bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Data Reveal The Flavonoid Biosynthesis Metabolic Pathway In Semen Ziziphi Spinosae Using Transcriptomic And Metabolomic
Authors: Jiang Tao , Liu Lingdi , Wen Chunxiu , Xie Xiaoliang , Wen Saiqun , Tian Wei 
Published: August 2021

Abstract
Semen Ziziphi Spinosae (SZS) is used to treat neurasthenia, insomnia, and anxiety in China. The extract from SZS contains many bioactive components, such as flavonoids, alkaloids, and terpenoids. Among these, the flavonoids are the main bioactive compounds that have been proven to be responsible for the sedative effects. In this study, a total of 13232 differentially expressed genes and 83 flavonoid metabolites were identified at three different growth and development stages (T1, T2, and T3) of SZS using transcriptomic and metabolomic. The main flavonoid metabolic components of SZS were catechin, L-epicatechin, (-)-epigallocatechin, (+)-gallocatechin, spinosin and its derivatives. A total of 53 unigenes encoding 15 enzymes were identified as candidate genes involved in flavonoid biosynthesis in SZS. Among, PAL, C4H, 4CL, CHS, CHI, FLS, FNS, ANS, ANR, LAR, and UFGT genes were all downregulated in T3 than in T1. The expression levels of these genes influence the accumulation of flavonoids in SZS. Our results should provide valuable information for flavonoid metabolites and candidate genes involved in flavonoid biosynthesis on SZS.
Chrysin Alleviates DNA Damage to Improve Disturbed Immuno-Homeostasis and Pro-Angiogenic Environment in Laser-Induced Choroidal Neovascularization
Authors: Wang Jing , Bo Qiyu , Zhou Minwen , Wang Hong , Zhu Hong , Wang Fenghua , Jiang Mei , Sun Xiaodong 
Published: August 2021

Abstract
Background: Choroidal neovascularization (CNV) is a devastating pathology of numerous ocular diseases, such as wet age-related macular degeneration (wAMD), which causes irreversible vision loss. Although anti-VEGF therapy has been widely used, poor response or no response exits in some patients, suggesting that some other important angiogenic components play roles. Therefore, the underlined mechanism need to be clarified and new target of anti-angiogenic therapy is urgently needed. Damaged retinal pigment epithelium (RPE) cells have been demonstrated to activate inflammasome, drive a degenerative tissue environment and an enhanced pro-angiogenic response, which emphasizes the dysfunction of RPE, may be the hallmark of the pathogenesis.Methods: C57BL/6J male mice aged between 6 and 8 weeks were subjected to laser-induced CNV models. Chrysin was administered intragastrically at 25 mg/kg daily for 3 days or one week after laser-treated. Then to observe the CNV areas and CNV thickness, immunofluorescence staining of choroidal flatmount, SD-OCT and fluorescein angiograghy were performed, respectively. To further confirm the effect of chrysin on stress-induced DNA damage in RPE cells, RPE cells were administered with A2E and western-blot, cell viability assay, immunofluorescence chromosome PNA-FISH and SA-β-gal staining were performed. To elucidate the underlying mechanism, we performed RNA-seq and bioinformatics analyses.Results: In this study, we demonstrated that chrysin could successfully alleviated choroidal neovascularization. We show that DNA damage of RPE cells is remarkable in laser-induced choroidal neovascularization, resulting in inflammation response, which can be ameliorated by chrysin through inactivation of STAT3. Also, we identify that chrysin can reduce DNA damage, especially telomere erosion, simultaneously compromise the dysfunction of RPE and the secretion of SASP factor in vitro. Mechanistically, KEGG pathway analyzes show that chrsyin improves inflammatory imbalance mainly through down-regulation of IL17 pathway in the laser- induced CNV development.Conclusions: Our results indicate the interplay between DNA damage, perturbed RPE homeostasis, inflammatory imbalance and angiogenesis in laser-induced choroidal neovascularization. Importantly, chrysin may be an effective therapeutic supplement for CNV.
QTL Mapping of a Brazilian Bioethanol Strain Unravels the Cell Wall Protein-Encoding Gene GAS1 as a Major Contributor to Low Ph Tolerance in S. Cerevisiae
Authors: Coradini Alessandro L V , de Mello Fellipe da Silveira Bezerra , Furlan Monique , Maneira Carla , Carazzolle Marcello Falsarella , Pereira Goncalo Amarante Guimarães , Teixeira Gleidson Silva 
Published: August 2021

Abstract
BACKGROUNDSaccharomyces cerevisiae is largely applied in many biotechnological processes, from traditional food and beverage industries to modern biofuel and biochemicals factories. During the fermentation process, yeast cells are usually challenged in different harsh conditions, which often impact productivity. Regarding bioethanol production, cell exposure to acidic environments is related to productivity loss on both first and second generation ethanol. In this scenario, indigenous strains traditionally used in fermentation stand out as a source of complex genetic architecture, mainly due to their highly robust background - including low pH tolerance. RESULTSIn this work, we pioneer the use of QTL mapping to uncover the genetic basis that endow industrial strain Pedra-2 (PE-2) with outstanding acid resistance. First, we developed a fluorescence-based high-throughput approach to collect a large number of haploid cells using flow cytometry. Then, we were able to apply a bulk segregant analysis to solve the genetic basis of low pH resistance in PE-2, which uncovered a region in chromosome XIII as the major QTL associated with the evaluated phenotype. A reciprocal hemizygosity analysis revealed allele GAS1, encoding a β-1,3-glucanosyltransferase, as the major contributor to this phenotype. The GAS1 sequence alignment of 48 S. cerevisiae strains pointed out a non-synonymous mutation (T211A) prevalence in wild type isolates, which is absent in laboratory strains. We further showcase that GAS1 allele swap between PE-2 and a low pH-susceptible strain can improve cell viability on the latter of up to 12% after a sulfuric acid wash process.CONCLUSIONThis work revealed GAS1 as the major causative gene associated with low pH resistance in PE-2, harboring a non-synonymous mutation persistent in industrial strains. We also showcase how GAS1PE-2 can improve acid resistance of a susceptible strain, suggesting that these findings can be a powerful foundation for the development of more robust and acid-tolerant strains for the industrial production of economically-relevant goods. Our results collectively show the importance of tailored industrial isolated strains in the discovery of the genetic architecture of relevant traits and its implications over productivity.
Very Early Onset of Leber’s Mitochondrial Optic Neuropathy in Pediatric Females: Case Report and Review of the Literature
Authors: Tagliani Sara , Malaventura Cristina , Ceccato Chiara , Parmeggiani Francesco , Suppiej Agnese 
Published: August 2021

Abstract
BackgroundLeber’s hereditary optic neuropathy is a rare mitochondrial disease that usually begins in the second/third decade of life and affects generally young adult males. The information is scarce on the female phenotype particularly when onset is at a very young age and the diagnosis is challenged by other more frequent conditions. Aim of this study is to highlight the pediatric female phenotype by a literature review and by adding a new case.MethodsThe literature search was conducted on Pubmed in the period September 2020-February 2021 using “Child”, “Leber Hereditary Optic Neuropathy”, “females” “girls” keywords. We add a three years old girl with genetically confirmed Leber’s hereditary optic neuropathy.Results55 of 968 articles reported pediatric in girls accounting for 226 cases, male to female ratio 1,8:1. Mean age at onset was 11 years. The onset at the age of 3 years was described in only 3 girls, including our case. Acute bilateral mild visual impairment was the most common clinical presentation, associated to papilledema in 14% of the cases who underwent fundus oculi examination. Partial visual recovery occurred in 50% (30/60). Idebenone treatment was administered in 5/30. ConclusionLHON is extremely rare in very young females and represents a diagnostic challenge for the pediatrician. It should be considered even in young girls with acute-subacute visual loss, bilateral pseudo-papilledema, VEP changes non responding to steroid therapy.
Efficient Degradation of Alginate And Preparation of Unsaturated Monosaccharides By A Novel Alginate Lyase And Effects of Domain Truncation On Biochemical Characteristics, Degradation Patterns
Authors: Li Qian , Cao Shengsheng , Zheng Ling , Zhu Benwei 
Published: August 2021

Abstract
BackgroundBrown algae are considered promising crops for the production of sustainable biofuels. However, its commercial application has been limited by lack of efficient methods for converting alginate into fermentable sugars. Recently, exo-type alginate lyases have received extensive attention due to their excellent ability of conversion of alginate into 4-deoxy-L-erythro-5-hexoseulose uronate (DEH), a promising material for bioethanol production and biorefinery systems.ResultsHerein, we cloned and characterized a novel alginate lyase AlyPL17 from Pedobacter hainanensis NJ-02. It possessed outstanding catalytic efficiency towards polymannuronic acid (polyM), polyguluronic acid (polyG) and alginate sodium, with kcat of 39.42 + 1.9 s-1, 32.53 + 0.88 s-1, and 38.30 + 2.12 s-1, respectively. In addition, AlyPL17 adopts a unique hybrid action mode to degrade alginate by the synergistic effect of two domains. Furthermore, the combination of AlyPL17 and AlyPL6 exhibited apparently synergistic effect for the preparation of unsaturated monosaccharides. ConclusionOverall, the results show that AlyPL17 is a PL17 exo-type alginate lyase with high activity and a high conversion rate at low/moderate temperatures, which provides a useful enzymatic tool for the conversion of brown algae into biofuels and enhance our understanding of the function of modular domain of alginate lyase.
Evaluation of Antioxidant Activity of Caffeine Extracted From Kolanut (Cola Nitida)
Authors: Onyeyilim Ebuka Leonard , Ugwu Ezinne Evelyn , Onugwu Adaeze Linda , Uzoewulu Chiamaka Peace , Otunomo Idowu Iyabo 
Published: August 2021

Abstract
Crude caffeine was isolated from kola nut, by treating the filtrate obtained from powdered kola nut with lead (II) acetate to precipitate acids and albumins, along with HCl to precipitate lead ions, and to make some insoluble tannins to be soluble, then Na2CO3 solution was added to neutralise the acidic HCl solution. Dichloromethane is added to the filtrate to extract the caffeine from the aqueous layer and then distilled to obtain the crude caffeine. The extracted crude caffeine is recrystallized with activated charcoal and tested for its antioxidant capacity, using the DPPH assay, which screens the antioxidant activity of plant extracts. The DPPH (2, 2-diphenyl-1-picrylhydrazyl) in methanol helps to facilitate the extraction of the antioxidant compounds from the sample. Ascorbic acid (Vitamin C) is used as the standard for this assay, due to its appreciable antioxidant activity. The IC50 value was calculated from the graph of % inhibition against concentration, and the extracted caffeine from kola nut was found out to have a high antioxidant activity comparable to that of the standard, ascorbic acid.
Association of Sonographic Features of Unifocal Papillary Thyroid Carcinoma With Cervical Lymph Node Metastasis
Authors: Zhou Liuhua , Zhu Qiaodan , Yao Jincao , Yang Chen , Xu Dong 
Published: August 2021

Abstract
Background Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid carcinoma. We aim to evaluate the association of sonographic features of PTC and cervical lymph node metastasis (CLNM) at the initial surgery.Methods Clinical information, ultrasonographic measurements and features for 1335 patients were acquired in data collection. Univariate analysis was performed to test CLNM by 7 independent variables. Receiver operating characteristic (ROC) curve was created to evaluate the diagnostic performance.Results Univariate analysis showed that gland, location, aspect ratio, margin and echogenic foci were independently associated with CLNM metastatic status (P < 0.05). Binary linear regression analysis showed that sex, age, tumour maximum diameter and volume, location, margin and echogenic foci were independent correlative factors. The ROC curves were established based on the relevant factors, the AUC of tumour maximum diameter, tumour volume and margin were 0.74, 0.73, and 0.71, respectively. The multiple-variable linear regression model was constructed with AUC of 0.81, specificity of 72.8%, and sensitivity of 75.0%. ANOVA variance analysis for sub-positive groups, tumour maximum diameter, tumour volume, margin and echogenic foci had statistical significance (P < 0.05).Conclusion Younger age, male, larger tumour, margin, and echogenic foci were high risk factors for CLNM in PTC. Cross-sectional aspect ratio with value ≥ 1 had higher predictive value for CLNM in PTC patients excluding papillary thyroid microcarcinoma (PTMC).
Disordered Climate Threatens Short-Distance Migrants
Authors: Yang Haile , Yu Luxian , Qi Hongfang , Fu Shengyun , Wang Yang , Yang Jianxin , Du Hao 
Published: August 2021

Abstract
In the global warming world, the migratory and breeding behaviors of many species have changed, and short-distance migrants may benefit from climate change. With climate change leading to an increasingly disordered climate, we show here that a disordered spring climate disturbs the migration and breeding of a short-distance anadromous fish. In 2020, on the Qinghai-Tibetan Plateau, an abnormally low temperature in April delayed the migration rhythm of Gymnocypris przewalskii by nearly 10 days, while the gonadal development rhythm of the breeding population was almost normal. The phenology mismatch decreased the migrating populations by 30–70%, reducing the larval flux by nearly 80%. This case reveals that for short-distance migrants, different phenologies within the same species respond to disordered climates differently, which leads to phenology mismatches and then threatens the species. Along with increasing local abnormal climate events, short-distance migrants need more attention and conservation actions.
Time To Complete hepatitis C Cascade of Care Among Patients Identified During Mass Screening Campaigns in Rural Rwanda: A Retrospective Cohort Study
Authors: Kamali Innocent , Shumbusho Fabienne , Barnhart Dale A , Nyirahabihirwe Françoise , Gakuru Jean de la Paix , Dusingizimana Wellars , Nizeyumuremyi Esdras , Habinshuti Placide , Walker Stephen , Makuza Jean Damascene , Serumondo Janvier , Rwibasira Gallican Nshogoza , Ndahimana Jean d'Amour 
Published: August 2021

Abstract
Background

Since the discovery of direct-acting antivirals, treatment for hepatitis C virus (HCV) is increasingly accessible in low-resource settings, but quality of care in these settings is not known. We described progression through the cascade of care among individuals who screened positive for HCV antibodies during a mass screening campaign in Kirehe and Kayonza, two rural Rwandan districts, in September 2019.
Methods

This retrospective cohort study used routine clinical data to assess proportions of participants completing each stage of the cascade of care, including: a) screening positive on rapid diagnostic test; b) return of initial viral load results; c) detectable viral load; d) treatment assessment; e) treatment initiation; f) return of sustained virological response (SVR12) results; and g) achieving SVR12. We proposed three indicators to assess timely care provision and used medians and interquartile ranges (IQR) to describe the time to complete the cascade of care.
Results

Overall, 666 participants screened HCV positive, among them, 452 (68.1%) were female and median age was 61 years (IQR: 47, 70). Viral load results were returned for 537 (80.6%) participants of whom 448 (83.4%) had detectable viral loads. Of these, 398 (88.8%) were assessed for treatment, 394 (99%) were initiated, but only 222 (56.3%) had results returned for SVR12. Among those with SVR12 results, 208 (93.7%) achieved SVR12. When assessing timely care provision, we found 65.9% (95% CI: 62.0, 69.7) of initial viral load results were returned ≤ 30 days of screening; 45% (95% CI: 40.1, 49.8) of people with detectable viral load completed treatment assessment ≤ 90 days of initial viral load results; and 12.5% (95% CI: 9.2,16.3) of SVR12 results were returned ≤ 210 days of treatment initiation among those who initiated treatment. The overall median time from screening to SVR12 assessment was 437 days.
Conclusion

Despite high rates of SVR12 among those who completed all stages of the cascade of care, we identified gaps and delays in the treatment cascade. Improving communication between viral load testing hubs and health facilities could reduce the turn-around time for viral load testing, and actively monitor timeliness of care provision could improve quality of HCV care.
Efficacy of Non-Invasive and Invasive Respiratory Managements in Adult Patients with Acute Hypoxaemic Respiratory Failure: A Systematic Review and Network Meta-Analysis
Authors: Sakuraya Masaaki , Okano Hiromu , Masuyama Tomoyuki , Kimata Shunsuke , Hokari Satoshi 
Published: August 2021

Abstract
Background: Although non-invasive respiratory managements are preformed to avoid intubation, patients with de novo acute hypoxaemic respiratory failure (AHRF) are high risk for treatment failure. Choosing the most effective primary respiratory management for adults with de novo AHRF is a complex problem. In the previous meta-analyses, the effect of non-invasive ventilation was not sufficiently evaluated according to ventilation modes in patients with AHRF. Furthermore, no meta-analyses comparing non-invasive respiratory managements with invasive mechanical ventilation (IMV) have been reported. We performed a network meta-analysis to compare the efficacy of non-invasive ventilation according to ventilation modes with high-flow nasal oxygen (HFNO), standard oxygen therapy (SOT), and IMV in adult patients with AHRF.Methods: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Ichushi databases were searched. Studies including adults with AHRF and randomised controlled trials comparing two different respiratory managements (continuous positive airway pressure [CPAP], pressure support ventilation [PSV], HFNO, SOT, or IMV) were reviewed. A network meta-analysis was performed via a frequentist approach with a multivariate random-effects meta-analysis. The certainty of evidence was assessed based on the Grades of Recommendation, Assessment, Development and Evaluation Working Group approach. The primary outcome was short-term mortality.Results: Using SOT as the reference, CPAP (risk ratio [RR], 0.55; 95% confidence interval [CI], 0.31–0.95; very low certainty) was significantly associated with a lower risk of mortality. Compared with SOT, PSV (RR, 0.81; 95% CI, 0.62–1.06; low certainty) and HFNO (RR, 0.90; 95% CI, 0.65–1.25; very low certainty) were not associated with a significantly lower risk of mortality. Compared with IMV, no non-invasive respiratory management was associated with a significantly lower risk of mortality, although all certainties of evidence were very low. The probability of being best in reducing short-term mortality among all possible interventions was higher for CPAP, followed by PSV and HFNO; IMV and SOT were tied for the worst.Conclusions: Our findings imply that CPAP may be the most effective strategy as the primary non-invasive respiratory management for AHRF to avoid unnecessary pressure support. Trial registration: protocols.io (Protocol integer ID 49375, April 23, 2021). dx.doi.org/10.17504/protocols.io.buf7ntrn.
Nursing Qualifications needed in Municipal Emergency Inpatient Units. A qualitative study
Authors: Landstad Bodil J. , Hole Torstein , Strand Aasta Marie Sveino , Kvangarsnes Marit 
Published: August 2021

Abstract
Background: Providing care to older individuals with complex needs and patients with chronic illness is a concern worldwide. In Norway, this situation led to the transfer of responsibility for care and treatment to the districts. Providing emergency care at the municipal level – thereby reducing the need for emergency hospital admissions – is part of the Coordination Reform in Norway. This reform from 2012 warrants a reconsideration of which nursing qualifications are needed in the municipalities.The aim of the study is to explore which professional qualifications nurses need to provide emergency care in municipal emergency inpatient units. A qualitative design with a hermeneutic approach was employed. Interviewing physicians about nursing qualifications may be considered inappropriate. We believe that this is important for developing knowledge that can strengthen interprofessional cooperation in emergency situations. Three focus groups were conducted. Physicians with experience in municipal emergency inpatient units were interviewed.Results: The physicians highlighted broad medical knowledge, clinical judgement, skills in treatment management and communication, a holistic understanding, and continuous learning as relevant professional qualifications for nurses in municipal emergency inpatient units. Taking a holistic approach requires ethical judgement and teamwork. Interpersonal skills and adopting a family perspective were considered important in facilitating care in municipal emergency inpatient units.Conclusions: Nurses have a considerable responsibility to work independently and safely in a setting where both the patient and the patient’s family play important roles. Nurses should adopt a family perspective when managing patients in municipal emergency inpatient units. Nursing education should prepare students to treat patients with complex needs and chronic illnesses. This requires an emphasis on broad medical knowledge, clinical judgement, and skills in communication, treatment management and continuous learning.