce valuable chemicals and fuels.
Bibliometric Analysis Study on the Mechanisms of Brain Energy Metabolism Disorders in Alzheimer's Disease From 2000 to 2020
Authors: Du Yi-Hong , Yang Ruo-Yu , Wang Qi , Wang Li-Yan , Liang Lei-Chao , Zhu Lei , Sun Yan , Cai Ming
Published: July 2021

Alzheimer's disease (AD) is currently one of the main diseases afflicting the elderly in the world. In recent years, more and more studies have shown that brain energy metabolism disorders are the key pathogenic factors and main early pathological features of AD. Many risk factors such as insulin resistance, mitochondrial dysfunction, oxidative stress, Aβ-amyloid plaques, neurofibrillary tangles of hyperphosphorylated tau, aging, and neuroinflammation are involved in brain energy metabolism disorders. In this study, 1,379 Web of Science publications on the mechanisms of brain energy metabolism disorders in AD, all published from 2000 to 2020, were analyzed. Some network maps were drawn using CiteSpace and VOSviewer software which can be used to clarify research focus, forecast research frontiers and development trends, and provide different perspectives and characteristics in AD brain energy metabolism disorder mechanisms.
Case Report: Visual Rehabilitation in Hemianopia Patients. Home-Based Visual Rehabilitation in Patients With Hemianopia Consecutive to Brain Tumor Treatment: Feasibility and Potential Effectiveness
Authors: Daibert-Nido Monica , Pyatova Yulia , Cheung Kyle , Nayomi Camilus , Markowitz Samuel N. , Bouffet Eric , Reber Michael
Published: July 2021

Background/Objectives: Visual field loss is frequent in patients with brain tumors, worsening their daily life and exacerbating the burden of disease, and no supportive care strategies exist. In this case series, we sought to characterize the feasibility and potential effectiveness of a home-based visual rehabilitation program in hemianopia patients using immersive virtual-reality stimulation.

Subjects/Methods: Two patients, one with homonymous hemianopia and the other with bitemporal hemianopia, consecutive to pediatric brain tumors, with no prior visual rehabilitation performed 15 min of home-based audiovisual stimulation every 2 days for 6 weeks (case 2) and 7 weeks (case 1) between February and August 2020. Patients used a virtual-reality, stand-alone, and remotely controlled device loaded with a non-commercial audiovisual stimulation program managed in real time from the laboratory. Standard visual outcomes assessed in usual care in visual rehabilitation were measured at the clinic. Following a mixed method approach in this pragmatic study of two cases, we collected quantitative and qualitative data on feasibility and potential effectiveness and compared the results pre- and post-treatment.

Results: Implementation and wireless delivery of the audiovisual stimulation, remote data collection, and analysis for cases 1 and 2 who completed 19/20 and 20/20 audiovisual stimulation sessions at home, respectively, altogether indicated feasibility. Contrast sensitivity increased in both eyes for cases 1 and 2. Visual fields, measured by binocular Esterman and monocular Humphrey full-field analyses, improved in case 1. A minor increase was observed in case 2. Cases 1 and 2 enhanced reading speed. Case 2 strongly improved quality of life scores.

Conclusion: This is the first report of a home-based virtual-reality visual rehabilitation program for adult patients with hemianopia consecutive to a pediatric brain tumor. We show the feasibility in real-world conditions and potential effectiveness of such technology on visual perception and quality of life.
Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice
Authors: Khatoon Saima , Agarwal Nidhi Bharal , Samim Mohammed , Alam Ozair
Published: July 2021

Epilepsy is a complex neurological disorder, characterized by frequent electrical activity in brain regions. Inflammation and apoptosis cascade activation are serious neurological sequelae during seizures. Fisetin (3, 3′,4′,7-tetrahydroxyflavone), a flavonoid molecule, is considered for its effective anti-inflammatory and anti-apoptotic properties. This study investigated the neuroprotective effect of fisetin on experimental epilepsy. For acute studies, increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizure tests were performed to evaluate the antiseizure activity of fisetin. For the chronic study, the kindling model was established by the administration of PTZ in subconvulsive dose (25 mg/kg, i.p.). Mice were treated with fisetin (5, 10, and 20 mg/kg, p.o.) to study its probable antiseizure mechanism. The kindled mice were evaluated for seizure scores. Their hippocampus and cortex were assessed for neuronal damage, inflammation, and apoptosis. Histological alterations were observed in the hippocampus of the experimental mice. Levels of high mobility group box 1 (HMGB1), Toll-like receptor-4 (TLR-4), interleukin-1 receptor 1 (IL-1R1), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed in the hippocampus and cortex by ELISA. The immunoreactivity and mRNA expressions of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), cytochrome C, and caspase-3 were quantified by immunohistochemical analysis and real-time PCR. Phosphorylation ELISA was performed to evaluate AkT/mTOR (mammalian target of rapamycin) activation in the hippocampus and cortex of the kindled mice. The results showed that fisetin administration increased the seizure threshold current (STC) in the ICES test. In PTZ-induced seizures, fisetin administration increased the latency for myoclonic jerks (MJs) and generalized seizures (GSs). In the PTZ-induced kindling model, fisetin administration dose-dependently suppressed the development of kindling and the associated neuronal damage in the experimental mice. Further, fisetin administration ameliorated kindling-induced neuroinflammation as evident from decreased levels of HMGB1, TLR-4, IL-1R1, IL-1β, IL-6, and TNF-α in the hippocampus and cortex of the kindled mice. Also, the immunoreactivity and mRNA expressions of inflammatory molecules, NF-κB, and COX-2 were decreased with fisetin administration in the kindled animals. Decreased phosphorylation of the AkT/mTOR pathway was reported with fisetin administration in the hippocampus and cortex of the kindled mice. The immunoreactivity and mRNA expressions of apoptotic molecules, cytochrome C, and caspase-3 were attenuated upon fisetin administration. The findings suggest that fisetin shows a neuroprotective effect by suppressing the release of inflammatory and apoptosis molecules and attenuating histological alterations during experimental epilepsy.
Eye-Neck Integrated Ultrasound in Idiopathic Intracranial Hypertension and Cerebral Venous Sinus Thrombosis
Authors: Liu Li , Xing Yingqi , Chen Ying , Ji Xiaorui , Ge Jiaojiao , Wang Lijuan
Published: July 2021

Background: The clinical presentation of cerebral venous sinus thrombosis (CVST) overlaps with that of idiopathic intracranial hypertension (IIH), but no screening tool exists. We investigated the role of eye-neck integrated ultrasound in the diagnosis and differentiation of IIH and CVST.

Methods: Twenty IIH patients, 30 CVST patients, and 40 healthy controls were retrospectively analyzed. The ultrasonographic optic nerve sheath diameter (ONSD) and hemodynamic characteristics of the internal jugular veins (IJVs) were recorded. The cerebrospinal fluid opening pressure was measured after ultrasonic examination.

Results: The ONSD was significantly larger in IIH patients than in controls (4.71 ± 0.41 vs. 3.93 ± 0.24 mm, p < 0.001). The ONSD cut-off for IIH diagnosis was 4.25 mm (AUC = 0.978; 95% CI: 0.95–1.0, p < 0.001, sensitivity: 90%, specificity: 93%). In the CVST group, 22 (73.3%) patients had elevated intracranial pressure (ICP); the mean ONSD was significantly higher in patients with increased ICP than in those without (4.43 ± 0.33 vs. 3.95 ± 0.17 mm, p < 0.001). The mean blood flow volume (BFV) was significantly reduced in CVST patients (425.17 ± 349.83 mL/min) compared to that in controls (680.37 ± 233.03 mL/min, p < 0.001) and IIH patients (617.67 ± 282.96 mL/min, p = 0.008). The optimal BFV cut-off for predicting CVST was 527.28 mL/min (AUC = 0.804, 95% CI: 0.68–0.93, p < 0.001, sensitivity: 80%, specificity: 78%). The velocity of the unilateral IJVs-J3 segment decreased or remained constant during deep inspiration (abnormal respiratory modulate blood flow test, ARMT) in 32.5% of controls, with no bilateral ARMT. The prevalence of bilateral ARMT was 25% in IIH patients (χ2 = 12.9, p = 0.005) and 27% in CVST patients (χ2 = 17.6, p = 0.001).

Conclusion: Eye-neck integrated ultrasound is an easily available bedside technique to assess ICP and hemodynamic characteristics of IJVs. ONSD measurement can identify patients with increased ICP, and reduced IJV BFV may aid the differentiation of CVST and IIH.
From Visual Perception to Aesthetic Appeal: Brain Responses to Aesthetically Appealing Natural Landscape Movies
Authors: Isik Ayse Ilkay , Vessel Edward A.
Published: July 2021

During aesthetically appealing visual experiences, visual content provides a basis for computation of affectively tinged representations of aesthetic value. How this happens in the brain is largely unexplored. Using engaging video clips of natural landscapes, we tested whether cortical regions that respond to perceptual aspects of an environment (e.g., spatial layout, object content and motion) were directly modulated by rated aesthetic appeal. Twenty-four participants watched a series of videos of natural landscapes while being scanned using functional magnetic resonance imaging (fMRI) and reported both continuous ratings of enjoyment (during the videos) and overall aesthetic judgments (after each video). Although landscape videos engaged a greater expanse of high-level visual cortex compared to that observed for images of landscapes, independently localized category-selective visual regions (e.g., scene-selective parahippocampal place area and motion-selective hMT+) were not significantly modulated by aesthetic appeal. Rather, a whole-brain analysis revealed modulations by aesthetic appeal in ventral (collateral sulcus) and lateral (middle occipital sulcus, posterior middle temporal gyrus) clusters that were adjacent to scene and motion selective regions. These findings suggest that aesthetic appealper seis not represented in well-characterized feature- and category-selective regions of visual cortex. Rather, we propose that the observed activations reflect a local transformation from a feature-based visual representation to a representation of “elemental affect,” computed through information-processing mechanisms that detect deviations from an observer’s expectations. Furthermore, we found modulation by aesthetic appeal in subcortical reward structures but not in regions of the default-mode network (DMN) nor orbitofrontal cortex, and only weak evidence for associated changes in functional connectivity. In contrast to other visual aesthetic domains, aesthetically appealing interactions with natural landscapes may rely more heavily on comparisons between ongoing stimulation and well-formed representations of the natural world, and less on top-down processes for resolving ambiguities or assessing self-relevance.
Nivolumab in Non-Small Cell Lung Cancer: Real World Long-Term Survival Results and Blood-Based Efficacy Biomarkers
Authors: Daher Sameh , Lawrence Yaacov R. , Dudnik Elizabeth , Hanovich Ekaterina , Urban Damien , Peled Nir , Navon Rossie , Leibowitz Raya , Hammerman Ariel , Battat Erez , Gottfried Teodor , Onn Amir , Bar Jair
Published: July 2021

Objectives

We aimed to examine clinical data and baseline blood test results as potential predictive biomarkers for benefit from nivolumab, in advanced non-small cell lung cancer patients (NSCLC).

Materials and Methods

A chart review was performed of 108 advanced NSCLC patients who commenced treatment with nivolumab between 2015-6 at three Israeli cancer centers, and for whom laboratory tests results were available. Data collected included sex, age, ECOG-PS, histology and number of previous lines of treatment. Baseline blood test results collected: absolute lymphocyte and neutrophil count (ANC), white blood cells (WBC), hemoglobin, platelets, albumin and lactate dehydrogenase (LDH). Neutrophil to Lymphocyte Ratio and ‘derived NLR’ (dNLR = (ANC/[WBC-ANC])) were calculated. Disease control at six months (DC6) was defined as any tumor shrinkage or stable disease during the first six months of nivolumab treatment. The association between clinical/laboratory variables and survival was tested with a Cox proportional hazard model. Data cut-off occurred in November 2019.

Results

35 patients (32.4%) achieved DC6. Median overall survival (OS) of entire study population was 5.4 months. Four year survival rate was 16%. Achievement of DC6 strongly correlated with longer OS (HR 0.12, 95% C.I. 0.07-0.21, p<0.001). In univariate and multivariate analysis, dNLR, albumin and LDH correlated significantly with OS. No variables correlated significantly with DC6 in multivariate analysis. Based on albumin and LDH, we produced a score called CLAS (combined LDH and albumin score), including four prognostic groups of patients. Patients having low albumin and high LDH had the worst prognosis.

Conclusion

In real-life setting, long-term efficacy of nivolumab in advanced line treatment of NSCLC is consistent with clinical trials. Response or stability of disease during first six months of treatment is associated with prolonged survival. We propose a novel score (CLAS) that may be useful for predicting outcome in nivolumab-treated NSCLC patients, but further validation is required.