bluuebunny/crossref_metadata_2025 huggingface dataset:
Precision Genome Engineering Through Cytidine Base Editing in Rapeseed (Brassica napus. L)
Authors: Hu Limin , Amoo Olalekan , Liu Qianqian , Cai Shengli , Zhu Miaoshan , Shen Xiaoxiao , Yu Kaidi , Zhai Yungu , Yang Yang , Xu Lei , Fan Chuchuan , Zhou Yongming
Published: November 2020

Rapeseed is one of the world's most important sources of oilseed crops. Single nucleotide substitution is the basis of most genetic variation underpinning important agronomic traits. Therefore, genome-wide and target-specific base editing will greatly facilitate precision plant molecular breeding. In this study, four CBE systems (BnPBE, BnA3A-PBE, BnA3A1-PBE, and BnPBGE14) were modified to achieve cytidine base editing at five target genes in rapeseed. The results indicated that genome editing is achievable in three CBEs systems, among which BnA3A1-PBE had the highest base-editing efficiency (average 29.8% and up to 50.5%) compared to all previous CBEs reported in rapeseed. The editing efficiency of BnA3A1-PBE is ~8.0% and fourfold higher, than those of BnA3A-PBE (averaging 27.6%) and BnPBE (averaging 6.5%), respectively. Moreover, BnA3A1-PBE and BnA3A-PBE could significantly increase the proportion of both the homozygous and biallelic genotypes, and also broaden the editing window compared to BnPBE. The cytidine substitution which occurred at the target sites of both BnaA06.RGA and BnaALS were stably inherited and conferred expected gain-of-function phenotype in the T1 generation (i.e., dwarf phenotype or herbicide resistance for weed control, respectively). Moreover, new alleles or epialleles with expected phenotype were also produced, which served as an important resource for crop improvement. Thus, the improved CBE system in the present study, BnA3A1-PBE, represents a powerful base editor for both gene function studies and molecular breeding in rapeseed.
Cascabel: A Scalable and Versatile Amplicon Sequence Data Analysis Pipeline Delivering Reproducible and Documented Results
Authors: Abdala Asbun Alejandro , Besseling Marc A. , Balzano Sergio , van Bleijswijk Judith D. L. , Witte Harry J. , Villanueva Laura , Engelmann Julia C.
Published: November 2020

Marker gene sequencing of the rRNA operon (16S, 18S, ITS) or cytochrome c oxidase I (CO1) is a popular means to assess microbial communities of the environment, microbiomes associated with plants and animals, as well as communities of multicellular organisms via environmental DNA sequencing. Since this technique is based on sequencing a single gene, or even only parts of a single gene rather than the entire genome, the number of reads needed per sample to assess the microbial community structure is lower than that required for metagenome sequencing. This makes marker gene sequencing affordable to nearly any laboratory. Despite the relative ease and cost-efficiency of data generation, analyzing the resulting sequence data requires computational skills that may go beyond the standard repertoire of a current molecular biologist/ecologist. We have developed Cascabel, a scalable, flexible, and easy-to-use amplicon sequence data analysis pipeline, which uses Snakemake and a combination of existing and newly developed solutions for its computational steps. Cascabel takes the raw data as input and delivers a table of operational taxonomic units (OTUs) or Amplicon Sequence Variants (ASVs) in BIOM and text format and representative sequences. Cascabel is a highly versatile software that allows users to customize several steps of the pipeline, such as selecting from a set of OTU clustering methods or performing ASV analysis. In addition, we designed Cascabel to run in any linux/unix computing environment from desktop computers to computing servers making use of parallel processing if possible. The analyses and results are fully reproducible and documented in an HTML and optional pdf report. Cascabel is freely available at Github: https://github.com/AlejandroAb/CASCABEL.
Module Analysis Using Single-Patient Differential Expression Signatures Improves the Power of Association Studies for Alzheimer's Disease
Authors: Huang Jialan , Lu Dong , Meng Guofeng
Published: November 2020

The causal mechanism of Alzheimer's disease is extremely complex. Achieving great statistical power in association studies usually requires a large number of samples. In this work, we illustrated a different strategy to identify AD risk genes by clustering AD patients into modules based on their single-patient differential expression signatures. The evaluation suggested that our method could enrich AD patients with similar clinical manifestations. Applying this to a cohort of only 310 AD patients, we identified 174 AD risk loci at a strict threshold of empirical p < 0.05, while only two loci were identified using all the AD patients. As an evaluation, we collected 23 AD risk genes reported in a recent large-scale meta-analysis and found that 18 of them were rediscovered by association studies using clustered AD patients, while only three of them were rediscovered using all AD patients. Functional annotation suggested that AD-associated genetic variants mainly disturbed neuronal/synaptic function. Our results suggested module analysis helped to enrich AD patients affected by the common risk variants.
Political and Legal Responses to Human Mobility in South America in the Context of the Covid-19 Crisis. More Fuel for the Fire?
Authors: Acosta Diego , Brumat Leiza
Published: November 2020

During the XXI century, South America has been the epicenter of vibrant discussions on human mobility. A new vocabulary emerged with legal principles such as the non-criminalization of irregular migration or the right to migrate as a fundamental right taking central stage. The combination of the arrival of COVID-19 together with the important emigration of Venezuelans in the region, as well as economic and political crisis are putting into question some of these advances and present a complex scenario of migration governance in the region for the years to come.
Thermoneutrality and Immunity: How Does Cold Stress Affect Disease?
Authors: Vialard Fiorella , Olivier Martin
Published: November 2020

One of the major challenges the scientific community faces today is the lack of translational data generated from mouse trials for human health application. Housing temperature-dependent chronic cold stress in laboratory rodents is one of the key factors contributing to lack of translatability because it reveals major metabolic differences between humans and rodents. While humans tend to operate at temperatures within their thermoneutral zone, most laboratory rodents are housed at temperatures below this zone and have an increased energy demand to generate heat. This has an impact on the immune system of mice and thus affects results obtained using murine models of human diseases. A limited number of studies and reviews have shown that results obtained on mice housed at thermoneutrality were different from those obtained from mice housed in traditional housing conditions. Most of those studies, focused on obesity and cancer, found that housing mice at thermoneutrality changed the outcomes of the diseases negatively and positively, respectively. In this review, we describe how thermoneutrality impacts the immune system of rodents generally and in the context of different disease models. We show that thermoneutrality exacerbates cardiovascular and auto-immune diseases; alleviates asthma and Alzheimer’s disease; and, changes gut microbiome populations. We also show that thermoneutrality can have exacerbating or alleviating effects on the outcome of infectious diseases. Thus, we join the call of others in this field to urge researchers to refine murine models of disease and increase their translational capacity by considering housing at thermoneutrality for trials involving rodents.
Light Limitation and Depth-Variable Sedimentation Drives Vertical Reef Compression on Turbid Coral Reefs
Authors: Morgan Kyle M. , Moynihan Molly A. , Sanwlani Nivedita , Switzer Adam D.
Published: November 2020

Turbid coral reefs experience high suspended sediment loads and low-light conditions that vertically compress the maximum depth of reef growth. Although vertical reef compression is hypothesized to further decrease available coral habitat as environmental conditions on reefs change, its causative processes have not been fully quantified. Here, we present a high-resolution time series of environmental parameters known to influence coral depth distribution (light, turbidity, sedimentation, currents) within reef crest (2–3 m) and reef slope (7 m) habitats on two turbid reefs in Singapore. Light levels on reef crests were low [mean daily light integral (DLI): 13.9 ± 5.6 and 6.4 ± 3.0 mol photons m–2 day–1 at Kusu and Hantu, respectively], and light differences between reefs were driven by a 2-fold increase in turbidity at Hantu (typically 10–50 mg l–1), despite its similar distance offshore. Light attenuation was rapid (KdPAR: 0.49–0.57 m–1) resulting in a shallow euphotic depth of <11 m, and daily fluctuations of up to 8 m. Remote sensing indicates a regional west-to-east gradient in light availability and turbidity across southern Singapore attributed to spatial variability in suspended sediment, chlorophyll-a and colored dissolved organic matter. Net sediment accumulation rates were ∼5% of gross rates on reefs (9.8–22.9 mg cm–2 day–1) due to the resuspension of sediment by tidal currents, which contribute to the ecological stability of reef crest coral communities. Lower current velocities on the reef slope deposit ∼4 kg m2 more silt annually, and result in high soft-sediment benthic cover. Our findings confirm that vertical reef compression is driven from the bottom-up, as the photic zone contracts and fine silt accumulates at depth, reducing available habitat for coral growth. Assuming no further declines in water quality, future sea level rise could decrease the depth distribution of these turbid reefs by a further 8–12%. This highlights the vulnerability of deeper coral communities on turbid reefs to the combined effects of both local anthropogenic inputs and climate-related impacts.
A Risk-Based Approach to the COVID-19 Pandemic: The Experience in National Dental Centre Singapore
Authors: Tay John Rong Hao , Ng Ethan , Ong Marianne Meng Ann , Sim Chelsia , Tan Ken , Seneviratne Chaminda Jayampath
Published: November 2020

The emergence of a highly infectious coronavirus strain, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a major global public health emergency. The increasing number of infected cases and fatalities worldwide forced several countries into lockdown in a bid to control virus transmission. The practice of dentistry is considered high-risk due to the generation of aerosols associated with most dental procedures, and healthcare professionals must take appropriate precautions whilst working in this challenging environment. This review aims to provide an overview on transmission routes and shares a risk-based approach to coronavirus disease 2019 (COVID-19) in a specialty tertiary center. Risk assessment and mitigation focussed on staff and patient safety, adopting a wide safety margin, and responding dynamically to the level of risk at the workplace. As the severity of the pandemic depends on many still-unknown factors and shows little sign of abating, the routine practice of dentistry will continue to be disrupted in the near future. We describe a color-coded framework to maximize safety and to minimize disease spread. Areas covered include healthcare team management, personal protective equipment, clinical work, and dental education. Guidelines in each category change with the corresponding severity of the situation, and we believe it will be useful for the safer practice of dentistry in this current climate and can be modified for future similar disease outbreaks.
Acute Kidney Injury Induces Innate Immune Response and Neutrophil Activation in the Lung
Authors: Maeda Akinori , Hayase Naoki , Doi Kent
Published: November 2020

Complication in acute kidney injury (AKI) is significantly associated with developing acute respiratory failure (ARF), while ARF is one of the most important risks for AKI. These data suggest AKI and ARF may synergistically worsen the outcomes of critically ill patients and these organ injuries may not occur independently. Organ crosstalk between the kidney and the lung has been investigated by using animal models so far. This review will focus on innate immune response and neutrophil activation among the mechanisms that contribute to this organ crosstalk. AKI increased the blood level of an inflammatory mediator in high-mobility group box 1, which induces an innate immune reaction via toll-like receptor 4. The remarkable infiltration of neutrophils to the lung was observed in animal AKI models. IL-6 and IL-8 have been demonstrated to contribute to pulmonary neutrophil activation in AKI. In addition, the formation of a neutrophil extracellular trap was also observed in the lung after the exposure of renal ischemia reperfusion in the animal model. Further investigation is necessary to determine whether targeting innate immune response and neutrophil activation will be useful for developing new therapeutics that could improve multiple organ failure in critically ill patients.
Distinct Dengue Disease Epidemiology, Clinical, and Diagnosis Features in Western, Central, and Eastern Regions of Indonesia, 2017–2019
Authors: Sasmono R. Tedjo , Santoso Marsha S. , Pamai Yanuarni W. B. , Yohan Benediktus , Afida Anna M. , Denis Dionisius , Hutagalung Ingrid A. , Johar Edison , Hayati Rahma F. , Yudhaputri Frilasita A. , Haryanto Sotianingsih , Stubbs Samuel C. B. , Blacklaws Barbara A. , Myint Khin S. A. , Frost Simon D. W.
Published: November 2020

The people of Indonesia have been afflicted by dengue, a mosquito-borne viral disease, for over 5 decades. The country is the world's largest archipelago with diverse geographic, climatic, and demographic conditions that may impact the dynamics of disease transmissions. A dengue epidemiology study was launched by us to compare and understand the dynamics of dengue and other arboviral diseases in three cities representing western, central, and eastern Indonesia, namely, Batam, Banjarmasin, and Ambon, respectively. A total of 732 febrile patients were recruited with dengue-like illness during September 2017–2019 and an analysis of their demographic, clinical, and virological features was performed. The seasonal patterns of dengue-like illness were found to be different in the three regions. Among all patients, 271 (37.0%) were virologically confirmed dengue, while 152 (20.8%) patients were diagnosed with probable dengue, giving a total number of 423 (57.8%) dengue patients. Patients' age and clinical manifestations also differed between cities. Mostly, mild dengue fever was observed in Batam, while more severe cases were prominent in Ambon. While all dengue virus (DENV) serotypes were detected, distinct serotypes dominated in different locations: DENV-1 in Batam and Ambon, and DENV-3 in Banjarmasin. We also assessed the diagnostic features in the study sites, which revealed different patterns of diagnostic agreements, particularly in Ambon. To detect the possibility of infection with other arboviruses, further testing on 461 DENV RT-PCR-negative samples was performed using pan-flavivirus and -alphavirus RT-PCRs; however, only one chikungunya infection was detected in Ambon. A diverse dengue epidemiology in western, central, and eastern Indonesia was observed, which is likely to be influenced by local geographic, climatic, and demographic conditions, as well as differences in the quality of healthcare providers and facilities. Our study adds a new understanding on dengue epidemiology in Indonesia.
A Systematic Review of Treatment Options and Clinical Outcomes in Pemphigoid Gestationis
Authors: Genovese Giovanni , Derlino Federica , Cerri Amilcare , Moltrasio Chiara , Muratori Simona , Berti Emilio , Marzano Angelo Valerio
Published: November 2020

Background: Treatment regimens for pemphigoid gestationis (PG) are non-standardized, with most evidence derived from individual case reports or small series.

Objectives: To systematically review current literature on treatments and clinical outcomes of PG and to establish recommendations on its therapeutic management.

Methods: An a priori protocol was designed based on PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched for English-language articles detailing PG treatments and clinical outcomes, published between 1970 and March 2020.

Results: In total, 109 articles including 140 PG patients were analyzed. No randomized controlled trials or robust observational studies detailing PG treatment were found. Systemic corticosteroids ± topical corticosteroids and/or antihistamines were the most frequently prescribed treatment modality (n = 74/137; 54%). Complete remission was achieved by 114/136 (83.8%) patients. Sixty-four patients (45.7%) were given more than one treatment modality due to side effects or ineffectiveness. Leaving aside topical corticosteroids as monotherapy ± antihistamines in patients with mild disease, systemic corticosteroids ± topical corticosteroids and/or antihistamines led to complete remission in the highest proportion of patients (83%), while steroid-sparing treatments ± topical corticosteroids and/or antihistamines were associated with the lowest proportion of flares (55.5%).

Limitations: The review has been drafted based on a limited number of single case reports and small case series. Underreporting/underdiagnosis of patients with mild-to-moderate PG, partial/absent follow-up, absence of precise description of neonatal outcomes and lack of validated objective scores for measuring disease severity are other limitations of our study. Our systematic review was affected by publication bias.

Conclusion: Systemic corticosteroids are the most frequently used treatment for PG. Whilst most patients achieve complete remission, many of them have refractory/persistent disease requiring multiple lines of therapy. Therefore, we provided an algorithm for PG treatment integrating the results of this systematic review with current knowledge available for bullous pemphigoid. High-quality studies will further help assess the effectiveness of different treatment options for PG.
Autoimmunity in Focal Segmental Glomerulosclerosis: A Long-Standing Yet Elusive Association
Authors: Podestà Manuel Alfredo , Ponticelli Claudio
Published: November 2020

Focal segmental glomerulosclerosis (FSGS) is a histological term that describes a pathologic renal entity affecting both adults and children, with a wide array of possible underlying etiologies. Podocyte damage with scarring, the hallmark of this condition, leads to altered permeability of the glomerular barrier, which may result in massive proteinuria and relentless renal function deterioration. A definite cause of focal segmental glomerulosclerosis can be confirmed in a minority of cases, while most forms have been traditionally labeled as primary or idiopathic. Despite this definition, increasing evidence indicates that primary forms are a heterogenous group rather than a single disease entity: several circulating factors that may affect glomerular permeability have been proposed as potential culprits, and both humoral and cellular immunity have been implicated in the pathogenesis of the disease. Consistently, immunosuppressive drugs are considered as the cornerstone of treatment for primary focal segmental glomerulosclerosis, but response to these agents and long-term outcomes are highly variable. In this review we provide a summary of historical and recent advances on the pathogenesis of primary focal segmental glomerulosclerosis, focusing on implications for its differential diagnosis and treatment.
Epidemiological Characteristics and Formation Mechanisms of Multidrug-Resistant Hypervirulent Klebsiella pneumoniae
Authors: Tang Miran , Kong Xin , Hao Jingchen , Liu Jinbo
Published: November 2020

Multi-drug resistance (MDR) and hypervirulence (hv) were exhibited by different well-separated Klebsiella pneumoniae lineages in the past, but their convergence clones—MDR-hypervirulent K. pneumoniae (HvKPs)—both highly pathogenic and resistant to most available antibiotics, have increasingly been reported. In light of the clonal lineages and molecular characteristics of the studied MDR-HvKP strains found in the literature since 2014, this review discusses the epidemiology of MDR-HvKPs, in particular summarizing the three general aspects of plasmids-associated mechanisms underlying the formation of MDR-HvKPs clones: MDR-classic K. pneumoniae (cKPs) acquiring hv plasmids, hvKPs obtaining MDR plasmids, and the acquisition of hybrid plasmids harboring virulence and resistance determinants. A deeper understanding of epidemiological characteristics and possible formation mechanisms of MDR-HvKPs is greatly needed for the proper surveillance and management of this potential threat.
Function-Driven Design of Lactic Acid Bacteria Co-cultures to Produce New Fermented Food Associating Milk and Lupin
Authors: Canon Fanny , Mariadassou Mahendra , Maillard Marie-Bernadette , Falentin Hélène , Parayre Sandrine , Madec Marie-Noëlle , Valence Florence , Henry Gwénaële , Laroute Valérie , Daveran-Mingot Marie-Line , Cocaign-Bousquet Muriel , Thierry Anne , Gagnaire Valérie
Published: November 2020

Designing bacterial co-cultures adapted to ferment mixes of vegetal and animal resources for food diversification and sustainability is becoming a challenge. Among bacteria used in food fermentation, lactic acid bacteria (LAB) are good candidates, as they are used as starter or adjunct in numerous fermented foods, where they allow preservation, enhanced digestibility, and improved flavor. We developed here a strategy to design LAB co-cultures able to ferment a new food made of bovine milk and lupin flour, consisting in: (i) in silico preselection of LAB species for targeted carbohydrate degradation; (ii) in vitro screening of 97 strains of the selected species for their ability to ferment carbohydrates and hydrolyze proteins from milk and lupin and clustering strains that displayed similar phenotypes; and (iii) assembling strains randomly sampled from clusters that showed complementary phenotypes. The designed co-cultures successfully expressed the targeted traits i.e., hydrolyzed proteins and degraded raffinose family oligosaccharides of lupin and lactose of milk in a large range of concentrations. They also reduced an off-flavor-generating volatile, hexanal, and produced various desirable flavor compounds. Most of the strains in co-cultures achieved higher cell counts than in monoculture, suggesting positive interactions. This work opens new avenues for the development of innovative fermented food products based on functionally complementary strains in the world-wide context of diet diversification.
AI-Blue-Carba: A Rapid and Improved Carbapenemase Producer Detection Assay Using Blue-Carba With Deep Learning
Authors: Jia Ling , Han Lu , Cai He-Xin , Cui Ze-Hua , Yang Run-Shi , Zhang Rong-Min , Bai Shuan-Cheng , Liu Xu-Wei , Wei Ran , Chen Liang , Liao Xiao-Ping , Liu Ya-Hong , Li Xi-Ming , Sun Jian
Published: November 2020

A rapid and accurate detection of carbapenemase-producing Gram-negative bacteria (CPGNB) has an immediate demand in the clinic. Here, we developed and validated a method for rapid detection of CPGNB using Blue-Carba combined with deep learning (designated as AI-Blue-Carba). The optimum bacterial suspension concentration and detection wavelength were determined using a Multimode Plate Reader and integrated with deep learning modeling. We examined 160 carbapenemase-producing and non-carbapenemase-producing bacteria using the Blue-Carba test and a series of time and optical density values were obtained to build and validate the machine models. Subsequently, a simplified model was re-evaluated by descending the dataset from 13 time points to 2 time points. The best suitable bacterial concentration was determined to be 1.5 optical density (OD) and the optimum detection wavelength for AI-Blue-Carba was set as 615 nm. Among the 2 models (LRM and LSTM), the LSTM model generated the higher ROC-AUC value. Moreover, the simplified LSTM model trained by short time points (0–15 min) did not impair the accuracy of LSTM model. Compared with the traditional Blue-Carba, the AI-Blue-Carba method has a sensitivity of 95.3% and a specificity of 95.7% at 15 min, which is a rapid and accurate method to detect CPGNB.
Serologic Evaluation of Healthcare Workers Caring for COVID-19 Patients in the Republic of Korea
Authors: Ko Jae-Hoon , Lee Ji Yeon , Kim Hyun Ah , Kang Seung-Ji , Baek Jin Yang , Park Su-Jin , Hyun Miri , Jo Ik Joon , Chung Chi Ryang , Kim Yae-Jean , Kang Eun-Suk , Choi Young Ki , Chang Hyun-Ha , Jung Sook In , Peck Kyong Ran
Published: November 2020

The safety of healthcare workers (HCWs) against severe acute respiratory syndrome virus 2 (SARS-CoV-2) transmission is an important aspect of managing the coronavirus disease 2019 (COVID-19) pandemic. In the South Korea, highly stringent infection prevention and control (IPC) guidelines are implemented, and reports of healthcare-associated SARS-CoV-2 transmission among HCWs are limited. However, subclinical infections may have been missed by the current symptom-based screening strategy. To evaluate the risk of undetected SARS-CoV-2 transmissions from COVID-19 patients to HCWs, we conducted a multicenter seroprevalence study after the first surge of the COVID-19 outbreak. A total of 432 HCWs were evaluated, comprising 309 HCWs designated to laboratory-confirmed COVID-19 patient care and 123 non-designated HCWs. Designated HCWs wore personal protective equipment including an N95 respirator, eye protection, hooded overalls, shoe covers, and inner and outer gloves. Use of a powered air-purifying respirator was recommended for aerosol-generating procedures or long-duration care activities. A high-sensitivity (99.1%) fluorescence immunoassay immunoglobulin G (IgG) kit was used as the initial screening test, and two enzyme-linked immunosorbent assay kits for total and IgG antibodies were used to confirm the test results. A microneutralization test was additionally performed to evaluate the neutralizing activity of positive specimens. Among the evaluated HCWs, none of the non-designated HCWs had a positive result, while one of the HCWs designated for COVID-19 patient care (1/309, 0.3%) was seropositive for SARS-CoV-2 with confirmed neutralizing activity (1:40). This finding suggests that subclinical seroconversion may occur among HCWs caring for COVID-19 patients, although the risk is low under strict IPC guidance.
Splicing Endonuclease Is an Important Player in rRNA and tRNA Maturation in Archaea
Authors: Schwarz Thandi S. , Berkemer Sarah J. , Bernhart Stephan H. , Weiß Matthias , Ferreira-Cerca Sébastien , Stadler Peter F. , Marchfelder Anita
Published: November 2020

In all three domains of life, tRNA genes contain introns that must be removed to yield functional tRNA. In archaea and eukarya, the first step of this process is catalyzed by a splicing endonuclease. The consensus structure recognized by the splicing endonuclease is a bulge-helix-bulge (BHB) motif which is also found in rRNA precursors. So far, a systematic analysis to identify all biological substrates of the splicing endonuclease has not been carried out. In this study, we employed CRISPRi to repress expression of the splicing endonuclease in the archaeonHaloferax volcaniito identify all substrates of this enzyme. Expression of the splicing endonuclease was reduced to 1% of its normal level, resulting in a significant extension of lag phase inH. volcaniigrowth. In the repression strain, 41 genes were down-regulated and 102 were up-regulated. As an additional approach in identifying new substrates of the splicing endonuclease, we isolated and sequenced circular RNAs, which identified excised introns removed from tRNA and rRNA precursors as well as from the 5′ UTR of the gene HVO_1309.In vitroprocessing assays showed that the BHB sites in the 5′ UTR of HVO_1309 and in a 16S rRNA-like precursor are processed by the recombinant splicing endonuclease. The splicing endonuclease is therefore an important player in RNA maturation in archaea.
Morphology, Multilocus Phylogeny, and Toxin Analysis Reveal Amanita albolimbata, the First Lethal Amanita Species From Benin, West Africa
Authors: Codjia Jean Evans I. , Cai Qing , Zhou Sheng Wen , Luo Hong , Ryberg Martin , Yorou Nourou S. , Yang Zhu L.
Published: November 2020

Many species of Amanita sect. Phalloideae (Fr.) Quél. cause death of people after consumption around the world. Amanita albolimbata, a new species of A. sect. Phalloideae from Benin, is described here. The taxon represents the first lethal species of A. sect. Phalloideae known from Benin. Morphology and molecular phylogenetic analyses based on five genes (ITS, nrLSU, rpb2, tef1-α, and β-tubulin) revealed that A. albolimbata is a distinct species. The species is characterized by its smooth, white pileus sometimes covered by a patchy volval remnant, a bulbous stipe with a white limbate volva, broadly ellipsoid to ellipsoid, amyloid basidiospores, and abundant inflated cells in the volva. Screening for the most notorious toxins by liquid chromatography–high-resolution mass spectrometry revealed the presence of α-amanitin, β-amanitin, and phallacidin in A. albolimbata.
Renal Carcinoma Is Associated With Increased Risk of Coronavirus Infections
Authors: Tripathi Satyendra C. , Deshmukh Vishwajit , Creighton Chad J. , Patil Ashlesh
Published: November 2020

Background: The current COVID-19 pandemic has affected most severely people with old age, or with comorbidities like hypertension, diabetes mellitus, and cancer. Cancer patients are twice more likely to contract the disease because of the malignancy or treatment-related immunosuppression; hence identification of the vulnerable population among these patients is essential.

Method: We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors (DPP4, ANPEP, ENPEP, TMPRSS2) in human normal and cancer tissues of multiple organs including the brain, liver, kidney, heart, lung, skin, GI tract, pancreas, endocrine tissues, and the reproductive organs. RNA-Seq data from The Cancer Genome Atlas (TCGA) and GTeX databases were used for extensive profiling analysis of these receptors across 9,736 tumors and 8,587 normal tissues comparing coronavirus receptors. Protein expression from immunohistochemistry data was assessed from The Human Protein Atlas database including 144 samples, corresponding to 48 different normal human tissue types, and 432 tumor samples from 216 different cancer patients. The correlations between immune cell infiltration, chemokine, and cytokines were investigated via Tumor Immune Estimation Resource (TIMER) and TCGA.

Result: We found that among all, renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP. Our results revealed that TMPRSS2 may not be the co-receptor for coronavirus infection in renal carcinoma patients. The other receptors DPP4, ANPEP, and ENPEP may act as the compensatory receptor proteins to help ACE2. The receptors' expression levels were variable in different tumor stage, molecular, and immune subtypes of renal carcinoma. Intriguingly, in clear cell renal cell carcinomas, coronavirus receptors were associated with high immune infiltration, markers of immunosuppression, and T cell exhaustion.

Conclusion: Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma. As our current knowledge of pathogenic mechanisms will improve, it may help us in designing focused therapeutic approaches.
Various Diseases and Clinical Heterogeneity Are Associated With “Hot Cross Bun”
Authors: Zhu Shuzhen , Li Hualing , Deng Bin , Zheng Jialing , Huang Zifeng , Chang Zihan , Huang Yanjun , Wen Zhibo , Liang Yanran , Yu Mengjue , Chan Ling-Ling , Tan Eng-King , Wang Qing
Published: November 2020

Objective: To characterize the clinical phenotypes associated with the “hot cross bun” sign (HCBs) on MRI and identify correlations between neuroimaging and clinical characteristics.

Methods: Firstly, we screened a cohort of patients with HCBs from our radiologic information system (RIS) in our center. Secondly, we systematically reviewed published cases on HCBs and classified all these cases according to their etiologies. Finally, we characterized all HCBs cases in detail and classified the disease spectra and their clinical heterogeneity.

Results: Out of a total of 3,546 patients who were screened, we identified 40 patients with HCBs imaging sign in our cohort; systemic literature review identified 39 cases, which were associated with 14 diseases. In our cohort, inflammation [neuromyelitis optica spectrum disorders (NMOSD), multiple sclerosis (MS), and acute disseminated encephalomyelitis (ADEM)] and toxicants [toxic encephalopathy caused by phenytoin sodium (TEPS)] were some of the underlying etiologies. Published cases by systemic literature review were linked to metabolic abnormality, degeneration, neoplasm, infection, and stroke. We demonstrated that the clinical phenotype, neuroimaging characteristics, and HCBs response to therapy varied greatly depending on underlying etiologies.

Conclusion: This is the first to report HCBs spectra in inflammatory and toxication diseases. Our study and systemic literature review demonstrated that the underpinning disease spectrum may be broader than previously recognized.
A Streamlined Study on Chitosan-Zinc Oxide Nanomicelle Properties to Mitigate a Drug-Resistant Biofilm Protection Mechanism
Authors: Limayem Alya , Patil Shrushti B. , Mehta Mausam , Cheng Feng , Nguyen Minh
Published: November 2020

The nosocomial multidrug resistant bacteria (MDR), are rapidly circulating from water surfaces to humans away from the clinical setting, forming a cyclical breeding ground of resistance, causing worldwide infections, and thus requiring urgent responses. The combination of chitosan and zinc oxide (CZNPs), with proven bactericidal effects on some MDRs, was further studied to set the stage for a broad-spectrum in vivo utilization of CZNPs. Toward ensuring CZNPs' uniformity and potency, when it faces not only biofilms but also their extracellular polymeric substances (EPS) defense mechanism, the size, zeta potential, and polydispersity index (PDI) were determined through dynamic light scattering (DLS). Furthermore, the efficacy of CZNPs was tested on the inhibition of MDR Gram-negative Escherichia coli BAA-2471 and Gram-positive Enterococcus faecium 1449 models, co-cultured in an Alvatex 3D fiber platform as a biofilm-like structure. The Biotek Synergy Neo2 fluorescent microplate reader was used to detect biofilm shrinkage. The biofilm protection mechanism was elucidated through detection of EPS using 3D confocal and transmission electronic microscopy. Results indicated that 200 μl/mL of CZNPs, made with 50 nm ZnO and 10,000 Da chitosan (N = 369.1 nm; PDI = 0.371; zeta potential = 22.8 mV), was the most promising nanocomposite for MDR biofilm reduction, when compared to CZNPs enclosing ZnO, 18 or 100 nm. This study depicts that CZNPs possess enough potency and versatility to face biofilms' defense mechanism in vivo.
Long Non-coding RNA Expression Profiling Identifies a Four-Long Non-coding RNA Prognostic Signature for Isocitrate Dehydrogenase Mutant Glioma
Authors: Chen Yusheng , Guo Yang , Chen Hang , Ma Fengjin
Published: November 2020

Background: Isocitrate dehydrogenase (IDH) mutant is one of the most robust and important genetic aberrations in glioma. However, the underlying regulation mechanism of long non-coding RNA (lncRNA) in IDH mutant glioma has not been systematically portrayed.

Methods:In this work, 775 IDH mutant glioma samples with transcriptome data, including 167 samples from the Chinese Glioma Genome Atlas (CGGA) RNAseq dataset, 390 samples from The Cancer Genome Atlas (TCGA) dataset, 79 samples from GSE16011 dataset, and 139 samples from CGGA microarray dataset, were enrolled. R language and GraphPad Prism software were applied for the statistical analysis and graphical work.

Results: By comparing the differentially lncRNA genes between IDH mutant and IDH wild-type glioma samples, a four-lncRNA (JAG1, PVT1, H19, and HAR1A) signature was identified in IDH mutant glioma patients. The signature model was established based on the expression level and the regression coefficient of the four lncRNA genes. IDH mutant glioma samples could be successfully stratified into low-risk and high-risk groups in CGGA RNAseq, TCGA, GSE16011, and CGGA microarray databases. Meanwhile, multivariate Cox analysis showed that the four-lncRNA signature was an independent prognostic biomarker after adjusting for other clinicopathologic factors. Moreover, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the immune response and cellular metabolism were significantly associated with the four-lncRNA risk signature.

Conclusion: Taken together, the four-lncRNA risk signature was identified as a novel prognostic marker for IDH mutant glioma patients and may potentially lead to improvements in the lives of glioma patients.
Identifying Training, Diagnostic and Therapeutic Needs From a Comparison in the Distribution of Vestibular Disorders in Primary Care and in a Neurotology Unit
Authors: Domínguez-Durán Emilio , Moreno-de-Jesús Carolina , Prieto-Sánchez-de-Puerta Lucía , Mármol-Szombathy Irene , Sánchez-Gómez Serafín
Published: November 2020

Introduction: Several epidemiological studies in Neurotology have been previously carried out in the general population. This approach is useful for learning about the most common disorders in clinical population, but it may fail when one is trying to help professionals to guide their training, to optimize their resources and to decide on the highest-priority research objectives.

Objective: To identify which of the neurotological diseases are most common in two different populations, those who attended a consultation in the Neurotology Unit of a tertiary level hospital and those who did so in Primary Care in order to infer which of them requires more attention in each context and their specific needs.

Methods: All the diagnoses made in Hospital Care between October 15, 2017 and October 14, 2018 were reviewed. These diagnoses were coded and classified into syndromes and diseases. Later, the proportions of each category were compared with the proportions of the neurotological diagnoses made in five Primary Care centers over the same period of time.

Results: BPPV is the most common cause of vestibular symptoms in both contexts. Vestibular migraine, ischemic vestibular symptoms, orthostatic hypotension and side effects of drugs are common in Primary Care, whereas Ménière's disease and undifferentiated episodic vestibular syndrome are common in specialized centers.

Conclusion: The proportion of diagnoses in neurotologic patients is different in the general population and in the specialized center population, and therefore they have different needs. Primary Care professionals would benefit from training on maneuvers for repositioning otoliths, the treatment of headache, the identification of cardiovascular risk factors, the orthostatic hypotension and the side effects of the most commonly used drugs. The professionals who work in specialized centers need strategies for dealing with cases of BPPV associated to other vestibular diseases and refractory cases and their research should focus on the development of new diagnostic tools for the diagnosis of undifferentiated episodic vestibular syndrome and new therapeutic options for Ménière's disease.
Comparative Assessment of the WNT/β-Catenin Pathway, CacyBP/SIP, and the Immunoproteasome Subunit LMP7 in Various Histological Types of Renal Cell Carcinoma
Authors: Piotrowska Żaneta , Niezgoda Michał , Młynarczyk Grzegorz , Acewicz Magdalena , Kasacka Irena
Published: November 2020

Objective

The Wnt/ß-catenin pathway plays an important role in pathogenesis of variety cancers. Most studies on changes in WNT/β-catenin pathway in renal cell carcinoma (RCC) apply only to clear cell RCC, while there are no comparative assessments of this signaling pathway in various histological types of renal tumors in the available literature. Additionally, considering the close relationship between WNT/β-catenin signaling, CacyBP/SIP and proteasomal activity, it seemed worth comparing WNT/β-catenin pathway, CacyBP/SIP and LMP7 immunoproteasome subunit in human samples of clear cell, papillary, and chromophobe RCC.

Methods

Tests were performed on sections of three types of kidney tumors together with surrounding unchanged tissue fragments collected from 50 patients. Samples were divided into three groups depending on the histological type of cancer: clear cell, papillary and chromophobe RCC. Immunohistochemistry and PCR methods were used to identify WNT10A, Fzd5, β-catenin, GSK-3ß, CacyBP/SIP, LMP7, and gene expression.

Results

Immunoreactivity and expression of WNT10A, Fzd5, β-catenin, GSK-3ß, CacyBP/SIP, LMP7 in clear cell RCC was markedly increased compared to non-cancerous kidney tissue. In papillary RCC, immunoreactivity and expression of WNT/β-catenin pathway, CacyBP/SIP, LMP7 was also increased compared to non-malignant kidneys, but it was less pronounced than in clear cell RCC. The least substantial increase in immunoreactivity and expression of WNT/β-catenin pathway, CacyBP/SIP, LMP7 was found in chromophobe RCC, compared to other RCC histological subtypes studied.

Conclusions

Study results suggest an important role of WNT/β-catenin pathway, CacyBP/SIP and LMP7 in RCC carcinogenesis, and may indicate new aspects of pathomechanisms leading to differences in the biology of clear cell, papillary and chromophobe RCC.
Clinical and Biological Significances of a Ferroptosis-Related Gene Signature in Glioma
Authors: Zhuo Shenghua , Chen Zhimin , Yang Yibei , Zhang Jinben , Tang Jianming , Yang Kun
Published: November 2020

Ferroptosis is a form of cell death characterized by non-apoptosis induced by small molecules in tumors. Studies have demonstrated that ferroptosis regulates the biological behaviors of tumors. Therefore, genes that control ferroptosis can be a promising candidate bioindicator in tumor therapy. Herein, functions of ferroptosis-related genes in glioma were investigated. We systematically assessed the relationship between ferroptosis-related genes expression profiles and prognosis in glioma patients based on The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) RNA sequencing datasets. Using the non-negative matrix factorization (NMF) clustering method, 84 ferroptosis-related genes in the RNA sequencing data were distinctly classified into two subgroups (named cluster 1 and cluster 2) in glioma. The least absolute shrinkage and selection operator (LASSO) was used to develop a 25 gene risk signature. The relationship between the gene risk signature and clinical features in glioma was characterized. Results show that the gene risk signature associated with clinical features can be as an independent prognostic indicator in glioma patients. Collectively, the ferroptosis-related risk signature presented in this study can potentially predict the outcome of glioma patients.
Cancer History and Systemic Anti-Cancer Therapy Independently Predict COVID-19 Mortality: A UK Tertiary Hospital Experience
Authors: Sng Christopher C. T. , Wong Yien Ning Sophia , Wu Anjui , Ottaviani Diego , Chopra Neha , Galazi Myria , Benafif Sarah , Soosaipillai Gehan , Roylance Rebecca , Lee Alvin J. X. , Shaw Heather
Published: November 2020

Background

The COVID-19 pandemic remains a pressing concern to patients with cancer as countries enter the second peak of the pandemic and beyond. It remains unclear whether cancer and its treatment contribute an independent risk for mortality in COVID-19.

Methods

We included patients at a London tertiary hospital with laboratory confirmed SARS-CoV-2 infection. All patients with a history of solid cancer were included. Age- and sex-matched patients without cancer were randomly selected. Patients with hematological malignancies were excluded.

Results

We identified 94 patients with cancer, matched to 226 patients without cancer. After adjusting for age, ethnicity, and co-morbidities, patients with cancer had increased mortality following COVID-19 (HR 1.57, 95% CI:1.04–2.4, p = 0.03). Increasing age (HR 1.49 every 10 years, 95% CI:1.25–1.8, p < 0.001), South Asian ethnicity (HR 2.92, 95% CI:1.73–4.9, p < 0.001), and cerebrovascular disease (HR 1.93, 95% CI:1.18–3.2, p = 0.008) also predicted mortality. Within the cancer cohort, systemic anti-cancer therapy (SACT) within 60 days of COVID-19 diagnosis was an independent risk factor for mortality (HR 2.30, 95% CI: 1.16–4.6, p = 0.02).

Conclusions

Along with known risk factors, cancer and SACT confer an independent risk for mortality following COVID-19. Further studies are needed to understand the socio-economic influences and pathophysiology of these associations.
A Rare Cause of Sleep-Disordered Breathing: ROHHAD Syndrome
Authors: Özcan Gizem , Özsu Elif , Şiklar Zeynep , Çobanoğlu Nazan
Published: November 2020

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) syndrome; is a rare but crucial disorder. Sleep-disordered breathing can occur at the beginning or after of obesity. A disease-specific test for diagnosis is not yet available. Neural crest tumors (ganglioneuroma, ganglioneuroblastoma) have been reported in 40% of patients. In our study, three patients diagnosed as having ROHHAD syndrome are presented from our hospital. In the evaluation of the hypothalamic functions of the patients, one of them had growth hormone deficiency and hyperprolactinemia; recurrent hypernatremia reflecting irregular water balance was detected in another. One of the patients had abnormal pupil reflex and heart rate irregularity while another had excessive sweating as autonomic dysfunction. One of the patients was diagnosed with paravertebral ganglioma accompanying ROHHAD syndrome. Non-invasive ventilation treatment was started in all patients because there was a sleep-disorder breathing clinic diagnosis. ROHHAD syndrome deserves a multidisciplinary team approach as it can affect more than one organ system. In these patients, should be sleep-disorder breathing determined early and appropriate treatment should be initiated immediately to reduce morbidity and mortality.