bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indirect Pathway Metabolic Engineering Strategies for Enhanced Biosynthesis of Hyaluronic Acid in Engineered Corynebacterium glutamicum
Authors: Du Yan , Cheng Fangyu , Wang Miaomiao , Xu Chunmeng , Yu Huimin 
Published: December 2021

Hyaluronic acid (HA) is composed of alternating d-glucuronic acid and N-acetyl-d-glucosamine, with excellent biocompatibility and water retention capacity. To achieve heterologous biosynthesis of HA, Corynebacterium glutamicum, a safe GRAS (generally recognized as safe) host, was utilized and metabolically engineered previously. In this work, to achieve further enhancement of HA yield, four strategies were proposed and performed separately first, i.e., (1) improvement of glucose uptake via iolR gene knockout, releasing the inhibition of transporter IolT1/IolT2 and glucokinases; (2) intensification of cardiolipin synthesis through overexpression of genes pgsA1/pgsA2/cls involved in cardiolipin synthesis; (3) duly expressed Vitreoscilla hemoglobin in genome, enhancing HA titer coupled with more ATP and improved NAD+/NADH (&gt;7.5) ratio; and (4) identification of the importance of glutamine for HA synthesis through transcriptome analyses and then enhancement of the HA titer via its supplement. After that, we combined different strategies together to further increase the HA titer. As a result, one of the optimal recombinant strains, Cg-dR-CLS, yielded 32 g/L of HA at 60 h in a fed-batch culture, which was increased by 30% compared with that of the starting strain. This high value of HA titer will enable the industrial production of HA via the engineered C. glutamicum.
Europium Fluorescent Nanoparticles-Based Multiplex Lateral Flow Immunoassay for Simultaneous Detection of Three Antibiotic Families Residue
Authors: Wang Yaping , Ma Biao , Liu Miaomiao , Chen Erjing , Xu Ying , Zhang Mingzhou 
Published: December 2021

A fluorescent immunoassay based on europium nanoparticles (EuNPs-FIA) was developed for the simultaneous detection of antibiotic residues, solving the problems of single target detection and low sensitivity of traditional immunoassay methods. In the EuNPs-FIA, EuNPs were used as indictive probes by binding to anti-tetracyclines monoclonal antibodies (anti-TCs mAb), anti-sulphonamides monoclonal antibodies (anti-SAs mAb) and anti-fluoroquinolones monoclonal antibodies (anti-FQs mAb), respectively. Different artificial antigens were assigned to different regions of the nitrocellulose membrane as capture reagents. The EuNPs-FIA allowed for the simultaneous detection of three classes of antibiotics (tetracyclines, fluoroquinolones and sulphonamides) within 15 min. It enabled both the qualitative determination with the naked eye under UV light and the quantitative detection of target antibiotics by scanning the fluorescence intensity of the detection probes on the corresponding detection lines. For qualitative analysis, the cut-off values for tetracyclines (TCs), fluoroquinolones (FQs) and sulphonamides (SAs) were 3.2 ng/ml, 2.4 ng/ml and 4.0 ng/ml, respectively, which were much lower than the maximum residue limit in food. For quantitative analysis, these ranged from 0.06 to 6.85 ng/ml for TCs, 0.03–5.14 ng/ml for FQs, and 0.04–4.40 ng/ml for SAs. The linear correlation coefficients were higher than 0.97. The mean spiked recoveries ranged from 92.1 to 106.2% with relative standard deviations less than 8.75%. Among them, the three monoclonal antibodies could recognize four types of TCs, seven types of FQs and 13 types of SAs, respectively, and the detection range could cover 24 antibiotic residues with different structural formulations. The results of the detection of antibiotic residues in real samples using this method were highly correlated with those of high performance liquid chromatography (R2 &gt; 0.98). The accuracy and precision of the EuNPs-FIA also met the requirements for quantitative analysis. These results suggested that this multiplex immunoassay method was a promising method for rapid screening of three families of antibiotic residues.
Tumor Macroscopic Morphology Is an Important Prognostic Factor in Predicting Chemotherapeutic Efficacy and Clinical Outcomes of Patients With Colorectal Neuroendocrine Neoplasms, One Multicenter Retrospective Cohort Study
Authors: Wang Zhijie , An Ke , Li Rui , Liu Qian 
Published: December 2021

Background and AimsLocally advanced and metastatic colorectal neuroendocrine neoplasm (NEN) is a rare disease with a dismal prognosis. We aimed to explore the value of the macroscopic morphology of NENs in the management of TNM stage II-IV colorectal NENs, which has not been fully elucidated in previous reports.MethodsWe retrospectively enrolled 125 eligible patients with TNM stage II-IV colorectal NENs who were diagnosed between 2000 and 2020 from three Chinese hospitals. All were categorized into either protruding or ulcerative NEN groups through endoscopic evaluation of their macroscopic morphology. Clinicopathological data were collected and compared between the two groups. Survival analysis was performed to assess the survival outcomes between the two groups.ResultsA total of 77 and 48 patients had protruding and ulcerative NENs, respectively. Patients with ulcerative NENs had a larger median tumor size (P&lt;0.001) and higher median Ki-67 index (P&lt;0.001), and a larger proportion of these patients had grade G3 disease (P=0.001) and poorly differentiated neoplasms (P=0.001), as well as higher frequencies of T3 and T4 tumors (P=0.006) than patients with protruding NENs. In addition, patients with ulcerative NENs showed a much lower response to first-line chemotherapy [50% (95% CI: 27.3% - 72.7%) versus 20% (95% CI: 3.1% - 36.9%), P=0.03] and a worse 3-year progression-free survival (PFS) rate [19.7% (95% CI: 7.2% - 32.2%) versus 49.5% (95% CI: 37.5% - 61.5%), P=0.001] and 3-year overall survival (OS) rate [30.7% (95% CI: 15.6% - 45.8%) versus 76.9% (95% CI: 66.5% - 87.3%), P&lt;0.001] than those with protruding NENs. The multivariate analysis results indicated that the macroscopic shape of NENs was an independent prognostic factor affecting both PFS (HR = 1.760, 95% CI: 1.024 – 3.026, P = 0.04) and OS (HR = 2.280, 95% CI: 1.123 – 4.628, P = 0.02).ConclusionsUlcerative NENs were more malignant and chemotherapy resistant than protruding NENs. Tumor macroscopic morphology is a valuable prognostic factor for stage II-IV colorectal NENs.
Network Pharmacology and Inflammatory Microenvironment Strategy Approach to Finding the Potential Target of Siraitia grosvenorii (Luo Han Guo) for Glioblastoma
Authors: Li Juan , Bi De , Zhang Xin , Cao Yunpeng , Lv Kun , Jiang Lan 
Published: December 2021

Background: Glioblastoma (GBM) is the most common and aggressive primary intracranial tumor of the central nervous system, and the prognosis of GBM remains a challenge using the standard methods of treatment—TMZ, radiation, and surgical resection. Traditional Chinese medicine (TCM) is a helpful complementary and alternative medicine. However, there are relatively few studies on TCM for GBM.Purpose: We aimed to find the connection between TCM and anti-GBM.Study design: Network pharmacology and inflammatory microenvironment strategy were used to predict Siraitia grosvenorii (Luo Han Guo) target for treating glioblastoma.Methods: We mainly used network pharmacology and bioinformatics.Results: CCL5 was significantly highly expressed in GBM with poor prognostics. Uni-cox and randomForest were used to determine that CCL5 was especially a biomarker in GBM. CCL5 was also the target for SG and TMZ. The active ingredient of Luo Han Guo — squalene and CCL5 —showed high binding efficiency. CCL5, a chemotactic ligand, was enriched and positively correlated in eosinophils. CCL5 was also the target of Luo Han Guo, and its effective active integrate compound –— squalene — might act on CCL5.Conclusion: SG might be a new complementary therapy of the same medicine and food, working on the target CCL5 and playing an anti-GBM effect. CCL5 might affect the immune microenvironment of GBM.
Prognostic Significance of Prolonged Corrected QT Interval in Acute Ischemic Stroke
Authors: Ahn Sung-Ho , Lee Ji-Sung , Kim Young-Hak , Yun Mi-Sook , Han Jung-Hee , Kim Soo-Young , Park Min-Gyu , Park Kyung-Pil , Kang Dong-Wha , Kim Jong S. , Kwon Sun U. 
Published: December 2021

Background and Purpose: The aim of this study was to determine the relationship between the heart rate-corrected QT (QTc) interval and the risk of incident long-term mortality in patients with acute ischemic stroke (AIS), considering the impact of sex differences on clinical characteristics, outcomes, and QTc intervals.Methods: We analyzed prospectively registered data included patients with AIS who visited the emergency room within 24 h of stroke onset and underwent routine cardiac testing, such as measurements of cardiac enzymes and 12-lead ECG. QTc interval was corrected for heart rate using Fridericia's formula and was stratified by sex-specific quartiles. Cox proportional hazards models were used to examine the association between baseline QTc interval and incident all-cause death.Results: A total of 1,668 patients with 1,018 (61.0%) men and mean age 66.0 ± 12.4 years were deemed eligible. Based on the categorized quartiles of the QTc interval, cardiovascular risk profile, and stroke severity increased with prolonged QTc interval, and the risk of long-term mortality increased over a median follow-up of 33 months. Cox proportional hazard model analysis showed that the highest quartile of QTc interval (≥479 msec in men and ≥498 msec in women; hazard ratio [HR]: 1.49, 95% confidence interval [CI]: 1.07–2.08) was associated with all-cause death. Furthermore, dichotomized QTc interval prolongation, defined by the highest septile of the QTc interval (≥501 ms in men and ≥517 m in women: HR: 1.33, 95% CI: 1.00–1.80) was significantly associated with all-cause mortality after adjusting for all clinically relevant variables, such as stroke severity.Conclusions: Prolonged QTc interval was associated with increased risk of long-term mortality, in parallel with the increasing trend of prevalence of cardiovascular risk profiles and stroke severity, across sex differences in AIS patients.
Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children’s Leukemia Group
Authors: Qiu Kun-yin , Xu Hong-gui , Luo Xue-qun , Mai Hui-rong , Liao Ning , Yang Li-hua , Zheng Min-cui , Wan Wu-qing , Wu Xue-dong , Liu Ri-yang , Chen Qi-wen , Chen Hui-qin , Sun Xiao-fei , Jiang Hua , Long Xing-jiang , Chen Guo-hua , Li Xin-yu , Li Chang-gang , Huang Li-bin , Ling Ya-yun , Lin Dan-na , Wen Chuan , Kuang Wen-yong , Feng Xiao-qin , Ye Zhong-lv , Wu Bei-yan , He Xiang-lin , Li Qiao-ru , Wang Li-na , Kong Xian-ling , Xu Lu-hong , Li Chi-kong , Fang Jian-pei 
Published: December 2021

PurposeTo analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value.MethodA total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers.ResultsIn total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age &lt;1 year or ≥10 years, WB≥50×109/L) in ETV6/RUNX1-positive group was significantly lower than that in negative group (P&lt;0.001), while the proportion of patients with good early response (good response to prednisone, D15 MRD &lt; 0.1%, and D33 MRD &lt; 0.01%) in ETV6/RUNX1-positive group was higher than that in the negative group (P&lt;0.001, 0.788 and 0.004, respectively). Multivariate analysis of 2,530 patients found that age &lt;1 or ≥10 years, SCCLG-ALL-2016 protocol, and MLL were independent predictor of outcome but not ETV6/RUNX1. The EFS and OS of the ETV6/RUNX1-positive group were significantly higher than those of the negative group (3-year EFS: 90.11 ± 4.21%vs82 ± 2.36%,P&lt;0.0001, 3-year OS: 91.99 ± 3.92%vs88.79 ± 1.87%,P=0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children.ConclusionsETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment.
Safety of SGLT2 Inhibitors: A Pharmacovigilance Study from 2013 to 2021 Based on FAERS
Authors: Zhou Xiang , Ye Xiaofei , Guo Xiaojing , Liu Dongxu , Xu Jinfang , Hu Fangyuan , Zhai Yinghong , Gao Yongqing , Xu Xiao , Dong Ziwei , He Jia 
Published: December 2021

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2is) are widely used in clinical practice for their demonstrated cardiorenal benefits, but multiple adverse events (AEs) have been reported. We aimed to describe the distribution of SGLT2i-related AEs in different systems and identify important medical event (IME) signals for SGLT2i.Methods: Data from the first quarter (Q1) of 2013–2021 Q2 in FAERS were selected to conduct disproportionality analysis. The definition of AEs and IMEs relied on the system organ classes (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA-version 24.0). Two signal indicators, the reported odds ratio (ROR) and information component (IC), were used to estimate the association between SGLT2is and IMEs.Results: A total of 57,818 records related to SGLT2i, with 22,537 SGLT2i-IME pairs. Most SGLT2i-related IMEs occurred in monotherapy (N = 21,408, 94.99%). Significant signals emerged at the following SOCs: “metabolism and nutrition disorders” (N = 9,103; IC025 = 4.26), “renal and urinary disorders” (3886; 1.20), “infections and infestations” (3457; 0.85). The common strong signals were observed in diabetic ketoacidosis, ketoacidosis, euglycaemic diabetic ketoacidosis and Fournier’s gangrene. Unexpected safety signals such as cellulitis, osteomyelitis, cerebral infarction and nephrolithiasis were detected.Conclusion: Our pharmacovigilance analysis showed that a high frequency was reported for IMEs triggered by SGLT2i monotherapy. Different SGLT2is caused different types and the association strengths of IMEs, while they also shared some specific PTs. Most of the results are generally consistent with previous studies, and more pharmacoepidemiological studies are needed to validate for unexpected AEs. Based on risk-benefit considerations, clinicians should be well informed about important medical events that may be aggravated by SGLT2is.
Effects of Low-Load Blood-Flow Restricted Resistance Training on Functional Capacity and Patient-Reported Outcome in a Young Male Suffering From Reactive Arthritis
Authors: Jørgensen Stian Langgård , Mechlenburg Inger 
Published: December 2021

Introduction: Reactive arthritis (ReA) is a chronic inflammatory disease usually caused by a preceding gastrointestinal or genitourinary bacterial infection. ReA usually occurs in the lower limbs causing joint pain and joint swelling. Physiotherapy-led exercise is recommended to prevent muscle atrophy. The purpose of this case report is to describe the outcome after 12 weeks of low-load blood flow restricted resistance training (BFR-RT) as a rehabilitation method for a young male suffering from ReA.Methods and materials: A 17-year-old male suffered from ReA in the both knee joints and the left hip joint. 36 months after the incident, he suffered from another ReA incident in his right knee. Non-steroid anti-inflammatory drugs and a new arthrocentesis added with corticosteroid injection was unsuccessful in treating the ReA. The patient performed 12 weeks of BFR-RT on the right lower limb with a low amount of supervision after the first week of training. Assessment of unilateral 30-sec chair stand test (u30-sec CST), low-thigh circumference above apex patella, The Knee Injury and Osteoarthritis Outcome Score (KOOS), The Forgotten Knee Joint Score (FJS), and Numeric Ranking Scale for pain (NRS) was performed at baseline and after 3,6,9, and 12 weeks of BFR-RT.Results: The patient completed all planned exercise sessions. u30-sec CST improved with 7 repetitions (reps) on the right limb and 5 reps on the left leg. Low-thigh circumference decreased 1.1 cm on the right leg and 1.0 on the left leg. KOOS symptoms, ADL, quality of life and FJS demonstrated a clinically relevant change on 10, 14 and 23 points.Conclusion: The present case study indicates that even with low amounts of supervision BFR-RT could increase functional performance, reduce knee joint swelling and improve key patient-reported outcome.
Plastid Deficient 1 Is Essential for the Accumulation of Plastid-Encoded RNA Polymerase Core Subunit β and Chloroplast Development in Arabidopsis
Authors: Yang Zhipan , Liu Mingxin , Ding Shunhua , Zhang Yi , Yang Huixia , Wen Xiaogang , Chi Wei , Lu Congming , Lu Qingtao 
Published: December 2021

Plastid-encoded RNA polymerase (PEP)-dependent transcription is an essential process for chloroplast development and plant growth. It is a complex event that is regulated by numerous nuclear-encoded proteins. In order to elucidate the complex regulation mechanism of PEP activity, identification and characterization of PEP activity regulation factors are needed. Here, we characterize Plastid Deficient 1 (PD1) as a novel regulator for PEP-dependent gene expression and chloroplast development in Arabidopsis. The PD1 gene encodes a protein that is conserved in photoautotrophic organisms. The Arabidopsis pd1 mutant showed albino and seedling-lethal phenotypes. The plastid development in the pd1 mutant was arrested. The PD1 protein localized in the chloroplasts, and it colocalized with nucleoid protein TRXz. RT-quantitative real-time PCR, northern blot, and run-on analyses indicated that the PEP-dependent transcription in the pd1 mutant was dramatically impaired, whereas the nuclear-encoded RNA polymerase-dependent transcription was up-regulated. The yeast two-hybrid assays and coimmunoprecipitation experiments showed that the PD1 protein interacts with PEP core subunit β (PEP-β), which has been verified to be essential for chloroplast development. The immunoblot analysis indicated that the accumulation of PEP-β was barely detected in the pd1 mutant, whereas the accumulation of the other essential components of the PEP complex, such as core subunits α and β′, were not affected in the pd1 mutant. These observations suggested that the PD1 protein is essential for the accumulation of PEP-β and chloroplast development in Arabidopsis, potentially by direct interaction with PEP-β.
Redes sociales y rendimiento académico en el área de comunicación en estudiantes de educación básica regular del Perú
Authors: Paniora Marroquín Fanny María , Mauricio Avalos Rubén Moisés , Paniora Marroquín Yda Juana , Quiñones Li Aura Elisa 
Published: December 2021

La presente investigación tiene como objetivo general Determinar la relación entre las redes sociales con el rendimiento académico en el área de comunicación en los estudiantes de 4to y 5to año de secundaria. Este estudio fue de tipo básico, con un diseño no experimental transversal, de nivel descriptivo correlacional, la población del estudio estuvo constituida por 194 estudiantes, con una muestra probabilística estratificada con aplicación de fórmula estadística con un total de 129 estudiantes, se empleó la técnica de la encuesta y la observación, se utilizaron como instrumentos se el cuestionario sobre redes sociales empleando la escala de Likert con una confiabilidad alta; y el registro de actas de evaluación de la asignatura de comunicación. Para la validación se aplicó el coeficiente de correlación de Spearman, con un valor de rs = 0,513, la cual muestra una correlación moderada positiva, con un p_valor = 0,000 < 0,05. Concluyendo que existe relación significativa entre las redes sociales con el rendimiento académico en el área de comunicación en los estudiantes de 4to y 5to año de secundaria.
Entrepreneurial Orientation among Arts Managers in Western Australia
Authors: Campbell Alistair , Rusak Helen 
Published: December 2021

As a region, Western Australia is the largest and most isolated state in Australia, and supports a community of vibrant Arts Organisations. The Arts is widely recognised for its creativity and innovation, but what about the managers of these organisations, are they equally innovative, or entrepreneurial? Rusak (2016) explored this question and found that their Entrepreneurial Orientation (EO) matched the three core dimensions of Innovativeness, Pro-activeness, and Risk-taking, but the study did not include the other two EO dimensions of Autonomy and Competitive Aggressiveness. It did however observe that "arts companies don’t generally try to take offensive postures or aggressive responses to competitive threats and rather work collaboratively, as this sample shows". This assertion was not the focus of the article, nor was it explored in any depth in that paper.
There are at least two possibilities here: it could be a passive aversion to competitive aggression, or a more deliberate counter-behaviour of collaboration. Either of these would appear to contradict the EO construct, in particular the expectation that all EO dimensions covary, which makes it interesting from a theory perspective. This paper explores this challenge to the EO theory in some detail, using software-aided analysis to tease out the finer nuances in this dimension of Competitive Aggressiveness. While the sample size and its geographical confines limit the generalisations that can be made, there is solid evidence that in this sample of Arts Managers, the Arts acts as a powerful contextual modifier to the expectations of EO theory. The dimension of Competitive Aggressiveness has not simply been altered or toned-down by this context, it has been replaced by a polar opposite.
Implikasi Hukum Penunjukan Ahli Waris Berdasarkan Klausul Asuransi Dalam Perspektif Hukum Waris Perdata
Authors: Suprima  , Rizkianti Wardani , Khoirur Rizal Lutfi  
Published: December 2021

IMPLIKASI HUKUM PENUNJUKAN AHLI WARIS BERDASARKAN KLAUSUL PERJANJIAN ASURANSI DALAM PERSPEKTIF HUKUM WARIS PERDATA (BW)
RINGKASAN

Penelitian ini bertujuan untuk (1) mengkaji dan menganalisis legalitas penunjukan ahli waris berdasarkan klausul asuransi dalam perspektif hukum perdata (BW) dan, (2) mengkaji dan memberikan implikasi hukum penunjukan ahli waris berdasarkan klausul asuransi dalam perspektif hukum perdata (BW)
Jenis penelitian ini adalah penelitian hukum yuridis normatif. Secara normatif, penelitian ini mengacu kepada norma-norma serta asas-asas hukum yang terdapat dalam peraturan perundang-undangan, Menggunakan data sekunder yang terdiri dari bahan hukum primer, sekunder dan yang relevan dengan fenomena hukum yang berkaitan dengan penelitian ini. Data dikumpulkan dengan cara melakukan penelitian kepustakaan (library research)
Dalam klausul asuransi pihak tertanggung diberikan kebebasan untuk menunjuk ahli waris. Padahal dalam perspektif hukum waris perdata telah ditentukan golongan-golongan ahli waris dengan asas golongan sat menutup golongan dua, golongan dua menutup golongan tiga, golongan tiga dapat mewaris bersama golongan empat. Olehkarena itu dibutuhkan penelitian mengenai lealitas dan implikasi hukum penunjukan ahli waris b erdasarkan klausul perjanjian asuransi.
Kata Kunci :klausul asuransi; penunjukan; wahli waris ; implikasi hukum.