bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunosuppressive Properties of Epidermal Keratinocytes Differ According to Their Immaturity Status
Authors: Mestrallet Guillaume , Carosella Edgardo D. , Martin Michele T. , Rouas-Freiss Nathalie , Fortunel Nicolas O. , LeMaoult Joel
Published: February 2022

Preservation of a functional keratinocyte stem cell pool is essential to ensure the long-term maintenance of epidermis integrity, through continuous physiological renewal and regeneration in case of injury. Protecting stem cells from inflammation and immune reactions is thus a critical issue that needs to be explored. Here, we show that the immature CD49fhigh precursor cell fraction from interfollicular epidermis keratinocytes, comprising stem cells and progenitors, is able to inhibit CD4+ T-cell proliferation. Of note, both the stem cell-enriched CD49fhigh/EGFRlow subpopulation and the less immature CD49fhigh/EGFRhigh progenitors ensure this effect. Moreover, we show that HLA-G and PD-L1 immune checkpoints are overexpressed in CD49fhigh precursors, as compared to CD49flow differentiated keratinocytes. This potency may limit immune reactions against immature precursors including stem cells, and protect them from exacerbated inflammation. Further exploring this correlation between immuno-modulation and immaturity may open perspectives in allogenic cell therapies.
Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring
Authors: Locy Hanne , Verhulst Stefaan , Cools Wilfried , Waelput Wim , Brock Stefanie , Cras Louise , Schiettecatte Ann , Jonckheere Jan , van Grunsven Leo A. , Vanhoeij Marian , Thielemans Kris , Breckpot Karine
Published: February 2022

Scoring of tumor-infiltrating lymphocytes (TILs) in breast cancer specimens has gained increasing attention, as TILs have prognostic and predictive value in HER2+ and triple-negative breast cancer. We evaluated the intra- and interrater variability when scoring TILs by visual inspection of hematoxylin and eosin-stained tissue sections. We further addressed whether immunohistochemical staining of these sections for immune cell surface markers CD45, CD3, CD4, and CD8 and combination with nanoString nCounter® gene expression analysis could refine TIL scoring. Formalin-fixed paraffin-embedded and fresh-frozen core needle biopsies of 12 female and treatment-naive breast cancer patients were included. Scoring of TILs was performed twice by three independent pathologists with a washout period of 3 days. Increasing intra- and interrater variability was observed with higher TIL numbers. The highest reproducibility was observed on tissue sections stained for CD3 and CD8. The latter TIL scores correlated well with the TIL scores obtained through nanoString nCounter® gene expression analysis. Gene expression analysis also revealed 104 and 62 genes that are positively and negatively related to both TIL scores. In conclusion, integration of immunohistochemistry and gene expression analysis is a valuable strategy to refine TIL scoring in breast tumors.
Ionizing Radiation Technologies for Vaccine Development - A Mini Review
Authors: Bhatia Sohini S. , Pillai Suresh D.
Published: February 2022

Given the current pandemic the world is struggling with, there is an urgent need to continually improve vaccine technologies. Ionizing radiation technology has a long history in the development of vaccines, dating back to the mid-20th century. Ionizing radiation technology is a highly versatile technology that has a variety of commercial applications around the world. This brief review summarizes the core technology, the overall effects of ionizing radiation on bacterial cells and reviews vaccine development efforts using ionizing technologies, namely gamma radiation, electron beam, and X-rays.
Ginsenosides Regulates Innate Immunity to Affect Immune Microenvironment of AIH Through Hippo-YAP/TAZ Signaling Pathway
Authors: Zhang Kehui , Li Jiacheng , Shi Zhe , Zhu Yingying , Yang Jing , Liu Xiaolin , Que Renye , Lin Liubing , Chen Yirong , Li Yong
Published: February 2022

Autoimmune hepatitis (AIH) is characterized by chronic progressive liver inflammatory, but there is still no safe and effective medicine. Therefore, glucocorticoid remains the top choice for AIH treatment. In previous studies, it has been confirmed that ginsenosides (GSS) can produce glucocorticoid-like effects and therapeutic effects on various autoimmune diseases. However, the mechanism of GSS for AIH remains unclear. As an important part of the innate immune system, bone marrow-derived suppressor cells (MDSC) have been identified as an important driver of follow-up acquired immune response in many autoimmune diseases, including AIH. Herein, it was found out that GSS intervention can be effective in regulating the immune microenvironment and liver impairment induced by Con A in AIH mice. In vitro, the MDSCs derived from healthy mice and the T cells deried from AIH mice were co-cultured. Then, different drugs were intervened with to explore the therapeutic mechanism. Besides, the proliferation and differentiation of MDSCs and T cells were analyzed by flow cytometry, while GR, Hippo-YAP signal pathway and the expression of MDSC-related genes and proteins were detected through qRT-PCR and Western Blot. The changes in NO and ROS levels were further analyzed. The trend of related cytokines expression (IFN- γ, TGF- β, IL-10, IL-6, IL-17) was detected by ELISA. Furthermore, an analysis was conducted as to the ALT and liver pathology of mice for evaluating the liver function of mice. It was discovered that MDSCs proliferation was inhibited, and that T cells tended to differentiate into Th17 rather than Treg in AIH mice. Moreover, the intervention of GSS activated GR and Yap, in addition to promoting the proliferation of MDSCs, especially M-MDSCs. This further promoted the differentiation of Treg to enable immune tolerance, thus alleviating liver impairment. Therefore, it was proposed that GSS can alleviate AIH by modulating the innate immunity and adaptive T cell immunity, which may be the underlying mechanism for GSS to mitigate the liver impairment induced by AIH.
Detection of Khapra Beetle Environmental DNA Using Portable Technologies in Australian Biosecurity
Authors: Trujillo-González Alejandro , Thuo David N. , Divi Uday , Sparks Kate , Wallenius Thomas , Gleeson Dianne
Published: February 2022

Khapra beetle, Trogoderma granarium Everts, 1898, is a serious pest of stored grain products globally. Environmental DNA (eDNA)-based methods offer sensitive detection tools used to inform biosecurity officers on the presence of high-risk pests. This study tested laboratory and portable molecular technologies to detect khapra beetle environmental DNA extracted from dust samples collected during biosecurity responses (Tuggeranong and Fyshwick) to khapra beetle incursions in Australia. Airborne and floor dust samples were collected opportunistically using handheld vacuum cleaners and eDNA was extracted using either field or laboratory-based extraction methods and analyzed using laboratory benchtop real time PCR machines and portable machines with two TaqMan and one LAMP-based assay. We successfully collected, extracted, and amplified khapra beetle eDNA from dust samples by qPCR, but failed to amplify T. granarium eDNA using LAMP. The Laboratory qPCR machine showed significantly higher mean Ct values (p < 0.001) and significantly higher positive detections for both assays (p < 0.001) compared to the portable thermocycler. DNA yield was significantly higher in samples extracted using laboratory-based kits compared to field kits (p < 0.001) for both vacuumed and airborne samples (Mean DNA ± S.D. = 5.52 ± 4.45 and 4.77 ± 1.68 ng/μL, respectively), compared to field kits, (1.75 ± 1.17 and 1.36± 1.29 ng/μL for vacuumed and airborne samples, respectively). There were no significant differences in DNA yield between collection methods or differences in amplification associated to extraction or collection methods in either platform tested in this study. Portable technologies tested in this study (Franklin™ Real Time Thermocycler and Genie III) accurately amplified all tissue derived DNA during assay optimisation and field testing, highlighting the capacity of these technologies to complement biosecurity in confirming specimen ID. There was a high incidence of positive detections in field negative controls (Tuggeranong = 12.3 % and Fyshwick = 50 %), mostly attributed to the use of contaminated vacuum cleaners. We discuss suitable methods to minimize sample cross-contamination, the potential of portable molecular technologies as tools for biosecurity applications, and the suitability of eDNA-based molecular detection methods to complement global trade biosecurity for one of the most invasive and important grain pests worldwide.
Lizards Are Important Hosts for Zoonotic Flavivirus Vectors, Subgenus Culex, in the Southern USA
Authors: Reeves Lawrence E. , Burkett-Cadena Nathan D.
Published: February 2022

Host association is among the most important factors that drive the transmission dynamics of mosquito-vectored pathogens. Competent vectors that feed exclusively upon non-competent hosts will not transmit pathogens, and highly competent hosts that are not bitten by competent vectors will not contribute to pathogen amplification. Therefore, characterizing the blood-feeding ecology of vector mosquitoes is critical to understanding how zoonotic pathogens amplify within ecosystems and spillover to humans and domesticated animals. In North America, mosquito species of the subgenus Culex are considered the most important vectors of zoonotic Flaviviruses, particularly West Nile virus (WNV), St. Louis encephalitis virus (SLEV), and western equine encephalitis virus. Many species of the Culex subgenus Culex are thought to feed predominantly upon birds and mammals, a behavior that facilitates the amplification and spillover of these zoonotic pathogens. Much of our understanding of the host associations of Culex vectors is based on research conducted in the 1960s and 1970s that used serological methods to infer host group(s). Here we reevaluate host associations of six Culex species from the southern US (Florida and Arizona) using DNA barcoding-based blood meal analysis. Our results demonstrate that reptiles, particularly lizards, constitute an important, and previously underappreciated, group of vertebrate hosts for several subgenus Culex mosquitoes. In Florida, >25% of Culex nigripalpus blood meals were derived from lizards (mainly Anolis spp.), and reptile host use generally increased from north to south with ~10%, ~25% and ~60% of Cx. nigripalpus blood meals derived from reptiles in northern, central, and southern Florida, respectively. In southern Arizona, lizards (mainly Sceloporus spp. and Urosaurus ornatus) constituted 40-45% of blood meals of Culex tarsalis, Culex thriambus, and Culex stigmatosoma. Other species of the subgenus Culex, including Culex quinquefasciatus, were not found to feed upon reptiles at the same sites, suggesting host association variation within Culex subgenus Culex. Whether or not lizards contribute to or dilute amplification of zoonotic Flaviviruses depends upon host competency of the lizard species bitten for WNV and SLEV. To date, very few studies have evaluated host competence of lizards for these viruses, so their roles in transmission cycles of zoonotic Flaviviruses remains obscure.
Development of a Binary Digestion System for Extraction Microplastics in Fish and Detection Method by Optical Photothermal Infrared
Authors: Yan Feifei , Wang Xiaochen , Sun Haoran , Zhu Zixian , Sun Weihong , Shi Xiangli , Zhang Jinpeng , Zhang Ling , Wang Xiaofeng , Liu Mengyang , Cai Minggang , Zhang Ying
Published: February 2022

Accumulating evidence indicates that aquatic organisms ingest microplastics (MPs), which may be a threat to essentially the entire global ecosystem. In current detection methods, even in cutting-edge nanoplastic technology, a major challenge for detecting microplastics (MPs) in aquatic organisms is removing complex biological matrices, such as fat. Herein we report combining HNO3 and H2O2 to form a binary digestive reagent system to determine MPs in biological tissue. With insights obtained from a Gaussian model, the adding manners of two reagents were discussed. Thus, in the final protocol, we mixed MPs and tissue with 20 mL of 30% (v/v) aqueous H2O2, 10 mL 0.5 M NaOH,1 mL 5 mM Fe2+, and 40 mL 11.5% (v/v) aqueous HNO3, in sequence at different time intervals. What’s more, sodium dodecyl sulfate (SDS) and ultrasound—alone or together—were explored to solve the problem of removing fat residues and thus membrane blockage during filtration. In this paper, we used the O-PTIR microscope to verify the feasibility of the protocol. Compared with traditional detection methods, the O-PTIR spectroscopy can significantly improve the lateral resolution, down to sub and super-micrometer, and the ability to quickly obtain high spatial resolution far-field non-contact infrared spectra, which provide a novel method for qualitative analysis of MPs. In field applications, in our attempt, the fixed wavenumber image by O-PTIR can realize sub and super-micrometer MPs in situ, far-field measurements. The present method is highly efficient, and facilitates the identification of plastic particles.
Publication Trends for Sarcopenia in the World: A 20-Year Bibliometric Analysis
Authors: Yuan Dongliang , Jin Hongfu , Liu Qianqi , Zhang Jinglve , Ma Boyan , Xiao Wenfeng , Li Yusheng
Published: February 2022

Background

Sarcopenia, an age-related degenerative disease, seriously affects the health and quality of life of the elder. The research of sarcopenia has changed dramatically around the world. This article aims to analyze global trends in this field over the past 20 years.

Methods

“Sarcopenia” was used as the search term to retrieve relevant publications from the WOS and PubMed databases. Co-occurrence, literature coupling, co-citation, and co-author analysis were performed by using the software VOS viewer. We analyzed the trends of sarcopenia research over the last 20 years from different aspects, such as the number of papers, total citations, average citations per item, h-index, research area, article types, institutions, country, journals, and funding.

Results

We retrieved 13,421 research articles published on sarcopenia between 2001 and 2020. The results showed that the USA made the highest contributions to this field. Geriatrics gerontology is the most study classification of sarcopenia. Basic research on sarcopenia in geriatric gerontology accounts for approximately 16.496% of global publications. The Osteoporosis International published the largest number of sarcopenia-related studies. The United States Department of Health Human Services was the leading funding organization, which sponsored 1,604 articles.

Conclusion

Global sarcopenia research increased rapidly from 2001 to 2020, especially recently. The research leader of sarcopenia is the USA. In the future, the study of sarcopenia will continue to focus on aging, nutrition, and exercise and will delve deeper into molecular mechanisms. On the other hand, revealing the link between sarcopenia and other diseases will be the next research hotspot.
Clinical Features, Diagnostic Test Performance, and Prognosis in Different Subtypes of Chronic Pulmonary Aspergillosis
Authors: Zhong Huanhuan , Wang Yaru , Gu Yu , Ni Yueyan , Wang Yu , Shen Kunlu , Shi Yi , Su Xin
Published: February 2022

Objective

The aim of this study was to describe clinical features in different subtypes of chronic pulmonary aspergillosis (CPA)-simple aspergilloma (SA), chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrosing pulmonary aspergillosis (CFPA), aspergillus nodule (AN), and subacute invasive aspergillosis (SAIA), respectively, and identify long-term prognosis of CPA.

Methods

We reviewed patients diagnosed with different subtypes of CPA from 2002 to 2020 at Nanjing Jinling Hospital, China. We analyzed the clinical and survival information of five different subgroups. A Cox regression model was used to explore proper antifungal duration and long-term survival factors of CCPA and SAIA.

Results

A total of 147 patients with CPA were included, consisting of 11 SA, 48 CCPA, 5 CFPA, 12 AN, and 71 SAIA. The most common underlying pulmonary disease was pulmonary tuberculosis (n = 49, 33%), followed by bronchiectasis (n = 46, 31.3%) and chronic obstructive pulmonary disease (COPD) or emphysema (n = 45, 30.6%), while in SAIA and CFPA groups, the most common was COPD or emphysema (45.1 and 100%). Cough (85%), expectoration (70.7%), hemoptysis (54.4%), and fever (29.9%) were common symptoms, especially in CCPA, CFPA, and SAIA groups. The common imaging manifestations included cavitation (n = 94, 63.9%), fungal ball (n = 54, 36.7%), pleural thickening (n = 47, 32.0%), and bronchiectasis (n = 46, 31.3%). SAIA and CFPA groups had a lower value of hemoglobin (HB) and serum albumin (ALB) with higher C-reactive protein and erythrocyte sedimentation rate. The positive rate of sputum culture, serum galactomannan (GM), and bronchoalveolar lavage fluid GM was 32.7% (36/110), 18.4% (18/98), and 48.7% (19/39), respectively. There were 64.6% (31/48) patients with CCPA and 25.4% (18/71) patients with SAIA who received surgery and the 5-year cumulative survival rate was 92.1 and 66.6%, respectively. SAIA, old age, male, low body mass index (BMI), COPD or emphysema, multiple distribution, low serum ALB, and positive sputum culture were adverse prognosis factors for SAIA and CCPA group, and BMI ≤ 20.0 kg/m2 was independently associated with increased mortality (hazard ratio (HR) 5.311, 95% CI 1.405–20.068, p = 0.014). Multivariable Cox regression indicated that surgery (HR 0.093, 95% CI 0.011–0.814, p = 0.032) and antifungal duration >6 months (HR 0.204, 95% CI 0.060–0.696 p = 0.011) were related to improved survival.

Conclusion

The clinical features and laboratory test performance are different among SA, CCPA, CFPA, AN, and SAIA. Low BMI was an independent risk factor for survival. Selective surgery and antifungal duration over 6 months were associated with improved survival.
Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis
Authors: Gavrielatou Evdokia , Xourgia Eleni , Xixi Nikoleta A. , Mantelou Athina G. , Ischaki Eleni , Kanavou Aggeliki , Zervakis Dimitris , Routsi Christina , Kotanidou Anastasia , Siempos Ilias I.
Published: February 2022

Background

Whether vitamin C provides any benefit when administered in critically ill patients, including those with coronavirus disease (COVID-19), is controversial. We endeavored to estimate the effect of administration of vitamin C on clinical outcomes of critically ill patients with COVID-19 by performing an observational study and subsequent meta-analysis.

Methods

Firstly, we conducted an observational study of critically ill patients with laboratory-confirmed COVID-19 who consecutively underwent invasive mechanical ventilation in an academic intensive care unit (ICU) during the second pandemic wave. We compared all-cause mortality of patients receiving vitamin C (“vitamin C” group) or not (“control” group) on top of standard-of-care. Subsequently, we systematically searched PubMed and CENTRAL for relevant studies, which reported on all-cause mortality (primary outcome) and/or morbidity of critically ill patients with COVID-19 receiving vitamin C or not treatment. Pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO.

Results

In the observational study, baseline characteristics were comparable between the two groups. Mortality was 20.0% (2/10) in the vitamin C group vs. 47.6% (49/103; p = 0.11) in the control group. Subsequently, the meta-analysis included 11 studies (6 observational; five randomized controlled trials) enrolling 1,807 critically ill patients with COVID-19. Mortality of patients receiving vitamin C on top of standard-of-care was not lower than patients receiving standard-of-care alone (25.8 vs. 34.7%; RR 0.85, 95% CI 0.57–1.26; p = 0.42).

Conclusions

After combining results of our observational cohort with those of relevant studies into a meta-analysis of data from 1,807 patients, we found that administration vitamin C as opposed to standard-of-care alone might not be associated with lower of mortality among critically ill patients with COVID-19. Additional evidence is anticipated from relevant large randomized controlled trials which are currently underway.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42021276655.
Comparison of Volumetric Quantitative PET Parameters Before and After a CT-Based Elastic Deformation on Dual-Time 18FDG-PET/CT Images: A Feasibility Study in a Perspective of Radiotherapy Planning in Head and Neck Cancer
Authors: Maajem Meriem , Leclère Jean-Christophe , Bourhis David , Tissot Valentin , Icard Nicolas , Arnaud Laëtitia , Le Pennec Romain , Dissaux Gurvan , Gujral Dorothy M. , Salaün Pierre-Yves , Schick Ulrike , Abgral Ronan
Published: February 2022

Background

The use of 18FDG-PET/CT for delineating a gross tumor volume (GTV, also called MTV metabolic tumor volume) in radiotherapy (RT) planning of head neck squamous cell carcinomas (HNSCC) is not included in current recommendations, although its interest for the radiotherapist is of evidence. Because pre-RT PET scans are rarely done simultaneously with dosimetry CT, the validation of a robust image registration tool and of a reproducible MTV delineation method is still required.

Objective

Our objective was to study a CT-based elastic registration method on dual-time pre-RT 18FDG-PET/CT images to assess the feasibility of PET-based RT planning in patients with HNSCC.

Methods

Dual-time 18FDG-PET/CT [whole-body examination (wbPET) + 1 dedicated step (headPET)] were selected to simulate a 2-times scenario of pre-RT PET images deformation on dosimetry CT. ER-headPET and RR-headPET images were, respectively, reconstructed after CT-to-CT rigid (RR) and elastic (ER) registrations of the headPET on the wbPET. The MTVs delineation was performed using two methods (40%SUVmax, PET-Edge). The percentage variations of several PET parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG) were calculated between wbPET, ER-headPET, and RR-headPET. Correlation between MTV values was calculated (Deming linear regression). MTVs intersections were assessed by two indices (OF, DICE) and compared together (Wilcoxon test). Additional per-volume analysis was evaluated (Mann-Whitney test). Inter- and intra-observer reproducibilities were evaluated (ICC = intra-class coefficient).

Results

36 patients (30M/6F; median age = 65 y) were retrospectively included. The changes in SUVmax, SUVmean and SUVpeak values between ER-headPET and RR-headPET images were <5%. The variations in MTV values between ER-headPET and wbPET images were −6 and −3% with 40%SUVmax and PET Edge, respectively. Their correlations were excellent whatever the delineation method (R2 > 0.99). The ER-headPET MTVs had significant higher mean OF and DICE with the wbPET MTVs, for both delineation methods (p ≤ 0.002); and also when lesions had a volume > 5cc (excellent OF = 0.80 with 40%SUVmax). The inter- and intra-observer reproducibilities for MTV delineation were excellent (ICC ≥ 0.8, close to 1 with PET-Edge).

Conclusion

Our study demonstrated no significant changes in MTV after an elastic deformation of pre-RT 18FDG-PET/CT images acquired in dual-time mode. This opens possibilities for HNSCC radiotherapy planning improvement by transferring GTV-PET on dosimetry CT.
Freshwater Microbial Eukaryotic Core Communities, Open-Water and Under-Ice Specialists in Southern Victoria Island Lakes (Ekaluktutiak, NU, Canada)
Authors: Potvin Marianne , Rautio Milla , Lovejoy Connie
Published: February 2022

Across much of the Arctic, lakes and ponds dominate the landscape. Starting in late September, the lakes are covered in ice, with ice persisting well into June or early July. In summer, the lakes are highly productive, supporting waterfowl and fish populations. However, little is known about the diversity and ecology of microscopic life in the lakes that influence biogeochemical cycles and contribute to ecosystem services. Even less is known about the prevalence of species that are characteristic of the seasons or whether some species persist year-round under both ice cover and summer open-water conditions. To begin to address these knowledge gaps, we sampled 10 morphometrically diverse lakes in the region of Ekaluktutiak (Cambridge Bay), on southern Victoria Island (NU, Canada). We focused on Greiner Lake, the lakes connected to it, isolated ponds, and two nearby larger lakes outside the Greiner watershed. The largest lakes sampled were Tahiryuaq (Ferguson Lake) and the nearby Spawning Lake, which support commercial sea-run Arctic char (Salvelinus alpinus) fisheries. Samples for nucleic acids were collected from the lakes along with limnological metadata. Microbial eukaryotes were identified with high-throughput amplicon sequencing targeting the V4 region of the 18S rRNA gene. Ciliates, dinoflagellates, chrysophytes, and cryptophytes dominated the lake assemblages. A Bray–Curtis dissimilarity matrix separated communities into under-ice and open-water clusters, with additional separation by superficial lake area. In all, 133 operational taxonomic units (OTUs) occurred either in all under-ice or all open-water samples and were considered “core” microbial species or ecotypes. These were further characterized as seasonal indicators. Ten of the OTUs were characteristic of all lakes and all seasons sampled. Eight of these were cryptophytes, suggesting diverse functional capacity within the lineage. The core open-water indicators were mostly chrysophytes, with a few ciliates and uncharacterized Cercozoa, suggesting that summer communities are mixotrophic with contributions by heterotrophic taxa. The core under-ice indicators included a dozen ciliates along with chrysophytes, cryptomonads, and dinoflagellates, indicating a more heterotrophic community augmented by mixotrophic taxa in winter.
Local Habitat Filtering Shapes Microbial Community Structure in Four Closely Spaced Lakes in the High Arctic
Authors: Marois Catherine , Girard Catherine , Klanten Yohanna , Vincent Warwick F. , Culley Alexander I. , Antoniades Dermot
Published: February 2022

Arctic lakes are experiencing increasingly shorter periods of ice cover due to accelerated warming at northern high latitudes. Given the control of ice cover thickness and duration over many limnological processes, these changes will have pervasive effects. However, due to their remote and extreme locations even first-order data on lake ecology is lacking for many ecosystems. The aim of this study was to characterize and compare the microbial communities of four closely spaced lakes in Stuckberry Valley (northern Ellesmere Island, Canadian Arctic Archipelago), in the coastal margin zone of the Last Ice Area, that differed in their physicochemical, morphological and catchment characteristics. We performed high-throughput amplicon sequencing of the V4 16S rRNA gene to provide inter- and intra-lake comparisons. Two deep (>25 m) and mostly oxygenated lakes showed highly similar community assemblages that were distinct from those of two shallower lakes (<10 m) with anoxic bottom waters. Proteobacteria, Verrucomicrobia, and Planctomycetes were the major phyla present in the four water bodies. One deep lake contained elevated proportions of Cyanobacteria and Thaumarchaeota that distinguished it from the others, while the shallow lakes had abundant communities of predatory bacteria, as well as microbes in their bottom waters that contribute to sulfur and methane cycles. Despite their proximity, our data suggest that local habitat filtering is the primary determinant of microbial diversity in these systems. This study provides the first detailed examination of the microbial assemblages of the Stuckberry lakes system, resulting in new insights into the microbial ecology of the High Arctic.
Ecological Interactions of Cyanobacteria and Heterotrophs Enhances the Robustness of Cyanobacterial Consortium for Carbon Sequestration
Authors: Ataeian Maryam , Liu Yihua , Kouris Angela , Hawley Alyse K. , Strous Marc
Published: February 2022

Lack of robustness is a major barrier to foster a sustainable cyanobacterial biotechnology. Use of cyanobacterial consortium increases biodiversity, which provides functional redundancy and prevents invading species from disrupting the production ecosystem. Here we characterized a cyanobacterial consortium enriched from microbial mats of alkaline soda lakes in BC, Canada, at high pH and alkalinity. This consortium has been grown in open laboratory culture for 4 years without crashes. Using shotgun metagenomic sequencing, 29 heterotrophic metagenome-assembled-genomes (MAGs) were retrieved and were assigned to Bacteroidota, Alphaproteobacteria, Gammaproteobacteria, Verrucomicrobiota, Patescibacteria, Planctomycetota, and Archaea. In combination with metaproteomics, the overall stability of the consortium was determined under different cultivation conditions. Genome information from each heterotrophic population was investigated for six ecological niches created by cyanobacterial metabolism and one niche for phototrophy. Genome-resolved metaproteomics with stable isotope probing using 13C-bicarbonate (protein/SIP) showed tight coupling of carbon transfer from cyanobacteria to the heterotrophic populations, specially Wenzhouxiangella. The community structure was compared to a previously described consortium of a closely related cyanobacteria, which indicated that the results may be generalized. Productivity losses associated with heterotrophic metabolism were relatively small compared to other losses during photosynthesis.
Marked Response of Rat Ileal and Colonic Microbiota After the Establishment of Alzheimer’s Disease Model With Bilateral Intraventricular Injection of Aβ (1-42)
Authors: Xu Qing , Wen Lingmiao , Wei Guihua , Zhao Xiaoqin , Liu Yanjun , Xiong Wei , Zhang Tinglan , Fan Yuqing , Chen Chunlan , Xiang Chunxiao , Chen Chang , Chen Yunhui , Yin Qiaozhi , Zhang Tian-e , Yan Zhiyong
Published: February 2022

Alzheimer’s disease (AD) is a common neurodegenerative disease. More evidence has shown that gut microbiota is closely associated with AD. Also, studies have shown that the distribution of gut microbiota vary in different sections of the intestine. In this study, a rat model of AD was established using a bilateral intraventricular injection of β-amyloid (1-42) [Aβ (1-42)], and the behavior of rats, hippocampal Aβ (1-42) deposition, and the ileal and colonic microbiota in each group were analyzed. We observed that the model rats had obvious memory and cognitive impairment, increased Aβ (1-42) deposition, indicating that the AD model was successfully established. Through 16S rRNA-sequencing analysis, we found that α diversity, β diversity, and dominant microbiota in the ileum and colon of normal rats were significantly different, showing spatial heterogeneity. Additionally, the surgery and injection of Aβ (1-42) caused various degrees of disturbances in the ileal and colonic microbiota of rats. These findings provide new insights for the study of the gut microbiota of AD rats and help advance the development of therapeutic strategies for intervening AD through the gut microbiota.
Meningitic Escherichia coli-Induced Interleukin-17A Facilitates Blood–Brain Barrier Disruption via Inhibiting Proteinase 3/Protease-Activated Receptor 2 Axis
Authors: Xu Bojie , Chen Jiaqi , Fu Jiyang , Yang Ruicheng , Yang Bo , Huo Dong , Tan Chen , Chen Huanchun , Wang Xiangru
Published: February 2022

Bacterial meningitis is a life-threatening infectious disease with high morbidity and mortality worldwide, among which meningitic Escherichia coli is a common Gram-negative pathogenic bacterium causing meningitis. It can penetrate the blood–brain barrier (BBB), invoke local inflammatory responses and consequently disrupt the integrity of the BBB. Interleukin-17A (IL-17A) is recognized as a pro-inflammatory cytokine that is released during meningitic E. coli infection. It has been reported that IL-17A is involved in several pathological tissue injuries. However, the function of IL-17A in BBB breakdown remains rarely discussed. Here, our study found that E. coli-induced IL-17A led to the degradation of tight junction proteins (TJs) and adherens junction proteins (AJs) in human brain microvascular endothelial cells (hBMECs) through inhibiting protease proteinase 3 (PRTN3)/protease-activated receptor 2 (PAR-2) axis, thus increasing the permeability of BBB. In summary, this study uncovered the involvement of IL-17A in regulating BBB integrity and proposed a novel regulatory mechanism, which could be potential therapeutic targets of E. coli meningitis.
A Simplified Plasticity Model Based on Synaptic Tagging and Capture Theory: Simplified STC
Authors: Ding Yiwen , Wang Ye , Cao Lihong
Published: February 2022

The formation and consolidation of memory play a vital role for survival in an ever-changing environment. In the brain, the change and stabilization of potentiated and depressed synapses are the neural basis of memory formation and maintenance. These changes can be induced by rather short stimuli (only a few seconds or even less) but should then be stable for months or years. Recently, the neural mechanism of conversion from rapid change during the early phase of synaptic plasticity into a stable memory trace in the late phase of synaptic plasticity is more and more clear at the protein and molecular levels, among which synaptic tagging and capture (STC) theory is one of the most popular theories. According to the STC theory, the change and stabilization of synaptic efficiency mainly depend on three processes related to calcium concentration, including synaptic tagging, synthesis of plasticity-related product (PRP), and the capture of PRP by tagged synapse. Based on the STC theory, several computational models are proposed. However, these models hardly take simplicity and biological interpretability into account simultaneously. Here, we propose a simplified STC (SM-STC) model to address this issue. In the SM-STC model, the concentration of calcium ion in each neuronal compartment and synapse is first calculated, and then the tag state of synapse and PRP are updated, and the coupling effect of tagged synapse and PRP is further considered to determine the plasticity state of the synapse, either potentiation or depression. We simulated the Schaffer collaterals pathway of the hippocampus targeting a multicompartment CA1 neuron for several hours of biological time. The results show that the SM-STC model can produce a broad range of experimental phenomena known in the physiological experiments, including long-term potentiation induced by high-frequency stimuli, long-term depression induced by low-frequency stimuli, and cross-capture with two stimuli separated by a delay. Thus, the SM-STC model proposed in this study provides an effective learning rule for brain-like computation on the premise of ensuring biological plausibility and computational efficiency.
A Transvenous Endovascular Approach in Straight Sinus Has Minor Impacts on Chordae Willisii
Authors: Ye Yuanliang , Ding Jiuyang , Liu Shoutang , Lan Tiancai , Chen Long , Wang Yingxue , Xia Bing , Yang Jianqing
Published: February 2022

Cerebral dural sinuses contain different types of chordae willisii (CW). The transvenous endovascular approach, which has become an optimal method for the treatment of cerebrovascular diseases, such as malformation, fistula, and chronic intracranial hypertension, due to sinus thromboses, frequently uses retrograde navigation through dural sinuses. Whether or how much the endoscopic procedure damages the chordae willisii is often not well-assessed. In our study, an overall number of 38 cadaveric heads were analyzed for the distribution and features of the chordae willisii in the straight sinus. We used an endoscope on these samples mimicking a mechanical thrombectomy procedure performed in the straight sinus. Both endoscopic gross observation and light microscopic histological examination were used to assess the damages to the chordae willisii by the procedure. We found that the valve-like lamellae and longitudinal lamellae structures were mainly found in the posterior part of straight sinus whereas trabeculae were present in both anterior and posterior portions. We treated a group of samples with a stent and another with a balloon. The stent-treated group had a significantly higher rate of Grade 1 damage comparing with the balloon-treated group (p = 0.02). The incidence of damage to the surface of chordae willisii was also higher in the stent-treated group (p = 0.00). Neither the use of stent nor of balloon increased the rate of damage to chordae willisii during repeated experiments. These findings indicated that stent or balloon navigation through the straight sinus can cause minor damages to the chordae willisii and frequent uses of retrograde navigation through the straight sinus do not appear to increase the rates of damage to chordae willisii.
Pre-Existing Non-Disabling Encephalomalacia Confers Risk to Stroke Outcomes After Endovascular Treatment
Authors: Li Zibao , Li Qiang , Ji Yachen , Chu Zhaohu , Zhao Shoucai , Ma Lingsong , Zhou Zhiming , Yang Qian , Huang Xianjun
Published: February 2022

Background

Patients with previous stroke episodes tend to have poor outcomes after an endovascular treatment (EVT). Encephalomalacia (EM) is an objective indicator of previous strokes but has not been systematically investigated. The fundamental aim of this exploration is to investigate the effects of a pre-existing non-disabling EM on clinical outcomes after EVT.

Methods

Consecutive patients undergoing an EVT due to the anterior circulation large vessel occlusion (LVO) strokes were enrolled in the study. The pre-existing EM was defined as the focal hypodense lesions (≥ 3 mm in maximum diameter) on a non-contrast cranial CT using axial images before EVT. The primary outcome was the 90-day functional assessment using the modified Rankin Scale (mRS) score. The safety outcome was the incidence of symptomatic intracranial hemorrhage (sICH) defined as any hemorrhage within 24 h after an EVT, which is responsible for an increase of ≥ 4 points in the score of National Institutes of Health Stroke Scale (NIHSS).

Results

Of the 433 patients analyzed in this investigation, a pre-existing non-disabling EM was observed in 106 (24.5%) patients. After adjusting for potential confounding factors, patients with contralateral EM (OR = 2.68, 95% CI = 1.13–6.31; P = 0.025) and with an EM+ > 20 mm in maximum diameter (OR = 2.21, 95% CI = 1.01–4.85; P =0.048) were substantially associated with unfavorable outcomes (mRS > 2). For the sICH, we did not observe any association with the pre-existing EM (P > 0.05).

Conclusions

A pre-existing non-disabling EM is common and safe in patients undergoing EVT. However, a contralateral EM and the large size of EM may predict an unfavorable outcome at 90 days, which should receive more attention before EVT.
Experimental Exploration of Objective Human Pain Assessment Using Multimodal Sensing Signals
Authors: Lin Yingzi , Xiao Yan , Wang Li , Guo Yikang , Zhu Wenchao , Dalip Biren , Kamarthi Sagar , Schreiber Kristin L. , Edwards Robert R. , Urman Richard D.
Published: February 2022

Optimization of pain assessment and treatment is an active area of research in healthcare. The purpose of this research is to create an objective pain intensity estimation system based on multimodal sensing signals through experimental studies. Twenty eight healthy subjects were recruited at Northeastern University. Nine physiological modalities were utilized in this research, namely facial expressions (FE), electroencephalography (EEG), eye movement (EM), skin conductance (SC), and blood volume pulse (BVP), electromyography (EMG), respiration rate (RR), skin temperature (ST), blood pressure (BP). Statistical analysis and machine learning algorithms were deployed to analyze the physiological data. FE, EEG, SC, BVP, and BP proved to be able to detect different pain states from healthy subjects. Multi-modalities proved to be promising in detecting different levels of painful states. A decision-level multi-modal fusion also proved to be efficient and accurate in classifying painful states.
Evolution of Milk Consumption and Its Psychological Determinants: A Mini-Review
Authors: Castellini Greta , Graffigna Guendalina
Published: February 2022

The consumption of lactose-free products and in particular lactose-free milk is increasing worldwide. Although many studies claim that this dietary trend is mainly determined by the number of lactose intolerant people that is growing, others state that most of them self-report an intolerance that has not been diagnosed by medical tests. However, many researchers reported that the consumption of lactose-free milk may put the consumers' health at risk especially when the subjects are not intolerant. Consequently, understanding this new dietary trend considering its main determinants it is necessary to generate educational and intervention campaigns useful to guide people toward healthier and more adequate eating styles. For these reasons we conducted a narrative mini review to summarize the factors contributing to the consumption of lactose-free milk as an alternative to cow's milk, exploring intrinsic and extrinsic product characteristics, biological and physiological, as well as psychological, situational and socio-cultural factors. This narrative mini-review shows that there are six categories of factors that affect the consumption of lactose-free milk. In particular, the intrinsic aspects linked to the product and the socio-demographic characteristics of the consumer are the most explored. On the contrary, situational and socio-cultural factors are the least studied. Finally, this study argues that there are too few studies that investigates the emotional, identity and social aspects underlying these food choices, suggesting the development of future research that investigate the implicit consumer subjective levers to decipher lactose-free milk consumptions.
Derived Neutrophil-to-Lymphocyte Ratio Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Ocaña Alberto , Chacón Jose Ignacio , Calvo Lourdes , Antón Antonio , Mansutti Mauro , Albanell Joan , Martínez María Teresa , Lahuerta Ainhara , Bisagni Giancarlo , Bermejo Begoña , Semiglazov Vladimir , Thill Marc , Chan Arlene , Morales Serafin , Herranz Jesús , Tusquets Ignacio , Chiesa Massimo , Caballero Rosalía , Valagussa Pinuccia , Bianchini Giampaolo , Alba Emilio , Gianni Luca
Published: February 2022

Background

Derived neutrophil-to-lymphocyte ratio (dNLR) is a biomarker associated with clinical outcome in breast cancer (BC). We analyzed the association of dNLR with pathological complete response (pCR) in triple-negative BC (TNBC) patients receiving neoadjuvant chemotherapy (CT).

Methods

This is a retrospective analysis of two randomized studies involving early stage/locally advanced TNBC patients receiving anthracycline/taxane-based CT+/−carboplatin (GEICAM/2006-03) or nab-paclitaxel/paclitaxel followed by anthracycline regimen (ETNA). dNLR was calculated as the ratio of neutrophils to the difference between total leukocytes and neutrophils in peripheral blood before CT (baseline) and at the end of treatment (EOT). Logistic regression analyses were used to explore dNLR association with pCR.

Results

In total, 308 TNBC patients were analyzed, 216 from ETNA and 92 from GEICAM/2006-03. Baseline median dNLR was 1.61 (interquartile range (IQR): 1.25–2.04) and at EOT 1.53 (IQR: 0.96–2.22). Baseline dNLR showed positive correlation with increased tumor size (p-value = 1e−04). High baseline dNLR, as continuous variable or using median cutoff, was associated with lower likelihood of pCR in univariate analysis. High EOT dNLR as continuous variable or using quartiles was also associated with lower pCR rate in uni- and multivariate analyses.

Conclusions

High baseline and EOT dNLR correlates with lower benefit from neoadjuvant CT in TNBC.
Elevated Levels of Soluble CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3 and Systemic Inflammatory Stress as Potential Contributors to Immune Suppression and Generalized Tumorigenesis in a Cohort of South African Xeroderma Pigmentosum Patients
Authors: Kgokolo Mahlatse C. M. , Anderson Katherine , Siwele Shalate C. , Steel Helen C. , Kwofie Luyanda L. I. , Sathekge Mike M. , Meyer Pieter W. A. , Rapoport Bernardo L. , Anderson Ronald
Published: February 2022

Xeroderma Pigmentosum (XP), an autosomal recessive disorder characterized by ultraviolet radiation-induced abnormalities of DNA excision and repair pathways is associated with early development of cutaneous cancers. Intracellular oxidative stress has also been proposed as a contributor to the occurrence of skin cancers. However, little is known about the possible augmentative contributions of chronic inflammation, immune suppression and oxidative stress to the pathogenesis of malignancies associated with other subtypes of XP. This has been addressed in the current study, focused on the measurement of systemic biomarkers of inflammation, immune dysfunction and oxidative damage in XP patients, consisting of XP-C, XP-D and XP-E cases, including those XP-C cases who had already developed multiple skin malignancies. The inflammatory biomarker profile measured in XP patients and healthy control subjects included the cytokines, interleukins (ILs)-2, -4, -6, -10, interferon-γ (IFN- γ) and tumor-necrosis factor-α (TNF-α), the acute phase reactant, C-reactive protein (CRP), and cotinine (as an objective indicator of smoking status). Immune suppression was detected according to the levels of five soluble inhibitory immune checkpoint proteins (CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3), as well as those of vitamin D, while oxidative stress was determined according to the circulating levels of the DNA adduct, 8-hydroxy-2-deoxyguanosine (8-OH-dG). These various biomarkers were measured in plasma using immunofluorimetric, nephelometric and ELISA procedures. Significant elevations in IL-6 (P<0.01) and TNF-α (P<0.0001), but none of the other cytokines, as well as increased levels of all five soluble inhibitory immune checkpoints (P=0.032-P=0.0001) were detected in the plasma of the XP patients. C-reactive protein and vitamin D were increased and decreased, respectively (both P<0.0001), while only one participant had an elevated level of plasma cotinine. Surprisingly, the levels of 8-OH-dG were significantly (P=0.0001) lower in the group of XP patients relative to a group of healthy control subjects. The findings of increased levels of pro-inflammatory cytokines and, in particular, those of the soluble immune checkpoints, in the setting of decreased vitamin D and moderately elevated levels of CRP in XP patients suggest a possible secondary role of ongoing, inflammatory stress and immune suppression in the pathogenesis of XP-associated malignancies.