bluuebunny/crossref_metadata_2025 huggingface dataset:
Auto-Fluorescence in Phytoliths—A Mechanistic Understanding Derived From Microscopic and Spectroscopic Analyses
Authors: Puppe Daniel , Leue Martin , Sommer Michael , Schaller Jörg , Kaczorek Danuta
Published: May 2022

The detection of auto-fluorescence in phytogenic, hydrated amorphous silica depositions (phytoliths) has been found to be a promising approach to verify if phytoliths were burnt or not, especially in archaeological contexts. However, it is unknown so far at what temperature and how auto-fluorescence is induced in phytoliths. We used fluorescence microscopy, scanning electron microscope-energy dispersive X-ray spectroscopy (SEM-EDX), and Fourier transform infrared spectroscopy to analyze auto-fluorescence in modern phytoliths extracted from plant samples or in intact leaves of winter wheat. Leaves and extracted phytoliths were heated at different temperatures up to 600°C. The aims of our experiments were i) to find out what temperature is needed to induce auto-fluorescence in phytoliths, ii) to detect temperature-dependent changes in the molecular structure of phytoliths related to auto-fluorescence, and iii) to derive a mechanistic understanding of auto-fluorescence in phytoliths. We found organic compounds associated with phytoliths to cause auto-fluorescence in phytoliths treated at temperatures below approx. 400°C. In phytoliths treated at higher temperatures, i.e., 450 and 600°C, phytolith auto-fluorescence was mainly caused by molecular changes of phytolith silica. Based on our results we propose that auto-fluorescence in phytoliths is caused by clusterization-triggered emissions, which are caused by overlapping electron clouds forming non-conventional chromophores. In phytoliths heated at temperatures above about 400°C dihydroxylation and the formation of siloxanes result in oxygen clusters that serve as non-conventional chromophores in fluorescence events. Furthermore, SEM-EDX analyses revealed that extractable phytoliths were dominated by lumen phytoliths (62%) compared to cell wall phytoliths (38%). Our findings might be not only relevant in archaeological phytolith-based examinations, but also for studies on the temperature-dependent release of silicon from phytoliths and the potential of long-term carbon sequestration in phytoliths.
Multiple Lines of Ecological Evidence Support Ancient Contact Between the African Wild Dog and the Dhole
Authors: Rocha Rita Gomes , Gonçalves João , Tarroso Pedro , Monterroso Pedro , Godinho Raquel
Published: May 2022

Genomic tools have greatly enhanced our ability to uncover ancient interspecific gene flow, including cases involving allopatric lineages and/or lineages that have gone extinct. Recently, a genomic analysis revealed the unexpected gene flow between the African wild dog (Lycaon pictus) and the dhole (Cuon alpinus). The two species have currently highly disjunct and patchy distributions in Africa and Asia, respectively, which are remnants of a much wider past distribution. Yet, no reported evidence of their past contact has ever been documented. By hindcasting the past potential distribution of both species during the Last Glacial Maximum and the Last Interglacial, validating paleoclimatic reconstructions with fossil evidence, quantifying the intersection of their bioclimatic niches, and assessing interspecific compatibility, we investigate the location and favorable conditions for such contact and its ecological validity. We were able to identify the Levant region in Eastern Mediterranean during the Last Interglacial as the most suitable spatio-ecological context for the co-occurrence of the two canids, and to provide evidence of a highly significant overlap of the African wild dog niche with the wider niche of the dhole. These results, combined with ecologic traits, including key compatibility features such as cooperative breeding and hunting, provide consistent support for the potential co-occurrence of both canids. We suggest that the ranges of these canids came into contact multiple times during periods resembling the Last Interglacial, eventually facilitating gene flow between the African wild dog and the dhole in their post-divergence history. Our results are highly supportive of the key role of the Levant region in providing connectivity between African and Eurasian faunas and provide further impetus to combine different tools and approaches in advancing the understanding of species evolutionary histories.
Developmental Integration of Endosymbionts in Insects
Authors: Rafiqi Ab. Matteen , Polo Priscila G. , Milat Nihan Sultan , Durmuş Zelal Özgür , Çolak-Al Birgül , Alarcón Mauricio E. , Çağıl Fatma Zehra , Rajakumar Arjuna
Published: May 2022

In endosymbiosis, two independently existing entities are inextricably intertwined such that they behave as a single unit. For multicellular hosts, the endosymbiont must be integrated within the host developmental genetic network to maintain the relationship. Developmental integration requires innovations in cell type, gene function, gene regulation, and metabolism. These innovations are contingent upon the existing ecological interactions and may evolve mutual interdependence. Recent studies have taken significant steps toward characterizing the proximate mechanisms underlying interdependence. However, the study of developmental integration is only in its early stages of investigation. Here, we review the literature on mutualistic endosymbiosis to explore how unicellular endosymbionts developmentally integrate into their multicellular hosts with emphasis on insects as a model. Exploration of this process will help gain a more complete understanding of endosymbiosis. This will pave the way for a better understanding of the endosymbiotic theory of evolution in the future.
Use of Molasses-Based Blocks to Modify Grazing Patterns and Increase Highland Cattle Impacts on Alnus viridis-Encroached Pastures
Authors: Svensk Mia , Nota Ginevra , Mariotte Pierre , Pittarello Marco , Barberis Davide , Lonati Michele , Allan Eric , Perotti Elisa , Probo Massimiliano
Published: May 2022

Alnus viridis is a pioneer species that has expanded in Central Europe in the last decades, causing a series of negative agro-environmental impacts. Robust livestock grazing could be used as a targeted tool to reduce its encroachment, but more information is needed to find the best approach to achieve this goal. In this study, we assessed the potential of molasses-based blocks (MB) to lure Highland cattle into A. viridis-encroached areas and monitored impacts on the vegetation after grazing. In 2019 and 2020, two Highland cattle herds equipped with GPS collars were placed in three paddocks in the Swiss and Italian Alps, differing in the degree of A. viridis encroachment. In 2020, MB were added to highly encroached areas within each paddock to attract the herds to feed on A. viridis. Botanical surveys were carried out before and after grazing, around MB and control areas. Highland cattle grazed significantly more around MB (up to 50 m from the MB) compared to the previous year (i.e., same area without MB) and compared to control areas. The increased targeted grazing around MB led to a significant decrease in herbaceous cover and an increase in bare soil compared to control areas. Livestock grazing and trampling significantly reduced the cover of ferns, tall herbs, medium and small herbs, and woody species around MB compared to control areas. A. viridis leaves and branches were significantly removed and damaged up to 10 m from the MB, due to the more intense livestock grazing. Such results highlight the potential of this management regime to effectively reduce A. viridis encroachment in montane grasslands.
Identification of Candidate Therapeutic Genes for More Precise Treatment of Esophageal Squamous Cell Carcinoma and Adenocarcinoma
Authors: Polewko-Klim Aneta , Zhu Sibo , Wu Weicheng , Xie Yijing , Cai Ning , Zhang Kexun , Zhu Zhen , Qing Tao , Yuan Ziyu , Xu Kelin , Zhang Tiejun , Lu Ming , Ye Weimin , Chen Xingdong , Suo Chen , Rudnicki Witold R.
Published: May 2022

The standard therapy administered to patients with advanced esophageal cancer remains uniform, despite its two main histological subtypes, namely esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinoma (AC), are being increasingly considered to be different. The identification of potential drug target genes between SCC and AC is crucial for more effective treatment of these diseases, given the high toxicity of chemotherapy and resistance to administered medications. Herein we attempted to identify and rank differentially expressed genes (DEGs) in SCC vs. AC using ensemble feature selection methods. RNA-seq data from The Cancer Genome Atlas and the Fudan-Taizhou Institute of Health Sciences (China). Six feature filters algorithms were used to identify DEGs. We built robust predictive models for histological subtypes with the random forest (RF) classification algorithm. Pathway analysis also be performed to investigate the functional role of genes. 294 informative DEGs (87 of them are newly discovered) have been identified. The areas under receiver operator curve (AUC) were higher than 99.5% for all feature selection (FS) methods. Nine genes (i.e., ERBB3, ATP7B, ABCC3, GALNT14, CLDN18, GUCY2C, FGFR4, KCNQ5, and CACNA1B) may play a key role in the development of more directed anticancer therapy for SCC and AC patients. The first four of them are drug targets for chemotherapy and immunotherapy of esophageal cancer and involved in pharmacokinetics and pharmacodynamics pathways. Research identified novel DEGs in SCC and AC, and detected four potential drug targeted genes (ERBB3, ATP7B, ABCC3, and GALNT14) and five drug-related genes.
Contrasting Patterns of Genetic Diversity and Divergence Between Landlocked and Migratory Populations of Fish Galaxias maculatus, Evaluated Through Mitochondrial DNA Sequencing and Nuclear DNA Microsatellites
Authors: Astorga Marcela P. , Valenzuela Andrea , Segovia Nicolás I. , Poulin Elie , Vargas-Chacoff Luis , González-Wevar Claudio A.
Published: May 2022

Galaxias species are interesting biogeographic models due to their distribution and different types of life cycles, with migratory and landlocked populations. To obtain a better understanding of the genetic consequences of the Quaternary glacial cycles in Galaxias maculatus, in this work we compared landlocked and migratory populations collected in areas that were differentially affected by ice advances and retreats. We included nine populations of G. maculatus, four collected from lakes (landlocked) and five from their associated estuaries/rivers (migratory) in three estuary-lake systems across southern Chile. Genetic analyses were performed using the mitochondrial control region and nine microsatellite loci. Genetic diversity measured with both markers was significantly higher in migratory than in landlocked populations across the study area. The levels of genetic differentiation showed higher differentiation among lakes than estuaries. Genetic diversity was higher in migratory populations located in areas that were less impacted by ice during Quaternary glacial processes. These results may be the consequence of recent recolonization of small freshwater bodies following the Last Glacial Maximum (LGM). Finally, the greatest differentiation was observed in populations that were exposed to continental ice advances and retreats during the LGM. Thus, in the present work we corroborate a pattern of differentiation between lakes and estuaries, using mtDNA sequences and microsatellite nuclear markers. This pattern may be due to a combination of biological factors, i.e., resident non-migratory behaviour or landlocking and natal homing-in, as well as geological factors, i.e., Expansion-Contraction Quaternary glacial biogeographic processes.
Phylogenetic Analysis of Small Hive Beetles From Native to Introduced Populations
Authors: Bai Wen Feng , Liu Junfeng , Liu Yuanzhen , Han Wensu , Evans Jay D. , Huang Qiang
Published: May 2022

The small hive beetle (SHB), a social parasite of beehives, is native to sub-Saharan Africa and has spread to America, Europe, and Australia. Recently, these beetles invaded China, causing widespread colony collapses in the honeybee, Apis cerana. In this study, single nucleotide polymorphisms (SNPs) were identified in the beetle genome from its native range (Africa), a region that was invaded by SHBs nearly 30 years ago (America), and more recent invasions (Asia). The beetles in the United States formed the earliest branch and show signs of two decades of gene flow and local adaptation to differentiate this population from the native ones. The beetles in China were deep branched and showed the highest fixation index when compared to the US populations. The number of SNPs in overexpressed genes was significantly higher than the transcriptome. Gene-expression profiles presented here distinguish the characters between adult and larvae SHBs.
Increased Tuberculosis Incidence Due to Immunotherapy Based on PD-1 and PD-L1 Blockade: A Systematic Review and Meta-Analysis
Authors: Liu Kewei , Wang Dongpo , Yao Cong , Qiao Min , Li Qing , Ren Weicong , Li Shanshan , Gao Mengqiu , Pang Yu
Published: May 2022

Objectives

In this study, we conducted a systematic review to determine tuberculosis (TB) incidence due to immunotherapy with programmed cell death protein-1 (PD-1)/PD ligand (PD-L1) blockade in cancer patients.

Methods

We searched PubMed, Cochrance Library, Excerpt Medica Database (Embase), ClinicalTrials.gov, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure Database (CNKI), Wanfang and China Science and Technology Journal Database to identify studies between January 1, 2000 and April 30, 2021, on the reports of TB cases in patients treated with PD-1/PD-L1 blockade. Methodological quality of eligible studies was assessed, and random-effect model meta-analysis was performed to generate the pooled incidence estimate of TB cases in patients undergoing PD-1/PD-L1 therapy.

Results

We initially identified 745 records, of which 27 studies ultimately met the inclusion criteria and were included in our meta-analysis. A total of 35 TB cases occurred among patients treated with PD-1/PD-L1 blockade. Nivolumab (51.4%) was the most frequently used PD-1/PD-L1 blockade for cancer treatment. In addition, pulmonary TB was the most common form of tuberculosis seen in 77.1% cases. Clinical outcomes were recorded in 18 patients, of whom 77.8% were cured or achieved remission, and 22.2% were died of TB. Pooled analysis determined that the TB rate in this population was 2,000 cases per 100,000 persons, and the estimated rate for TB associated with PD-1/PD-L1 blockade was 35 times higher than that in the general population.

Conclusion

To conclude, our results demonstrate that the clinical use of PD-1/PD-L1 inhibitors significantly increases risk of TB reactivation. An extremely high mortality rate due to TB disease is noted in the patients with PD-1/PD-L1 blockade.
Natural Compounds Tapinarof and Galactomyces Ferment Filtrate Downregulate IL-33 Expression via the AHR/IL-37 Axis in Human Keratinocytes
Authors: Tsuji Gaku , Hashimoto-Hachiya Akiko , Matsuda-Taniguchi Tomoyo , Takai-Yumine Ayako , Takemura Masaki , Yan Xianghong , Furue Masutaka , Nakahara Takeshi
Published: May 2022

Interleukin (IL)-37 suppresses systemic and local inflammation. It is expressed in the epidermis, the external layer of the skin, and is decreased in inflammatory skin diseases including atopic dermatitis (AD) and psoriasis. Therefore, an agent applied topically on the skin that can increase IL-37 could be promising for treating AD and psoriasis; however, the mechanism regulating IL-37 remains largely unknown. Given that IL-37 expression is induced in differentiated keratinocytes, a major component of the epidermis, and that activation of aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, promotes keratinocyte differentiation, we hypothesized that AHR might be involved in the IL-37 expression in human keratinocytes. We analyzed normal epidermal human keratinocytes (NHEKs) treated with tapinarof and Galactomyces ferment filtrate (GFF), which are potent AHR modulators. We found that tapinarof and GFF upregulated IL-37 in NHEKs, which was canceled by the knockdown of AHR using siRNA transfection, indicating that AHR mediates IL-37 expression in NHEKs. Furthermore, we found that the knockdown of IL-37 resulted in the upregulation of IL-33, an alarmin cytokine with crucial roles in the pathogenesis of AD and psoriasis. These findings suggest that IL-37 negatively regulates IL-33 expression in NHEKs. Finally, we examined whether tapinarof and GFF treatment modulates IL-33 expression in NHEKs. Such treatment inhibited IL-33 expression, which was partially reversed by the knockdown of either AHR or IL-37. Taken together, our findings provide the first evidence that tapinarof and GFF could have potential to prevent IL-33-overexpressing disorders such as AD and psoriasis via the AHR/IL-37 axis.
N6-Acetyl-L-Lysine and p-Cresol as Key Metabolites in the Pathogenesis of COVID-19 in Obese Patients
Authors: Jalaleddine Nour , Hachim Mahmood , Al-Hroub Hamza , Saheb Sharif-Askari Narjes , Senok Abiola , Elmoselhi Adel , Mahboub Bassam , Samuel Kurien Nimmi Moni , Kandasamy Richard K. , Semreen Mohammad H. , Halwani Rabih , Soares Nelson C. , Al Heialy Saba
Published: May 2022

Despite the growing number of the vaccinated population, COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global health burden. Obesity, a metabolic syndrome affecting one-third of the population, has proven to be a major risk factor for COVID-19 severe complications. Several studies have identified metabolic signatures and disrupted metabolic pathways associated with COVID-19, however there are no reports evaluating the role of obesity in the COVID-19 metabolic regulation. In this study we highlight the involvement of obesity metabolically in affecting SARS-CoV-2 infection and the consequent health complications, mainly cardiovascular disease. We measured one hundred and forty-four (144) metabolites using ultra high-performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) to identify metabolic changes in response to SARS-CoV-2 infection, in lean and obese COVID-19 positive (n=82) and COVID-19 negative (n=24) patients. The identified metabolites are found to be mainly correlating with glucose, energy and steroid metabolisms. Further data analysis indicated twelve (12) significantly yet differentially abundant metabolites associated with viral infection and health complications, in COVID-19 obese patients. Two of the detected metabolites, n6-acetyl-l-lysine and p-cresol, are detected only among the COVID-19 cohort, exhibiting significantly higher levels in COVID-19 obese patients when compared to COVID-19 lean patients. These metabolites have important roles in viral entry and could explain the increased susceptibility of obese patients. On the same note, a set of six metabolites associated with antiviral and anti-inflammatory functions displayed significantly lower abundance in COVID-19 obese patients. In conclusion, this report highlights the plasma metabolome of COVID-19 obese patients as a metabolic feature and signature to help improve clinical outcomes. We propose n6-acetyl-l-lysine and p-cresol as potential metabolic markers which warrant further investigations to better understand their involvement in different metabolic pathways in COVID-19.
Recent Progress in Recombinant Influenza Vaccine Development Toward Heterosubtypic Immune Response
Authors: Carascal Mark B. , Pavon Rance Derrick N. , Rivera Windell L.
Published: May 2022

Flu, a viral infection caused by the influenza virus, is still a global public health concern with potential to cause seasonal epidemics and pandemics. Vaccination is considered the most effective protective strategy against the infection. However, given the high plasticity of the virus and the suboptimal immunogenicity of existing influenza vaccines, scientists are moving toward the development of universal vaccines. An important property of universal vaccines is their ability to induce heterosubtypic immunity, i.e., a wide immune response coverage toward different influenza subtypes. With the increasing number of studies and mounting evidence on the safety and efficacy of recombinant influenza vaccines (RIVs), they have been proposed as promising platforms for the development of universal vaccines. This review highlights the current progress and advances in the development of RIVs in the context of heterosubtypic immunity induction toward universal vaccine production. In particular, this review discussed existing knowledge on influenza and vaccine development, current hemagglutinin-based RIVs in the market and in the pipeline, other potential vaccine targets for RIVs (neuraminidase, matrix 1 and 2, nucleoprotein, polymerase acidic, and basic 1 and 2 antigens), and deantigenization process. This review also provided discussion points and future perspectives in looking at RIVs as potential universal vaccine candidates for influenza.
High Expression of CKS2 Predicts Adverse Outcomes: A Potential Therapeutic Target for Glioma
Authors: Yu Kai , Ji Yulong , Liu Min , Shen Fugeng , Xiong Xiaoxing , Gu Lijuan , Lu Tianzhu , Ye Yingze , Feng Shi , He Jianying
Published: May 2022

Cyclin-dependent kinase regulatory subunit 2 (CKS2) is a potential prognostic marker and is overexpressed in various cancers. This study analyzed sequencing and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus, with external validation using the Chinese Glioma Genome Atlas (CGGA) data. CKS2 expression in the normal brain and tumor tissue was compared. cBioPortal and MethSurv were utilized to scrutinize the prognostic value of CKS2 methylation. Gene set enrichment examination and single-sample gene set enrichment analysis were employed to explore the potential biological functions of CKS2. Cell viability, colony formation, and transwell assays were conducted to evaluate the influence of CKS2 on glioma cell proliferation and invasion. Compared with normal brain tissue, the expression of CKS2 was upregulated in glioma samples (p < 0.001). Multivariate data analysis from TCGA and CGGA indicated that increased expression of CKS2 was an independent risk factor for the prognosis of overall survival in glioma patients. CKS2 methylation was negatively associated with CKS2 expression. Patients with CKS2 hypomethylation had worse overall survival compared with patients with CKS2 methylation, as suggested by the analysis of both TCGA and CGGA datasets. The expression level of CKS2 is closely related to tumor immunity, including the correlation of tumor immune cell infiltration, immune score, and co-expression of multiple immune-related genes. In addition, CKS2 is associated with several immune checkpoints and responses to the chemotherapy drug cisplatin. CKS2 knockdown impeded the expansion and aggression of glioma cell lines. The changes in CKS2 expression may provide a novel prognostic biomarker that can be used to improve patient overall survival rates.
Modulation of Lymphocyte Functions in the Microenvironment by Tumor Oncogenic Pathways
Authors: Seliger Barbara , Massa Chiara
Published: May 2022

Despite the broad application of different immunotherapeutic strategies for the treatment of solid as well as hematopoietic cancers, the efficacy of these therapies is still limited, with only a minority of patients having a long-term benefit resulting in an improved survival rate. In order to increase the response rates of patients to the currently available immunotherapies, a better understanding of the molecular mechanisms underlying the intrinsic and/or extrinsic resistance to treatment is required. There exist increasing evidences that activation of different oncogenic pathways as well as inactivation of tumor suppressor genes (TSG) in tumor cells inhibit the immune cell recognition and influegnce the composition of the tumor microenvironment (TME), thus leading to an impaired anti-tumoral immune response. A deeper understanding of the link between the tumor milieu and genomic alterations of TSGs and oncogenes is indispensable for the optimization of immunotherapies and to predict the patients’ response to these treatments. This review summarizes the role of different cancer-related, oncogene- and TSG-controlled pathways in the context of anti-tumoral immunity and response to different immunotherapies.
Effects of Fucoidan Isolated From Laminaria japonica on Immune Response and Gut Microbiota in Cyclophosphamide-Treated Mice
Authors: Tang Yunping , Pu Qiuyan , Zhao Qiaoling , Zhou Yafeng , Jiang Xiaoxia , Han Tao
Published: May 2022

The effects of Laminaria japonica fucoidan (LF) on immune regulation and intestinal microflora in cyclophosphamide (CTX)-treated mice were investigated in this work. Results indicated that LF significantly enhanced the spleen and thymus indices, promoted spleen lymphocyte and peritoneal macrophages proliferation, and increased the immune-related cytokines production in serum. Moreover, LF could regulate intestinal flora composition, increasing the abundance of Lactobacillaceae and Alistipes, and inhibiting Erysipelotrichia, Turicibacter, Romboutsia, Peptostreptococcaceae, and Faecalibaculum. These results were positively correlated with immune characteristics. Overall, LF could be useful as a new potential strategy to mitigate CTX immunosuppression and intestinal microbiota disorders.
Generation of Transgenic Mosquitoes Harboring a Replication-Restricted Virus
Authors: Shinzawa Naoaki , Kashima Chisako , Aonuma Hiroka , Takahashi Kei , Shimojima Masayuki , Fukumoto Shinya , Saiki Erisha , Yamamoto Daisuke S. , Yoshida Shigeto , Matsuoka Hiroyuki , Kawaoka Yoshihiro , Kanuka Hirotaka
Published: May 2022

Live microbe vaccines are designed to elicit strong cellular and antibody responses without developing the symptoms of the disease, and these are effective in preventing infectious diseases. A flying vaccinator (also known as a flying syringe) is a conceptual, genetically engineered hematophagous insect that is used to deliver vaccines such as an antigen from a parasite produced in mosquito saliva; bites from such insects may elicit antibody production by immunizing the host with an antigen through blood-feeding. In addition to a simple vaccine antigen, a flying vaccinator may potentially load a live attenuated microbe with an appropriate mechanism for sustaining its constitutive proliferation in the insect. In this study, a recombinant vesicular stomatitis virus (VSV) lacking the glycoprotein gene (VSV-G) was used to produce replication-restricted VSV (rrVSV) containing GFP. Transgenic Anopheles stephensi mosquitoes, in which the salivary glands expressed a VSV-G gene driven by an aapp salivary gland-specific promoter, were generated and injected intraperitoneally with rrVSV. The injected rrVSV entered the cells of the salivary gland and stimulated endogenous production of progeny rrVSV particles, as seen in rrVSV-infected Drosophila melanogaster expressing VSV-G. These data suggested the possibility of developing a valuable tool for delivering genetically attenuated virus vaccines via mosquito saliva, although efficient replication-restricted virus production is required.
Temporal Variability of Co-Occurring Calanus finmarchicus and C. helgolandicus in Skagerrak
Authors: Falkenhaug Tone , Broms Cecilie , Bagøien Espen , Nikolioudakis Nikolaos
Published: May 2022

The congeneric copepods Calanus finmarchicus and C. helgolandicus co-occur in the northern North Sea and Skagerrak where they play important roles as prey for higher trophic levels. This study analyses a 26-year time series (1994-2019) with a ~ two-week temporal resolution for Calanus spp. at a fixed monitoring station in Skagerrak, off southern Norway. Seasonal variation, inter-annual variability and long-term trends for the two species were examined. Strong differences in the species-specific seasonality were revealed, with C. finmarchicus dominating in spring and C. helgolandicus in autumn. The seasonal peak of C. finmarchicus was associated with relatively low temperatures (6-8°C) and high chlorophyll a concentration, while C. helgolandicus displayed its seasonal maximum at higher temperatures (11-16°C). C. finmarchicus was found to produce one dominant annual generation (in spring), but two or more generations are considered likely. Contrasting long-term trends in abundances were found for the two species, suggesting that their population sizes were affected by different mechanisms. The abundance of C. helgolandicus showed an increasing trend over the time period studied, apart from the last years. The abundance of C. finmarchicus was more variable and displayed no unidirectional long-term trends over the time series. The study revealed a shift in the phenology of Calanus spp. over the last 25 years at this site. Since 1994 the timing of the annual peaks in both C. finmarchicus and C. helgolandicus have advanced by about one month. Moreover, the seasonal pattern of C. helgolandicus, switched from a unimodal to a bimodal pattern around 2002, with a small additional peak also appearing in spring. The results suggest that the proximity to the Norwegian Trench influences the demography and abundance of C. finmarchicus in this coastal area, both as a gateway for the advective supply, as well as a habitat for local overwintering.
Evaluation of UV-B Ameliorating Properties of Indigenous Plants Ashwagandha Withania somnifera (Dunal), Amla Emblica officinalis (Gaertn), and Prickly Chaff Flower Achyranthes aspera (L.) Supplemented Diets in Prior UV-B Exposed Catla catla
Authors: Sharma JaiGopal , Singh Moirangthem Kameshwor , Chakrabarti Rina
Published: May 2022

Ultraviolet B (UV-B) radiation is a potent environmental stressor and it severely affects the survival, growth, and physiology of aquatic organisms. The UV-B protective properties of three herbal ingredients enriched diets were evaluated in pre-exposedCatla catla. Fish (70.38 ± 1.18 g) were divided into five sets with three replicates each. Four sets were exposed to UV-B (80 µW/cm2) for an initial 10 days (20 min/day), and the fifth one remained unexposed (control). On day 11, feeding with enriched diets started. These diets were: diet 1 (D1) containingWithania somnifera(0.5%) root powder, diet 2 (D2) containingEmblica officinalis(1.25%) fruit powder, diet 3 (D3) containing seeds ofAchyranthes aspera(0.5%), and diet 4 (D4) control. There were two batches of D4 diet-fed fish, D4a, UV-B exposed, and D4b unexposed. Blood and tissue samples were collected on days 0, 7, 14, and 21 of feeding. The average weight reduced 26.32% in UV-B exposed catla compared to the unexposed one on day 0. Among the exposed fish, average weight was significantly higher in D3 compared to others throughout the study period. Significantly lower nitric oxide synthase (NOS) and higher thiobarbituric acid reactive substances (TBARS), carbonyl protein, superoxide dismutase (SOD), and heat shock proteins (Hsp) 70 and 90 were observed in D4a compared to the enriched diet fed catla. The NOS level was significantly higher in D3 on day 21. The TBARS level was significantly lower in D3 on days 7 and 14 and in D2 and D3 on day 21. The carbonyl protein, SOD, and Hsp70 levels were always significantly lower in D3 compared to others, and D2 followed D3 treatment. Hsp 90 was significantly lower in D2 compared to others on day 7 and in D3 on days 14 and 21. All three enriched diets helped the fish overcome the harmful effect of UV-B radiation, and the D3 diet-fed fish showed the best performance.
Bone Response to Osteopontin-Functionalized Carboxyethylphosphonic Acid-Modified Implants. Experimental Study in a Minipig Model
Authors: Aragoneses Javier , López-Valverde Nansi , López-Valverde Antonio , Rodríguez Cinthia , Macedo De Sousa Bruno , Aragoneses Juan Manuel
Published: May 2022

Currently, dental implants have become a common and reliable treatment for restoring masticatory function in edentulous patients. Their surface topography is of great importance for the adhesion and remodeling of bone cells, both in the initial phases and over time, and different strategies have been proposed to improve the biological performance of conventional sandblasted, large-grit, acid-etched implant surfaces. Corrosion has been identified as one of the causes of implant failure due to contact with oral fluids. Carboxyethylphosphonic acid is a potent anticorrosive that would form stable bonds with titanium oxide, generating an organic layer on which modifications could be made to improve cell adhesion. Osteopontin is considered a molecule capable of improving the osseointegration of titanium. Our study evaluated the osseointegration capacity of titanium implants modified with carboxyethylphosphonic acid and functionalized with osteopontin in a minipig model. A total of 16 implants were inserted in the tibial diaphysis of two minipigs, 8 implants modified with carboxyethylphosphonic acid and functionalized with osteopontin from the experimental group and 8 from the control group with sandblasted, large-grit, acid-etched surface treatment. After 4 weeks, the animals were sacrificed and the samples were analyzed by histomorphometric analysis, assessing bone-implant contact, cortical bone-implant contact, percentage of new bone, peri-implant bone density and interthread bone area interthread. Statistical analysis was performed using SPSS v.18. Statistical significance was found between groups for the percentage of new bone (p = 0.04) and for interthread bone area interthread (p = 0.01). Functionalization of titanium surfaces by osteopontin may be of interest for conditioning bone remodeling in the early stages of osseointegration, although more in vivo studies are needed to determine its real influence in this aspect.
Identification of Clinical Phenotypes in Septic Patients Presenting With Hypotension or Elevated Lactate
Authors: Aldewereld Zachary T. , Zhang Li Ang , Urbano Alisa , Parker Robert S. , Swigon David , Banerjee Ipsita , Gómez Hernando , Clermont Gilles
Published: May 2022

Introduction

Targeted therapies for sepsis have failed to show benefit due to high variability among subjects. We sought to demonstrate different phenotypes of septic shock based solely on clinical features and show that these relate to outcome.

Methods

A retrospective analysis was performed of a 1,023-subject cohort with early septic shock from the ProCESS trial. Twenty-three clinical variables at baseline were analyzed using hierarchical clustering, with consensus clustering used to identify and validate the ideal number of clusters in a derivation cohort of 642 subjects from 20 hospitals. Clusters were visualized using heatmaps over 0, 6, 24, and 72 h. Clinical outcomes were 14-day all-cause mortality and organ failure pattern. Cluster robustness was confirmed in a validation cohort of 381 subjects from 11 hospitals.

Results

Five phenotypes were identified, each with unique organ failure patterns that persisted in time. By enrollment criteria, all patients had shock. The two high-risk phenotypes were characterized by distinct multi-organ failure patterns and cytokine signatures, with the highest mortality group characterized most notably by liver dysfunction and coagulopathy while the other group exhibited primarily respiratory failure, neurologic dysfunction, and renal dysfunction. The moderate risk phenotype was that of respiratory failure, while low-risk phenotypes did not have a high degree of additional organ failure.

Conclusions

Sepsis phenotypes with distinct biochemical abnormalities may be identified by clinical characteristics alone and likely provide an opportunity for early clinical actionability and prognosis.
Contrast Sensitivity Deficits and Its Structural Correlates in Fuchs Uveitis Syndrome
Authors: Zhou Fang-Yue , Li Yi-Sha , Guo Xingneng , Shi Xiutong , Wu Ke , Zheng Jing-Wei , Li Xia-Xin , Wu Jiaqing , Liu Ruru , Dai Ma-Li , Huang Xiu-Feng , Hou Fang , Lin Dan , Wang Yu-Qin
Published: May 2022

Purpose

To investigate the deficits in contrast sensitivity in patients with Fuchs uveitis syndrome (FUS) and to explore the potential relationship between contrast sensitivity and ocular structure.

Methods

In this prospective study, 25 patients with FUS and 30 healthy volunteers were recruited. Eyes were divided into three groups: FUS-affected eyes (AE), fellow eyes (FE), and healthy eyes. The contrast sensitivity function (CSF) of all participants was evaluated using the quick CSF (qCSF) method. Fundus photographs were collected for the analysis of refractive media, and vascular density (VD) was assessed using optical coherence tomography angiography (OCTA). Data were analyzed and compared using the generalized estimating equation (GEE).

Results

The CSF of AE was significantly lower than that of FE and controls, while no significant difference was observed between FE and controls. Contrast sensitivity was negatively correlated with the grade of haze. No significant correlation was found between visual function and VDs in FUS eyes.

Conclusions

We found that the CSF of FUS-affected eyes was significantly reduced, and the visual impairment was predominantly caused by the refractive media turbidity.
Experiences, Challenges, and Coping Strategies of Frontline Healthcare Providers in Response to the COVID-19 Pandemic in Kelantan, Malaysia
Authors: Che Yusof Ruhana , Norhayati Mohd Noor , Azman Yacob Mohd
Published: May 2022

Introduction

In the fight against the COVID-19 pandemic, frontline healthcare providers who are engaged in the direct diagnosis, treatment, and care of patients face a high risk of infection and inadequate protection from contamination, overwork, frustration, and exhaustion. These impose significant psychological and mental health concerns for frontline healthcare providers.

Objectives

This study aimed to explore the experiences and challenges faced and coping strategies adopted by frontline healthcare providers in response to the COVID-19 pandemic in Kelantan, Malaysia.

Methodology

This phenomenological approach to qualitative study used a telephone-based in-depth interview that followed a semistructured interview guide. The number of frontline healthcare providers was based on saturation theory. All the participants recruited fulfilled the inclusion and exclusion criteria from May to July 2020 in Raja Perempuan Zainab II Hospital. All interviews were audio recorded and transcribed verbatim. Thematic data analysis using NVIVO version 10 was performed.

Result

The 10 respondents involved in this study consisted of doctors, medical assistants, and nurses. The findings were divided into four main themes: invaluable experiences during the pandemic, challenges, coping strategies, and future expectations. The providers responded well in facing the disease even though they felt psychologically disturbed at the initial phase of the COVID-19 pandemic.

Conclusion

Healthcare providers perceived themselves as being more resilient and less vulnerable to psychological impacts than they were before the pandemic.
Monitoring Long Term Noninvasive Ventilation: Benefits, Caveats and Perspectives
Authors: Janssens Jean-Paul , Cantero Chloé , Pasquina Patrick , Georges Marjolaine , Rabec Claudio
Published: May 2022

Long term noninvasive ventilation (LTNIV) is a recognized treatment for chronic hypercapnic respiratory failure (CHRF). COPD, obesity-hypoventilation syndrome, neuromuscular disorders, various restrictive disorders, and patients with sleep-disordered breathing are the major groups concerned. The purpose of this narrative review is to summarize current knowledge in the field of monitoring during home ventilation. LTNIV improves symptoms related to CHRF, diurnal and nocturnal blood gases, survival, and health-related quality of life. Initially, patients with LTNIV were most often followed through elective short in-hospital stays to ensure patient comfort, correction of daytime blood gases and nocturnal oxygenation, and control of nocturnal respiratory events. Because of the widespread use of LTNIV, elective in-hospital monitoring has become logistically problematic, time consuming, and costly. LTNIV devices presently have a built-in software which records compliance, leaks, tidal volume, minute ventilation, cycles triggered and cycled by the patient and provides detailed pressure and flow curves. Although the engineering behind this information is remarkable, the quality and reliability of certain signals may vary. Interpretation of the curves provided requires a certain level of training. Coupling ventilator software with nocturnal pulse oximetry or transcutaneous capnography performed at the patient's home can however provide important information and allow adjustments of ventilator settings thus potentially avoiding hospital admissions. Strategies have been described to combine different tools for optimal detection of an inefficient ventilation. Recent devices also allow adapting certain parameters at a distance (pressure support, expiratory positive airway pressure, back-up respiratory rate), thus allowing progressive changes in these settings for increased patient comfort and tolerance, and reducing the requirement for in-hospital titration. Because we live in a connected world, analyzing large groups of patients through treatment of “big data” will probably improve our knowledge of clinical pathways of our patients, and factors associated with treatment success or failure, adherence and efficacy. This approach provides a useful add-on to randomized controlled studies and allows generating hypotheses for better management of HMV.
Occurrence and Risk Factors for New Dependency on Chronic Care, Respiratory Support, Dialysis and Mortality in the First Year After Sepsis
Authors: Spoden Melissa , Hartog Christiane S. , Schlattmann Peter , Freytag Antje , Ostermann Marlies , Wedekind Lisa , Storch Josephine , Reinhart Konrad , Günster Christian , Fleischmann-Struzek Carolin
Published: May 2022

Sepsis survival is associated with adverse outcomes. Knowledge about risk factors for adverse outcomes is lacking. We performed a population-based cohort study of 116,507 survivors of hospital-treated sepsis identified in health claims data of a German health insurance provider. We determined the development and risk factors for long-term adverse events: new dependency on chronic care, chronic dialysis, long-term respiratory support, and 12-month mortality. At-risk patients were defined by absence of these conditions prior to sepsis. Risk factors were identified using simple and multivariable logistic regression analyses. In the first year post-sepsis, 48.9% (56,957) of survivors had one or more adverse outcome, including new dependency on chronic care (31.9%), dialysis (2.8%) or respiratory support (1.6%), and death (30.7%). While pre-existing comorbidities adversely affected all studied outcomes (>4 comorbidities: OR 3.2 for chronic care, OR 4.9 for dialysis, OR 2.7 for respiratory support, OR 4.7 for 12-month mortality), increased age increased the odds for chronic care dependency and 12-month mortality, but not for dialysis or respiratory support. Hospital-acquired and multi-resistant infections were associated with increased risk of chronic care dependency, dialysis, and 12-month mortality. Multi-resistant infections also increased the odds of respiratory support. Urinary or respiratory infections or organ dysfunction increased the odds of new dialysis or respiratory support, respectively. Central nervous system infection and organ dysfunction had the highest OR for chronic care dependency among all infections and organ dysfunctions. Our results imply that patient- and infection-related factors have a differential impact on adverse life changing outcomes after sepsis. There is an urgent need for targeted interventions to reduce the risk.
Efficient Assay and Marker Significance of NAD+ in Human Blood
Authors: Balashova Natalia V. , Zavileyskiy Lev G. , Artiukhov Artem V. , Shaposhnikov Leonid A. , Sidorova Olga P. , Tishkov Vladimir I. , Tramonti Angela , Pometun Anastasia A. , Bunik Victoria I.
Published: May 2022

Oxidized nicotinamide adenine dinucleotide (NAD+) is a biological molecule of systemic importance. Essential role of NAD+ in cellular metabolism relies on the substrate action in various redox reactions and cellular signaling. This work introduces an efficient enzymatic assay of NAD+ content in human blood using recombinant formate dehydrogenase (FDH, EC 1.2.1.2), and demonstrates its diagnostic potential, comparing NAD+ content in the whole blood of control subjects and patients with cardiac or neurological pathologies. In the control group (n = 22, 25–70 years old), our quantification of the blood concentration of NAD+ (18 μM, minimum 15, max 23) corresponds well to NAD+ quantifications reported in literature. In patients with demyelinating neurological diseases (n = 10, 18–55 years old), the NAD+ levels significantly (p < 0.0001) decrease (to 14 μM, min 13, max 16), compared to the control group. In cardiac patients with the heart failure of stage II and III according to the New York Heart Association (NYHA) functional classification (n = 24, 42–83 years old), the blood levels of NAD+ (13 μM, min 9, max 18) are lower than those in the control subjects (p < 0.0001) or neurological patients (p = 0.1). A better discrimination of the cardiac and neurological patients is achieved when the ratios of NAD+ to the blood creatinine levels, mean corpuscular volume or potassium ions are compared. The proposed NAD+ assay provides an easy and robust tool for clinical analyses of an important metabolic indicator in the human blood.
Association Between Monocyte to High-Density Lipoprotein Cholesterol Ratio and Risk of Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study
Authors: Wang Liping , Dong Jinzhong , Xu Miao , Li Li , Yang Naibin , Qian Guoqing
Published: May 2022

Background:

Non-alcoholic fatty liver disease (NAFLD) is a global health problem affecting more than a quarter of the entire adult population. Both monocytes and high-density lipoprotein cholesterol (HDL-C) were found to participate in the progression of hepatic inflammation and oxidative stress. We speculated that the monocyte-to-HDL-C ratio (MHR) may be associated with the risk of NAFLD.

Methods

We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018. NAFLD was identified using a controlled attenuation parameter (CAP) of ≥274 dB/m. Degree of liver fibrosis were assessed by liver stiffness measurement (LSM) and LSM values≥8.0, ≥ 9.7, and ≥13.7 kPa were defined as significant fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis (F4), respectively. The association between MHR and the risk of NAFLD and liver fibrosis was estimated using weighted multivariable logistic regression. The non-linear relationship between MHR and the risk of NAFLD was further described using smooth curve fittings and threshold effect analysis.

Results

Of 4,319 participants, a total of 1,703 (39.4%) participants were diagnosed with NAFLD. After complete adjustment for potential confounders, MHR was positively associated with the risk of NAFLD (OR = 2.87, 95% CI: 1.95–4.22). The risk of NAFLD increased progressively as the MHR quarter increased (P for trend < 0.001). In subgroup analysis stratified by sex, a positive association existed in both sexes; Women displayed higher risk (men: OR = 2.12, 95% CI: 1.33–3.39; women: OR = 2.64, 95%CI: 1.40–4.97). MHR was positively associated with the risk of significant liver fibrosis (OR = 1.60, 95% CI: 1.08–2.37) and cirrhosis (OR = 1.83, 95% CI: 1.08–3.13), but not with advanced liver fibrosis (OR = 1.53, 95% CI: 0.98–2.39) after full adjustment for potential confounders. In the subgroup analysis by sex, the association between MHR and different degrees of liver fibrosis was significantly positive in women. When analyzing the relationship between MHR and NAFLD risk, a reverse U-shaped curve with an inflection point of 0.36 for MHR was found in women.

Conclusion

Higher MHR was associated with increased odds of NAFLD among Americans of both sexes. However, an association between MHR and liver fibrosis was found mainly among women.