bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-clinical studies of EC2629, a highly potent folate- receptor-targeted DNA crosslinking agent
Authors: Reddy Joseph A. , Nelson Melissa , Dircksen Christina , Vetzel Marilynn , Johnson Theresa , Cross Vicky , Westrick Elaine , Qi LongWu , Hahn Spencer , Santhapuram Hari Krishna , Parham Garth , Wang Kevin , Vaughn Jeremy F. , Felten Albert , Pugh Michael , Lu June , Klein Patrick , Vlahov Iontcho R. , Leamon Christopher P. 
Published: July 2020

AbstractFolate receptor (FR)-targeted small molecule drug conjugates (SMDCs) have shown promising results in early stage clinical trials with microtubule destabilizing agents, such as vintafolide and EC1456. In our effort to develop FR-targeted SMDCs with varying mechanisms of action, we synthesized EC2629, a folate conjugate of a DNA crosslinking agent based on a novel DNA-alkylating moiety. This agent was found to be extremely potent with an in vitro IC50 ~ 100× lower than folate SMDCs constructed with various microtubule inhibitors. EC2629 treatment of nude mice bearing FR-positive KB human xenografts led to cures in 100% of the test animals with very low dose levels (300 nmol/kg) following a convenient once a week schedule. The observed activity was not accompanied by any noticeable weight loss (up to 20 weeks post end of dosing). Complete responses were also observed against FR-positive paclitaxel (KB-PR) and cisplatin (KB-CR) resistant models. When evaluated against FR-positive patient derived xenograft (PDX) models of ovarian (ST070), endometrial (ST040) and triple negative breast cancers (ST502, ST738), EC2629 showed significantly greater anti-tumor activity compared to their corresponding standard of care treatments. Taken together, these studies thus demonstrated that EC2629, with its distinct DNA reacting mechanism, may be useful in treating FR-positive tumors, including those that are classified as drug resistant.
Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology
Authors: Zhou Wei , Wu Jiarui , Zhang Jingyuan , Liu Xinkui , Guo Siyu , Jia ShanShan , Zhang Xiaomeng , Zhu Yingli , Wang Miaomiao 
Published: July 2020

AbstractCompound Kushen injection (CKI), a medicine in widespread clinical use in China, has proven therapeutic effects on cancer. However, few molecular mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network analysis with network pharmacology methods were undertaken to elucidate the underlying molecular mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clinical traits of ESCA were analysed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacology. Molecular docking simulation was performed to recognize the binding activity of hub genes with CKI compounds. The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the molecular mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment.
Plant endophytes promote growth and alleviate salt stress in Arabidopsis thaliana
Authors: Fan Di , Subramanian Sowmyalakshmi , Smith Donald L. 
Published: July 2020

AbstractPlant growth promoting rhizobacteria (PGPR) are a functionally diverse group of microbes having immense potential as biostimulants and stress alleviators. Their exploitation in agro-ecosystems as an eco-friendly and cost-effective alternative to traditional chemical inputs may positively affect agricultural productivity and environmental sustainability. The present study describes selected rhizobacteria, from a range of origins, having plant growth promoting potential under controlled conditions. A total of 98 isolates (ectophytic or endophytic) from various crop and uncultivated plants were screened, out of which four endophytes (n, L, K and Y) from Phalaris arundinacea, Solanum dulcamara, Scorzoneroides autumnalis, and Glycine max, respectively, were selected in vitro for their vegetative growth stimulating effects on Arabidopsis thaliana Col-0 seedlings with regard to leaf surface area and shoot fresh weight. A 16S rRNA gene sequencing analysis of the strains indicated that these isolates belong to the genera Pseudomonas, Bacillus, Mucilaginibacter and Rhizobium. Strains were then further tested for their effects on abiotic stress alleviation under both Petri-plate and pot conditions. Results from Petri-dish assay indicated strains L, K and Y alleviated salt stress in Arabidopsis seedlings, while strains K and Y conferred increases in fresh weight and leaf area under osmotic stress. Results from subsequent in vivo trials indicated all the isolates, especially strains L, K and Y, distinctly increased A. thaliana growth under both normal and high salinity conditions, as compared to control plants. The activity of antioxidant enzymes (ascorbate peroxidase, catalase and peroxidase), proline content and total antioxidative capacity also differed in the inoculated A. thaliana plants. Furthermore, a study on spatial distribution of the four strains, using either conventional Petri-plate counts or GFP-tagged bacteria, indicated that all four strains were able to colonize the endosphere of A. thaliana root tissue. Thus, the study revealed that the four selected rhizobacteria are good candidates to be explored as plant growth stimulators, which also possess salt stress mitigating property, partially by regulating osmolytes and antioxidant enzymes. Moreover, the study is the first report of Scorzoneroides autumnalis (fall dandelion) and Solanum dulcamara (bittersweet) associated endophytes with PGP effects.
Incidence, reasons, and risk factors for 30-day readmission after lumbar spine surgery for degenerative spinal disease
Authors: Cho Pyung Goo , Kim Tae Hyun , Lee Hana , Ji Gyu Yeul , Park Sang Hyuk , Shin Dong Ah 
Published: July 2020

AbstractThis study investigated risk factors for 30-day readmission of discharged patients who had undergone lumbar spinal surgery. This retrospective, case–control study reviewed 3,933 patients discharged after elective spinal surgery for lumbar degenerative diseases from 2005 to 2012 at a university hospital. Of these patients, 102 were re-hospitalized within 30 days of discharge. Patient medical records were reviewed. The incidence of readmission within 30 days was 2.6%, and uncontrolled pain was the most common reason for readmission. In the univariate analysis, age, mental illness, the number of medical comorbidities, previous spinal surgery, fusion surgery, number of fusion levels, estimated blood loss, operation time, intensive care unit (ICU) admission, length of hospital stays, and total medical expenses were associated with a higher risk of readmission within 30 days. Multiple logistic regression analysis revealed that previous spinal surgery, operation time, ICU admission, length of hospital stays, and total medical expenses were independent risk factors for 30-day readmission. Independent risk factors for readmission were longer operation time, a previous spinal surgery, ICU admission, longer hospital stays, and higher medical expenses. Further studies controlling these risk factors could contribute to reducing readmission and thus improving the quality of care.
Confined transverse-electric graphene plasmons in negative refractive-index systems
Authors: Zhang Xinyan , Hu Hao , Lin Xiao , Shen Lian , Zhang Baile , Chen Hongsheng 
Published: July 2020

AbstractTransverse electric graphene plasmons are generally weakly confined in the direction perpendicular to the graphene plane. They are featured by a skin depth δ, namely the penetration depth of their evanescent fields into the surrounding environment, much larger than the wavelength λ in free space (e.g., δ > 10λ). The weak spatial confinement of transverse electric graphene plasmons is now the key drawback that limits their practical applications. Here we report the skin depth of TE graphene plasmons can be largely decreased down to the subwavelength scale (e.g., δ < λ/10) in negative refractive-index environments. The underlying mechanism originates from the different existence conditions for TE graphene plasmons in negative and positive refractive-index environments. To be specific, their existence in negative (positive) refractive-index environments requires Im(σs) > 0 (Im(σs) < 0) and lies in the frequency range of ħω/μc < 1.667 (ħω/μc > 1.667), where σs and μc are the surface conductivity and chemical potential of monolayer graphene, respectively.
Making drugs out of sunlight and ‘thin air’: an emerging synergy of synthetic biology and natural product chemistry
Authors: Stephenson Michael J. , Osbourn Anne 
Published: July 2020

Nature has long served as a rich source of structurally diverse small organic molecules with medicinally relevant biological activities. Despite the historical success of these so-called natural products, the enthusiasm of big pharma to explore these compounds as leads in drug design has waxed and waned. A major contributor to this is their often inherent structural complexity. Such compounds are difficult (often impossible) to access synthetically, a hurdle that can stifle lead development and hinder sustainable large-scale production of promising leads for clinical evaluation. However, in recent years, an emerging synergy between synthetic biology and natural product chemistry offers the potential for a renaissance in our ability to access natural products for drug discovery and development. Advances in genome sequencing, bioinformatics and the maturing of heterologous expression platforms are increasing, enabling the study, and ultimately, the manipulation of plant biosynthetic pathways.
The triterpenes are one of the most structurally diverse families of natural products and arguably one of the most underrepresented in the clinic. The plant kingdom is the richest source of triterpene diversity, with &gt;20,000 triterpenes reported so far. Transient expression of genes for candidate enzymes and pathways in amenable plant species is emerging as a powerful and rapid means of investigating and harnessing the plant enzymes involved in generating this diversity. Such platforms also have the potential to serve as production systems in their own right, with the possibility of upscaling these discoveries into commercially useful products using the same overall basic procedure. Ultimately, the carbon source for generation of high-value compounds in plants is photosynthesis. Therefore, we could, with the help of plants, be producing new medicines out of sunlight and ‘thin air’ in green factories in the not too distant future.
Acquisition and Acoustic Patterns of Southern American English /l/ in Young Children
Authors: Chung Hyunju 
Published: July 2020

Purpose
The aim of the current study was to examine /l/ developmental patterns in young learners of Southern American English, especially in relation to the effect of word position and phonetic contexts.

Method
Eighteen children with typically developing speech, aged between 2 and 5 years, produced monosyllabic single words containing singleton /l/ in different word positions (pre- vs. postvocalic /l/) across different vowel contexts (high front vs. low back) and cluster /l/ in different consonant contexts (/pl, bl/ vs. /kl, gl/). Each production was analyzed for its accuracy and acoustic patterns as measured by the first two formant frequencies and their difference (F1, F2, and F2-F1).

Results
There was great individual variability in /l/ acquisition patterns, with some 2- and 3-year-olds reaching 100% accuracy for prevocalic /l/, while others were below 70%. Overall, accuracy of prevocalic /l/ was higher than that of postvocalic /l/. Acoustic patterns of pre- and postvocalic /l/ showed greater differences in younger children and less apparent differences in 5-year-olds. There were no statistically significant differences between the acoustic patterns of /l/ coded as perceptually acceptable and those coded as misarticulated. There was also no apparent effect of vowel and consonant contexts on /l/ patterns.

Conclusion
The accuracy patterns of this study suggest an earlier development of /l/, especially prevocalic /l/, than has been reported in previous studies. The differences in acoustic patterns between pre- and postvocalic /l/, which become less apparent with age, may suggest that children alter the way they articulate /l/ with age. No significant acoustic differences between acceptable and misarticulated /l/, especially postvocalic /l/, suggest a gradient nature of /l/ that is dialect specific. This suggests the need for careful consideration of a child's dialect/language background when studying /l/.
Knock-Down of Long Non-Coding RNA ANRIL Suppresses Mouse Mesangial
Cell Proliferation, Fibrosis, Inflammation via Regulating
Wnt/β-Catenin and MEK/ERK Pathways in Diabetic
Nephropathy
Authors: Fang Xun , Hu Jun , Zhou Hongyan 
Published: July 2020

Abstract
Aims Our study aimed to investigate the role of long non-coding RNA ANRIL
(lnc-ANRIL) knock-down in regulating cell activities, inflammation and
downstream signaling pathways in mouse mesangial cellular diabetic nephropathy
(DN) model.

Methods The mouse mesangial cells (SV40-MES13 cells) were treated with
high-glucose (HG) to construct cellular DN model. Lnc-ANRIL knock-down plasmid
and control knock-down plasmid were transfected into HG-treated SV40-MES13 cells
as Sh-ANRIL group and Sh-NC group respectively.
Results Lnc-ANRIL expression was significantly higher in HG-treated
SV40-MES13 cells compared with normal glucose-treated SV40-MES13 cells and
osmotic control-treated SV40-MES13 cells. Lnc-ANRIL knock-down suppressed cell
proliferation and promoted cell apoptosis in HG-treated SV40-MES13 cells. As for
fibrosis, lnc-ANRIL knock-down reduced fibronectin and collagen I expressions in
HG-treated SV40-MES13 cells. Besides, the expressions of supernatant tumor
necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1
(MCP-1), interleukin (IL)-1β, IL-6, IL-8 and IL-18 were reduced in
Sh-ANRIL group compared with Sh-NC group. Furthermore, Wnt3, β-catenin,
p-MEK1 and p-ERK1 expressions were suppressed in Sh-ANRIL group compared with
Sh-NC group, which suggested that lnc-ANRIL knock-down inhibited
Wnt/β-catenin and MEK/ERK pathways in HG-treated
SV40-MES13 cells.
Conclusions Lnc-ANRIL knock-down suppresses mouse mesangial cell
proliferation, fibrosis, inflammation, Wnt/β-catenin and
MEK/ERK pathways in DN.
Radikale Nephrektomie und Nierenteilentfernung
Authors: Eich Caroline , Giessing Markus 
Published: July 2020

ZusammenfassungDas Nierenzellkarzinom ist der zweithäufigste bzw. dritthäufigste urologische maligne Tumor der Frau bzw. des Mannes mit einem Erkrankungsgipfel in der 7. Lebensdekade. Früh erkannt ist es gut heilbar, sofern der Tumor nicht metastasiert ist. Im Gegensatz zu früher ist bei lokal begrenzten Nierenzellkarzinomen die lokale Therapie (Teil-Entfernung/topische Energieapplikation wie Radio-Frequenz-Ablation oder Kryoablation) die leitliniengerechte operative Therapie, wobei je nach Expertise des Operateurs die minimalinvasive (laparoskopisch/roboterassistiert) oder offene Operation ihre Berechtigung haben. Die verschiedenen Leitlinien setzen hier unterschiedliche Akzente. Bei der individuellen Therapieentscheidung müssen aber insbesondere Alter und Komorbiditäten in die Überlegung einbezogen werden. Dies kann dazu führen, dass auch bei lokal begrenzten Tumoren aufgrund der geringen perioperativen Morbidität eine (minimalinvasive) radikale Nephrektomie an Stelle einer Teil-Nephrektomie zu empfehlen ist oder aber eine aktive Überwachungsstrategie die richtige Behandlungsoption darstellt, ohne die Lebenserwartung des Karzinomträgers zu kompromittieren. Höhergradige Tumoren hingegen sollen – vorausgesetzt es sind keine Metastasen nachweisbar – Indikation zur Nephrektomie sein, auch wenn z. B. Tumorthromben bis in den Vorhof reichen. Mögliche Komplikationen eines operativen Eingriffs sind in aller Regel selten und gut beherrschbar.
Taming Nitrene Reactivity with Silver Catalysts
Authors: Schomaker Jennifer M. , Vine Logan E. , Zerull Emily E. 
Published: July 2020

Nitrene transfer (NT) is a convenient strategy to directly transform C–H bonds into more valuable C–N bonds and exciting advances have been made to improve selectivity. Our work in silver-based NT has shown the unique ability of this metal to enable tunable chemo-, site-, and stereoselective reactions using simple N-dentate ligand scaffolds. Manipulation of the coordination environment and noncovalent interactions around the silver center furnish unprecedented catalyst control in selective NT and provide insights for further improvements in the field.1	Introduction1.1	Strategies for Nitrene Transfer1.2	Brief Summary of Chemocatalyzed Nitrene Transfer1.3	Focus of this Account2	Challenges in Chemocatalyzed Nitrene Transfer2.1	Reactivity Challenges2.2	Selectivity Challenges2.3	Chemoselective Nitrene Transfer2.4	Site-Selective Nitrene Transfer2.5	Enantioselective Nitrene Transfer3	Summary and Perspective3.1	Future Opportunities and Challenges3.2	Conclusion
Assessment of Serum ST2 Receptor Levels in Female Coronary Artery Disease Patients with LV Dysfunction in Comparison to Males
Authors: Rama Kishore Y. , Lalitha N. , Naveen Kumar M. 
Published: July 2020

AbstractBackground Heart failure is shown to be associated with elevated levels of ST2 levels in blood. The data about the relation of blood ST2 levels, in patients of significant coronary artery disease (CAD) with left ventricular (LV) dysfunction is limited. The impact of gender on ST2 levels not studied until now, so this study aimed to assess the blood ST2 levels measured for males and females patients in comparisons, of CAD with LV dysfunction and their relation to the outcomes at the end of 1-year post intervention.Material and Methods Out of the 60 patients with 1:2 ratio of females and males with CAD and LV dysfunction, baseline quantitative assessment of ST2 levels in blood was done by rapid lateral flow immunoassay method; > 35 mg/mL was considered as abnormal. Postintervention patients followed up to one year, adverse cardiovascular events noted at the end of 1 year. By using binary logistic regression, the outcomes in females compared with males for statistical significance in relation to baseline blood ST 2 levels. The p value of < 0.05 considered was significant.Results Among the 60 patients (females 33.3% and males 66.6 %) presented with CAD with LV dysfunction in the study, 40 (66.6 %) patients diagnosed of acute coronary syndrome (ACS), and 20 (33.3%) patients with chronic stable angina (CSA). In both the genders, ACS is most common presentation (55% in females and 72.5 % in males). Eighteen (90%) females and 20 (50%) males were hypertensive, 12 (60%) females and 18 (45%) males were diabetics. Twenty-seven (67.5%) males were smokers and 14 (35%) were alcoholics. Nine (45%) female and 14 (35%) male patients had elevated ST2 levels. At the end of 1 year 9 females had events including 2 mortalities, 2 heart failures, and 7 repeat revascularizations. At the same time 7 male patients had events at the end of 1 year including 4 mortalities, 5 heart failures, and 2 repeat revascularizations. The difference in the event rates between male and female patients were statistically significance (p = 0.03). Elevated ST2 levels were correlated with echocardiographic parameter end systolic volume which was statistically significant (p= 0.03). Similarly elevated ST2 levels correlated with presence of diabetes (p= 0.01) and low LV EF.Conclusion Mean Blood ST2 levels were higher in females who associated with diabetes, high echo cardio graphic end-systolic volume, and a low ejection fraction of LV in severe LV dysfunction with statistical significance. At the end of 1 year in patients with elevated baseline ST2 levels, the female patient had more events than males with statistical significance.
Comparison of Resting Full Cycle Ratio with Fractional Flow Reserve in Indian Population
Authors: Ch Shravan Kumar , Kanumuri Sudhakar , Indrani Garre , Kumar M. Naveen 
Published: July 2020

Abstract
Background From the previous studies fractional flow reserve (FFR) was considered best for hemodynamic assessment of bordersline coronary lesions. In literature, previous studies compared instant wave-free ratio (IFR) with resting full cycle ratio (RFR) which concluded that both were equally effective diagnostically. Studies comparing RFR with FFR are still lacking in number.So we have done a prospective study comparing RFR and FFR in predominately chronic stable angina patients, whose coronary angiogram suggestive of borderline coronary lesions.
Material and Methods In the department of cardiology in our institution, we have done a prospective study in chronic stable angina patients whose coronary angiogram was suggestive of borderline coronary lesions from March 2019 to June 2019. We recorded RFR value, basal FFR value, and after-adenosine FFR values in borderline coronary lesion patients.
Results A total of 33 patients were included in the study. The study population was predominantly male (93.9%). Hypertension was noted in 81.8% and diabetes was noted in 51.5% patients. We compared RFR and FFR by regression analysis; it suggested that both RFR and FFR were significantly correlated, with p = 0.000. This is true even in subgroup analysis of sex (p = 0.001).
Conclusion From our study, we conclude that RFR may be used instead of FFR for physiologic assessment of inducible ischemia in borderline coronary artery lesions as it is independent of gender also.
Noninvasive Ventilation and High-Flow Nasal Therapy Administration in Chronic Obstructive Pulmonary Disease Exacerbations
Authors: Ferrer Miquel , Torres Antoni 
Published: July 2020

AbstractNoninvasive ventilation (NIV) is considered to be the standard of care for the management of acute hypercapnic respiratory failure in patients with chronic obstructive pulmonary disease exacerbation. It can be delivered safely in any dedicated setting, from emergency rooms to high dependency or intensive care units and wards. NIV helps improving dyspnea and gas exchange, reduces the need for endotracheal intubation, and morbidity and mortality rates. It is therefore recognized as the gold standard in this condition. High-flow nasal therapy helps improving ventilatory efficiency and reducing the work of breathing in patients with severe chronic obstructive pulmonary disease. Early studies indicate that some patients with acute hypercapnic respiratory failure can be managed with high-flow nasal therapy, but more information is needed before specific recommendations for this therapy can be made. Therefore, high-flow nasal therapy use should be individualized in each particular situation and institution, taking into account resources, and local and personal experience with all respiratory support therapies.