bluuebunny/crossref_metadata_2025_split huggingface dataset:
Niloticin binds to MD-2 to promote anti-inflammatory pathway activation in macrophage cells
Authors: Chen Guirong , Liu Chang , Zhang Mingbo , Wang Xiaobo , Xu Yubin 
Published: October 2022

Objectives Niloticin is an active compound isolated from Cortex phellodendri with uncharacterized anti-inflammatory activity. We assessed the drug potential of niloticin and examined its ability to target myeloid differentiation protein 2 (MD-2) to ascertain the mechanism for its anti-inflammatory activity. Methods The Traditional Chinese Medicine Systems Pharmacology Database was used to evaluate niloticin. Bio-layer interferometry and molecular docking technologies were used to explore how niloticin targets MD-2, which mediates a series of toll-like receptor 4 (TLR4)-dependent inflammatory responses. The cytokines involved in the lipopolysaccharide (LPS)-TLR4/MD-2-NF-κB pathway were evaluated using ELISA, RT-qPCR, and western blotting. Results Niloticin could bind to MD-2 and had no evident effects on cell viability. Niloticin treatment significantly decreased the levels of NO, IL-6, TNF-α, and IL-1β induced by LPS ( p < 0.01). IL-1β, IL-6, iNOS, TNF-α, and COX-2 mRNA expression levels were decreased by niloticin (all p < 0.01). Compared with that in the control group, the increase in TLR4, p65, MyD88, p-p65, and iNOS expression levels induced by LPS were suppressed by niloticin (all p < 0.01). Conclusion Our results suggest that niloticin has therapeutic potential and binds to MD-2. Niloticin binding to MD-2 antagonized the effects of LPS binding to the TLR4/MD-2 complex, resulting in the inhibition of the LPS-TLR4/MD-2-NF-κB signaling pathway.
Early patient-reported outcomes of cataract surgery with implantation of the trifocal liberty 677MY intraocular lens: A pilot study
Authors: Villarrubia Cuadrado Alberto , Sánchez Ventosa Álvaro , Palacín Miranda Elisa , López Pérez Maria Dolores , González-Cruces Timoteo , Morales López Pablo , Piñero David P , Cano-Ortiz Antonio 
Published: October 2022

Purpose To report our first clinical and patient-reported outcomes in the early postoperative period with a new model of trifocal diffractive intraocular lens (IOL). Methods Pilot prospective analysis of the results of 26 eyes of 13 patients (age, 44–79 years) undergoing cataract surgery with implantation of the trifocal diffractive IOL Liberty 677MY (Medicontur Medical Engineering Ltd., Zsámbék, Hungary). The following clinical outcomes were evaluated during the first postoperative month: measurement of distance, intermediate and near visual acuity, binocular defocus curve, and level of spectacle independence, patient satisfaction, perception of photic phenomena, and difficulty in performing several vision-related daily tasks by means of a questionnaire. Results Mean binocular LogMAR uncorrected distance, intermediate and near visual acuities were −0.03 ± 0.13, 0.21 ± 0.16, and 0.16 ± 0.09, respectively. Furthermore, 100.0%, 84.6% and 92.3% of patients achieved a binocular corrected distance, distance-corrected intermediate and distance-corrected near visual acuity of 20/32 or better, respectively. In the defocus curve, visual acuities were better than 0.2 logMAR for defocus levels between +1.00 and −3.00 D. Spectacle independence was referred by all patients, with any of them reporting dissatisfaction with the outcome of the surgery. The postoperative vision did not lead to difficulties in the daily life in 92.3% of patients. Bothersome halos, glare or starbursts were only reported by only 7.7% of patients. Conclusions The trifocal IOL evaluated provides a successful visual rehabilitation with minimal photic phenomena associated, leading to high levels of spectacle independence and patient satisfaction.
Staphylococcus aureus Nasopharyngeal Carriage and Antimicrobial Resistance among Adults with Sickle Cell Disease at the Korle Bu Teaching Hospital in Accra, Ghana
Authors: Dayie Nicholas TKD , Sekoh Deborah NK , Tetteh-Quarcoo Patience B , Dayie Alberta D , Osei Mary-Magdalene , Kotey Fleischer CN , Donkor Eric S 
Published: October 2022

Background: Sickle cell disease (SCD) patients are an important risk group for Staphylococcus aureus ( S. aureus) carriage and infections. Little is, however, known about the nasopharyngeal carriage epidemiology of the pathogen in this vulnerable population. Aim: The aim of this study was to evaluate S. aureus and methicillin-resistant S. aureus (MRSA) nasopharyngeal carriage prevalence, carriage determinants, and antimicrobial resistance among SCD adults in Ghana. Methodology: Nasopharyngeal swabs, obtained from 200 SCD adults recruited at the Korle Bu Teaching Hospital, were cultured for S. aureus, and these isolates were subjected to antimicrobial susceptibility testing via the Kirby-Bauer method. Results: The prevalence of S. aureus carriage was 41.5% (n = 83), and that of MRSA carriage was 1.0% (n = 2). Moreover, carriage of coagulase-negative Staphylococcus (CoNS) was the only determinant of S. aureus carriage identified (OR = 0.012, P < .0001). However, neither this variable nor the other features of the participants emerged as a determinant of MRSA carriage. The antimicrobial resistance rates decreased across penicillin (98.8%, n = 82), tetracycline (54.2%, n = 45), gentamicin (32.5%, n = 27), ciprofloxacin (21.7%, n = 18), erythromycin (18.1%, n = 15), clindamycin (10.8%, n = 9), amoxicillin-clavulanic acid (10.8%, n = 9), teicoplanin (1.2%, n = 1), and linezolid (0.0%, n = 0), and the multidrug resistance rate was 45.8% (n = 38). Conclusion: The nasopharyngeal carriage prevalence of S. aureus in the current study was high, while that of MRSA was low. The isolates were highly resistant to several of the antibiotics tested, but not teicoplanin and linezolid, making these antibiotics suitable for treatment of S. aureus infections among the SCD population.
Real-world evidence of subcutaneous treprostinil use in pulmonary arterial hypertension in Argentina
Authors: Lescano Adrián , Giacommi Guillermo , Botta Cristian E. , Soricetti Julieta , Rodriguez Manuel , Vargas Mielles Paul , Diez Fabián 
Published: October 2022

Introduction: Pulmonary arterial hypertension is a progressive haemodynamic disease with high morbidity and mortality. Of the different treatments available, the prostacyclin analogues are the drugs of choice for high-risk patients, with treprostinil being the most commonly used drug in Argentina. Methodology: The objective of this study is to perform a retrospective evaluation of the efficacy and safety of subcutaneous treprostinil in regular clinical practice in Argentina in 51 patients with pulmonary arterial hypertension after 12 months of follow-up. Results: The results showed that treatment with subcutaneous treprostinil is associated with a significant improvement in different clinical efficacy parameters: 65% reduction in advanced functional class ( p < 0.0001), 130-m increase in the 6-min walk test ( p < 0.0001), 65% reduction in the pro B-type natriuretic peptide value (–531 pg/dL; p < 0.0001), significant reduction of 15.7% in pulmonary vascular resistance [–1.3 wood units (WU); p < 0.0001], improved cardiac index with an increase of 16.7% (+0.4 L/min/m2; p = 0.002), as well as a high survival rate (92%) and a 44% incidence of combined events (mortality, heart failure, syncope and/or lung transplantation), without a significant increase in previously reported adverse events. The risk stratification evaluation according to ESC/ERS guidelines showed a significant decrease in the proportion of patients at high risk after the treatment period ( p = 0.004). Conclusions: These real-world results corroborate the efficacy and safety of subcutaneous treprostinil, even at high doses, and open up the possibility of improving its current use in clinical practice as a first-line therapy, especially in high-risk patient profiles.
Circulating tumour DNA biomarkers in savolitinib-treated patients with non-small cell lung cancer harbouring MET exon 14 skipping alterations: a post hoc analysis of a pivotal phase 2 study
Authors: Yu Yongfeng , Ren Yongxin , Fang Jian , Cao Lejie , Liang Zongan , Guo Qisen , Han Sen , Ji Zimei , Wang Ye , Sun Yulan , Chen Yuan , Li Xingya , Xu Hua , Zhou Jianying , Jiang Liyan , Cheng Ying , Han Zhigang , Shi Jianhua , Chen Gongyan , Ma Rui , Fan Yun , Sun Sanyuan , Jiao Longxian , Jia Xiaoyun , Wang Linfang , Lu Puhan , Xu Qian , Luo Xian , Su Weiguo , Lu Shun 
Published: October 2022

Background: Savolitinib, a selective MET inhibitor, showed efficacy in patients with non-small cell lung cancer (NSCLC), including pulmonary sarcomatoid carcinoma (PSC), harbouring MET exon 14 skipping alteration ( METex14). Objective: To analyse post hoc, the association between circulating tumour DNA (ctDNA) biomarkers and clinical outcomes, including resistance, with savolitinib. Design: A multicentre, single-arm, open-label phase 2 study. Methods: All enrolled patients with baseline plasma samples were included. Outcomes were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) by baseline METex14 and post-treatment clearance, coexisting gene alterations at baseline and disease progression. Results: Among 66 patients with baseline ctDNA sequencing, 46 (70%) had detectable METex14. Frequent coexisting baseline gene alterations included TP53 and POT1 mutations. Patients with detectable baseline METex14 exhibited worse PFS [hazard ratio (HR), 1.77; 95% confidence interval (CI), 0.88–3.57; p = 0.108] and OS (HR, 3.26; 95% CI, 1.35–7.89; p = 0.006) than those without, despite showing a numerically higher ORR. Among 24 patients with baseline detectable METex14 and evaluable postbaseline samples, 13 achieved METex14 clearance post-treatment. Median time to first clearance was 1.3 months (range, 0.7–1.5). METex14 post-treatment clearance was associated with better ORR (92.3%; 95% CI, 64.0–99.8 versus 36.4%; 95% CI, 10.9–69.2; p = 0.0078), PFS (HR, 0.44; 95% CI, 0.2–1.3; p = 0.1225) and OS (HR, 0.31; 95% CI, 0.1–1.0; p = 0.0397) versus non-clearance. Among 22 patients with disease progression, 10 acquired pathway alterations (e.g. in RAS/RAF and PI3K/PTEN) alone or with secondary MET mutations (D1228H/N and Y1230C/H/S). Conclusion: ctDNA biomarkers may allow for longitudinal monitoring of clinical outcomes with savolitinib in patients with METex14-positive PSC and other NSCLC subtypes. Specifically, undetectable baseline METex14 or post-treatment clearance may predict favourable clinical outcomes, while secondary MET mutations and other acquired gene alterations may explain resistance to savolitinib. Registration: The trial was registered with ClinicalTrials.gov (NCT02897479) on 13 September 2016.
Association between Common Variants in VEGFA Gene and the Susceptibility of Primary Knee Osteoarthritis
Authors: Saetan Natthaphon , Honsawek Sittisak , Tanavalee Aree , Ngarmukos Srihatach , Yuktanandana Pongsak , Poovorawan Yong 
Published: October 2022

Objectives This study aimed to analyze the relationship between vascular endothelial growth factor A ( VEGFA) gene polymorphisms, plasma VEGFA, and the susceptibility of knee osteoarthritis (OA). Design A total of 404 subjects, 202 knee OA subjects and 202 healthy volunteers, were enrolled into the study. Four distinct polymorphisms of the VEGFA gene were evaluated using polymerase chain reaction-restriction fragment length polymorphism: −2578C/A (rs699947), −1154G/A (rs1570360), −634C/G (rs2010963), and +936C/T (rs3025039). Plasma VEGFA levels were analyzed using enzyme-linked immunosorbent assay. Results The most common nucleotides in both knee OA subjects and healthy controls were CC for −2578C/A, GG for −1154G/A, CG for −634C/G, and CC for +936C/T in the VEGFA gene. Genotype distribution and allele frequencies of VEGFA −2578C/A, −1154G/A, −634C/G, and +936C/T single nucleotide polymorphisms did not differ between OA patients and the controls. Plasma VEGFA levels showed no difference between OA patients and the controls. In contrast, plasma VEGFA levels of −634C/C genotype were significantly higher in OA patients than in the controls ( P = 0.035). According to the −2578A/A genotype, patients with early stage OA had a higher odds ratio than those with advanced stage OA ( P = 0.023). Conclusions VEGFA −2578C/A (rs699947), −1154G/A (rs1570360), −634C/G (rs2010963), and +936C/T (rs3025039) polymorphisms may not be responsible for OA susceptibility in the Thai population. However, the OA patients with A/A genotype at the −2578C/A seemed to have a lower potential risk of developing severe OA than those with the C/A and C/C genotypes. These findings would help elucidate and facilitate a better understanding of the genetic fundamentals of OA.
Noncanonical β-catenin interactions promote leukemia-initiating activity in early T-cell acute lymphoblastic leukemia
Authors: Panelli Patrizio , De Santis Elisabetta , Colucci Mattia , Tamiro Francesco , Sansico Francesca , Miroballo Mattia , Murgo Emanuele , Padovano Costanzo , Gusscott Sam , Ciavarella Michele , Chavez Elizabeth A. , Bianchi Fabrizio , Rossi Giovanni , Carella Angelo M. , Steidl Christian , Weng Andrew P. , Giambra Vincenzo 
Published: October 2022

Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is a T-cell malignancy characterized by cell subsets and enriched with leukemia-initiating cells (LICs). β-Catenin modulates LIC activity in T-ALL. However, its role in maintaining established leukemia stem cells remains largely unknown. To identify functionally relevant protein interactions of β-catenin in T-ALL, we performed coimmunoprecipitation followed by liquid chromatography–mass spectrometry. Here, we report that a noncanonical functional interaction of β-catenin with the Forkhead box O3 (FOXO3) transcription factor positively regulates LIC-related genes, including the cyclin-dependent kinase 4, which is a crucial modulator of cell cycle and tumor maintenance. We also confirm the relevance of these findings using stably integrated fluorescent reporters of β-catenin and FOXO3 activity in patient-derived xenografts, which identify minor subpopulations with enriched LIC activity. In addition, gene expression data at the single-cell level of leukemic cells of primary patients at the time of diagnosis and minimal residual disease (MRD) up to 30 days after the standard treatments reveal that the expression of β-catenin– and FOXO3-dependent genes is present in the CD82+CD117+ cell fraction, which is substantially enriched with LICs in MRD as well as in early T-cell precursor ALL. These findings highlight key functional roles for β-catenin and FOXO3 and suggest novel therapeutic strategies to eradicate aggressive cell subsets in T-ALL.
Simultaneous Enhancement of iron Deficiency Tolerance and Iron Accumulation in Rice by Combining the Knockdown of OsHRZ Ubiquitin Ligases with the Introduction of Engineered Ferric-chelate Reductase
Authors: Kobayashi Takanori , Maeda Keisuke , Suzuki Yutaro , Nishizawa Naoko K. 
Published: October 2022

AbstractIron is an essential micronutrient for living organisms, but its solubility is extremely low under alkaline conditions. Plants often suffer from iron deficiency chlorosis in calcareous soils, which consist of approximately 30% of the world’s cultivated area, severely limiting plant productivity. Iron deficiency anemia is also a widespread problem in humans, especially in Asian and African people who take up iron mainly from staple foods containing low iron concentrations. Transgenic manipulation of genes involved in plant iron uptake, translocation, and storage has made improvements in enhancing iron deficiency tolerance or iron accumulation in edible parts, but these two properties have been characterized separately. We previously produced transgenic rice lines, with concomitant improvement of iron deficiency tolerance and grain iron accumulation by knocking-down OsHRZ ubiquitin ligases, which negatively regulate iron deficiency response and iron accumulation in rice. In the present report, we aimed to further improve the iron deficiency tolerance and grain iron accumulation of OsHRZ knockdown rice by the simultaneous introduction of the engineered ferric-chelate reductase gene Refre1/372 under the control of the OsIRT1 promoter for further enhancement of iron uptake. We obtained several transgenic rice lines with repressed OsHRZ expression and induced Refre1/372 expression. These lines showed a variable degree of iron deficiency tolerance in calcareous soils, with increased iron accumulation in brown seeds under both iron-deficient and iron-sufficient soil cultures. Selected OsHRZ knockdown plus Refre1/372 lines showed similar or better growth compared with that of singly introduced OsHRZ knockdown or Refre1/372 lines in calcareous soils under both non-submerged and submerged conditions. After submerged calcareous soil cultivation, these OsHRZ knockdown plus Refre1/372 lines accumulated 2.5–4.3 times and 17–23 times more iron concentrations than that of non-transformants in brown rice and straw, respectively, which was comparable or superior to a single OsHRZ knockdown line. Our results indicate that the combined introduction of OsHRZ knockdown and OsIRT1 promoter-Refre1/372 is highly effective in further improving the iron deficiency tolerance without compromising the iron accumulation of the OsHRZ knockdown effects.
Densest subgraph-based methods for protein-protein interaction hot spot prediction
Authors: Li Ruiming , Lee Jung-Yu , Yang Jinn-Moon , Akutsu Tatsuya 
Published: October 2022

Abstract
Background
Hot spots play an important role in protein binding analysis. The residue interaction network is a key point in hot spot prediction, and several graph theory-based methods have been proposed to detect hot spots. Although the existing methods can yield some interesting residues by network analysis, low recall has limited their abilities in finding more potential hot spots.

Result
In this study, we develop three graph theory-based methods to predict hot spots from only a single residue interaction network. We detect the important residues by finding subgraphs with high densities, i.e., high average degrees. Generally, a high degree implies a high binding possibility between protein chains, and thus a subgraph with high density usually relates to binding sites that have a high rate of hot spots. By evaluating the results on 67 complexes from the SKEMPI database, our methods clearly outperform existing graph theory-based methods on recall and F-score. In particular, our main method, Min-SDS, has an average recall of over 0.665 and an f2-score of over 0.364, while the recall and f2-score of the existing methods are less than 0.400 and 0.224, respectively.

Conclusion
The Min-SDS method performs best among all tested methods on the hot spot prediction problem, and all three of our methods provide useful approaches for analyzing bionetworks. In addition, the densest subgraph-based methods predict hot spots with only one residue interaction network, which is constructed from spatial atomic coordinate data to mitigate the shortage of data from wet-lab experiments.
New cycle, same old mistakes? Overlapping vs. discrete generations in long-term recurrent selection
Authors: Labroo Marlee R. , Rutkoski Jessica E. 
Published: October 2022

Abstract
Background
Recurrent selection is a foundational breeding method for quantitative trait improvement. It typically features rapid breeding cycles that can lead to high rates of genetic gain. Usually, generations are discrete in recurrent selection, which means that breeding candidates are evaluated and considered for selection for only one cycle. Alternately, generations can overlap, with breeding candidates considered for selection as parents for multiple cycles. With recurrent genomic selection but not phenotypic selection, candidates can be re-evaluated by using genomic estimated breeding values without additional phenotyping of the candidates themselves. Therefore, it may be that candidates with true high breeding values discarded in one cycle due to underestimation of breeding value could be identified and selected in subsequent cycles. The consequences of allowing generations to overlap in recurrent selection are unknown. We assessed whether maintaining overlapping and discrete generations led to differences in genetic gain for phenotypic, genomic truncation, and genomic optimum contribution recurrent selection by stochastic simulation.

Results
With phenotypic selection, overlapping generations led to decreased genetic gain compared to discrete generations due to increased selection error bias. Selected individuals, which were in the upper tail of the distribution of phenotypic values, tended to also have high absolute error relative to their true breeding value compared to the overall population. Without repeated phenotyping, these individuals erroneously believed to have high value were repeatedly selected across cycles, leading to decreased genetic gain. With genomic truncation selection, overlapping and discrete generations performed similarly as updating breeding values precluded repeatedly selecting individuals with inaccurately high estimates of breeding values in subsequent cycles. Overlapping generations did not outperform discrete generations in the presence of a positive genetic trend with genomic truncation selection, as individuals from previous breeding cycles typically had truly lower breeding values than candidates from the current generation. With genomic optimum contribution selection, overlapping and discrete generations performed similarly, but overlapping generations slightly outperformed discrete generations in the long term if the targeted inbreeding rate was extremely low.

Conclusion
Maintaining discrete generations in recurrent phenotypic selection leads to increased genetic gain, especially at low heritabilities, by preventing selection error bias. With genomic truncation selection and genomic optimum contribution selection, genetic gain does not differ between discrete and overlapping generations assuming non-genetic effects are not present. Overlapping generations may increase genetic gain in the long term with very low targeted rates of inbreeding in genomic optimum contribution selection.
Gamma-glutamyl transpeptidase to platelet and gamma-glutamyl transpeptidase to lymphocyte ratio in a sample of Chinese Han population
Authors: Chen Weijie , Hong Danmian , Chen Zeliang , Dai Xiaoqing , Cao Jing , Yu Min , Li Liping 
Published: October 2022

Abstract
Background
Gamma-glutamyl transpeptidase to platelet ratio (GPR) and gamma-glutamyl transpeptidase to lymphocyte ratio (GLR) are assumed to be prognostic factors in liver fibrosis, cirrhosis and hepatocellular carcinoma. However, the reference values of GPR and GLR were not known.

Objectives
The study aimed to investigate the reference ranges of GPR and GLR in Chinese Han population in Chaoshan region in South China.

Methods
A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College in South China. 2400 healthy adults aged 20~79 years were included. GPR and GLR were determined.

Results
Of 2400 healthy adults, 1200 men and 1200 women were included. The median GPR and GLR for men were 0.22 and 11.28, for women were 0.18 and 7.86, respectively. The 95% reference range of GPR in normal male and female are 0.09~0.54 and 0.08~0.55, GLR are 4.55~29.64 and 3.52~23.08, respectively. The male had a higher GPR at age 20~49 than the female while the GPR at age 60~79 was higher in the female than in the male. The GPR was affected by age, decreased with aging in male and increased in female. The GLR was higher in the male than in the female and varied with aging in the female but not in the male.

Conclusion
The study provides reference data on GPR and GLR from different age and sex groups in South China. GPR and GLR varied with age and sex.