bluuebunny/crossref_metadata_2025 huggingface dataset:
Greater Mitochondrial Energy Production Provides Resistance to Ocean Acidification in “Winning” Hermatypic Corals
Authors: Agostini Sylvain , Houlbrèque Fanny , Biscéré Tom , Harvey Ben P. , Heitzman Joshua M. , Takimoto Risa , Yamazaki Wataru , Milazzo Marco , Rodolfo-Metalpa Riccardo
Published: January 2021

Coral communities around the world are projected to be negatively affected by ocean acidification. Not all coral species will respond in the same manner to rising CO2 levels. Evidence from naturally acidified areas such as CO2 seeps have shown that although a few species are resistant to elevated CO2, most lack sufficient resistance resulting in their decline. This has led to the simple grouping of coral species into “winners” and “losers,” but the physiological traits supporting this ecological assessment are yet to be fully understood. Here using CO2 seeps, in two biogeographically distinct regions, we investigated whether physiological traits related to energy production [mitochondrial electron transport systems (ETSAs) activities] and biomass (protein contents) differed between winning and losing species in order to identify possible physiological traits of resistance to ocean acidification and whether they can be acquired during short-term transplantations. We show that winning species had a lower biomass (protein contents per coral surface area) resulting in a higher potential for energy production (biomass specific ETSA: ETSA per protein contents) compared to losing species. We hypothesize that winning species inherently allocate more energy toward inorganic growth (calcification) compared to somatic (tissue) growth. In contrast, we found that losing species that show a higher biomass under reference pCO2 experienced a loss in biomass and variable response in area-specific ETSA that did not translate in an increase in biomass-specific ETSA following either short-term (4–5 months) or even life-long acclimation to elevated pCO2 conditions. Our results suggest that resistance to ocean acidification in corals may not be acquired within a single generation or through the selection of physiologically resistant individuals. This reinforces current evidence suggesting that ocean acidification will reshape coral communities around the world, selecting species that have an inherent resistance to elevated pCO2.
Macro and Microstructural Characteristics of North Atlantic Deep-Sea Sponges as Bioinspired Models for Tissue Engineering Scaffolding
Authors: Martins Eva , Rapp Hans Tore , Xavier Joana R. , Diogo Gabriela S. , Reis Rui L. , Silva Tiago H.
Published: January 2021

Sponges occur ubiquitously in the marine realm and in some deep-sea areas they dominate the benthic communities forming complex biogenic habitats – sponge grounds, aggregations, gardens and reefs. However, deep-sea sponges and sponge-grounds are still poorly investigated with regards to biotechnological potential in support of a Blue growth strategy. Under the scope of this study, five dominant North Atlantic deep-sea sponges, were characterized to elucidate promising applications in human health, namely for bone tissue engineering approaches. Geodia barretti (Gb), Geodia atlantica (Ga), Stelletta normani (Sn), Phakellia ventilabrum (Pv), and Axinella infundibuliformis (Ai), were morphologically characterized to assess macro and microstructural features, as well as chemical composition of the skeletons, using optical and scanning electron microscopy, energy dispersive x-ray spectroscopy and microcomputed tomography analyses. Moreover, compress tests were conducted to determine the mechanical properties of the skeletons. Results showed that all studied sponges have porous skeletons with porosity higher than 68%, pore size superior than 149 μm and higher interconnectivity (>96%), thus providing interesting models for the development of scaffolds for tissue engineering. Besides that, EDS analyses revealed that the chemical composition of sponges, pointed that demosponge skeletons are mainly constituted by carbon, silicon, sulfur, and oxygen combined mutually with organic and inorganic elements embedded its internal architecture that can be important features for promoting bone matrix quality and bone mineralization. Finally, the morphological, mechanical, and chemical characteristics here investigated unraveled the potential of deep-sea sponges as a source of biomaterials and biomimetic models envisaging tissue engineering applications for bone regeneration.
Case Report: Glucocorticoids Combined With Immunosuppressant in the Treatment of Acromegaly Complicated With Focal Segmental Glomerulosclerosis
Authors: Wang Ruiqiang , Wu Yunqi , An Dongyue , Ma Pupu , Guo Yuanyuan , Tang Lin
Published: January 2021

Background: Acromegaly is a chronic disease caused by excessive secretion of growth hormone (GH), which circulates and stimulates the liver and body tissues to produce insulin-like growth factor type 1 (IGF-1). Experimental studies have shown that excessive secretion of GH is related to glomerular sclerosis, and elevated IGF-1 levels may be involved in the occurrence of glomerular hypertrophy. But relevant clinical cases are rare. Here, we reported a case of acromegaly complicated with focal segmental glomerulosclerosis (FSGS).

Case Presentation: A 49-year-old man was admitted to our hospital because of acromegaly for more than 10 years and proteinuria for more than 3 years. Acromegaly was confirmed by contrast-enhanced magnetic resonance imaging, minimally invasive surgery and pathology. The results of renal biopsy showed FSGS-NOS (not otherwise specified) with ischemic renal injury and mesangial IgA deposition. One month after transnasal transsphenoidal space occupying resection, GH and urinary protein decreased significantly, and nephropathy was partially relieved. In the next 4 months, GH stabilized at the normal level, while urinary protein gradually increased. When the urinary protein increased to 4.2 g/d, the dosage of glucocorticoids increased to 20 mg/d, and tacrolimus 1 mg/d were added, and the urinary protein decreased again. However, when the urinary protein decreased to 0.43 g/d, the patient stopped taking glucocorticoids and tacrolimus, and the urinary protein increased to 2.85 g/d after 8 months, but the GH was still in the normal range.

Conclusion: In this case, GH is partially involved in the formation of FSGS. Not only does surgery reduce the effects of GH, but low doses of glucocorticoids and immunosuppressant are effective in slowing the progression of kidney disease, at least in reducing urinary protein.
Gene Annotation in High Schools: Successful Student Pipeline and Teacher Professional Development in Bioscience Using GENI-ACT
Authors: Koury Stephen T. , Carlin-Menter Shannon , Dey-Rao Rama , Kelly Kimberle
Published: January 2021

Knowledge of genomics is an essential component of science for high school student health literacy. However, few high school teachers have received genomics training or any guidance on how to teach the subject to their students. This project explored the impact of a genomics and bioinformatics research pipeline for high school teachers and students using an introduction to genome annotation research as the catalyst. The Western New York-based project had three major components: (1) a summer teacher professional development workshop to introduce genome annotation research, (2) teacher-guided student genome annotation group projects during the school year, (3) with an end of the academic year capstone symposium to showcase student work in a poster session. Both teachers and students performed manual gene annotations using an online annotation toolkit known as Genomics Education National Initiative-Annotation Collaboration Toolkit (GENI-ACT), originally developed for use in a college undergraduate teaching environment. During the school year, students were asked to evaluate the data they had collected, formulate a hypothesis about the correctness of the computer pipeline annotation, and present the data to support their conclusions in poster form at the symposium. Evaluation of the project documented increased content knowledge in basic genomics and bioinformatics as well as increased confidence in using tools and the scientific process using GENI-ACT, thus demonstrating that high school students are capable of using the same tools as scientists to conduct a real-world research task.
Analysis of Hepatitis B Virus Genotype D in Greenland Suggests the Presence of a Novel Quasi-Subgenotype
Authors: de Bernardi Schneider Adriano , Osiowy Carla , Hostager Reilly , Krarup Henrik , Børresen Malene , Tanaka Yasuhito , Morriseau Taylor , Wertheim Joel O.
Published: January 2021

A disproportionate number of Greenland's Inuit population are chronically infected with Hepatitis B virus (HBV; 5–10%). HBV genotypes B and D are most prevalent in the circumpolar Arctic. Here, we report 39 novel HBV/D sequences from individuals residing in southwestern Greenland. We performed phylodynamic analyses with ancient HBV DNA calibrators to investigate the origin and relationship of these taxa to other HBV sequences. We inferred a substitution rate of 1.4 × 10−5[95% HPD 8.8 × 10−6, 2.0 × 10−5] and a time to the most recent common ancestor of 629 CE [95% HPD 37–1138 CE]. The Greenland taxa form a sister clade to HBV/D2 sequences, specifically New Caledonian and Indigenous Taiwanese sequences. The Greenland sequences share amino acid signatures with subgenotypes D1 and D2 and ~97% sequence identity. Our results suggest the classification of these novel sequences does not fit within the current nomenclature. Thus, we propose these taxa be considered a novel quasi-subgenotype.
Modification of Transfer RNA Levels Affects Cyclin Aggregation and the Correct Duplication of Yeast Cells
Authors: Arias Loreto , Martínez Fabián , González Daniela , Flores-Ríos Rodrigo , Katz Assaf , Tello Mario , Moreira Sandra , Orellana Omar
Published: January 2021

Codon usage bias (the preferential use of certain synonymous codons (optimal) over others is found at the organism level (intergenomic) within specific genomes (intragenomic) and even in certain genes. Whether it is the result of genetic drift due to GC/AT content and/or natural selection is a topic of intense debate. Preferential codons are mostly found in genes encoding highly-expressed proteins, while lowly-expressed proteins usually contain a high proportion of rare (lowly-represented) codons. While optimal codons are decoded by highly expressed tRNAs, rare codons are usually decoded by lowly-represented tRNAs. Whether rare codons play a role in controlling the expression of lowly- or temporarily-expressed proteins is an open question. In this work we approached this question using two strategies, either by replacing rare glycine codons with optimal counterparts in the gene that encodes the cell cycle protein Cdc13, or by overexpression the tRNAGly that decodes rare codons from the fission yeast, Schizosaccharomyces pombe. While the replacement of synonymous codons severely affected cell growth, increasing tRNA levels affected the aggregation status of Cdc13 and cell division. These lead us to think that rare codons in lowly-expressed cyclin proteins are crucial for cell division, and that the overexpression of tRNA that decodes rare codons affects the expression of proteins containing these rare codons. These codons may be the result of the natural selection of codons in genes that encode lowly-expressed proteins.
Development of a Novel Chimeric Endolysin, Lys109 With Enhanced Lytic Activity Against Staphylococcus aureus
Authors: Son Bokyung , Kong Minsuk , Lee Yoona , Ryu Sangryeol
Published: January 2021

As the incidence of antibiotic-resistant bacteria has become increased, phage endolysins are believed as one of the promising alternatives to antibiotics. However, the discovery of potent endolysin is still challenging because it is labor intensive and difficult to obtain a soluble form with high lytic activity. In this respect, the modular structures of Gram-positive endolysins can provide an opportunity to develop novel endolysins by domain rearrangement. In this study, a random domain swapping library of four different endolysins from phages infectingStaphylococcus aureuswas constructed and screened to obtain engineered endolysins. The novel chimeric endolysin, Lys109 was selected and characterized for its staphylolytic activity. Lys109 exhibited greater bacterial cell lytic activity than its parental endolysins against staphylococcal planktonic cells and biofilms, showing highly improved activity in eliminatingS. aureusfrom milk and on the surface of stainless steel. These results demonstrate that a novel chimeric endolysin with higher activity and solubility can be developed by random domain swapping and that this chimeric endolysin has a great potential as an antimicrobial agent.
Mass Spectrometry Guided Discovery and Design of Novel Asperphenamate Analogs From Penicillium astrolabium Reveals an Extraordinary NRPS Flexibility
Authors: Subko Karolina , Wang Xinhui , Nielsen Frederik H. , Isbrandt Thomas , Gotfredsen Charlotte H. , Ramos Maria C. , Mackenzie Thomas , Vicente Francisca , Genilloud Olga , Frisvad Jens C. , Larsen Thomas O.
Published: January 2021

Asperphenamate is a small peptide natural product that has gained much interest due to its antitumor activity. In the recent years numerous bioactive synthetic asperphenamate analogs have been reported, whereas only a handful of natural analogs either of microbial or plant origin has been discovered. Herein we describe a UHPLC-HRMS/MS and amino acid supplement approach for discovery and design of novel asperphenamate analogs. Chemical analysis of Penicillium astrolabium, a prolific producer of asperphenamate, revealed three previously described and two novel asperphenamate analogs produced in significant amounts, suggesting a potential for biosynthesis of further asperphenamate analogs by varying the amino acid availability. Subsequent growth on proteogenic and non-proteogenic amino acid enriched media, revealed a series of novel asperphenamate analogs, including single or double amino acid exchange, as well as benzoic acid exchange for nicotinic acid, with the latter observed from a natural source for the first time. In total, 22 new asperphenamate analogs were characterized by HRMS/MS, with one additionally confirmed by isolation and NMR structure elucidation. This study indicates an extraordinary nonribosomal peptide synthetase (NRPS) flexibility based on substrate availability, and therefore the potential for manipulating and designing novel peptide natural products in filamentous fungi.
Evaluation and Comparison of the Efficiency of Transcription Terminators in Different Cyanobacterial Species
Authors: Gale Grant A. R. , Wang Baojun , McCormick Alistair J.
Published: January 2021

Cyanobacteria utilize sunlight to convert carbon dioxide into a wide variety of secondary metabolites and show great potential for green biotechnology applications. Although cyanobacterial synthetic biology is less mature than for other heterotrophic model organisms, there are now a range of molecular tools available to modulate and control gene expression. One area of gene regulation that still lags behind other model organisms is the modulation of gene transcription, particularly transcription termination. A vast number of intrinsic transcription terminators are now available in heterotrophs, but only a small number have been investigated in cyanobacteria. As artificial gene expression systems become larger and more complex, with short stretches of DNA harboring strong promoters and multiple gene expression cassettes, the need to stop transcription efficiently and insulate downstream regions from unwanted interference is becoming more important. In this study, we adapted a dual reporter tool for use with the CyanoGate MoClo Assembly system that can quantify and compare the efficiency of terminator sequences within and between different species. We characterized 34 intrinsic terminators in Escherichia coli, Synechocystis sp. PCC 6803, and Synechococcus elongatus UTEX 2973 and observed significant differences in termination efficiencies. However, we also identified five terminators with termination efficiencies of >96% in all three species, indicating that some terminators can behave consistently in both heterotrophic species and cyanobacteria.
Efficacy and Safety of TACE Combined With Sorafenib Plus Immune Checkpoint Inhibitors for the Treatment of Intermediate and Advanced TACE-Refractory Hepatocellular Carcinoma: A Retrospective Study
Authors: Zheng Liyun , Fang Shiji , Wu Fazong , Chen Weiqian , Chen Minjiang , Weng Qiaoyou , Wu Xulu , Song Jingjing , Zhao Zhongwei , Ji Jiansong
Published: January 2021

Purpose: The study aims to retrospectively investigate the efficacy and safety of sorafenib combined with transarterial chemoembolization (TACE) (TACE+Sor) vs. TACE combined with sorafenib plus immune checkpoint inhibitors (TACE+Sor+ICIs) in treating intermediate and advanced TACE-refractory hepatocellular carcinoma (HCC).

Materials and Methods: This study was approved by the ethics committee of Lisui Hospital, Zhejiang University, China. From January 2016 to June 2020, 51 eligible patients with intermediate or advanced TACE-refractory HCC received TACE+Sor (n = 29) or TACE+Sor+ICIs (n = 22). The differences in tumor response, adverse events (AEs), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Factors affecting PFS and OS were determined by Cox regression.

Results: The disease control rate was higher in the TACE+Sor+ICIs group than in the TACE+Sor group (81.82 vs. 55.17%, P = 0.046). Compared with the TACE+Sor group, PFS and OS were prolonged in the TACE+Sor+ICIs group (median PFS: 16.26 vs. 7.30 months, P < 0.001; median OS: 23.3 vs. 13.8 months, P = 0.012). Multivariate analysis showed that BCLC stage, alpha-fetoprotein and treatment were independent factors of PFS; BCLC, Child-Pugh class, ablation after disease progression and treatment were independent predictive factors of OS. Four patients in the TACE+Sor+ICIs group and three patients in the TACE+Sor group suffered from dose reduction or interruption (18.18 vs. 10.34%, P = 0.421). The incidence of ICI-related AEs in the TACE+Sor+ICIs group was well-controlled.

Conclusion: The therapeutic schedule of TACE+Sor+ICIs demonstrated efficacy and safety in intermediate and advanced TACE-refractory HCC.
Subsampled Directed-Percolation Models Explain Scaling Relations Experimentally Observed in the Brain
Authors: Carvalho Tawan T. A. , Fontenele Antonio J. , Girardi-Schappo Mauricio , Feliciano Thaís , Aguiar Leandro A. A. , Silva Thais P. L. , de Vasconcelos Nivaldo A. P. , Carelli Pedro V. , Copelli Mauro
Published: January 2021

Recent experimental results on spike avalanches measured in the urethane-anesthetized rat cortex have revealed scaling relations that indicate a phase transition at a specific level of cortical firing rate variability. The scaling relations point to critical exponents whose values differ from those of a branching process, which has been the canonical model employed to understand brain criticality. This suggested that a different model, with a different phase transition, might be required to explain the data. Here we show that this is not necessarily the case. By employing two different models belonging to the same universality class as the branching process (mean-field directed percolation) and treating the simulation data exactly like experimental data, we reproduce most of the experimental results. We find that subsampling the model and adjusting the time bin used to define avalanches (as done with experimental data) are sufficient ingredients to change the apparent exponents of the critical point. Moreover, experimental data is only reproduced within a very narrow range in parameter space around the phase transition.
A Novel INCNS Score for Prediction of Mortality and Functional Outcome of Comatose Patients
Authors: Zhao Zhihan , Zhang Xiao , Song Changgeng , Zhao Jingjing , Gao Qiong , Jiang Wen
Published: January 2021

Objectives: The purpose of this study was to verify the veracity and reliability of the INCNS score for prediction of neurological ICU (NICU) mortality and 3-month functional outcome and mortality in comatose patients.

Methods: In this prospective study, data of the patients admitted to NICU from January 2013 to January 2019 were collected for validation. The 3-month functional outcomes were evaluated using modified Rankin Scale (mRS). By using the receiver operating characteristics curve (ROC) analysis, we compared the INCNS score with Glasgow Coma Scale (GCS), Full Outline of Un-Responsiveness Score (FOUR) and Acute Physiology and Chronic Health Evaluation II (APACHE II) for assessment of the predictive performance of these scales for 3-month functional outcome and mortality and NICU mortality performed at 24- and 72-h after admission to the NICU.

Results: Totally 271 patients were used for evaluation; the INCNS score achieved an AUC (area under the receiver operating characteristic curve) of 0.766 (95% CI: 0.711–0.815) and 0.824 (95% CI: 0.774–0.868) for unfavorable functional outcomes, an AUC of 0.848 (95% CI: 0.800–0.889) and 0.892 (95% CI: 0.848–0.926) for NICU mortality, and an AUC of 0.811 (95% CI: 0.760–0.856) and 0.832 (95% CI: 0.782–0.874) for the 3-month mortality after discharge from the NICU at 24- and 72-h. The INCNS score exhibited a significantly better predictive performance of mortality and 3-month functional outcomes than FOUR and GCS. There was no significant difference in predicting NICU mortality and 3-month functional outcomes between INCNS and APACHE II, but INCNS had better predictive performance of 3-month mortality than APACHE II.

Conclusions: The INCNS score could be used for predicting the functional outcomes and mortality rate of comatose patients.
Olfactory Cues in Infant Feeds: Volatile Profiles of Different Milks Fed to Preterm Infants
Authors: Muelbert Mariana , Bloomfield Frank H. , Pundir Shikha , Harding Jane E. , Pook Chris
Published: January 2021

Background: Smell is determined by odor-active volatile compounds that bind to specific olfactory receptors, allowing us to discriminate different smells. Olfactory stimulation may assist with digestion and metabolism of feeds in the neonate by activation of the cephalic phase response of digestion. Infants' physiological responses to the smell of different milks suggest they can distinguish between breastmilk and infant formula. We aimed to describe the profile of volatile compounds in preterm breastmilk and investigate how this differed from that of other preterm infant feeding options including pasteurized donor breastmilk, breastmilk with bovine milk-based fortifier, human milk-based products and various infant formulas.

Methods: Forty-seven milk samples (13 different infant formulas and 34 human milk-based samples) were analyzed. Volatile compounds were extracted using Solid Phase Micro Extraction. Identification and relative quantification were carried out by Gas Chromatography with Mass Spectrometry. Principal Component Analysis (PCA) and one-way Analysis of Variance (ANOVA) with Tukey's HSD (parametric data) or Conover's post-hoc test (non-parametric data) were used as appropriate to explore differences in volatile profiles among milk types.

Results: In total, 122 compounds were identified. Breastmilk containing bovine milk-based fortifier presented the highest number of compounds (109) and liquid formula the lowest (70). The profile of volatile compounds varied with 51 compounds significantly different (adjusted p < 0.001) among milk types. PCA explained 47% of variability. Compared to preterm breastmilk, the profile of volatile compounds in breastmilk with added bovine milk-based fortifier was marked by presence of fatty acids and their esters, ketones and aldehydes; infant formulas were characterized by alkyls, aldehydes and furans, and human milk-based products presented high concentrations of aromatic hydrocarbons, terpenoids and specific fatty acids.

Conclusions: Sensory-active products of fatty acid oxidation are the major contributors to olfactory cues in infant feeds. Analysis of volatile compounds might be useful for monitoring quality of milk and detection of oxidation products and environmental contaminants. Further research is needed to determine whether these different volatile compounds have biological or physiological effects in nutrition of preterm infants.
Concomitant Pathogenic Mutations and Fusions of Driver Oncogenes in Tumors
Authors: Zhang Runjiao , Dong Li , Yu Jinpu
Published: January 2021

Driver oncogene alterations have always been one of leading causes in the process of occurrence and development of tumors. And the effects of driver oncogene alterations on tumorigenesis and progression in different kinds of tumors have been studied heatedly. And the roles that the driver oncogenes alterations play have been elucidated clearly in previous studies. The phenomenon of concomitant driver oncogenes mutations and driver genes fusions has gained much concentration in the past two decades. And a growing number of studies reported this phenomenon, either coexistence or mutually exclusivity. Here we reviewed on the phenomenon of concomitant mutations in three common types of carcinomas—lung cancer, thyroid cancer, and leukemia, which have been studied relatively more detailed and more general compared with others.
Malignant Progression Contributes to the Failure of Combination Therapy for Atypical Meningiomas
Authors: Zhang Qing , Wen Zheng , Ni Ming , Li Da , Wang Ke , Jia Gui-Jun , Wu Zhen , Zhang Li-Wei , Jia Wang , Wang Liang , Zhang Jun-Ting
Published: January 2021

Objective

To investigate the independent risk factors for recurrence in intracranial atypical meningiomas (AMs) treated with gross total resection (GTR) and early external beam radiotherapy (EBRT).

Methods

Clinical, radiological, and pathological data of intracranial AMs treated with GTR-plus-early-EBRT between January 2008 and July 2016 were reviewed. Immunohistochemical staining for Ki-67 was performed. Kaplan–Meier curves and univariate and multivariate Cox proportional hazards regression analyses were used to explore independent predictors of tumor recurrence. Chi square test was performed to compare variables between subgroups.

Results

Forty-six patients with intracranial AMs underwent GTR and early EBRT. Ten (21.7%) recurred and three (6.5%) died during a median follow-up of 76.00 months. Univariate and multivariate Cox analyses revealed that malignant progression (MP) (P = 0.009) was the only independent predictor for recurrence, while Ki-67 was of minor value in this aspect (P = 0.362). MP-AMs had a significantly higher recurrence rate (P = 0.008), a higher proportion of irregularly shaped tumors (P = 0.013) and significantly lower preoperative Karnofsky Performance Scale (KPS) scores (P = 0.040) than primary (Pri) AMs. No significant difference in Ki-67 expression was detected between these subgroups (P = 0.713).

Conclusions

MP was significantly correlated with an increased incidence of recurrence in GTR-plus-early-EBRT-treated intracranial AMs. Significantly higher frequencies of tumor relapse and irregularly shaped tumors and lower preoperative KPS scores were observed in MP-AMs compared with Pri-AMs. Ki-67 expression is of minor value in predicting tumor recurrence or distinguishing tumor origins in AMs.
Prognostic Analysis and Influencing Serum Biomarkers of Patients With Resectable Pancreatic Adenosquamous Cancer
Authors: Shi Yusheng , Wang Xinjing , Wu Weize , Xie Junjie , Jin Jiabin , Peng Chenghong , Deng Xiaxing , Chen Hao , Shen Baiyong
Published: January 2021

Objectives

There are few reports about the survival rate of patients with pancreatic adenosquamous cancer (PASC). This study evaluated and analyzed prognostic factors of patients with resectable pancreatic adenosquamous cancer (rPASC), which might fulfill the blank in the research of PASC.

Methods

In this study, we identified and analyzed 55 patients who were diagnosed with rPASC from January 2013 to May 2019 at the Pancreatic Disease Center of the Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine. Age, sex, BMI, tumor position, and other important demographic data were collected and analyzed. The follow-up was updated by December 31th, 2019 with a median follow-up of nine months.

Results

Among the 55 patients, 23 (41.8%) patients were female, and the mean age was 62.0 ± 10.3 years. The median overall survival (OS) time was 10 ± 2.1 months, and the median disease-free survival (DFS) time was 4 ± 0.9 months. The 1-year, 3-year, and 5-year survival rates were 40.9, 17.5, and 11.6%, respectively. The multivariate analysis showed that normal serum level of Ca199 (HR = 0.464, 95% CI = 0.222–0.970, P = 0.041) and Ca125 (HR = 0.441, 95% CI = 0.233–0.835, P = 0.012) were independent favorable prognostic factors.

Conclusion

Patients with rPASC had poor survival. The 5-year survival rate was only 11.6%. Normal serum levels of Ca199 and Ca125 were independent favorable prognostic factors that predicted prognosis.
Isoprostanes as Biomarker for White Matter Injury in Extremely Preterm Infants
Authors: Coviello Caterina , Perrone Serafina , Buonocore Giuseppe , Negro Simona , Longini Mariangela , Dani Carlo , de Vries Linda S. , Groenendaal Floris , Vijlbrief Daniel C. , Benders Manon J. N. L. , Tataranno Maria Luisa
Published: January 2021

Background and Aim: Preterm white matter is vulnerable to lipid peroxidation-mediated injury. F2-isoprostanes (IPs), are a useful biomarker for lipid peroxidation. Aim was to assess the association between early peri-postnatal IPs, white matter injury (WMI) at term equivalent age (TEA), and neurodevelopmental outcome in preterm infants.

Methods: Infants with a gestational age (GA) below 28 weeks who had an MRI at TEA were included. IPs were measured in cord blood (cb) at birth and on plasma (pl) between 24 and 48 h after birth. WMI was assessed using Woodward MRI scoring system. Multiple regression analyses were performed to assess the association between IPs with WMI and then with BSITD-III scores at 24 months corrected age (CA). Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of pl-IPs for the development of WMI.

Results: Forty-four patients were included. cb-IPs were not correlated with WMI score at TEA, whereas higher pl-IPs and lower GA predicted higher WMI score (p = 0.037 and 0.006, respectively) after controlling for GA, FiO2 at sampling and severity of IVH. The area under the curve was 0.72 (CI 95% = 0.51–0.92). The pl-IPs levels plotted curve indicated that 31.8 pg/ml had the best predictive threshold with a sensitivity of 86% and a specificity of 60%, to discriminate newborns with any WMI from newborns without WMI. IPs were not associated with outcome at 24 months.

Conclusion: Early measurement of pl-IPs may help discriminate patients showing abnormal WMI score at TEA, thus representing an early biomarker to identify newborns at risk for brain injury.
EFEMP1 Overexpression Contributes to Neovascularization in Age-Related Macular Degeneration
Authors: Cheng Lu , Chen Chong , Guo Wenke , Liu Kun , Zhao Qianqian , Lu Ping , Yu Fudong , Xu Xun
Published: January 2021

Purpose: Age-related macular degeneration (AMD) is one of the leading causes of blindness, and choroidal neovascularization (CNV) in AMD can lead to serious visual impairment. Gene expression profiling of human ocular tissues have a great potential to reveal the pathophysiology of AMD. This study aimed to identify novel molecular biomarkers and gene expression signatures of AMD.

Methods: We analyzed transcriptome profiles in retinal-choroid tissues derived from donor patients with AMD in comparison with those from healthy controls using a publicly available dataset (GSE29801). We focused on the EFEMP1 gene, which was found to be differentially upregulated in AMD, especially in wet AMD eyes. Serological validation analysis was carried out to verify the expression of EFEMP1 in 39 wet AMD patients and 39 age- and gender-matched cataract controls, using an enzyme-linked immunosorbent assay (ELISA). We then investigated the role of EFEMP1 in angiogenesis through in vitro experiments involving EFEMP1 overexpression (OE) and knockdown in human umbilical vein endothelial cells (HUVECs).

Results: An increase in EFEMP1 expression was observed in the retinal-choroid tissues of eyes with AMD, which was more significant in wet AMD than in dry AMD. In addition, there was a significant increase in serum fibulin-3 (EFEMP1 encoded protein) concentration in patients with wet AMD compared with that in the controls. Tube formation and proliferation of EFEMP1-OE HUVECs increased significantly, whereas those of EFEMP1 knockdown HUVECs decreased significantly compared with those of the control. Additional extracellular fibulin-3 treatments did not increase tube formation and proliferation of wildtype and EFEMP1 knockdown HUVECs, indicating that the proangiogenic properties of EFEMP1 are of cell origin. We also found that vascular endothelial growth factor expression in HUVECs was upregulated by EFEMP1 overexpression and downregulated by EFEMP1 knockdown.

Conclusion: Our findings demonstrate EFEMP1 as a novel biomarker for CNV in AMD, providing a new target for the development of wet AMD-directed pharmaceuticals and diagnostics.
Utilisation, Availability and Price Changes of Medicines and Protection Equipment for COVID-19 Among Selected Regions in India: Findings and Implications
Authors: Haque Mainul , Kumar Santosh , Charan Jaykaran , Bhatt Rohan , Islam Salequl , Dutta Siddhartha , Abhayanand Jha Pallavi , Sharma Yesh , Sefah Israel , Kurdi Amanj , Wale Janney , Godman Brian
Published: January 2021

Background: COVID-19 has already claimed a considerable number of lives worldwide. However, there are concerns with treatment recommendations given the extent of conflicting results with suggested treatments and misinformation, some of which has resulted in increased prices and shortages alongside increasing use and prices of personal protective equipment (PPE). This is a concern in countries such as India where there have been high patient co-payments and an appreciable number of families going into poverty when members become ill. However, balanced against pricing controls. Community pharmacists play a significant role in disease management in India, and this will remain. Consequently, there is a need to review prices and availability of pertinent medicines during the early stages of the COVID-19 pandemic in India to provide future direction.

Objective: Assess current utilisation and price changes as well as shortages of pertinent medicines and equipment during the early stages of the pandemic.

Our Approach: Multiple approach involving a review of treatments and ongoing activities across India to reduce the spread of the virus alongside questioning pharmacies in selected cities from early March to end May 2020.

Our Activities: 111 pharmacies took part, giving a response rate of 80%. Encouragingly, no change in utilisation of antimalarial medicines in 45% of pharmacies despite endorsements and for antibiotics in 57.7% of pharmacies, helped by increasing need for a prescription for dispensing. In addition, increased purchasing of PPE (over 98%). No price increases were seen for antimalarials and antibiotics in 83.8 and 91.9% of pharmacies respectively although shortages were seen for antimalarials in 70.3% of pharmacies, lower for antibiotics (9.9% of pharmacies). However, price increases were typically seen for PPE (over 90% of stores) as well as for analgesics (over 50% of pharmacies). Shortages were also seen for PPE (88.3%).

Conclusion: The pandemic has impacted on utilisation and prices of pertinent medicines and PPE in India but moderated by increased scrutiny. Key stakeholder groups can play a role with enhancing evidenced-based approaches and reducing inappropriate purchasing in the future.
Pioglitazone-Mediated Attenuation of Experimental Colitis Relies on Cleaving of Annexin A1 Released by Macrophages
Authors: da Rocha Gustavo Henrique Oliveira , de Paula-Silva Marina , Broering Milena Fronza , Scharf Pablo Rhasan dos Santos , Matsuyama Larissa Satiko Alcântara Sekimoto , Maria-Engler Silvya Stuchi , Farsky Sandra Helena Poliselli
Published: January 2021

Ulcerative colitis and Crohn’s disease are chronic inflammatory bowel diseases (IBDs) which burden health systems worldwide; available pharmacological therapies are limited and cost-intensive. Use of peroxisome proliferator activated-receptor γ (PPARγ) ligands for IBD treatment, while promising, lacks solid evidences to ensure its efficacy. Annexin A1 (AnxA1), a glucocorticoid-modulated anti-inflammatory protein, plays a key role on IBD control and is a potential biomarker of IBD progression. We here investigated whether effects of pioglitazone, a PPARγ ligand, rely on AnxA1 actions to modulate IBD inflammation. Experimental colitis was evoked by 2% dextran sodium sulfate (DSS) in AnxA1 knockout (AnxA1−/−) or wild type (WT) C57BL/6 mice. Clinical and histological parameters were more severe for AnxA−/−than WT mice, and 10 mg/kg pioglitazone treatment attenuated disease parameters in WT mice only. AnxA1 expression was increased in tissue sections of diseased WT mice, correlating positively with presence of CD68+macrophages. Metalloproteinase-9 (MMP-9) and inactive 33 kDa AnxA1 levels were increased in the colon of diseased WT mice, which were reduced by pioglitazone treatment. Cytokine secretion, reactive oxygen species generation and MMP-9 expression caused by lipopolysaccharide (LPS) treatment in AnxA1-expressing RAW 264.7 macrophages were reduced by pioglitazone treatment, effects not detected in AnxA1 knockdown macrophages.LPS-mediated increase of AnxA1 cleaving in RAW 264.7 macrophages was also attenuated by pioglitazone treatment. Finally, pioglitazone treatment increased extracellular signal-regulated kinase (ERK) phosphorylation in AnxA1-expressing RAW 264.7 macrophages, but not in AnxA1-knockdown macrophages. Thus, our data highlight AnxA1 as a crucial factor for the therapeutic actions of pioglitazone on IBDs.
Morphophysiology of Potato (Solanum tuberosum) in Response to Drought Stress: Paving the Way Forward
Authors: Hill Dominic , Nelson David , Hammond John , Bell Luke
Published: January 2021

The cultivated potato (Solanum tuberosum L.) is currently the third most important food crop in the world and is becoming increasingly important to the local economies of developing countries. Climate change threatens to drastically reduce potato yields in areas of the world where the growing season is predicted to become hotter and drier. Modern potato is well known as an extremely drought susceptible crop, which has primarily been attributed to its shallow root system. This review addresses this decades old consensus, and highlights other, less well understood, morphophysiological features of potato which likely contribute to drought susceptibility. This review explores the effects of drought on these traits and goes on to discuss phenotypes which may be associated with drought tolerance in potato. Small canopies which increase harvest index and decrease evapotranspiration, open stem-type canopies which increase light penetration, and shallow but densely rooted cultivars, which increase water uptake, have all been associated with drought tolerance in the past, but have largely been ignored. While individual studies on a limited number of cultivars may have examined these phenotypes, they are typically overlooked due to the consensus that root depth is the only significant cause of drought susceptibility in potato. We review this work, particularly with respect to potato morphology, in the context of a changing climate, and highlight the gaps in our understanding of drought tolerance in potato that such work implies.
NbWRKY40 Positively Regulates the Response of Nicotiana benthamiana to Tomato Mosaic Virus via Salicylic Acid Signaling
Authors: Jiang Yaoyao , Zheng Weiran , Li Jing , Liu Peng , Zhong Kaili , Jin Peng , Xu Miaoze , Yang Jian , Chen Jianping
Published: January 2021

WRKY transcription factors play important roles in plants, including responses to stress; however, our understanding of the function of WRKY genes in plant responses to viral infection remains limited. In this study, we investigate the role of NbWRKY40 in Nicotiana benthamiana resistance to tomato mosaic virus (ToMV). NbWRKY40 is significantly downregulated by ToMV infection, and subcellular localization analysis indicates that NbWRKY40 is targeted to the nucleus. In addition, NbWRKY40 activates W-box-dependent transcription in plants and shows transcriptional activation in yeast cells. Overexpressing NbWRKY40 (OEWRKY40) inhibits ToMV infection, whereas NbWRKY40 silencing confers susceptibility. The level of salicylic acid (SA) is significantly higher in OEWRKY40 plants compared with that of wild-type plants. In addition, transcript levels of the SA-biosynthesis gene (ICS1) and SA-signaling genes (PR1b and PR2) are dramatically higher in OEWRKY40 plants than in the control but lower in NbWRKY40-silenced plants than in the control. Furthermore, electrophoretic mobility shift assays show that NbWRKY40 can bind the W-box element of ICS1. Callose staining reveals that the plasmodesmata is decreased in OEWRKY40 plants but increased in NbWRKY40-silenced plants. Exogenous application of SA also reduces viral accumulation in NbWRKY40-silenced plants infected with ToMV. RT-qPCR indicates that NbWRKY40 does not affect the replication of ToMV in protoplasts. Collectively, our findings suggest that NbWRKY40 likely regulates anti-ToMV resistance by regulating the expression of SA, resulting in the deposition of callose at the neck of plasmodesmata, which inhibits viral movement.
The Beginning of More Worries: Doctoral Candidates’ Untold Stories After Submission of Dissertation
Authors: Waheed Syed Abdul , Gilani Nadia , Raza Mehwish , Ahmad Farooq
Published: January 2021

The present study focused on this particular situation in which doctoral candidates become anxious, impatient, and disappointed while experiencing a prolonged delay in processing their dissertation during and after the submission. The researchers tend to explore doctoral candidates’ storied experiences they had while confronting such procedural barriers and delays. We undertook a narrative mode of inquiry to explore the events and storied experiences through interviewing doctoral candidates from public universities in the province of Punjab, Pakistan. Nine doctoral candidates were selected through snowball sampling with the criterion of including those participants who were waiting for their external reviews at least for more than 1 year. From the narratives, the emergent themes include supervisors’ mutual relationships, the pressure of paper publication, lack of administrative support, external evaluation and follow-up and stress of delayed evaluation. The study has implications for relaxing procedural formalities during and after submission of a doctoral dissertation to facilitate students in the timely attainment of their doctoral degrees.
Post-traumatic Growth Dimensions Differently Mediate the Relationship Between National Identity and Interpersonal Trust Among Young Adults: A Study on COVID-19 Crisis in Italy
Authors: Ellena Adriano Mauro , Aresi Giovanni , Marta Elena , Pozzi Maura
Published: January 2021

Background

In Italy, the COVID-19 pandemic has caused a collective trauma. Post-traumatic growth (PTG) has been defined as the subjective experience of positive psychological changes as a result of a traumatic event. PTG can involve changes in five psychological main dimensions: relating to others, new possibilities, personal strength, spiritual change, and appreciation of life. In the context of national emergencies, those PTG dimensions encompassing changes at the social level (e.g., relating to others) can play a role in coping strategies that involve a renewed sense of self and one’s social identities, including national identities, and in turn, foster a stronger sense of trust and connection to others.

Aim

To investigate how each of the five PTG dimensions mediates the association between the salience of national identity and interpersonal trust in a sample of Italian young adults. Trust in national and European institutions were expected to positively predict the strength of the Italian national identity which in turn was expected to be positively associated with interpersonal trust, and the PTG relating to others dimension to mediate this association.

Method

This study involves the secondary analysis of data from a representative sample of 2,000 Italian young adults (age range 18–34 years). Participants completed a web survey during the peak of the COVID-19 crisis in Italy with measures of trust in EU and national institutions, national identity, interpersonal trust, and the PTG Inventory. Structural equation modeling procedures were employed for key hypotheses tests.

Results

Trust in national institutions positively predicted national identity, which in turn was positively associated with interpersonal trust. Evidence of a full mediation effect of the PTG relating to others dimension on the association between national identity and interpersonal trust was found.

Discussion

Findings contribute to clarify the psychological responses to collective traumas. In the context of Italy’s COVID-19 crisis, trust in national institutions reinforced Italian national identity, which was in turn associated with greater interpersonal trust, but only when psychological responses to the trauma involved changes in how individuals perceived and related to others, and not merely a focus on the self. Theoretical and practical implications are discussed.
Individual Chunking Ability Predicts Efficient or Shallow L2 Processing: Eye-Tracking Evidence From Multiword Units in Relative Clauses
Authors: Pulido Manuel F.
Published: January 2021

Behavioral studies on language processing rely on the eye-mind assumption, which states that the time spent looking at text is an index of the time spent processing it. In most cases, relatively shorter reading times are interpreted as evidence of greater processing efficiency. However, previous evidence from L2 research indicates that non-native participants who present fast reading times are not always more efficient readers, but rather shallow parsers. Because earlier studies did not identify a reliable predictor of variability in L2 processing, such uncertainty around the interpretation of reading times introduces a potential confound that undermines the credibility and the conclusions of online measures of processing. The present study proposes that a recently developed modulator of online processing efficiency, namely, chunking ability, may account for the observed variability in L2 online reading performance. L1 English – L2 Spanish learners’ eye movements were analyzed during natural reading. Chunking ability was predictive of overall reading speed. Target relative clauses contained L2 Verb-Noun multiword units, which were manipulated with regards to their L1-L2 congruency. The results indicated that processing of the L1-L2 incongruent units was modulated by an interaction of L2 chunking ability and level of knowledge of multiword units. Critically, the data revealed an inverse U-shaped pattern, with faster reading times in both learners with the highest and the lowest chunking ability scores, suggesting fast integration in the former, and lack of integration in the latter. Additionally, the presence of significant differences between conditions was correlated with individual chunking ability. The findings point at chunking ability as a significant modulator of general L2 processing efficiency, and of cross-language differences in particular, and add clarity to the interpretation of variability in the online reading performance of non-native speakers.