bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast Cancer Vaccines: Disappointing or Promising?
Authors: Zhu Si-Yuan , Yu Ke-Da
Published: January 2022

Breast cancer has become the most commonly diagnosed cancer globally. The relapse and metastasis of breast cancer remain a great challenge despite advances in chemotherapy, endocrine therapy, and HER2 targeted therapy in the past decades. Innovative therapeutic strategies are still critically in need. Cancer vaccine is an attractive option as it aims to induce a durable immunologic response to eradicate tumor cells. Different types of breast cancer vaccines have been evaluated in clinical trials, but none has led to significant benefits. Despite the disappointing results at present, new promise from the latest study indicates the possibility of applying vaccines in combination with anti-HER2 monoclonal antibodies or immune checkpoint blockade. This review summarizes the principles and mechanisms underlying breast cancer vaccines, recapitulates the type and administration routes of vaccine, reviews the current results of relevant clinical trials, and addresses the potential reasons for the setbacks and future directions to explore.
Predicted HLA Class I and Class II Epitopes From Licensed Vaccines Are Largely Conserved in New SARS-CoV-2 Omicron Variant of Concern
Authors: López Daniel
Published: January 2022

The potential effect of emerging SARS-CoV-2 variants on vaccine efficacy is an issue of critical importance. In this study, the possible impact of mutations that facilitate virus escape from the cytotoxic and the helper cellular immune responses in the new SARS-CoV-2 Omicron variant of concern was analyzed for the 551 and 41 most abundant HLA class I and II alleles, respectively. Computational prediction showed that almost all of these 592 alleles, which cover >90% of the human population, contain enough epitopes without escape mutations in the emerging SARS-CoV-2 Omicron variant of concern. These data suggest that both cytotoxic and helper cellular immune protection elicited by currently licensed vaccines are virtually unaffected by the highly contagious SARS-CoV-2 Omicron variant of concern.
High Interferon Signature Leads to Increased STAT1/3/5 Phosphorylation in PBMCs From SLE Patients by Single Cell Mass Cytometry
Authors: Yiu Gloria , Rasmussen Tue Kruse , Tsai Brandon L. , Diep Vivian K. , Haddon David J. , Tsoi Jennifer , Miller Gopika D. , Comin-Anduix Begoña , Deleuran Bent , Crooks Gay M. , Utz Paul J.
Published: January 2022

The establishment of an “interferon (IFN) signature” to subset SLE patients on disease severity has led to therapeutics targeting IFNα. Here, we investigate IFN signaling in SLE using multiplexed protein arrays and single cell cytometry by time of flight (CyTOF). First, the IFN signature for SLE patients (n=81) from the Stanford Lupus Registry is determined using fluidigm qPCR measuring 44 previously determined IFN-inducible transcripts. IFN-high (IFN-H) patients have increased SLE criteria and renal/CNS/immunologic involvement, and increased autoantibody reactivity against spliceosome-associated antigens. CyTOF analysis is performed on non-stimulated and stimulated (IFNα, IFNγ, IL-21) PBMCs from SLE patients (n=25) and HCs (n=9) in a panel identifying changes in phosphorylation of intracellular signaling proteins (pTOF). Another panel is utilized to detect changes in intracellular cytokine (ICTOF) production in non-stimulated and stimulated (PMA/ionomycin) PBMCs from SLE patients (n=31) and HCs (n=17). Bioinformatic analysis by MetaCyto and OMIQ reveal phenotypic changes in immune cell subsets between IFN-H and IFN-low (IFN-L) patients. Most notably, IFN-H patients exhibit increased STAT1/3/5 phosphorylation downstream of cytokine stimulation and increased phosphorylation of non-canonical STAT proteins. These results suggest that IFN signaling in SLE modulates STAT phosphorylation, potentially uncovering possible targets for future therapeutic approaches.
Global Patterns of Coastal Cephalopod Diversity Under Climate Change
Authors: Boavida-Portugal Joana , Guilhaumon François , Rosa Rui , Araújo Miguel B.
Published: January 2022

Coastal marine ecosystems are currently being exposed to climate change at a much faster rate than many other ecosystems, with coastal species being exposed to multiple stressors. Cephalopod mollusks play a pivotal role in marine trophic webs, and most are “keystone” species due to their influence on ecosystem dynamics. In this study, we characterized the global patterns of coastal cephalopod diversity and present, for the first time, a global forecast of potential changes in richness, mean body size, and assemblage composition (i.e., species replacement, nestedness, and combinations of both) for 161 coastal cephalopod species under climate change, using an ensemble of ecological niche models (ENMs) for an end of the century mitigation scenario. We have shown that, for the baseline period, coastal cephalopod diversity is higher in the Central Indo-Pacific area and that body size patterns follow the temperature-size rule, with larger animals occurring at higher latitudes. The end-century projections of habitat suitability show a different picture, with 96% of cephalopod species predicted to experience range contraction and 15% completely losing their environmental space. Nestedness is projected to be the main effect of species compositional change. Maximum body size is projected to increase in 44% of the pixels and decrease in 37%. Regarding fisheries, the projected changes are more favorable to the countries at higher latitudes, although the search for refugia of smaller tropical species might potentially lead to a mitigation of the negative effects of climate change in these areas, as measured by the total capture (ton). While the model has limitations, our findings reflect major climatic drivers of change and highlight the idea that even though cephalopod species seem good candidates to replace overexploited fish stocks in the near future, they may not have the environmental space to do so.
Attributing Controlling Factors of Acidification and Hypoxia in a Deep, Nutrient-Enriched Estuarine Embayment
Authors: Zeldis John R. , Currie Kim I. , Graham Scott L. , Gall Mark P.
Published: January 2022

Measuring and attributing controlling factors of acidification and hypoxia are essential for management of coastal ecosystems affected by those stressors. We address this using surveys in the Firth of Thames, a deep, seasonally stratified estuarine embayment adjoing the Hauraki Gulf in northern Aotearoa/New Zealand. The Firth’s catchment has undergone historic land-use intensification transforming it from native forest cover to dominance by pastoral use, increasing its riverine total nitrogen loading by ∼82% over natural levels and switching it’s predominate loading source from offshore to the catchment. We hypothesised that seasonal variation in net ecosystem metabolism [NEM: dissolved inorganic carbon (DIC) uptake/release] will be a primary factor determining carbonate and oxic responses in the Firth, and that organic matter involved in the metabolism will originate primarily by fixation within the Firth system and be driven by catchment dissolved inorganic nitrogen (DIN) loading. Seasonal ship-based and biophysical mooring surveys across the Hauraki Gulf and Firth showed depressed pH and O2 reaching pH ∼7.8 and O2 ∼4.8 mg L–1 in autumn in the inner Firth, matched by shoreward increasing nutrient loading, phytoplankton, organic matter, gross primary production (GPP) and apparent O2 utilization. A carbonate system deconvolution of the ship survey data, combined with other ship survey and mooring results, showed how CO2 partial pressure responded to seasonal shifts in temperature, NEM, phytoplankton sinking and mineralisation and water column stratification, that underlay the late-season expression of acidification and hypoxia. This aligned with seasonal shifts in net DIC fluxes determined in a coincident nutrient mass-balance analysis, showing near-neutral fluxes from spring to summer, but respiratory NEM from summer to autumn. Particulate C:N and ratios of organic C fixed by Firth GPP to that from river inputs (∼29- to 100-fold in summer and autumn) showed that the dominant source of organic matter fuelling heterotrophy in autumn was autochthonous GPP, driven by riverine DIN loading. The results signified the sensitivity of deep, long-residence time, seasonally stratifying estuaries to acidification and hypoxia, and are important for coastal resource management, including aquaculture developments and catchment runoff limit-setting for maintenance of ecosystem health.
Molecular Identification of Species Diversity Using Pelagic Fish Eggs in Spring and Late Autumn-Winter in the Eastern Beibu Gulf, China
Authors: Hou Gang , Chen Yanying , Wang Jinrun , Pan Chuanhao , Lin Jianbin , Feng Bo , Zhang Hui
Published: January 2022

The Beibu Gulf is considered as one of China’s four major fishing grounds, although the substantial overexploitation of fisheries has led to the collapse of many fish stocks, and to changes to spawning grounds in recent decades. Classifying fish eggs is an important way to monitor the recruitment process and identify the spawning sites of fish. However, the lack of a basis for morphological identification and difficulties in correctly identifying fish eggs based on morphological characteristics has limited scientific studies. In the present study, we identified fish eggs using molecular detection of cytochrome c oxidase subunit I and cytochrome b fragments. Ichthyoplankton surveys were conducted in the spring and late autumn–winter of 2020 in the eastern Beibu Gulf. Among the DNA extracted from the 873 chosen fish eggs, we successfully obtained 541 high-quality cytochrome c oxidase subunit I sequences and 41 high-quality cytochrome b sequences. We successfully identified 212 fish eggs (36.4%) from 32 species; 291 eggs (50.0%) showed ambiguous species delimitation, and 79 eggs (13.6%) could not be identified. Among the identified species, we found 25 species in spring and 25 species in late autumn–winter, out of which 18 species occurred in both seasons. We also obtained high resolution photographs of fish eggs at the species level for further morphological analysis and identification. The present study confirms the efficacy of using molecular methods to identify fish species from eggs and provides valuable information for protecting the spawning ground of economically valuable fish and for managing fishery resources.
Formation and Evolution of the Corrosion Scales on Super 13Cr Stainless Steel in a Formate Completion Fluid With Aggressive Substances
Authors: Yue Xiaoqi , Huang Luyao , Qu Zhihao , Yang Zhile , Zhang Lei , Hua Yong
Published: January 2022

The formation and evolution of the corrosion scales on the super 13Cr stainless steel (SS) surface after exposure in a formate completion fluid with the presence of various aggressive substances was investigated. The results indicate that the formation of Fe3O4 covered the surface of super 13Cr SS as the inner layer accompanied with outer scattered FeS. The corrosion rate was below 0.07 mm/year after 120 h of exposure in the formate fluid at 180°C under N2 environments; the presence of aggressive substances such as sulfide and CO2 in the formate fluid promoted the proceeding of anodic dissolution in the early period, and the ingress of CO2 progressively increased the general corrosion rate to 1.7 mm/year. For CO2-containing conditions, the formation of FeCr2O4 and Cr(OH)3 was detected in the inner corrosion product layers, and the precipitation of “sheet”-shaped iron carbonate (FeCO3) was detected as the outer layer. The accumulation rate of corrosion products increases by two orders of magnitude with the ingress of CO2, corresponding to thicker corrosion products, but the dissolution rate is still three orders of magnitude higher than when CO2 was absent.
Considerations for Polymers Used in Ocular Drug Delivery
Authors: Allyn Megan M. , Luo Richard H. , Hellwarth Elle B. , Swindle-Reilly Katelyn E.
Published: January 2022

Purpose

Age-related eye diseases are becoming more prevalent. A notable increase has been seen in the most common causes including glaucoma, age-related macular degeneration (AMD), and cataract. Current clinical treatments vary from tissue replacement with polymers to topical eye drops and intravitreal injections. Research and development efforts have increased using polymers for sustained release to the eye to overcome treatment challenges, showing promise in improving drug release and delivery, patient experience, and treatment compliance. Polymers provide unique properties that allow for specific engineered devices to provide improved treatment options. Recent work has shown the utilization of synthetic and biopolymer derived biomaterials in various forms, with this review containing a focus on polymers Food and Drug Administration (FDA) approved for ocular use.

Methods

This provides an overview of some prevalent synthetic polymers and biopolymers used in ocular delivery and their benefits, brief discussion of the various types and synthesis methods used, and administration techniques. Polymers approved by the FDA for different applications in the eye are listed and compared to new polymers being explored in the literature. This article summarizes research findings using polymers for ocular drug delivery from various stages: laboratory, preclinical studies, clinical trials, and currently approved. This review also focuses on some of the challenges to bringing these new innovations to the clinic, including limited selection of approved polymers.

Results

Polymers help improve drug delivery by increasing solubility, controlling pharmacokinetics, and extending release. Several polymer classes including synthetic, biopolymer, and combinations were discussed along with the benefits and challenges of each class. The ways both polymer synthesis and processing techniques can influence drug release in the eye were discussed.

Conclusion

The use of biomaterials, specifically polymers, is a well-studied field for drug delivery, and polymers have been used as implants in the eye for over 75 years. Promising new ocular drug delivery systems are emerging using polymers an innovative option for treating ocular diseases because of their tunable properties. This review touches on important considerations and challenges of using polymers for sustained ocular drug delivery with the goal translating research to the clinic.
Epidemiological, Clinical, and Phylogenetic Characteristics of the First SARS-CoV-2 Transmission in a Nursing Home of Singapore: A Prospective Observational Investigation
Authors: Pang Junxiong , Tan Huei Nuo , Mak Tze Minn , Octavia Sophie , Maurer-Stroh Sebastian , Sirota Fernanda L. , Chan Mark Peng Chew , Leong Ian Yi Onn , Koh Valerie T. J. , Ooi Peng Lim , Vasoo Shawn , Fisher Dale , Cui Lin , Rafman Heidi , Cutter Jeffery , Lee Vernon J.
Published: January 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has resulted in a significant burden among nursing home facilities globally. This prospective observational cohort study aims to define the potential sources of introduction and characteristics of SARS-CoV-2 transmission of the first nursing home facility in Singapore. An epidemiological serial point-prevalence survey of SARS-CoV-2 was conducted among 108 residents and 56 healthcare staff (HCS). In the current study, 14 (13%) residents and two (3.6%) HCS were diagnosed with coronavirus disease 2019 (COVID-19), with a case fatality rate (CFR) of 28.6% (4/14) among the residents. The median age of the infected residents was 86.5 [interquartile range (IQR) 78.5–88] and 85.7% were women. Five residents were symptomatic (35.7%) and the others were asymptomatic (64.3%). A higher proportion of residents who succumbed to COVID-19 had hypertension than those who recovered. The SARS-CoV-2 whole-genome sequencing showed lineage B.6 which is rare globally but common regionally during the early phase of the pandemic. Household transmission is a potential source of introduction into the nursing home, with at least six epidemiologically linked secondary cases. Male residents were less implicated due to the staff segregation plan by block. Among residents, a higher proportion of the non-survivors were asymptomatic and had hypertension compared with survivors.
Insights Into Thiamine Supplementation in Patients With Septic Shock
Authors: Costa Nara Aline , Pereira Amanda Gomes , Sugizaki Clara Sandra Araujo , Vieira Nayane Maria , Garcia Leonardo Rufino , Paiva Sérgio Alberto Rupp de , Zornoff Leonardo Antonio Mamede , Azevedo Paula Schmidt , Polegato Bertha Furlan , Minicucci Marcos Ferreira
Published: January 2022

Septic shock is associated with unacceptably high mortality rates, mainly in developing countries. New adjunctive therapies have been explored to reduce global mortality related to sepsis. Considering that metabolic changes, mitochondrial dysfunction and increased oxidative stress are specific disorders within the path of septic shock, several micronutrients that could act in cellular homeostasis have been studied in recent decades. Thiamine, also known as vitamin B1, plays critical roles in several biological processes, including the metabolism of glucose, synthesis of nucleic acids and reduction of oxidative stress. Thiamine deficiency could affect up to 70% of critically ill patients, and thiamine supplementation appears to increase lactate clearance and decrease the vasopressor dose. However, there is no evident improvement in the survival of septic patients. Other micronutrients such as vitamin C and D, selenium and zinc have been tested in the same context but have not been shown to improve the outcomes of these patients. Some problems related to the neutrality of these clinical trials are the study design, doses, route, timing, length of intervention and the choice of endpoints. Recently, the concept that multi-micronutrient administration may be better than single-micronutrient administration has gained strength. In general, clinical trials consider the administration of a single micronutrient as a drug. However, the antioxidant defense is a complex system of endogenous agents in which micronutrients act as cofactors, and the physiological interactions between micronutrients are little discussed. In this context, the association of thiamine, vitamin C and corticoids was tested as an adjunctive therapy in septic shock resulting in a significant decrease in mortality. However, after these initial results, no other study conducted with this combination could reproduce those benefits. In addition, the use of low-dose corticosteroids is recommended in patients with septic shock who do not respond to vasopressors, which can affect the action of thiamine. Therefore, given the excellent safety profile, good biologic rationale and promising clinical studies, this review aims to discuss the mechanisms behind and the evidence for single or combined thiamine supplementation improving the prognosis of patients with septic shock.
Wired to Doubt: Why People Fear Vaccines and Climate Change and Mistrust Science
Authors: Dobson Geoffrey P.
Published: January 2022

We all want to be right in our thinking. Vaccine hesitancy and global warming denial share much in common: (1) both are threats to personal, community and global health, (2) action is contingent on co-operation and social policy, and (3) public support relies on trust in science. The irony is, however, as the science has become more convincing, public opinion has become more divided. A number of early polls showed that ~70% of people supported COVID-19 vaccine use and global warming, ~20% adopted a wait-and-see approach, and ~10% were staunch objectors. Although these percentages are approximate, what factors are responsible for the differences in engagement, doubt and distrust? How can we reduce the consensus gap? One approach is to return to grass roots and provide a brief history of the issues, understand the difference between fact and opinion, truth and falsehood, the problem of certainty, and how scientific consensus is reached. To doubt is a healthy response to new information, and it too has a scientific basis. Doubt and distrust reside in that region of the brain called the dorsolateral prefrontal cortex, which is responsible for suppressing unwanted representations. Bridging the consensus gap requires shifting human thinking patterns from doubt to belief, and belief to action. Education and improved public messaging are key, and social media providers require urgent oversight or regulation to remove false and harmful/dangerous content from our digital lives. Delays to vaccinate and failure to reduce greenhouse gases will dramatically change the way we live. The new norm may be more deadly COVID variants, strained healthcare systems, extreme weather patterns, diminished food supply, delays in goods and services, damage to world's economies and widespread global instability.
Case Report: Community-Acquired Legionella gormanii Pneumonia in an Immunocompetent Patient Detected by Metagenomic Next-Generation Sequencing
Authors: Lei Cheng , Zhou Xianglin , Ding Shuizi , Xu Yingjie , Yang Binyi , Guo Wei , Song Min , Yang Min , Jia Yunan , Luo Hong
Published: January 2022

Background

Legionella spp. has been well-recognized as an important cause of community-acquired pneumonia. Current community-acquired pneumonia guidelines recommended covering the treatment of Legionella because of the high mortality associated with inadequate antibiotic treatments. However, the symptom of Legionella pneumonia is non-specific, and routine diagnostic tests exhibit low sensitivity for Legionella spp., especially for non-Legionella pneumophila serogroup 1 strains.

Case Presentation

We report a 53-year-old man without underlying diseases admitted to respiratory intensive care unit because of severe community-acquired pneumonia and respiratory failure. Although, the results of routine culture of bronchoalveolar lavage fluid and the Legionella urinary antigen test were all negative, metagenomic next-generation sequencing (mNGS) identified a great amount of DNA and RNA sequences of Legionella gormanii in bronchoalveolar lavage fluid while negative in blood sample. The presence of Legionella gormanii in bronchoalveolar lavage fluid was further confirmed by polymerase-chain-reaction and Sanger sequencing.

Conclusion

Legionella gormanii has rarely been reported in patients with community-acquired pneumonia mainly due to lack of diagnostic test for non-Legionella pneumophila serogroup 1 strains. This is the first report of Legionella gormanii pneumonia in an immunocompetent patient detected by mNGS, which indicates that mNGS is a high-resolution and sensitive assay for the diagnosis and surveillance of Legionella infection.
Demographic, Virological Characteristics and Prognosis of Asymptomatic COVID-19 Patients in South China
Authors: Xu Hui , Xie Cheng-yuan , Li Pei-hong , Ji Zhong-liang , Sun Jiu-feng , Hu Bei , Li Xin , Fang Ming
Published: January 2022

Background

Asymptomatic transmission is a major concern for SARS-CoV-2 community spread; however, little information is available on demographic, virological characteristics and prognosis of asymptomatic cases.

Methods

All COVID-19 patients hospitalized in Guangdong Province from September 1, 2020 to February 28, 2021, were included and were divided into asymptomatic and symptomaticgroup. The source country of all patients, clinical laboratory test results, the genotype of virus and the time of SARS-CoV-2 RNA turning negative or hospitalization were confirmed.

Results

Total 233 patients from 57 different countries or regions were included, with 83 (35.6%) asymptomatic and 150 (64.4%) symptomatic patients. Asymptomatic cases were younger (P = 0.019), lower rate in comorbidities (P = 0.021) such as hypertension (P = 0.083) and chronic liver disease (P = 0.045), lower PCT (P = 0.021), DDI (P < 0.001) and ALT (P = 0.029), but higher WBC count (P = 0.002) and lymphocyte (P = 0.011) than symptomatic patients. As for SARS-CoV-2 subtypes, patients infected with B.1.1 (53.8%), B.1.351 (81.8%) and B.1.524 (60%) are mainly asymptomatic, while infected with B, B.1, B.1.1.63, B.1.1.7, B.1.36, B.1.36.1, B.1.36.16, B.1.5 and B.6 were inclined to be symptomatic. Patients infected with variant B.1.351 and B.1.524 spent longer time in SARS-CoV-2 RNA turn negative (26 days, P = 0.085; 41 days, P = 0.007) and hospitalization (28 days, P = 0.085; 43 days, P = 0.004).

Conclusions

The asymptomatic cases are prone to develop in patients with younger age, less comorbidities andinfected with B.1.1 and B.1.524 variants. More attention should be paid for lineage B.1.524 because it can significantly prolong the SARS-CoV-2 RNA negative conversion time and hospitalization in infected cases.
Characterization of a Novel Hot-Spring Cyanobacterium Leptodesmis sichuanensis sp. Nov. and Genomic Insights of Molecular Adaptations Into Its Habitat
Authors: Tang Jie , Du Lian-Ming , Li Meijin , Yao Dan , Jiang Ying , Waleron Malgorzata , Waleron Krzysztof , Daroch Maurycy
Published: January 2022

The newly described genus Leptodesmis comprises several strains of filamentous cyanobacteria from diverse, primarily cold, habitats. Here, we sequenced the complete genome of a novel hot-spring strain, Leptodesmis sp. PKUAC-SCTA121 (hereafter A121), isolated from Erdaoqiao hot springs (pH 6.32, 40.8°C), China. The analyses of 16S rRNA/16S-23S ITS phylogenies, secondary structures, and morphology strongly support strain A121 as a new species within Leptodesmis, Leptodesmis sichuanensis sp. nov. Notably, strain A121 is the first thermophilic representative of genus Leptodesmis and more broadly the first Leptodesmis sp. to have its genome sequenced. In addition, results of genome-scale phylogenetic analysis and average nucleotide/amino acid identity as well as in silico DNA-DNA hybridization and patristic analysis verify the establishment of genus Leptodesmis previously cryptic to Phormidesmis. Comparative genomic analyses reveal that the Leptodesmis A121 and Thermoleptolyngbya sichuanensis A183 from the same hot-spring biome exhibit different genome structures but similar functional classifications of protein-coding genes. Although the core molecular components of photosynthesis, metabolism, and signal transduction were shared by the two strains, distinct genes associated with photosynthesis and signal transduction were identified, indicating that different strategies might be used by these strains to adapt to that specific niche. Furthermore, the complete genome of strain A121 provides the first insight into the genomic features of genus Leptodesmis and lays the foundation for future global ecogenomic and geogenomic studies.
Definition of the Metagenomic Profile of Ocean Water Samples From the Gulf of Mexico Based on Comparison With Reference Samples From Sites Worldwide
Authors: Loza Antonio , García-Guevara Fernando , Segovia Lorenzo , Escobar-Zepeda Alejandra , Sanchez-Olmos Maria del Carmen , Merino Enrique , Sanchez-Flores Alejandro , Pardo-Lopez Liliana , Juarez Katy , Gutierrez-Rios Rosa-Maria
Published: January 2022

Computational and statistical analysis of shotgun metagenomes can predict gene abundance and is helpful for elucidating the functional and taxonomic compositions of environmental samples. Gene products are compared against physicochemical conditions or perturbations to shed light on the functions performed by the microbial community of an environmental sample; however, this information is not always available. The present study proposes a method for inferring the metabolic potential of metagenome samples by constructing a reference based on determining the probability distribution of the counts of each enzyme annotated. To test the methodology, we used marine water samples distributed worldwide as references. Then, the references were utilized to compare the annotated enzymes of two different water samples extracted from the Gulf of Mexico (GoM) to distinguish those enzymes with atypical behavior. The enzymes whose annotation counts presented frequencies significantly different from those of the reference were used to perform metabolic reconstruction, which naturally identified pathways. We found that several of the enzymes were involved in the biodegradation of petroleum, which is consistent with the impact of human hydrocarbon extraction activity and its ubiquitous presence in the GoM. The examination of other reconstructed pathways revealed significant enzymes indicating the presence of microbial communities characterizing each ocean depth and ocean cycle, providing a fingerprint of each sampled site.
Genomic Insights Into Cadmium Resistance of a Newly Isolated, Plasmid-Free Cellulomonas sp. Strain Y8
Authors: Chen Jinghao , Wang Likun , Li Wenjun , Zheng Xin , Li Xiaofang
Published: January 2022

Our current knowledge on bacterial cadmium (Cd) resistance is mainly based on the functional exploration of specific Cd-resistance genes. In this study, we carried out a genomic study on Cd resistance of a newly isolated Cellulomonas strain with a MIC of 5 mM Cd. Full genome of the strain, with a genome size of 4.47 M bp and GC-content of 75.35%, was obtained through high-quality sequencing. Genome-wide annotations identified 54 heavy metal-related genes. Four potential Cd-resistance genes, namely zntAY8, copAY8, HMTY8, and czcDY8, were subjected to functional exploration. Quantitative PCR determination of in vivo expression showed that zntAY8, copAY8, and HMTY8 were strongly Cd-inducible. Expression of the three inducible genes against time and Cd concentrations were further quantified. It is found that zntAY8 responded more strongly to higher Cd concentrations, while expression of copAY8 and HMTY8 increased over time at lower Cd concentrations. Heterologous expression of the four genes in Cd-sensitive Escherichia coli led to different impacts on hosts’ Cd sorption, with an 87% reduction by zntAY8 and a 3.7-fold increase by HMTY8. In conclusion, a Cd-resistant Cellulomonas sp. strain was isolated, whose genome harbors a diverse panel of metal-resistance genes. Cd resistance in the strain is not controlled by a dedicated gene alone, but by several gene systems collectively whose roles are probably time- and dose-dependent. The plasmid-free, high-GC strain Y8 may provide a platform for exploring heavy metal genomics of the Cellulomonas genus.
The Influence of Genes on the “Killer Plasmid” of Dinoroseobacter shibae on Its Symbiosis With the Dinoflagellate Prorocentrum minimum
Authors: Mansky Johannes , Wang Hui , Ebert Matthias , Härtig Elisabeth , Jahn Dieter , Tomasch Jürgen , Wagner-Döbler Irene
Published: January 2022

The marine bacterium Dinoroseobacter shibae shows a Jekyll-and-Hyde behavior in co-culture with the dinoflagellate Prorocentrum minimum: In the initial symbiotic phase it provides the essential vitamins B12 (cobalamin) and B1 (thiamine) to the algae. In the later pathogenic phase it kills the dinoflagellate. The killing phenotype is determined by the 191 kb plasmid and can be conjugated into other Roseobacters. From a transposon-library of D. shibae we retrieved 28 mutants whose insertion sites were located on the 191 kb plasmid. We co-cultivated each of them with P. minimum in L1 medium lacking vitamin B12. With 20 mutant strains no algal growth beyond the axenic control lacking B12 occurred. Several of these genes were predicted to encode proteins from the type IV secretion system (T4SS). They are apparently essential for establishing the symbiosis. With five transposon mutant strains, the initial symbiotic phase was intact but the later pathogenic phase was lost in co-culture. In three of them the insertion sites were located in an operon predicted to encode genes for biotin (B7) uptake. Both P. minimum and D. shibae are auxotrophic for biotin. We hypothesize that the bacterium depletes the medium from biotin resulting in apoptosis of the dinoflagellate.
Activity of Trichoderma asperellum Strain ICC 012 and Trichoderma gamsii Strain ICC 080 Toward Diseases of Esca Complex and Associated Pathogens
Authors: Di Marco Stefano , Metruccio Elisa Giorgia , Moretti Samuele , Nocentini Marco , Carella Giuseppe , Pacetti Andrea , Battiston Enrico , Osti Fabio , Mugnai Laura
Published: January 2022

Grapevine trunk diseases are widespread in all grape-growing countries. The diseases included in the Esca complex of diseases are particularly common in European vineyards. Their distinctive foliar symptoms are well known to be associated not only with losses in quantity, as with all grapevine wood diseases, but also with losses in the quality of the crop. Protection of pruning wounds is known to reduce infections in artificial inoculations and, to some extent, reduce the external leaf symptoms. The application of biological control agents in the field is typically started at the first appearance of symptoms. In this article, the two strains belonging to two different species,Trichoderma asperellumICC 012 andT. gamsiiICC 080, which are present in a commercial formulation, were testedin vitro,in vivoin artificial inoculation, and in the field in long-term experiments where the wounds on four young asymptomatic vineyards were protected since 1 or 2 years after planting. Thein vitrotrials highlighted the different temperature requirements of the two strains, the direct mycoparasitizing activity ofT. asperellum, and the indirect activity shown by bothTrichodermastrains. Thein vivotrials confirmed the ability of the two strains to reduce the colonization following artificial inoculations with the high, unnatural concentration of spores used in artificial infections, even if with variable efficacy, and with long persistence as they could be reisolated 7 months post-application. The preventive applications carried out over 9 years showed a very high reduction in symptom development in the treated vines, on annual and cumulated incidence and on the death of vines, with disease reduction varying from 66 to almost 90%. Early and annual application of protection to the pruning wounds appears to be the best method for reducing damages caused by grapevine leaf stripe disease (a disease of the Esca complex of diseases).Trichodermaappears to offer an efficient, environmentally friendly, and long-lasting protection in the presence of a natural inoculum concentration.
Mathematical Modeling of Proliferative Immune Response Initiated by Interactions Between Classical Antigen-Presenting Cells Under Joint Antagonistic IL-2 and IL-4 Signaling
Authors: Atitey Komlan , Anchang Benedict
Published: January 2022

During an adaptive immune response from pathogen invasion, multiple cytokines are produced by various immune cells interacting jointly at the cellular level to mediate several processes. For example, studies have shown that regulation of interleukin-4 (IL-4) correlates with interleukin-2 (IL-2) induced lymphocyte proliferation. This motivates the need to better understand and model the mechanisms driving the dynamic interplay of proliferation of lymphocytes with the complex interaction effects of cytokines during an immune response. To address this challenge, we adopt a hybrid computational approach comprising of continuous, discrete and stochastic non-linear model formulations to predict a system-level immune response as a function of multiple dependent signals and interacting agents including cytokines and targeted immune cells. We propose a hybrid ordinary differential equation-based (ODE) multicellular model system with a stochastic component of antigen microscopic states denoted as Multiscale Multicellular Quantitative Evaluator (MMQE) implemented using MATLAB. MMQE combines well-defined immune response network-based rules and ODE models to capture the complex dynamic interactions between the proliferation levels of different types of communicating lymphocyte agents mediated by joint regulation of IL-2 and IL-4 to predict the emergent global behavior of the system during an immune response. We model the activation of the immune system in terms of different activation protocols of helper T cells by the interplay of independent biological agents of classic antigen-presenting cells (APCs) and their joint activation which is confounded by the exposure time to external pathogens. MMQE quantifies the dynamics of lymphocyte proliferation during pathogen invasion as bivariate distributions of IL-2 and IL-4 concentration levels. Specifically, by varying activation agents such as dendritic cells (DC), B cells and their joint mechanism of activation, we quantify how lymphocyte activation and differentiation protocols boost the immune response against pathogen invasion mediated by a joint downregulation of IL-4 and upregulation of IL-2. We further compare our in-silico results toin-vivoandin-vitroexperimental studies for validation. In general, MMQE combines intracellular and extracellular effects from multiple interacting systems into simpler dynamic behaviors for better interpretability. It can be used to aid engineering of anti-infection drugs or optimizing drug combination therapies against several diseases.
Prevalence and Associated Risk Factors of Cognitive Frailty: A Systematic Review and Meta-Analysis
Authors: Zhang Tao , Ren Yan , Shen Ping , Jiang Shixie , Yang Yanrong , Wang Yan , Li Zheng , Yang Ying
Published: January 2022

Objective

Currently, the prevalence of CF (Cognitive Frailty) is not very clear, and the relationship between CF and its associated risk factors has not been accurately evaluated. Therefore, it is necessary to conduct a systematic review and meta-analysis further to understand CF's prevalence and associated factors.

Methods

Embase, PubMed, Web of Science, Ovid, and Cochrane were systematically searched for articles exploring the prevalence of CF, the deadline of searching date was up to March 2021. For the prevalence of CF, the events of CF and the total number of patients in every included study were extracted to estimate the prevalence of CF. For associated factors of CF, Odds Ratios (ORs) with (corresponding) 95% confidence intervals (CIs) were used for estimations.

Results

Firstly, the estimated prevalence of CF I (Cognitive Frailty in the model I) was 16%, 95% CI (0.13–0.19), and the estimated prevalence of CF II (Cognitive Frailty in model II) was 6%, 95% CI (0.05–0.07). Secondly, both lower engagement in activities and age were calculated to be independent risk factors of CF, and the OR (95% CI) was 3.31 (2.28–4.81) and 1.10 (1.04–1.16), respectively. Finally, depression was also a prominent risk factor of CF, with the overall OR (95% CI) as 1.57 (1.32–1.87).

Conclusion

CF was a high prevalence in community older. The various assessment scales and the different cutoff values of diagnostic criteria would affect the prevalence of CF. Lower engagement in activities, age, and depression was the risky factor of CF.

Systematic Review Registration

http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42019121369.
Intrinsic Brain Activity of Inferior Temporal Region Increased in Prodromal Alzheimer's Disease With Hearing Loss
Authors: Hong Luwei , Zeng Qingze , Li Kaicheng , Luo Xiao , Xu Xiaopei , Liu Xiaocao , Li Zheyu , Fu Yanv , Wang Yanbo , Zhang Tianyi , Chen Yanxing , Liu Zhirong , Huang Peiyu , Zhang Minming
Published: January 2022

Background and Objective

Hearing loss (HL) is one of the modifiable risk factors for Alzheimer's disease (AD). However, the underlying mechanism behind HL in AD remains elusive. A possible mechanism is cognitive load hypothesis, which postulates that over-processing of degraded auditory signals in the auditory cortex leads to deficits in other cognitive functions. Given mild cognitive impairment (MCI) is a prodromal stage of AD, untangling the association between HL and MCI might provide insights for potential mechanism behind HL.

Methods

We included 85 cognitively normal (CN) subjects with no hearing loss (NHL), 24 CN with HL, 103 mild cognitive impairment (MCI) patients with NHL, and 23 MCI with HL from the ADNI database. All subjects underwent resting-state functional MRI and neuropsychological scale assessments. Fractional amplitude of low-frequency fluctuation (fALFF) was used to reflect spontaneous brain activity. The mixed-effects analysis was applied to explore the interactive effects between HL and cognitive status (GRF corrected, voxel p-value <0.005, cluster p-value < 0.05, two-tailed). Then, the FDG data was included to further reflect the regional neuronal abnormalities. Finally, Pearson correlation analysis was performed between imaging metrics and cognitive scores to explore the clinical significance (Bonferroni corrected, p < 0.05).

Results

The interactive effects primarily located in the left superior temporal gyrus (STG) and bilateral inferior temporal gyrus (ITG). Post-hoc analysis showed that NC with HL had lower fALFF in bilateral ITG compared to NC with NHL. NC with HL had higher fALFF in the left STG and decreased fALFF in bilateral ITG compared to MCI with HL. In addition, NC with HL had lower fALFF in the right ITG compared to MCI with NHL. Correlation analysis revealed that fALFF was associated with MMSE and ADNI-VS, while SUVR was associated with MMSE, MoCA, ADNI-EF and ADNI-Lan.

Conclusion

HL showed different effects on NC and MCI stages. NC had increased spontaneous brain activity in auditory cortex while decreased activity in the ITG. Such pattern altered with disease stage changing and manifested as decreased activity in auditory cortex along with increased activity in ITG in MCI. This suggested that the cognitive load hypothesis may be the underlying mechanism behind HL.
The Essential DNA Damage Response Complex MRN Is Dispensable for the Survival and Function of Purkinje Neurons
Authors: Ding Mingmei , Qing Xiaobing , Zhang Guangyu , Baade-Büttner Carolin , Gruber Ralph , Lu Haizhen , Ferguson David O. , Geis Christian , Wang Zhao-Qi , Zhou Zhong-Wei
Published: January 2022

MRE11, RAD50, and NBS1 form the MRN complex in response to DNA damage to activate ATM, a gene responsible for Ataxia-Telangiectasia (A-T). Loss of any components of the MRN complex compromises cell life. Mutations in MRE11, RAD50, and NBS1 cause human genomic instability syndromes Ataxia-Telangiectasia-like disorder (A-TLD), NBS-like disorder (NBSLD), and Nijmegen Breakage Syndrome (NBS), respectively. Among other pathologies, neuronal deficits, including microcephaly, intellectual disabilities, and progressive cerebellar degeneration, are common in these disorders. Nbs1 deletion in neural stem cells of mouse models resulted in cerebellar atrophy and ataxia, mimicking the A-T syndrome suggesting an etiological function of MRN-mediated DDR in neuronal homeostasis and neuropathology. Here we show that deletion of Nbs1 or Mre11 specifically in Purkinje neurons of mouse models (Nbs1-PCΔ and Mre11-PCΔ, respectively) is compatible with cerebellar development. Deleting Nbs1 in Purkinje cells disrupts the cellular localization pattern of MRE11 or RAD50 without inducing apparent DNA damage, albeit impaired DNA damage response (judged by 53BP1 focus formation) to ionizing radiation (IR). However, neither survival nor morphology of Purkinje cells and thus locomotor capabilities is affected by Nbs1 deletion under physiological conditions. Similarly, deletion of Mre11 in Purkinje cells does not affect the numbers or morphology of Purkinje cells and causes no accumulation of DNA damage. Mre11-deleted Purkinje cells have regular intrinsic neuronal activity. Taken together, these data indicate that the MRN complex is not essential for the survival and functionality of postmitotic neurons such as Purkinje cells. Thus, cerebellar deficits in MRN defect-related disorders and mouse models are unlikely to be a direct consequence of loss of these factors compromising DDR in postmitotic neurons such as Purkinje cells.
Changes in Serum Cystatin C Levels and the Associations With Cognitive Function in Alzheimer's Disease Patients
Authors: Chen Xueping , Huang Yan , Bao Ting , Jia Fu , Ou Ruwei , Wei Qianqian , Chen Yongping , Liu Jiao , Yang Jing , Shang Huifang
Published: January 2022

Background and Objective

Cystatin C is indicated to be involved in the pathogenesis of Alzheimer's disease (AD) and cognitive impairment. Our objective is to examine the serum Cystatin C levels, and to clarify the correlations between serum Cystatin C and cognitive performance in Chinese AD patients.

Methods

The serum Cystatin C concentrations in AD patients and age, sex, and body mass index (BMI) matched-healthy controls were measured. The cognitive functions of the AD patients were evaluated by using the Mini-mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The severity of dementia was determined with clinical dementia rating (CDR).

Results

A total of 463 AD patients and 1,389 matched healthy subjects were included. AD patients had higher serum Cystatin C than healthy controls. Serum cystatin C levels were correlated with MoCA scores in AD patients. In an ordinal logistic regression model, AD patients with higher serum cystatin C levels had increased odds of severe cognitive dysfunction.

Conclusion

Our study suggested that AD patients had higher levels of serum cystatin C than age/sex/BMI-matched normal control subjects. Higher serum cystatin C may be associated with worse cognitive performance, but more studies are required to verify such association.
Short Sleep Duration on the Night Before Surgery Is Associated With Postoperative Cognitive Decline in Elderly Patients: A Prospective Cohort Study
Authors: Takamino Ayasa , Kotoda Masakazu , Nakadate Yosuke , Hishiyama Sohei , Iijima Tetsuya , Matsukawa Takashi
Published: January 2022

As the world is rapidly aging, and the number of elderly patients who undergo surgery is rising, postoperative cognitive decline among those patients has become an increasing healthcare problem. Although understanding the risk factors and mechanisms underlying the pathogenesis of postoperative cognitive decline is critically important from a preventative viewpoint, such knowledge and evidence are lacking. A growing body of evidence suggest an association between cognitive function and sleep duration. The purpose of this study was to investigate the association between postoperative cognitive function and sleep duration on the night before surgery using a wearable sleep tracker. In this 6-month prospective cohort study, we analyzed data from 194 patients aged ≥ 65 years who underwent elective non-cardiac and non-cranial surgery under general anesthesia. According to the sleep duration on the night before surgery, patients were categorized into following four groups: <5, 5–7, 7–9, and >9 h. Perioperative cognitive function and domains were assessed using a neuropsychological test battery, and the incidence and prevalence of cognitive decline over 6 months after surgery were analyzed using the multiple logistic regression analysis. During the 6-month follow-up period, 41 patients (21%) developed cognitive decline. The incidence of cognitive decline was significantly elevated for the patients with sleep duration < 5 h (vs. 7–9 h; surgical duration-adjusted odds ratio, 3.50; 95% confidence interval, 1.20–10.2; P < 0.05). The association between sleep duration and prevalence of cognitive decline was limited to the early postoperative period (at 1 week and 1 month). Among the cognitive domains assessed, attentional function was significantly impaired in patients with a sleep duration < 5 h [vs. 7–9 h at 1 week; 4/37 (10.8%) vs. 0/73 (0%); P < 0.05]. In conclusion, sleep duration < 5 h on the night before surgery was significantly associated with worse attentional function after surgery and higher incidence of cognitive decline. The present results indicate that sleep deprivation on the night before surgery may have a temporary but significantly negative influence on the patient's postoperative cognitive function and is a potential target for preventing cognitive decline.