bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and Clinical Features of Heterotaxy in a Prenatal Cohort
Authors: Yi Tong , Sun Hairui , Fu Yuwei , Hao Xiaoyan , Sun Lin , Zhang Ye , Han Jiancheng , Gu Xiaoyan , Liu Xiaowei , Guo Yong , Wang Xin , Zhou Xiaoxue , Zhang Siyao , Yang Qi , Fan Jiaqi , He Yihua
Published: April 2022

Objectives:Some genetic causes of heterotaxy have been identified in a small number of heterotaxy familial cases or animal models. However, knowledge on the genetic causes of heterotaxy in the fetal population remains scarce. Here, we aimed to investigate the clinical characteristics and genetic spectrum of a fetal cohort with heterotaxy.

Methods:We retrospectively investigated all fetuses with a prenatal diagnosis of heterotaxy at a single center between October 2015 and November 2020. These cases were studied using the genetic testing data acquired from a combination of copy number variation sequencing (CNV-seq) and whole-exome sequencing (WES), and their clinical phenotypes were also reviewed.

Result:A total of 72 fetuses diagnosed with heterotaxy and complete clinical and genetic results were enrolled in our research. Of the 72 fetuses, 18 (25%) and 54 (75%) had left and right isomerism, respectively. Consistent with the results of a previous study, intracardiac anomalies were more severe in patients with right atrial isomerism than in those with left atrial isomerism (LAI) and mainly manifested as atrial situs inversus, bilateral right atrial appendages, abnormal pulmonary venous connection, single ventricles or single atria, and pulmonary stenosis or atresia. In 18 fetuses diagnosed with LAI, the main intracardiac anomalies were bilateral left atrial appendages. Of the 72 fetuses that underwent CNV-seq and WES, 11 (15.3%) had positive genetic results, eight had definitive pathogenic variants, and three had likely pathogenic variants. The diagnostic genetic variant rate identified using WES was 11.1% (8/72), in which primary ciliary dyskinesia (PCD)-associated gene mutations (CCDC40, CCDC114, DNAH5, DNAH11, and ARMC4) accounted for the vast majority (n = 5). Other diagnostic genetic variants, such as KMT2D and FOXC1, have been rarely reported in heterotaxy cases, although they have been verified to play roles in congenital heart disease.

Conclusion:Thus, diagnostic genetic variants contributed to a substantial fraction in the etiology of fetal heterotaxy. PCD mutations accounted for approximately 6.9% of heterotaxy cases in our fetal cohort. WES was identified as an effective tool to detect genetic causes prenatally in heterotaxy patients.
DBSCAN-SWA: An Integrated Tool for Rapid Prophage Detection and Annotation
Authors: Gan Rui , Zhou FengXia , Si Yu , Yang Han , Chen Chuangeng , Ren Chunyan , Wu Jiqiu , Zhang Fan
Published: April 2022

As an intracellular form of a bacteriophage in the bacterial host genome, a prophage usually integrates into bacterial DNA with high specificity and contributes to horizontal gene transfer (HGT). With the exponentially increasing number of microbial sequences uncovered in genomic or metagenomics studies, there is a massive demand for a tool that is capable of fast and accurate identification of prophages. Here, we introduce DBSCAN-SWA, a command line software tool developed to predict prophage regions in bacterial genomes. DBSCAN-SWA runs faster than any previous tools. Importantly, it has great detection power based on analysis using 184 manually curated prophages, with a recall of 85% compared with Phage_Finder (63%), VirSorter (74%), and PHASTER (82%) for (Multi-) FASTA sequences. Moreover, DBSCAN-SWA outperforms the existing standalone prophage prediction tools for high-throughput sequencing data based on the analysis of 19,989 contigs of 400 bacterial genomes collected from Human Microbiome Project (HMP) project. DBSCAN-SWA also provides user-friendly result visualizations including a circular prophage viewer and interactive DataTables. DBSCAN-SWA is implemented in Python3 and is available under an open source GPLv2 license from https://github.com/HIT-ImmunologyLab/DBSCAN-SWA/.
B Cell Characteristics at Baseline Predict Vaccination Response in RTX Treated Patients
Authors: Stefanski Ana-Luisa , Rincon-Arevalo Hector , Schrezenmeier Eva , Karberg Kirsten , Szelinski Franziska , Ritter Jacob , Chen Yidan , Jahrsdörfer Bernd , Ludwig Carolin , Schrezenmeier Hubert , Lino Andreia C. , Dörner Thomas
Published: April 2022

Background

Vaccination is considered as most efficient strategy in controlling SARS-CoV-2 pandemic spread. Nevertheless, patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) are at increased risk to fail humoral and cellular responses upon vaccination. The ability to predict vaccination responses is essential to guide adequate safety and optimal protection in these patients.

Methods

B- and T- cell data before vaccination were evaluated for characteristics predicting vaccine responses in altogether 15 patients with autoimmune inflammatory rheumatic diseases receiving RTX. Eleven patients with rheumatoid arthritis (RA) on other therapies, 11 kidney transplant recipients (KTR) on regular immunosuppression and 15 healthy controls (HC) served as controls. A multidimensional analysis of B cell subsets via UMAP algorithm and a correlation matrix were performed in order to identify predictive markers of response in patients under RTX therapy.

Results

Significant differences regarding absolute B cell counts and specific subset distribution pattern between the groups were identified at baseline. In this context, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) were naïve and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells. Moreover, there was a positive correlation between neutralizing antibodies and B cells expressing HLA-DR and CXCR5 as well as an inverse correlation with CD95 expression and CD21low expression by B cells among vaccination responders.

Substantial repopulation of the naïve B cell compartment after RTX therapy appeared to be essential for an adequate vaccination response, which seem to require the additional capability of antigen presentation and germinal center formation. Moreover, expression of exhaustion markers represent negative predictors of vaccination responses.
A Prognostic Analysis of the Outcomes in Patients With Anti-γ-Aminobutyric Acid B Receptor Encephalitis
Authors: Chen Weibi , Wang Yunyun , Guo Xiaoyuan , Gao Lehong , Huang Zhaoyang , Lin Yicong , Xue Qin , Liu Gang , Zhang Yan , Su Yingying
Published: April 2022

Objective

To evaluate neurological function and its influencing factors in patients with anti-γ -aminobutyric acid B receptor (GABABR) encephalitis.

Methods

This was a clinical cohort study of patients diagnosed with anti-GABABR encephalitis; long-term follow-up was performed by telephone. Clinical factors associated with prognosis were analyzed, including clinical manifestations, laboratory examinations, imaging features, tumor comorbidities and therapeutic responses.

Results

Twenty-two patients with anti-GABABR encephalitis were evaluated (median age: 55 years). Lung cancer was detected in eight patients. All were with serum tumor markers (mainly NSE), and three of them had additional onconeuronal antibodies. The patients with tumors were older than the patients without tumors and more likely to develop status epilepticus (62.5% vs. 14.3%; p = 0.052), central hypoventilation (50% vs. 7.1%; p = 0.039), and hyponatremia (87.5% vs. 14.3%; p = 0.001). The patients with tumors had higher mortality (87.5% vs. 0%; p < 0.05). Although 92.9% of the patients without tumors became functionally independent (mRS ≤2), sequelae of symptomatic seizures, neuropsychiatric symptoms, and cognitive impairment were still observed in 14.3%, 21.4%, and 21.4% of patients, respectively.

Conclusions

(1) Elderly patients with anti-GABABR antibodies, especially those with severe symptoms, serum tumor markers, and additional onconeuronal antibodies, should be screened for lung cancer. (2) Anti-GABABR encephalitis with tumors has a poor prognosis. (3) Most patients without tumors achieve self-care, but some still experience remaining neurological deficits.
Oleamide-Mediated Polarization of M1 Macrophages and IL-1β Production by Regulating NLRP3-Inflammasome Activation in Primary Human Monocyte-Derived Macrophages
Authors: Wisitpongpun Prapakorn , Potup Pachuen , Usuwanthim Kanchana
Published: April 2022

Macrophages are a type of innate immune cell that activates the NLRP3 inflammasome, causing the release of the cytokine IL-1β, which is a crucial mediator of the inflammatory response. NLRP3 activation that is dysregulated worsens a variety of inflammatory and autoimmune diseases, as well as neurodegenerative diseases. Oleamide is an endogenous fatty acid amide that was first determined as a sleep-inducing molecule and later shown to have wide-ranging beneficial effects on the central nervous system. How oleamide influences human macrophage polarization and NLRP3-inflammasome activation remains unclear. The effect of oleamide on macrophage polarization was explored using anin vitroculture of primary human monocyte-derived macrophages (MDMs) supplemented with human serum-containing media. Cellular and molecular mechanisms of oleamide-regulated MDMs polarization were also investigated. Results showed that oleamide promoted naïve macrophages (M0) toward the M1 phenotype by upregulating M1-associated genes (IL-1β,iNOS,CXCL10), along with downregulation of M2-associated genes (Arg-1,CD206,CCL22). Cell surface expression indicated that oleamide enhanced CD80 expression in M0 naïve macrophages and hider CD206 and CD163 expression in M2 macrophages. Higher production of IL-1β cytokine was observed but with no alteration in IL-6 and TNF-α levels by MDMs and differentiated THP-1 models. Whether oleamide functioned as a second signal that activated the NLRP3 inflammasome and mediated IL-1β production was further investigated using LPS-primed MDMs followed by oleamide treatment that induced activation of inflammasome-related proteins including NLRP3, ASC, cleaved casp-1, and cleaved IL-1β. These findings suggested that oleamide promoted M1 macrophage polarization and increased IL-1β production by activating the NLRP3 inflammasome in primary MDMs. This research reveals a new function for oleamide as well as prospective targets for treating NLRP3-related inflammatory disorders.
Case Report: Use of Obinutuzumab as an Alternative Monoclonal Anti-CD20 Antibody in a Patient With Refractory Immune Thrombocytopenia Complicated by Rituximab-Induced Serum Sickness and Anti-Rituximab Antibodies
Authors: Blase Jennifer R. , Frame David , Michniacki Thomas F. , Walkovich Kelly
Published: April 2022

Management of refractory immune thrombocytopenia frequently involves rituximab, a chimeric anti-CD20 monoclonal antibody, to target B cells and induce remission in most patients. However, neutralizing antibodies to rituximab that nullify therapeutic response and may lead to serum sickness have been rarely reported. Here, we present a case of a young adult woman with Evans syndrome treated with rituximab, complicated by the development of serum sickness, acute respiratory distress syndrome, and platelet refractoriness presumed secondary to neutralizing antibodies to rituximab. She was successfully treated with the humanized anti-CD20 monoclonal antibody, obinutuzumab, with subsequent symptom resolution. Additionally, a review of 10 previously published cases of serum-sickness associated with the use of rituximab for idiopathic thrombocytopenic purpura (ITP) is summarized. This case highlights that recognition of more subtle or rare symptoms of rituximab-induced serum sickness is important to facilitate rapid intervention.
Proximal and Distal Regions of Pathogenic Th17 Related Chromatin Loci Are Sequentially Accessible During Pathogenicity of Th17
Authors: Hu Luni , Zhao Xingyu , Li Peng , Zeng Yanyu , Zhang Yime , Shen Yang , Wang Yukai , Sun Xiaolin , Lai Binbin , Zhong Chao
Published: April 2022

Pathogenic Th17, featured by their production of pro-inflammatory cytokines, are considered as a key player in most autoimmune diseases. The transcriptome of them is obviously distinct from that of conventional regulatory Th17. However, chromatin accessibility of the two Th17 groups have not been comprehensively compared yet. Here, we found that their chromatin-accessible regions(ChARs) significantly correlated with the expression of related genes, indicating that they might engage in the regulation of these genes. Indeed, pathogenic Th17 specific ChARs (patho-ChARs) exhibited a significant distribution preference in TSS-proximal region. We further filtered the patho-ChARs based on their conservation among mammalians or their concordance with the expression of their related genes. In either situation, the filtered patho-ChARs also showed a preference for TSS-proximal region. Enrichment of expression concordant patho-ChARs related genes suggested that they might involve in the pathogenicity of Th17. Thus, we also examined all ChARs of patho-ChARs related genes, and defined an opening ChAR set according to their changes in the Th17 to Th1 conversion. Interestingly, these opening ChARs displayed a sequential accessibility change from TSS-proximal region to TSS-distal region. Meanwhile, a group of patho-TFs (transcription factors) were identified based on the appearance of their binding motifs in the opening ChARs. Consistently, some of them also displayed a similar preference for binding the TSS-proximal region. Single-cell transcriptome analysis further confirmed that these patho-TFs were involved in the generation of pathogenic Th17. Therefore, our results shed light on a new regulatory mechanism underlying the generation of pathogenic Th17, which is worth to be considered for autoimmune disease therapy.
Influenza Vaccination Results in Differential Hemagglutinin Stalk-Specific Fc-Mediated Functions in Individuals Living With or Without HIV
Authors: Motsoeneng Boitumelo M. , Dhar Nisha , Nunes Marta C. , Krammer Florian , Madhi Shabir A. , Moore Penny L. , Richardson Simone I.
Published: April 2022

Influenza virus hemagglutinin (HA) stalk-specific antibodies have been shown to potently induce Fc-mediated effector functions which are important in protection from disease. In placebo-controlled maternal influenza (MatFlu) vaccination trials of pregnant women living with or without HIV, reduced risk of influenza illness was associated with high HA stalk antibody titers following trivalent inactivated vaccination (TIV). However, the mechanisms of immunity conferred by the HA stalk antibodies were not well understood. Here, we investigated HA stalk-specific Fc effector functions including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent complement deposition (ADCD), and FcγRIIa and FcγRIIIa binding in response to seasonal influenza vaccination. These were measured pre- and 1-month post-vaccination in 141 HIV-uninfected women (67 TIV and 74 placebo recipients) and 119 women living with HIV (WLWH; 66 TIV and 53 placebo recipients). In contrast to HIV-uninfected women, where HA stalk-specific ADCP and FcγRIIa binding were significantly boosted, WLWH showed no increase in response to vaccination. HA stalk-specific ADCC potential and FcγRIIIa binding were not boosted regardless of HIV status but were higher in WLWH compared with HIV-uninfected women prior to vaccination. HA stalk-specific ADCD was significantly increased by vaccination in all women, but was significantly lower in the WLWH both pre- and post- vaccination. Co-ordination between HA stalk-specific ADCP and ADCD in WLWH was improved by vaccination. Fc polyfunctionality was enhanced by vaccination in HIV-uninfected women and driven by the HA stalk antibody titers. However, in the WLWH, higher pre-vaccination Fc polyfunctionality was maintained post-vaccination but was decoupled from titer. Overall, we showed differential regulation of Fc effector HA stalk responses, suggesting that HIV infection results in unique humoral immunity in response to influenza vaccination, with relevance for future strategies that aim to target the HA stalk in this population.
Spatial Patterns of Larval and Juvenile Fish Assemblages in an Eddy Area in the Western South China Sea
Authors: Wu ChenYan , Wang XiaoGu , Zhong JunSheng , Ju JiaLi , Li ChenHong
Published: April 2022

The objective of this study was to investigate influence of meso-scale eddies in the western South China Sea on species composition and spatial patterns of fish larvae and juveniles based on the data collected during summer and autumn in 2012. Nintyeight species belonging to 38 families were collected, including 78 species in summer and 41 species in autumn. The dominant species in summer were Vinciguerria sp. (39.70%), Stephanolepis cirrhifer (11.21%), Caranx sp. (5.45%) and Benthosema pterotum (1.97%). The dominant species in autumn were Gobiidae sp. (15.32%), Ceratoscopelus townsendi (7.26%), Diaphus sp. (6.45%), Astronesthes sp. (5.65%) and Callionymidae sp. (4.03%). Abundance of fish larvae and juveniles in summer was higher than that found in autumn. Similarity cluster analysis results indicated that larval fish assemblages in summer can be divided into two communities: (1) larval fish in the cyclonic eddy; (2) larval fish in the anticyclonic eddies. While in autumn, the larval fish assemblages can be divided into three communities: (1) larval fish without influence of the cyclonic eddy; (2) larval fish influenced slightly by the cyclonic eddy; (3) larval fish gathered near the center of the cyclonic eddy. The variations of abundance and assemblage of larval fish might be attributed to sea surface temperature (SST), sea surface salinity (SSS) and sea level anomaly (SLA).
External and Internal Forcings for Hypoxia Formation in an Urban Harbour in Hong Kong
Authors: Lu Zhongming , Yu Liuqian , Gan Jianping
Published: April 2022

Eutrophication-driven hypoxia is one of the reasons for the deterioration of coastal waters, especially those adjacent to densely inhabited urban cities. Thus, effective hypoxia management is urgently needed, and quantitative knowledge of factors controlling hypoxia is required. A case in point is the coastal water around Hong Kong, a megacity that has over 7.5 million residents and is located downstream of the large and nutrient-rich Pearl River. The Victoria Harbour (VH) is the core area of Hong Kong water and has been suffering from marine environment deterioration for years because of external biogeochemical influxes from adjacent waters and internal physical and biogeochemical responses. Three channels orienting from south to north (C1), southeast to northwest (C2), and west to east (C3) connect the VH to adjacent waters and serve as the primary exchange pathways for water mass and biogeochemical substances. Using observational data and a coupled physical–biogeochemical model, we showed that the northward transport of low dissolved oxygen (DO) water from the coastal transition zone by the shoreward bottom current mainly through C1 directly contributes to the hypoxia formation in VH. The external influx of anthropogenic nutrients and organic matter through C2 further enhances the bottom water hypoxia in VH by stimulating phytoplankton bloom and microbial consumption of oxygen in water columns and sediments. Although the horizontal oxygen influx to VH is weak, the comparatively strong vertical mixing in C3 facilitates the replenishment of bottom water in the VH, mitigating bottom hypoxia. Locally in the VH, sediment oxygen demand is the dominant biogeochemical contributor (~93%) to hypoxia formation, while the contribution of water column remineralization is relatively minor (~6-7%). In general, vertical diffusion serves as the largest source (~57%) of DO in the VH because of the strong vertical DO gradient, whereas vertical motion ranks the second largest source of DO (~24%) and serves as a critical physical factor regulating the oxygen budget of the entire VH. In the spatial constriction area where the vertical DO gradient is weak, the magnitude of vertical motion exceeds vertical diffusion to become the largest source of DO (~48%).
Fabrication of Poly(o-Chloroaniline) to MMT Clay as Potential Flame-Resistant Material
Authors: Iqbal Shahid , Nadeem Sohail , Ahmad Mirza Nadeem , Javed Mohsin , Alsaab Hashem O. , Awwad Nasser S. , Ibrahium Hala A. , Elkaeed Eslam B. , Alshammari Fwzah H. , Alwadai Norah , Alahmdi Mohammed Issa , Bahadur Ali , Hassan Sadaf ul , Mohyuddin Ayesha
Published: April 2022

Polyorthochloroaniline (POC) nanocomposites with montmorillonite (MMT) clay (POC/MMT) nanocomposites (POC/MMT clay NCs) are the most widespread and attractive among organic/inorganic nanocomposites due to their distinctive properties in addition to inexpensive, abundance, and attractive characteristics such as ion-exchange and great surface area properties and have ample applications. The preparation of polyorthochloroaniline nanocomposites with montmorillonite (POC/MMT) clay nanocomposite has been completed chemically with the help of oxidative polymerization of orthochloroaniline in the presence of montmorillonite (MMT) clay. POC will be admixed with montmorillonite (MMT) clay at various concentrations, by keeping the o-chloroaniline monomer in the reaction mixture constant. To investigate the influence of MMT clay on the characteristics of POC, the load percentage of MMT clay in the nanocomposites was adjusted. The characterization and properties have been determined by using different techniques. FTIR spectroscopy was used to investigate the interactions between POC and MMT. The complete homogeneous dispersion of MMT clay in the POC matrix was examined by scanning electron microscope (SEM) analysis that revealed the compactness. The thermal stability of polymer–clay nanocomposites was determined by thermogravimetric analysis (TGA). The results of DSC/TGA measurements revealed that the flame retardancy and thermal stability of POC/MMT clay nanocomposites were considerably improved.
Possible Association of Periodontal Diseases With Helicobacter pylori Gastric Infection: A Systematic Review and Meta-Analysis
Authors: López-Valverde Nansi , Macedo de Sousa Bruno , López-Valverde Antonio , Suárez Ana , Rodríguez Cinthia , Aragoneses Juan Manuel
Published: April 2022

Some research has suggested that dental plaque and saliva could be reservoirs of Helicobacter pylori (H. pylori) and be capable of infecting or re-infecting the gastric mucosa after eradication, with certain studies showing a significant association between PD and gastric infection by this bacterium. An electronic search was performed in PubMed, EMBASE, and Web of Science databases with the terms “Helicobacter pylori AND periodontal diseases”; “Helicobacter pylori AND gingivitis”; “Helicobacter pylori AND chronic periodontitis”; “Helicobacter pylori AND periodontitis”; “Helicobacter pylori AND dental plaque”, to identify articles up to September 2021. The Newcastle-Ottawa scale was used to assess study quality. A meta-analysis was performed using RevMan 2020 (Cochane Collaboration) software. A total of 1,315 studies were identified and 12 were included, analyzing 226,086 patients with mean age between 10.5 and 63.4 years. The prevalence of H. pylori in the oral cavity ranged from 5.4 to 83.3%. A random-effects model was used to analyze the presence of H. pylori and subgroups were made according to the method of evaluation (PCR or RUT). Statistical significance was found in the overall analysis (p = 0.01). There is no clear evidence that H. pylori present in oral bacterial plaque causes gastric infection and vice versa.

Systematic Review Registration

www.INPLASY.COM, identifier: INPLASY2021100097.
Preferences for HIV Testing Services and HIV Self-Testing Distribution Among Migrant Gay, Bisexual, and Other Men Who Have Sex With Men in Australia
Authors: Zhang Ye , Wiseman Virginia , Applegate Tanya L. , Lourenco Richard De Abreu , Street Deborah J. , Smith Kirsty , Jamil Muhammad S. , Terris-Prestholt Fern , Fairley Christopher K. , McNulty Anna , Hynes Adam , Johnson Karl , Chow Eric P. F. , Bavinton Benjamin R. , Grulich Andrew , Stoove Mark , Holt Martin , Kaldor John , Guy Rebecca , Ong Jason J.
Published: April 2022

Background

In Australia, undiagnosed HIV rates are much higher among migrant gay, bisexual, or other men who have sex with men (GBMSM) than Australian-born GBMSM. HIV self-testing is a promising tool to overcome barriers to HIV testing and improve HIV testing uptake among migrant GBMSM. We compared the preferences for HIV testing services, including HIV self-testing, among migrant and Australian-born GBMSM.

Methods

Preferences were assessed via two discrete choice experiments (DCEs). Participants were recruited between December 2017 and January 2018 using online and offline advertising and randomly assigned to complete one of two online DCE surveys. Migrant GBMSM were classified as being born in a country with a reciprocal healthcare agreement (RHCA) with Australia (providing free or subsided health care) or not. Latent class analysis and mixed logit models were used to explore heterogeneity in preferences.

Findings

We recruited 1,606 GBMSM, including 583 migrant men of whom 419 (72%) were born in non-RHCA countries. Most participants preferred a free or cheap oral test with higher accuracy and a shorter window period to facilitate early detection of infections. Cost was more important for men born in non-RHCA countries than for men from RHCA countries or Australia. All groups preferred accessing kits through online distributers or off the shelf purchasing from pharmacies. Men born in RHCA countries least preferred accessing HIV self-testing kits from a medical clinic, while more than half of men from non-RHCA countries most preferred sourcing kits from a clinic. Sex-on-premises venues were the least preferred location to access test kits among all groups. In addition, two latent class analyses explored heterogeneity in preferences among men from non-RHCA countries and we found four latent classes for HIV testing services and two latent classes for HIVST distribution.

Interpretation

Our findings emphasise the need for high-performing and low-cost HIV self-testing kits that are accessible from a variety of distribution points as a component of Australia's HIV response, especially for those who do not have access to free or subsidised health care in Australia.
Clinico-Epidemiological Characteristics of Patients With Inflammatory Bowel Disease in Egypt: A Nationwide Multicenter Study
Authors: Elbadry Mohamed , Nour Mohamed O. , Hussien Mohamed , Ghoneem Elsayed Awad , Medhat Mohammed A. , Shehab Hany , Galal Sherif , Eltabbakh Mohamed , El-Raey Fathiya , Negm Mohamed , Afify Shimaa , Abdelhamed Walaa , Sherief Ahmed , Abdelaziz Ahmed , Abo Elkasem Mohamed , Mahrous Aya , Kamal Ghada , Maher Maha , Abdel-Hameed Omar , Elbasuny Abubakr , El-Zayyadi Islam , Bassiony Ahmed , Moussa Abdelmajeed , Bedewy Essam , Elfert Asem , El Kassas Mohamed
Published: April 2022

Background and Aims

Ulcerative colitis (UC) and Crohn's disease (CD) are the most common types of Inflammatory bowel disease (IBD), with variable responses to traditional therapies and unpredicted prognosis. In Egypt and most developing countries, the lack of recent epidemiological and prognostic data adversely affects management strategies. We collected and analyzed data of patients with IBD from multiple centers across Egypt to evaluate patients' clinical and epidemiological characteristics.

Methods

This retrospective multicenter study included patients diagnosed with IBD between May 2018 and August 2021, at 14 tertiary gastroenterology units across Egypt. Record analysis addressed a combination of clinico-epidemiological characteristics, biochemical tests, stool markers, endoscopic features, histological information, and different lines for IBD treatment.

Results

We identified 1104 patients with an established diagnosis of IBD; 81% of them had UC, and 19% showed CD. The mean age of onset was 35.1 ± 12.5 years ranging from 5 to 88 years, the mean duration of illness at inclusion was 13.6 ± 16.7 years, gender distribution was almost equal with a significant male dominance (60.4%,p= 0.003) among patients with CD, 57% were living in rural areas, and 70.5% were from Delta and Coastal areas. Two hundred nineteen patients (19.8%) displayed comorbid conditions, primarily associated with CD. The most frequent complaints were diarrhea (73.2%), rectal bleeding (54.6%) that was significantly higher among patients with UC (64%,p<0.001), and 46.8% with abdominal pain (more often with CD: 71%,p<0.001). Conventional therapy was effective in treating 94.7% of patients. The main lesion in patients with CD was ileal (47.8%); patients with UC mainly exhibited proctosigmoiditis (28.4%). Dysplasia was detected in 7.2% of patients, mainly subjects with UC.

Conclusions

To our knowledge, our effort is the first and largest cohort of Egyptian patients with IBD to describe clinical and epidemiological characteristics, and diagnostic and management approaches. More extensive prospective studies are still needed to fully characterize disease distribution, environmental factors, and pathological features of the disease.
Application of Manure Rather Than Plant-Origin Organic Fertilizers Alters the Fungal Community in Continuous Cropping Tobacco Soil
Authors: Su Yan , Zi Haiyun , Wei Xiaomeng , Hu Binbin , Deng Xiaopeng , Chen Yi , Jiang Yonglei
Published: April 2022

Continuous cropping leads to the development of serious fungal diseases in tobacco plants and depleted yield of tobacco (Nicotiana tabacum), which can be mitigated by organic fertilization. Yet, we know little about how organic fertilizers affect the fungal community of continuous cropping tobacco soil. In this study, we investigated the soil fungal community after 11 years of tobacco planting with chemical fertilization (CF) or chemical fertilization combined with organic fertilizers obtained from plant or animal origin, including oil cake (CFO), straw (CFS), and farmyard fertilizer (CFM). The predominant phyla of Ascomycota (70%) and Mortierellomycota (15%) were identified in all the treatments. A significantly higher proportion of Pyrenochaetopsis and lower relative abundance of Sordariomycetes were observed in the CFM group compared to the controls. Compared to CF and non-fertilized control (CK), CFO and CFS led to higher species richness (P < 0.05), while CFM led to a less uniform fungal community, indicated by lower Shannon and higher Simpson diversity indices (P < 0.05). Pearson’s correlation and redundancy analysis suggested that fertilizations primarily influenced the fungal community by altering the soil nutrient conditions, among which soil organic carbon and total phosphorus significantly correlated with the fungal diversity and community composition (P < 0.05). Notably, FUNGuild annotation suggested that while other treatments showed no significant effect on the fungal trophic modes, CFM strongly increased the abundance of saprotrophic fungi by more than 30% (P < 0.05), thus preventing the prevalence of potential pathotypes and symbionts. The results suggest that the type of organic fertilizers is essential to the long-term effects of organic application on the fungal community, and the animal-origin manure seems to be a better choice than plant-origin materials in continuous cropping tobacco fields.
Peptidomimetics as Potential Anti-Virulence Drugs Against Resistant Bacterial Pathogens
Authors: Martínez Osmel Fleitas , Duque Harry Morales , Franco Octávio Luiz
Published: April 2022

The uncontrollable spread of superbugs calls for new approaches in dealing with microbial-antibiotic resistance. Accordingly, the anti-virulence approach has arisen as an attractive unconventional strategy to face multidrug-resistant pathogens. As an emergent strategy, there is an imperative demand for discovery, design, and development of anti-virulence drugs. In this regard, peptidomimetic compounds could be a valuable source of anti-virulence drugs, since these molecules circumvent several shortcomings of natural peptide-based drugs like proteolytic instability, immunogenicity, toxicity, and low bioavailability. Some emerging evidence points to the feasibility of peptidomimetics to impair pathogen virulence. Consequently, in this review, we shed some light on the potential of peptidomimetics as anti-virulence drugs to overcome antibiotic resistance. Specifically, we address the anti-virulence activity of peptidomimetics against pathogens’ secretion systems, biofilms, and quorum-sensing systems.
Prediction and Inferred Evolution of Acid Tolerance Genes in the Biotechnologically Important Acidihalobacter Genus
Authors: Boase Katelyn , González Carolina , Vergara Eva , Neira Gonzalo , Holmes David , Watkin Elizabeth
Published: April 2022

Acidihalobacter is a genus of acidophilic, gram-negative bacteria known for its ability to oxidize pyrite minerals in the presence of elevated chloride ions, a capability rare in other iron-sulfur oxidizing acidophiles. Previous research involving Acidihalobacter spp. has focused on their applicability in saline biomining operations and their genetic arsenal that allows them to cope with chloride, metal and oxidative stress. However, an understanding of the molecular adaptations that enable Acidihalobacter spp. to thrive under both acid and chloride stress is needed to provide a more comprehensive understanding of how this genus can thrive in such extreme biomining conditions. Currently, four genomes of the Acidihalobacter genus have been sequenced: Acidihalobacter prosperus DSM 5130T, Acidihalobacter yilgarnensis DSM 105917T, Acidihalobacter aeolianus DSM 14174T, and Acidihalobacter ferrooxydans DSM 14175T. Phylogenetic analysis shows that the Acidihalobacter genus roots to the Chromatiales class consisting of mostly halophilic microorganisms. In this study, we aim to advance our knowledge of the genetic repertoire of the Acidihalobacter genus that has enabled it to cope with acidic stress. We provide evidence of gene gain events that are hypothesized to help the Acidihalobacter genus cope with acid stress. Potential acid tolerance mechanisms that were found in the Acidihalobacter genomes include multiple potassium transporters, chloride/proton antiporters, glutamate decarboxylase system, arginine decarboxylase system, urease system, slp genes, squalene synthesis, and hopanoid synthesis. Some of these genes are hypothesized to have entered the Acidihalobacter via vertical decent from an inferred non-acidophilic ancestor, however, horizontal gene transfer (HGT) from other acidophilic lineages is probably responsible for the introduction of many acid resistance genes.
Complete Genome Analysis Reveals the Quorum Sensing-Related Spoilage Potential of Pseudomonas fluorescens PF08, a Specific Spoilage Organism of Turbot (Scophthalmus maximus)
Authors: Wang Dangfeng , Cui Fangchao , Ren Likun , Tan Xiqian , Lv Xinran , Li Qiuying , Li Jianrong , Li Tingting
Published: April 2022

Pseudomonas fluorescens is a common specific spoilage organism (SSO) of aquatic products. The spoilage ability of SSO can be regulated by the quorum sensing (QS) system. However, the QS system in P. fluorescens and their relationship with the spoilage potential have not been systematically analyzed. In the present study, the complete genome of P. fluorescens PF08 isolated from spoilage turbot was sequenced. The identification of key genes that involved in the QS, enzyme synthesis, sulfur, and amino acid metabolism explained the spoilage potential of P. fluorescens PF08. Results of quantitative real-time PCR revealed the key role of the P. fluorescens PF08 QS system in regulating the transcription of spoilage-related genes and its sensitivity to environmental stress. These findings provide insight into the spoilage features of P. fluorescens PF08 from a genomic perspective. The knowledge may be valuable in the development of new strategies for the targeted inhibition of aquatic product spoilage based on QS interference.
Metatranscriptomic Assessment of the Microbial Community Associated With the Flavescence dorée Phytoplasma Insect Vector Scaphoideus titanus
Authors: Abbà Simona , Rossi Marika , Vallino Marta , Galetto Luciana , Marzachì Cristina , Turina Massimo
Published: April 2022

Phytoplasmas are insect-borne pathogenic bacteria that cause major economic losses to several crops worldwide. The dynamic microbial community associated with insect vectors influences several aspects of their biology, including their vector competence for pathogens. Unraveling the diversity of the microbiome of phytoplasma insect vectors is gaining increasing importance in the quest to develop novel microbe-based pest control strategies that can minimize the use of insecticides for better environmental quality. The leafhopperScaphoideus titanusis the primary vector of the Flavescence dorée phytoplasma, a quarantine pest which is dramatically affecting the main grape-growing European countries. In this study, the RNA-Seq data, which were previously used for insect virus discovery, were further explored to assess the composition of the whole microbial community associated with insects caught in the wild in both its native (the United States) and invasive (Europe) areas. The firstde novoassembly of the insect transcriptome was used to filter the host sequencing reads. The remaining ones were assembled into contigs and analyzed by blastx to provide the taxonomic identification of the microorganisms associated withS. titanus, including the non-bacterial components. By comparing the transcriptomic libraries, we could differentiate the stable and consistent associations from the more ephemeral and flexible ones. Two species appeared to be universal to the core microbiome ofS. titanus:the obligate bacterial symbiontCandidatusSulcia muelleri and anOphiocordyceps-allied fungus distantly related to yeast-like symbionts described from other hemipterans. Bacteria of the genusCardiniumhave been identified as another dominant member of the microbiome, but only in the European specimens. Although we are yet to witness how the interplay among the microorganisms influences the vector competence ofS. titanus, this unbiasedin silicocharacterization of its microbiome is paramount for identifying the naturally occurring targets for new biocontrol strategies to counteract Flavescence dorée spread in Europe.
Oral Shedding of an Oncogenic Virus Alters the Oral Microbiome in HIV+ Patients
Authors: Dai Lu , Lu Yong-Chen , Chen Jungang , Plaisance-Bonstaff Karlie , Mu Shengyu , Forrest J. Craig , Whitby Denise , Post Steven R. , Qin Zhiqiang
Published: April 2022

Kaposi’s Sarcoma (KS) caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) continues to be the most common AIDS-associated tumor. Involvement of the oral cavity represents one of the most common clinical manifestations of this tumor. Numerous types of cancer are associated with the alterations of in components of the microbiome. However, little is known about how KSHV coinfection affects the oral microbiome in HIV+ patients, especially in a “pre-cancer” niche. Using 16S rRNA pyrosequencing, we found that oral shedding of KSHV correlated with altered oral microbiome signatures in HIV+ patients, including a reduction in the microbiota diversity, changing the relative composition of specific phyla and species, and regulating microbial functions. Furthermore, we found that Streptococcus sp., one of the most increased species in the oral cavity of HIV+/KSHV+ patients, induced KSHV lytic reactivation in primary oral cells. Together, these data indicate that oral shedding of KSHV may manipulate the oral microbiome to promote viral pathogenesis and tumorigenesis especially in immunocompromised patients.
Targeting the N-Terminus Domain of the Coronavirus Nucleocapsid Protein Induces Abnormal Oligomerization via Allosteric Modulation
Authors: Hsu Jia-Ning , Chen Jyun-Siao , Lin Shan-Meng , Hong Jhen-Yi , Chen Yi-Jheng , Jeng U-Ser , Luo Shun-Yuan , Hou Ming-Hon
Published: April 2022

Epidemics caused by coronaviruses (CoVs), namely the severe acute respiratory syndrome (SARS) (2003), Middle East respiratory syndrome (MERS) (2012), and coronavirus disease 2019 (COVID-19) (2019), have triggered a global public health emergency. Drug development against CoVs is inherently arduous. The nucleocapsid (N) protein forms an oligomer and facilitates binding with the viral RNA genome, which is critical in the life cycle of the virus. In the current study, we found a potential allosteric site (Site 1) using PARS, an online allosteric site predictor, in the CoV N-N-terminal RNA-binding domain (NTD) to modulate the N protein conformation. We identified 5-hydroxyindole as the lead via molecular docking to target Site 1. We designed and synthesized four 5-hydroxyindole derivatives, named P4-1 to P4-4, based on the pose of 5-hydroxyindole in the docking model complex. Small-angle X-ray scattering (SAXS) data indicate that two 5-hydroxyindole compounds with higher hydrophobic R-groups mediate the binding between N-NTD and N-C-terminal dimerization domain (CTD) and elicit high-order oligomerization of the whole N protein. Furthermore, the crystal structures suggested that these two compounds act on this novel cavity and create a flat surface with higher hydrophobicity, which may mediate the interaction between N-NTD and N-CTD. Taken together, we discovered an allosteric binding pocket targeting small molecules that induces abnormal aggregation of the CoV N protein. These novel concepts will facilitate protein-protein interaction (PPI)-based drug design against various CoVs.
Mice Cohabiting With Familiar Conspecific in Chronic Stress Condition Exhibit Methamphetamine-Induced Locomotor Sensitization and Augmented Consolation Behavior
Authors: Carneiro de Oliveira Paulo Eduardo , Carmona Isabela Miranda , Casarotto Mariana , Silveira Lara Maria , Oliveira Anna Cecília Bezerra , Canto-de-Souza Azair
Published: April 2022

Recognizing and sharing emotions are essential for species survival, but in some cases, living with a conspecific in distress condition may induce negative emotional states through empathy-like processes. Studies have reported that stressors promote psychiatric disorders in both, those who suffer directly and who witness these aversive episodes, principally whether social proximity is involved. However, the mechanisms underlying the harmful outcomes of emotional contagion need more studies, mainly in the drug addiction-related behaviors. Here, we investigated the relevance of familiarity and the effects of cohabitation with a partner submitted to chronic stress in the anxiety-like, locomotor sensitization, and consolation behaviors. Male Swiss mice were housed in pairs during different periods to test the establishment of familiarity and the stress-induced anxiety behavior in the elevated plus maze. Another cohort was housed with a conspecific subjected to repeated restraint stress (1 h/day) for 14 days. During chronic restraint the allogrooming was measured and after the stress period mice were tested in the open field for evaluation of anxiety and locomotor cross-sensitization induced by methamphetamine. We found that familiarity was established after 14 days of cohabitation and the anxiogenic behavior appeared after 14 days of stress. Repeated restraint stress also increased anxiety in the open field test and induced locomotor cross-sensitization in the stressed mice and their cagemates. Cagemates also exhibited an increase in the consolation behavior after stress sessions when compared to control mice. These results indicate that changes in drug abuse-related, consolation, and affective behaviors may be precipitated through emotional contagion in familiar conspecifics.
Transient Receptor Potential Vanilloid 1 Function at Central Synapses in Health and Disease
Authors: Meza Rodrigo C. , Ancatén-González Carlos , Chiu Chiayu Q. , Chávez Andrés E.
Published: April 2022

The transient receptor potential vanilloid 1 (TRPV1), a ligand-gated nonselective cation channel, is well known for mediating heat and pain sensation in the periphery. Increasing evidence suggests that TRPV1 is also expressed at various central synapses, where it plays a role in different types of activity-dependent synaptic changes. Although its precise localizations remain a matter of debate, TRPV1 has been shown to modulate both neurotransmitter release at presynaptic terminals and synaptic efficacy in postsynaptic compartments. In addition to being required in these forms of synaptic plasticity, TRPV1 can also modify the inducibility of other types of plasticity. Here, we highlight current evidence of the potential roles for TRPV1 in regulating synaptic function in various brain regions, with an emphasis on principal mechanisms underlying TRPV1-mediated synaptic plasticity and metaplasticity. Finally, we discuss the putative contributions of TRPV1 in diverse brain disorders in order to expedite the development of next-generation therapeutic treatments.
Interlayer Connectivity Affects the Coherence Resonance and Population Activity Patterns in Two-Layered Networks of Excitatory and Inhibitory Neurons
Authors: Ristič David , Gosak Marko
Published: April 2022

The firing patterns of neuronal populations often exhibit emergent collective oscillations, which can display substantial regularity even though the dynamics of individual elements is very stochastic. One of the many phenomena that is often studied in this context is coherence resonance, where additional noise leads to improved regularity of spiking activity in neurons. In this work, we investigate how the coherence resonance phenomenon manifests itself in populations of excitatory and inhibitory neurons. In our simulations, we use the coupled FitzHugh-Nagumo oscillators in the excitable regime and in the presence of neuronal noise. Formally, our model is based on the concept of a two-layered network, where one layer contains inhibitory neurons, the other excitatory neurons, and the interlayer connections represent heterotypic interactions. The neuronal activity is simulated in realistic coupling schemes in which neurons within each layer are connected with undirected connections, whereas neurons of different types are connected with directed interlayer connections. In this setting, we investigate how different neurophysiological determinants affect the coherence resonance. Specifically, we focus on the proportion of inhibitory neurons, the proportion of excitatory interlayer axons, and the architecture of interlayer connections between inhibitory and excitatory neurons. Our results reveal that the regularity of simulated neural activity can be increased by a stronger damping of the excitatory layer. This can be accomplished with a higher proportion of inhibitory neurons, a higher fraction of inhibitory interlayer axons, a stronger coupling between inhibitory axons, or by a heterogeneous configuration of interlayer connections. Our approach of modeling multilayered neuronal networks in combination with stochastic dynamics offers a novel perspective on how the neural architecture can affect neural information processing and provide possible applications in designing networks of artificial neural circuits to optimize their function via noise-induced phenomena.