bluuebunny/crossref_metadata_2025 huggingface dataset:
When Is a Barrier Island Not an Island? When It Is Preserved in the Rock Record
Authors: Mulhern Julia S. , Johnson Cari L. , Green Andrew N.
Published: February 2021

Existing barrier island facies models are largely based on modern observations. This approach highlights the heterogeneous and dynamic nature of barrier island systems, but it overlooks processes tied to geologic time scales, such as multi-directional motion, erosion, and reworking, and their expressions as preserved strata. Accordingly, this study uses characteristic outcrop expressions from paralic strata of the Upper Cretaceous Straight Cliffs Formation in southern Utah to update models for barrier island motion and preservation to include geologic time-scale processes. Results indicate that the key distinguishing facies and architectural elements of preserved barrier island systems have very little to do with “island” morphology as observed in modern systems. Four facies associations are used to describe and characterize these barrier island architectural elements. Barrier islands occur in association with backbarrier fill (FA1) and internally contain lower and upper shoreface (FA2), proximal upper shoreface (FA3), and tidal channel facies (FA4). Three main architectural elements (barrier island shorefaces, shoreface-dominated inlet fill, and channel-dominated inlet fill) occur independently or in combination to create stacked barrier island deposits. Barrier island shorefaces record progradation, while shoreface-dominated inlet fill records lateral migration, and channel-dominated inlet fill records aggradation within the tidal inlet. Barrier islands are bound by lagoons or estuaries and are distinguished from other shoreface deposits by their internal facies and outcrop geometry, association with backbarrier facies, and position within transgressive successions. Tidal processes, in particular, tidal inlet migration and reworking of the upper shoreface, also distinguish barrier island successions. In sum, this study expands barrier island facies models and provides new recognition criteria to account for the complex geometries of time-transgressive, preserved barrier island deposits.
Ultrafine Magnetic Particles: A DIET-Proxy in Organic Rich Sediments?
Authors: Ustra Andrea Teixeira , Mendonça Carlos , Leite Aruã da Silva , Macouin Melina , Doherty Rory , Respaud Marc , Tocuti Giovana
Published: February 2021

In this work we present results of the magnetic properties characterization of sediment samples from a brownfield site that is generating methane biogas in São Paulo–Brazil. We applied interpretation procedures (frequency dependent susceptibility and time-dependent Isothermal Remanent Magnetization) appropriate to study the ultrafine magnetic fraction response of the samples. The higher content of superparamagnetic (SP) particles correlates well with the detected biogas pockets, suggesting that the methanogens activity produces these ultrafine particles, different from the magnetic particles at other depth levels. We propose the use of two simple measurement and interpretation techniques to identify such magnetic particles fingerprints. The results presented here support the use of environmental magnetism techniques to investigate biogeochemical processes of anaerobic microbial activity.
Sensitivity of ENSO Simulation to the Convection Schemes in the NESM3 Climate System Model: Atmospheric Processes
Authors: Ma Libin , Jiang Zijun
Published: February 2021

The El Niño-Southern Oscillation (ENSO) is the most prominent climate system in the tropical Pacific. However, its simulation, including the amplitude, phase locking, and asymmetry of its two phases, is not well reproduced by the current climate system models. In this study, the sensitivity of the ENSO simulation to the convection schemes is discussed using the Nanjing University of Information Science and Technology Earth System version 3.0 (NESM3) model. Three convection schemes, including the default, the default coupled with the stochastic multicloud model (SMCM), and the default used in the Coupled Model Intercomparison Project Phase 6 (CMIP6), are implemented. The model results reveal that the low-level cloud cover and surface net shortwave radiation are best represented over the tropical Pacific in the model containing the SMCM. The simulations of the ENSO behavior’s response to changes in the convection scheme are not uniform. The model results reveal that the model containing the SMCM performs best in terms of simulating the seasonal cycle of the sea surface temperature anomaly along the equatorial Pacific, the phase locking, and the power spectrum of ENSO but with a modest ENSO amplitude. Compared to the model containing the default convection scheme, the coupling of the default scheme and the SMCM provides a good simulation of the ENSO’s asymmetry, while the model containing the CMIP6 convection scheme outperforms the others in terms of the simulation of the ENSO’s amplitude. Two atmospheric feedback processes were further discussed to investigate the factors controlling the ENSO’s amplitude. The analyses revealed that the strongest positive atmospheric Bjerknes feedback and the thermodynamic damping of the surface net heat flux occurred in the model containing the CMIP6 convection scheme, suggesting that the atmospheric Bjerknes feedback may overwhelm the heat flux damping feedback when determining the ENSO’s amplitude. The results of this study demonstrate that perfectly modeling and predicting the ENSO is not simple, and it is still a large challenge and issue for the entire model community in the future.
Controls on the Precipitation of Carbonate Minerals Within Marine Sediments
Authors: Turchyn Alexandra V. , Bradbury Harold J. , Walker Kathryn , Sun Xiaole
Published: February 2021

The vast majority of carbonate minerals in modern marine sediments are biogenic, derived from the skeletal remains of organisms living in the ocean. However, carbonate minerals can also precipitate abiotically within marine sediments, and this carbonate mineral precipitation within sediments has been suggested as a third major, and isotopically distinct, sink in the global carbon cycle, particularly important earlier in Earth history. Here we present a global compilation of pore fluid data and compare the sulfate, calcium, phosphate and magnesium concentrations with pore fluid alkalinity to explore the emerging relationships and explore what drives carbonate mineral precipitation in sediments. Our data compilation shows that the gradient of pore fluid sulfate concentrations correlates strongly with the gradient of alkalinity as well as with the gradient of calcium, and that these correlations improve dramatically in sediments where methane is present. We also note that sedimentary pore fluids that are high in phosphate concentration are also high in alkalinity, which may indicate suppression of carbonate mineral precipitation in the presence of sedimentary phosphate. Our data can be used to highlight sediments where both dolomite formation and dolomitization of previously deposited calcium carbonate minerals is occurring. We explore how carbonate mineral saturation state changes as a function of calcium concentrations, alkalinity, and pH, and suggest a reason why calcium concentrations are never fully depleted in sedimentary pore fluids. We conclude that carbonate minerals precipitate in sediments with methane, where the anaerobic oxidation of this methane helps promote particularly high saturation states for carbonate minerals.
Variations in the Profiles of Vascular-Related Factors Among Different Sub-Types of Polycystic Ovarian Syndrome in Northern China
Authors: Liu Mei-mei , Chen Xiu-hui , Lu Xiu-min , Wang Fang-fang , Wang Chao , Liu Yu , Li Pei-ling , Du Bo-tao , Liang Sha , Gong Pi-dong , Wang Yu-xin
Published: February 2021

Recently, a growing body of evidence has suggested that abnormal ovarian angiogenesis, secondary to the imbalance between various angiogenic markers, is involved in the pathogenesis of PCOS, and this has led to the use of various interventions (such as Diane-35) to restore the normal ovarian angiogenesis. Therefore, we conducted the current investigation to determine the role of such markers (endothelial growth factor (VEGF), endostatin (ES), and thrombospondin-1 (TSP-1)) in the pathogenesis of PCOS along with the associated changes in ovarian blood flow in patients with PCOS compared to healthy controls, both before and after a course of oral contraception. A total of 381 patients with PCOS and 98 healthy females of childbearing age were recruited from July 2014 to June 2017 at the Reproductive Center of the Second Affiliated Hospital of Harbin Medical University. The serum levels of VEGF, ES, and TSP-1 were determined by enzyme-linked immunosorbent assay, while ovarian perfusion was measured by the pulsatility index (PI) and resistance index (RI) by using transvaginal color Doppler ultrasound. Repeated analyses were carried out after 3 months of Diane-35 treatment. Post-treatment serum levels of luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio of patients with PCOS decreased significantly (P <0.05). The RI values of most PCOS patients increased after treatment (P<0.05), while PI was significantly increased in all patients (P<0.05). However, variable changes in the serum levels of TSP-1, VEGF, and ES after treatment were observed. Serum VEGF levels showed a negative correlation with serum LH/FSH ratio, T concentration, and ES (P <0.05), while ES levels were negatively correlated with serum T concentrations only (P<0.05). The markers of angiogenesis (VEGF, ES, and TSP-1) were expressed differently among PCOS patients, who also responded differently to the same course of Diane-35 treatment. This field still warrants further investigation to reach a more definitive conclusion.
RETRACTED: SHCBP1 Promotes Papillary Thyroid Carcinoma Carcinogenesis and Progression Through Promoting Formation of Integrin and Collagen and Maintaining Cell Stemness
Authors: Geng Houfa , Guo Mengzhe , Xu Wei , Zang Xiu , Wu Tingting , Teng Fei , Wang Yu , Liu Xuekui , Wang Xiuli , Sun Qiang , Liang Jun
Published: February 2021

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer with a rapidly increasing incidence globally. Bioinformatics analyses suggested that SHCBP1 (SHC SH2 Domain-Binding Protein 1) was significantly up-regulated in PTC tumor tissues, which was further confirmed by immunohistochemical staining and qPCR analyses in Xuzhou cohort. Moreover, the results indicated that the mRNA level of SHCBP1 was negatively associated with patients’ disease-free survival rate, and further analysis reveals that patients with high SHCBP1 expression tend to have more lymph node metastasis. Afterward, MTT, colony formation, cell-cycle assay, FACS apoptosis assay, invasion, migration, as well as scratch assay were performed to study the phenotypes change of PTC cells after knocking down SHCBP1. The in vivo subcutaneous tumor model was developed to study the proliferation ability of PTC cells after SHCBP1 knockdown. We show that knock down of SHCBP1 significantly inhibits PTC cell proliferation, cell cycle, invasion and migration in vivo and in vitro. Western blot and qRT-PCR showed that knockdown of SHCBP1 could significantly reduce MYC, KLF4, CD44, ITGA6, ITGB1, ITGB5, and COL4A2 expression at both RNA and protein levels, which indicated that SHCBP1 might be involved in PTC carcinogenesis and progression through targeting formation of integrin and collagen and cell stemness pathways, and can be a potential diagnosis biomarker and therapeutic target for PTC.
Alternative RNA Splicing in Fatty Liver Disease
Authors: Wu Panyisha , Zhang Moya , Webster Nicholas J. G.
Published: February 2021

Alternative RNA splicing is a process by which introns are removed and exons are assembled to construct different RNA transcript isoforms from a single pre-mRNA. Previous studies have demonstrated an association between dysregulation of RNA splicing and a number of clinical syndromes, but the generality to common disease has not been established. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease affecting one-third of adults worldwide, increasing the risk of cirrhosis and hepatocellular carcinoma (HCC). In this review we focus on the change in alternative RNA splicing in fatty liver disease and the role for splicing regulation in disease progression.
Clinical Features, Management, and Molecular Characteristics of Familial Small Bowel Neuroendocrine Tumors
Authors: Lim James Y. , Pommier Rodney F.
Published: February 2021

Small bowel neuroendocrine tumors are rare tumors with an increasing incidence over the last several decades. Early detection remains challenging because patients commonly develop symptoms late in the disease course, often after the tumors have metastasized. Although these tumors were thought to arise from sporadic genetic mutations, large epidemiological studies strongly support genetic predisposition and increased risk of disease in affected families. Recent studies of familial small bowel neuroendocrine tumors have identified several novel genetic mutations. Screening for familial small bowel neuroendocrine tumors can lead to earlier diagnosis and improved patient outcomes. This review aims to summarize the current knowledge of molecular changes seen in familial small bowel neuroendocrine tumors, identify clinical features specific to familial disease, and provide strategies for screening and treatment.
Comparison of the Microsatellite Distribution Patterns in the Genomes of Euarchontoglires at the Taxonomic Level
Authors: Song Xuhao , Yang Tingbang , Zhang Xinyi , Yuan Ying , Yan Xianghui , Wei Yi , Zhang Jun , Zhou Caiquan
Published: February 2021

Microsatellite or simple sequence repeat (SSR) instability within genes can induce genetic variation. The SSR signatures remain largely unknown in different clades within Euarchontoglires, one of the most successful mammalian radiations. Here, we conducted a genome-wide characterization of microsatellite distribution patterns at different taxonomic levels in 153 Euarchontoglires genomes. Our results showed that the abundance and density of the SSRs were significantly positively correlated with primate genome size, but no significant relationship with the genome size of rodents was found. Furthermore, a higher level of complexity for perfect SSR (P-SSR) attributes was observed in rodents than in primates. The most frequent type of P-SSR was the mononucleotide P-SSR in the genomes of primates, tree shrews, and colugos, while mononucleotide or dinucleotide motif types were dominant in the genomes of rodents and lagomorphs. Furthermore, (A)n was the most abundant motif in primate genomes, but (A)n, (AC)n, or (AG)n was the most abundant motif in rodent genomes which even varied within the same genus. The GC content and the repeat copy numbers of P-SSRs varied in different species when compared at different taxonomic levels, reflecting underlying differences in SSR mutation processes. Notably, the CDSs containing P-SSRs were categorized by functions and pathways using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations, highlighting their roles in transcription regulation. Generally, this work will aid future studies of the functional roles of the taxonomic features of microsatellites during the evolution of mammals in Euarchontoglires.
Virus–Host Interactions in Foot-and-Mouth Disease Virus Infection
Authors: Li Kangli , Wang Congcong , Yang Fan , Cao Weijun , Zhu Zixiang , Zheng Haixue
Published: February 2021

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, which has been regarded as a persistent challenge for the livestock industry in many countries. Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD that can spread rapidly by direct and indirect transmission. FMDV is internalized into host cell by the interaction between FMDV capsid proteins and cellular receptors. When the virus invades into the cells, the host antiviral system is quickly activated to suppress the replication of the virus and remove the virus. To retain fitness and host adaptation, various viruses have evolved multiple elegant strategies to manipulate host machine and circumvent the host antiviral responses. Therefore, identification of virus-host interactions is critical for understanding the host defense against virus infections and the pathogenesis of the viral infectious diseases. This review elaborates on the virus-host interactions during FMDV infection to summarize the pathogenic mechanisms of FMD, and we hope it can provide insights for designing effective vaccines or drugs to prevent and control the spread of FMD and other diseases caused by picornaviruses.
Genetic Susceptibility to Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto’s Thyroiditis: How Far Is Our Understanding?
Authors: Zeber-Lubecka Natalia , Hennig Ewa E.
Published: February 2021

Polycystic ovary syndrome (PCOS) and Hashimoto’s thyroiditis (HT) are endocrine disorders that commonly occur among young women. A higher prevalence of HT in women with PCOS, relative to healthy individuals, is observed consistently. Combined occurrence of both diseases is associated with a higher risk of severe metabolic and reproductive complications. Genetic factors strongly impact the pathogenesis of both PCOS and HT and several susceptibility loci associated with a higher risk of both disorders have been identified. Furthermore, some candidate gene polymorphisms are thought to be functionally relevant; however, few genetic variants are proposed to be causally associated with the incidence of both disorders together.
Validation and Optimization of Host Immunological Bio-Signatures for a Point-of-Care Test for TB Disease
Authors: Mutavhatsindi Hygon , van der Spuy Gian D. , Malherbe Stephanus T. , Sutherland Jayne S. , Geluk Annemieke , Mayanja-Kizza Harriet , Crampin Amelia C. , Kassa Desta , Howe Rawleigh , Mihret Adane , Sheehama Jacob A. , Nepolo Emmanuel , Günther Gunar , Dockrell Hazel M. , Corstjens Paul L. A. M. , Stanley Kim , Walzl Gerhard , Chegou Novel N. ,   the AE-TBC ScreenTB Consortia
Published: February 2021

The development of a non-sputum-based, point-of-care diagnostic test for tuberculosis (TB) is a priority in the global effort to combat this disease, particularly in resource-constrained settings. Previous studies have identified host biomarker signatures which showed potential, but there is a need to validate and refine these for development as a test. We recruited 1,403 adults presenting with symptoms suggestive of pulmonary TB at primary healthcare clinics in six countries from West, East and Southern Africa. Of the study cohort, 326 were diagnosed with TB and 787 with other respiratory diseases, from whom we randomly selected 1005 participants. Using Luminex® technology, we measured the levels of 20 host biomarkers in serum samples which we used to evaluate the diagnostic accuracy of previously identified and novel bio-signatures. Our previously identified seven-marker bio-signature did not perform well (sensitivity: 89%, specificity: 60%). We also identified an optimal, two-marker bio-signature with a sensitivity of 94% and specificity of 69% in patients with no history of previous TB. This signature performed slightly better than C-reactive protein (CRP) alone. The cut-off value for a positive diagnosis differed for human immuno-deficiency virus (HIV)-positive and -negative individuals. Notably, we also found that no signature was able to diagnose TB adequately in patients with a prior history of the disease. We have identified a two-marker, pan-African bio-signature which is more robust than CRP alone and meets the World Health Organization (WHO) target product profile requirements for a triage test in both HIV-negative and HIV-positive individuals. This signature could be incorporated into a point-of-care device, greatly reducing the necessity for expensive confirmatory diagnostics and potentially reducing the number of cases currently lost to follow-up. It might also potentially be useful with individuals unable to provide sputum or with paucibacillary disease. We suggest that the performance of TB diagnostic signatures can be improved by incorporating the HIV-status of the patient. We further suggest that only patients who have never had TB be subjected to a triage test and that those with a history of previous TB be evaluated using more direct diagnostic techniques.
The Development, Fine Specificity, and Importance of High-Avidity Antibodies to VAR2CSA in Pregnant Cameroonian Women Living in Yaoundé, an Urban City
Authors: Vanda Koko , Bobbili Naveen , Matsunaga Masako , Chen John J. , Salanti Ali , Leke Rose F. G. , Taylor Diane Wallace
Published: February 2021

Pregnant women infected with Plasmodium falciparum often produce antibodies (Abs) to VAR2CSA, a ligand that binds to placental chondroitin sulfate A causing placental malaria (PM). Antibodies to VAR2CSA are associated with improved pregnancy outcomes. Antibody avidity is a surrogate marker for the extent of maturation of the humoral immune response. Little is known about high avidity Abs to VAR2CSA for women living in urban African cities. Therefore, this study sought to determine: i) if high avidity Abs to full-length VAR2CSA (FV2) increase with gravidity in women in Yaoundé, Cameroon exposed to ~ 0.3-1.1 infectious mosquito bites per month, ii) if high avidity Abs to FV2 are directed against a specific region of VAR2CSA, and iii) if having high avidity Abs to FV2 improve pregnancy outcomes. Plasma samples collected at delivery from 695 women who had Abs to FV2 were evaluated. Ab levels and the Avidity Index (AI), defined as the percent Abs remaining bound to FV2 after incubation with 3M NH4SCN, were determined. Similar Ab levels to FV2 were present in women of all gravidities (G1 through 6+; p=0.80), except significantly lower levels were detected in PM−negative (PM−) primigravidae (p <0.001). Median Ab avidities increased between gravidity 1 and 2 (p<0.001) and remained stable thereafter (G3-G6+: p=0.51). These results suggest that B cell clonal expansion began during the first pregnancy, with clonal selection primarily occurring during the second. However, the majority of women (84%) had AI <35, a level of high avidity Abs previously reported to be associated with improved pregnancy outcomes. When plasma from 107 Cameroonian women was tested against 8 different regions of FV2, high avidity Abs were predominately restricted to DBL5 with median AI of 50 compared to AI <25 for the other domains. The only significance influence of high avidity Abs on pregnancy outcome was that babies born to mothers with AI above the median were 104 g heavier than babies born to women with AI below the median (p=0.045). These results suggest that a vaccine that boosts maturation of the immune response to VAR2CSA may be beneficial for women residing in urban areas.
GMP-Compliant Universal Antigen Presenting Cells (uAPC) Promote the Metabolic Fitness and Antitumor Activity of Armored Cord Blood CAR-NK Cells
Authors: Liu Enli , Ang Sonny O. T. , Kerbauy Lucila , Basar Rafet , Kaur Indreshpal , Kaplan Mecit , Li Li , Tong Yijiu , Daher May , Ensley Emily L. , Uprety Nadima , Nunez Cortes Ana Karen , Yang Ryan Z. , Li Ye , Shaim Hila , Reyes Silva Francia , Lin Paul , Mohanty Vakul , Acharya Sunil , Shanley Mayra , Muniz-Feliciano Luis , Banerjee Pinaki P. , Chen Ken , Champlin Richard E. , Shpall Elizabeth J. , Rezvani Katayoun
Published: February 2021

Natural killer (NK) cells are innate lymphocytes recognized for their important role against tumor cells. NK cells expressing chimeric antigen receptors (CARs) have enhanced effector function against various type of cancer and are attractive contenders for the next generation of cancer immunotherapies. However, a number of factors have hindered the application of NK cells for cellular therapy, including their poorin vitrogrowth kinetics and relatively low starting percentages within the mononuclear cell fraction of peripheral blood or cord blood (CB). To overcome these limitations, we genetically-engineered human leukocyte antigen (HLA)-A−and HLA-B−K562 cells to enforce the expression of CD48, 4-1BBL, and membrane-bound IL-21 (mbIL21), creating a universal antigen presenting cell (uAPC) capable of stimulating their cognate receptors on NK cells. We have shown that uAPC can drive the expansion of both non-transduced (NT) and CAR-transduced CB derived NK cells by >900-fold in 2 weeks of co-culture with excellent purity (>99.9%) and without indications of senescence/exhaustion. We confirmed that uAPC-expanded research- and clinical-grade NT and CAR-transduced NK cells have higher metabolic fitness and display enhanced effector function against tumor targets compared to the corresponding cell fractions cultured without uAPCs. This novel approach allowed the expansion of highly pure GMP-grade CAR NK cells at optimal cell numbers to be used for adoptive CAR NK cell-based cancer immunotherapy.
Clinical Profile of Hyper-IgE Syndrome in India
Authors: Saikia Biman , Rawat Amit , Minz Ranjana W. , Suri Deepti , Pandiarajan Vignesh , Jindal Ankur , Sahu Smrity , Karim Adil , Desai Mukesh , Taur Prasad D. , Pandrowala Ambreen , Gowri Vijaya , Madkaikar Manisha , Dalvi Aparna , Yadav Reetika Mallik , Lashkari Harsha Prasada , Raj Revathi , Uppuluri Ramya , Swaminathan Venkateswaran V. , Bhattad Sagar , Cyril Gladys , Kumar Harish , Shukla Anuj , Kalra Manas , Govindaraj Geeta , Singh Surjit
Published: February 2021

Introduction:Hyper-IgE Syndrome (HIES) is a rare inborn error of immunity (IEI) characterized by a constellation of symptoms related to susceptibility toStaphylococcalskin and pulmonary infections, eczema, raised serum IgE (>2,000 IU/ml), craniofacial anomalies, and recurrent bone fractures. Data on HIES from the Indian subcontinent is scarce and restricted to small case series and case reports. This is the first compilation of national data on HIES.

Materials and Methods:A total 103 cases clinically diagnosed and treated as HIES were analyzed from nine centers. Cases with clinical and/or molecular diagnosis of DOCK8 deficiency were not included. Patients were divided into two groups: group I for whom a heterozygous rare variant of STAT3 was identified, and group II, with clinical features similar to those of AD STAT3 deficiency, but without any genetic diagnosis.

Results:Genetic diagnosis was available in 27 patients (26.2%) and all harbored rare variants in the STAT3 gene. Majority of these STAT3 HIES patients presented with recurrent skin abscesses (77.7%) or pneumonia (62.9%) or both (59.2%). Other features included eczema (37%), candidiasis (55.5%), facial dysmorphism (55.5%), recurrent fractures (11.1%), and retained primary teeth (7.4%).Mycobacterialinfections were seen in a significant 18.5%. Mortality was seen in three subjects (11.1%). A similar trend in the clinical presentation was observed when all the 103 patients were analyzed together. Twenty percent of patients without a rare variant in the STAT3 gene had an NIH score of ≥40, whereas, 51.9% of STAT3 HIES subjects had scores below the cut off of ≥40. TH17 cell numbers were low in 10/11 (90.9%) STAT3 HIES tested. Rare variants observed were 8 in exon 21; 8 in exon 13; 3 in exon 10; 2 in exon 15, and one each in exon 6, 16, 17, 19, 22, and splice site downstream of exon 12. Seven variants were novel and included F174S, N567D, L404Sfs*8, G419 =, M329K, T714I, R518X, and a splice site variant downstream of exon 12.

Conclusions:The report includes seven novel STAT3 variants, including a rare linker domain nonsense variant and a CC domain variant.Mycobacterialdiseases were more frequent, compared to western literature.
MCPIP-1 Restricts Inflammation via Promoting Apoptosis of Neutrophils
Authors: Dobosz Ewelina , Wadowska Marta , Kaminska Marta , Wilamowski Mateusz , Honarpisheh Mohsen , Bryzek Danuta , Potempa Jan , Jura Jolanta , Lech Maciej , Koziel Joanna
Published: February 2021

Monocyte chemoattractant protein-induced protein-1 (MCPIP-1) is a potent inhibitor of inflammatory response to pathogens. Acting as endonuclease against transcripts of inflammatory cytokines or transcription factors MCPIP-1 can significantly reduce the cytokine storm, thus limiting the tissue damage. As the adequate resolution of inflammation depends also on the efficient clearance of accumulated neutrophils, we focused on the role of MCPIP-1 in apoptosis and retention of neutrophils. We used peritoneal neutrophils from cell-specific MCPIP-1 knockout mice and showed prolonged survival of these cells. Moreover, we confirmed that MCPIP-1-dependent degradation of transcripts of antiapoptotic genes, includingBCL3, BCL2A1, BCL2L1, and for the first timeMCL-1, serves as an early event in spontaneous apoptosis of primary neutrophils. Additionally, we identified previously unknown miRNAs as potential binding partners to theMCPIP-1transcript and their regulation suggest a role in MCPIP-1 half-life and translation. These phenomena may play a role as a molecular switch that balances the MCPIP-1-dependent apoptosis. Besides that, we determined these particular miRNAs as integral components of the GM-CSF-MCPIP-1 axis. Taken together, we identified the novel anti-inflammatory role of MCPIP-1 as a regulator of accumulation and survival of neutrophils that simultaneously promotes an adequate resolution of inflammation.
The Role of Nucleases and Nucleic Acid Editing Enzymes in the Regulation of Self-Nucleic Acid Sensing
Authors: Santa Pauline , Garreau Anne , Serpas Lee , Ferriere Amandine , Blanco Patrick , Soni Chetna , Sisirak Vanja
Published: February 2021

Detection of microbial nucleic acids by the innate immune system is mediated by numerous intracellular nucleic acids sensors. Upon the detection of nucleic acids these sensors induce the production of inflammatory cytokines, and thus play a crucial role in the activation of anti-microbial immunity. In addition to microbial genetic material, nucleic acid sensors can also recognize self-nucleic acids exposed extracellularly during turn-over of cells, inefficient efferocytosis, or intracellularly upon mislocalization. Safeguard mechanisms have evolved to dispose of such self-nucleic acids to impede the development of autoinflammatory and autoimmune responses. These safeguard mechanisms involve nucleases that are either specific to DNA (DNases) or RNA (RNases) as well as nucleic acid editing enzymes, whose biochemical properties, expression profiles, functions and mechanisms of action will be detailed in this review. Fully elucidating the role of these enzymes in degrading and/or processing of self-nucleic acids to thwart their immunostimulatory potential is of utmost importance to develop novel therapeutic strategies for patients affected by inflammatory and autoimmune diseases.
Club Cell Loss as a Feature of Bronchiolization in ILD
Authors: Reynaud Paul , Ahmed Engi , Serre Isabelle , Knabe Lucie , Bommart Sébastien , Suehs Carey , Vachier Isabelle , Berthet Jean Philippe , Romagnoli Micaela , Vernisse Charlotte , Mallet Jean Pierre , Gamez Anne Sophie , Bourdin Arnaud
Published: February 2021

Background: Distal airway metaplasia may precede honeycombing in progressive fibrosing interstitial lung disease (ILD). The SCGB1A1+ bronchiolar-specific club cell may play a role in this aberrant regenerative process.

Objective: To assess the presence of club cells in the small airways of patients suffering from ILD.

Methods: Small airways (internal diameter <2 mm) in lung samples [surgical lung biopsy (SLB) and/or transbronchial lung cryobiopsy (TBLC)] from 14 patients suffering from ILD and 10 controls were morphologically assessed and stained for SCGB1A1. SCGB1A1 was weighted by epithelial height as a marker of airway generation (SCGB1A1/EH). Correlations between clinical, functional, and high-resolution CT (HRCT) prognostic factors and histomorphometry were assessed.

Results: Small airways from samples with ILD patterns were significantly less dense in terms of SCGB1A1+ cells [0.064 (0.020–0.172)] as compared to controls' sample's small airways [0.393 (0.082–0.698), p < 0.0001]. Usual interstitial pneumonia (UIP) patterns most frequently contained small airways with limited or absent SCGB1A1 expression (SCGB1A1/EH <0.025): UIP (18/33; 55%) as compared with non-UIP patterns (4/31; 13%) or controls (0/29; 0%): p < 0.0001. In addition, correlations with HRCT indicated a significant negative relationship between SCGB1A1 and bronchiectasis as a feature of bronchiolization (Rho −0.63, p < 0.001) and a positive relationship with both forced vital capacity (FVC) and Hounsfield unit (HU)-distribution pattern in kurtosis (Rho 0.38 and 0.50, respectively, both p < 0.001) as markers of fibrotic changes.

Conclusion: Compared with controls, the small airways of patients with ILD more often lack SCGB1A1, especially so in UIP. Low densities of SCGB1A1-marked cells correlate with bronchiectasis and fibrotic changes. Further research investigating SCGB1A1 staining as a pathological feature of the bronchiolization process is merited.
A Comprehensive Review of Viral Characteristics, Transmission, Pathophysiology, Immune Response, and Management of SARS-CoV-2 and COVID-19 as a Basis for Controlling the Pandemic
Authors: Triggle Chris R. , Bansal Devendra , Ding Hong , Islam Md Mazharul , Farag Elmoubashar Abu Baker Abd , Hadi Hamad Abdel , Sultan Ali A.
Published: February 2021

COVID-19 emerged from China in December 2019 and during 2020 spread to every continent including Antarctica. The coronavirus, SARS-CoV-2, has been identified as the causative pathogen, and its spread has stretched the capacities of healthcare systems and negatively affected the global economy. This review provides an update on the virus, including the genome, the risks associated with the emergence of variants, mode of transmission, immune response, COVID-19 in children and the elderly, and advances made to contain, prevent and manage the disease. Although our knowledge of the mechanics of virus transmission and the immune response has been substantially demystified, concerns over reinfection, susceptibility of the elderly and whether asymptomatic children promote transmission remain unanswered. There are also uncertainties about the pathophysiology of COVID-19 and why there are variations in clinical presentations and why some patients suffer from long lasting symptoms—“the long haulers.” To date, there are no significantly effective curative drugs for COVID-19, especially after failure of hydroxychloroquine trials to produce positive results. The RNA polymerase inhibitor, remdesivir, facilitates recovery of severely infected cases but, unlike the anti-inflammatory drug, dexamethasone, does not reduce mortality. However, vaccine development witnessed substantial progress with several being approved in countries around the globe.
Treatment of Intestinal Inflammation With Epicutaneous Immunotherapy Requires TGF-β and IL-10 but Not Foxp3+ Tregs
Authors: Chen Xin , Berin M. Cecilia , Gillespie Virginia L. , Sampson Hugh A. , Dunkin David
Published: February 2021

Background: Inflammatory bowel disease (IBD) involves an increase in T effector cells in the intestines that disrupts the normal balance with T regulatory cells (Tregs). A therapy that restores this balance has the potential to treat IBD. We have shown that epicutaneous exposure to OVA induces Tregs that are able to induce tolerance. The Tregs also migrate to the intestines where they alleviate colitis in mice, demonstrating the potential for skin induced Tregs to treat intestinal inflammation. We investigated the role of Foxp3, IL-10, and TGF-β in the suppression of colitis by epicutaneous immunotherapy (ET).

Methods: RAG1−/− mice were transferred with CD4+CD45RBhi T cells from wild type mice to induce colitis. To determine whether Foxp3+ Tregs, IL-10-, or TGF-β-producing Tregs were necessary, Foxp3-DTR, IL-10−/−, or CD4-dnTGFBRII mice were immunized with OVA and OVA TCR enriched T cells were added. As control groups, some mice were given OVA TCR enriched T cells from wild type mice or no OVA TCR enriched T cells. Half of the mice in each group were then exposed on the skin to Viaskin patches containing OVA weekly for 3 weeks. Mice given OVA TCR enriched T cells from Foxp3-DTR mice were given diphtheria toxin (DT) or not in addition to ET. Mice were assessed for weight loss, colon length, colonic cytokine production, and histological inflammation.

Results: ET, after injection with OVA TCR enriched T cells derived from wild type mice, prevented weight loss, decreased colonic inflammatory cytokine production and histological colitis. ET in the absence of the OVA TCR enriched T cells did not alleviate colitis. ET, after injection with OVA TCR enriched T cells derived from Foxp3-DTR mice, prevented weight loss, decreased colonic inflammatory cytokine production, and histological colitis. Ablation with DT did not impair the ability of ET to alleviate colitis. ET failed to alleviate colitis when OVA TCR enriched T cells were derived from IL-10−/− or CD4-dnTGFBRII mice.

Conclusions: ET through induction of Tregs, which produce IL-10 and TGF-β, could be a promising treatment for IBD.
A Novel DNA Vaccine Against SARS-CoV-2 Encoding a Chimeric Protein of Its Receptor-Binding Domain (RBD) Fused to the Amino-Terminal Region of Hepatitis B Virus preS1 With a W4P Mutation
Authors: Jeong Hyein , Choi Yu-Min , Seo Hyejun , Kim Bum-Joon
Published: February 2021

A coronavirus SARS-CoV-2, which has caused the pandemic viral pneumonia disease COVID-19, significantly threatens global public health, highlighting the need to develop effective and safe vaccines against its infection. In this study, we developed a novel DNA vaccine candidate against SARS-CoV-2 by expressing a chimeric protein of its receptor-binding domain (RBD) fused to a 33-bp sequence (11 aa) from the hepatitis B virus (HBV) preS1 region with a W4P mutation (W4P-RBD) at the N-terminal region and evaluated its immunogenicity. In vitro transfection experiments in multiple cell lines demonstrated that W4P-RBD vs. wild-type RBD protein (W-RBD) led to enhanced production of IL-6 and TNFα at the transcription and translation levels, suggesting the adjuvant potential of N-terminal HBV preS1 sequences for DNA vaccines against SARS-CoV-2. W4P-RBD also led to enhanced production of IgG and IgA, which can neutralize and block SARS-CoV-2 infection in both blood sera and bronchoalveolar lavage (BAL) fluid from the lung in vaccinated mice. Additionally, W4P-RBD led to an enhanced T-cell-mediated cellular immune response under S1 protein stimulation. In summary, W4P-RBD led to robust humoral and cell-mediated immune responses against SARS-CoV-2 in vaccinated mice, highlighting its feasibility as a novel DNA vaccine to protect against SARS-CoV-2 infection.
The Importance of Marine Bivalves in Invasive Host–Parasite Introductions
Authors: Costello Katie E. , Lynch Sharon A. , O’Riordan Ruth M. , McAllen Rob , Culloty Sarah C.
Published: February 2021

Although research into the ecology and impacts of invasive species is prevalent, there are knowledge gaps relating to the role of invasive species in parasite transmission. This work synthesises invasive host–parasite interactions and impacts, using marine bivalves as a model group, to consider how global movement of shellfish consignments for aquaculture purposes facilitates the unintentional transfer of invasives. We discuss how invasive species can act as both hosts or parasitic organisms themselves, and introductions may lead to diseases within the bivalve aquaculture sector. This review highlights the importance of interdisciplinary research, with particular regard to the fields of parasitology and invasion ecology. We suggest that further integrating these fields will enhance critical knowledge of marine diseases, parasite-invasive-bivalve interplay dynamics, and potential mitigation strategies, including temperature-based disease surveillance models. We also address how climate change might impact invasive species, again with a focus on marine bivalves, and the potential outcomes for parasite transmission, including changes in host/parasite distribution, life-history and virulence. We acknowledge the importance of horizon scanning for future invasive host–parasite introductions and note that increased screening of invasive species, both in their native and invaded ranges, will provide clarity on invasion dynamics and potential impacts.
Gastronautidae Deroux, 1994 and Trithigmostoma Jankowski, 1967: Evolutionary Links Among Cyrtophorian Ciliates (Protista, Ciliophora, and Phyllopharyngea)
Authors: Qu Zhishuai , Pan Hongbo , Wang Congcong , Ma Honggang , Stoeck Thorsten , Hu Xiaozhong
Published: February 2021

Studies on cyrtophorian ciliates (Cyrtophoria) have accumulated much knowledge on morphological taxonomy and molecular phylogeny, and the general classification and phylogenetic relationships of most families have thereby been revealed. However, the phylogenetic position of the family Gastronautidae Deroux, 1994 remains uncertain. This is due to the presence of specialized characteristics (in particular a circumoral kinety in a closed circle), and most importantly, the lack of molecular data of this family. In addition, TrithigmostomaJankowski, 1967 holds a special position among genera in Chilodonellidae Deroux, 1976 due to its divergent characteristics. In the present work, we studied a new gastronautid, Gastronauta paraloisi sp. n., and three populations of Trithigmostoma cucullulus (Müller, 1786) Jankowski, 1967, using integrative methods. Species identifications were confirmed by morphological research. We also obtained SSU rDNA sequences, which included the first available sequence of Gastronautidae. The following SSU rDNA-inferred phylogenetic analyses showed that the establishment of the family Gastronautidae is necessary, and Gastronautidae and Trithigmostoma may represent intermediate evolutionary links in the order Chlamydodontida.
BIC-Based Data-Driven Rail Track Deterioration Adaptive Piecewise Modeling Framework
Authors: Yang Yaqin , Xu Peng , Yang Guotao , Chen Long , Li Junbo
Published: February 2021

The records of maintenance activities are required for modeling the track irregularity deterioration process. However, it is hard to guarantee the completeness and accuracy of the maintenance records. To tackle this problem, an adaptive piecewise modeling framework for the rail track deterioration process driven by historical measurement data from the comprehensive inspection train (referred to as CIT) is proposed. The identification of when maintenance activities occurred is reformulated as a model selection optimization problem based on Bayesian Information Criterion. An efficient solution algorithm utilizing adaptive thresholding and dynamic programming is proposed for solving this optimization problem. This framework’s validity and practicability are illustrated by the measurement data from the CIT inspection of the mileage section of K21 + 184 to K220 + 308 on the Nanchang-Fuzhou railway track from 2014 to 2019. The results indicate that this framework can overcome the disturbance of contaminated measurement data and accurately estimate when maintenance activities were undertaken without any historical maintenance records. What is more, the adaptive piecewise fitting model provided by this framework can describe the irregular deterioration process of corresponding rail track sections.
Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review
Authors: Delli Bovi Anna Pia , Marciano Francesca , Mandato Claudia , Siano Maria Anna , Savoia Marcella , Vajro Pietro
Published: February 2021

Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it remains still orphan of an adequate therapeutic strategy. Herein we focus on the interplay between oxidative stress (OS) and the other causal pathogenetic factors. Different reactive oxygen species (ROS) generators contribute to NAFLD inflammatory and fibrotic progression, which is quite strictly linked to the lipotoxic liver injury from fatty acids and/or a wide variety of their biologically active metabolites in the context of either a two-hit or a (more recent) multiple parallel hits theory. An antioxidant defense system is usually able to protect hepatic cells from damaging effects caused by ROS, including those produced into the gastrointestinal tract, i.e., by-products generated by usual cellular metabolic processes, normal or dysbiotic microbiota, and/or diet through an enhanced gut–liver axis. Oxidative stress originating from the imbalance between ROS generation and antioxidant defenses is under the influence of individual genetic and epigenetic factors as well. Healthy diet and physical activity have been shown to be effective on NAFLD also with antioxidant mechanisms, but compliance to these lifestyles is very low. Among several considered antioxidants, vitamin E has been particularly studied; however, data are still contradictory. Some studies with natural polyphenols proposed for NAFLD prevention and treatment are encouraging. Probiotics, prebiotics, diet, or fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors will likely assist in further selecting the treatment that could work best for a specific patient.
Evaluation of an Automatic Classification Algorithm Using Convolutional Neural Networks in Oncological Positron Emission Tomography
Authors: Pinochet Pierre , Eude Florian , Becker Stéphanie , Shah Vijay , Sibille Ludovic , Toledano Mathieu Nessim , Modzelewski Romain , Vera Pierre , Decazes Pierre
Published: February 2021

Introduction: Our aim was to evaluate the performance in clinical research and in clinical routine of a research prototype, called positron emission tomography (PET) Assisted Reporting System (PARS) (Siemens Healthineers) and based on a convolutional neural network (CNN), which is designed to detect suspected cancer sites in fluorine-18 fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT).

Method: We retrospectively studied two cohorts of patients. The first cohort consisted of research-based patients who underwent PET scans as part of the initial workup for diffuse large B-cell lymphoma (DLBCL). The second cohort consisted of patients who underwent PET scans as part of the evaluation of miscellaneous cancers in clinical routine. In both cohorts, we assessed the correlation between manually and automatically segmented total metabolic tumor volumes (TMTVs), and the overlap between both segmentations (Dice score). For the research cohort, we also compared the prognostic value for progression-free survival (PFS) and overall survival (OS) of manually and automatically obtained TMTVs.

Results: For the first cohort (research cohort), data from 119 patients were retrospectively analyzed. The median Dice score between automatic and manual segmentations was 0.65. The intraclass correlation coefficient between automatically and manually obtained TMTVs was 0.68. Both TMTV results were predictive of PFS (hazard ratio: 2.1 and 3.3 for automatically based and manually based TMTVs, respectively) and OS (hazard ratio: 2.4 and 3.1 for automatically based and manually based TMTVs, respectively). For the second cohort (routine cohort), data from 430 patients were retrospectively analyzed. The median Dice score between automatic and manual segmentations was 0.48. The intraclass correlation coefficient between automatically and manually obtained TMTVs was 0.61.

Conclusion: The TMTVs determined for the research cohort remain predictive of total and PFS for DLBCL. However, the segmentations and TMTVs determined automatically by the algorithm need to be verified and, sometimes, corrected to be similar to the manual segmentation.