bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective Role of Fisetin in STZ Induced Diabetic Nephropathy in Rats
Authors: Kumari Savita , Kamboj Anjoo , Wanjari Manish , Sharma Anil Kumar 
Published: June 2021

Objectives: Chronic diabetes mellitus associated with devastating complication the diabetic nephropathy, that further progress to ESRD,a major cause of morbidity and premature mortality in many countries worldwide. Accumulated evidences demonstrated that long standing hyperglycemia induced oxidative stress, inflammatory cytokines, and fibrosis plays a significant role in DN. Fisetin, a bioflavonoid, exhibited variety of promising pharmacological properties such as, anti-diabetic, antioxidant, anti-inflammatory, anti-hyperlipidemic ,and anti-carcinogenics. Hence, the present study was hypothesized to investigate, the effect of fisetin on streptozotocin-induced diabetic nephropathy in rats.
Materials and Methods: Sprague Dawley rats were divided into 6 groups (n=6) as normal control, diabetic control (vehicle), Glimepiride (0.5 mg/kg, orally) and Fisetin treatment (2.5, 5 and 10 mg/kg, orally) groups. After the confirmation of diabetes, vehicle/drug treatments were started and continued for 6 weeks. Serum glucose, body weight, were measured on weekly basis.Thereafter, on the last day of treatment protocol, ie 42 day, serum insulin, HbA1c in blood, lipid parameters, creatinine, albumin and urea in serum and in urine creatinine excretion, albumin were measured along with urine volume and creatinine clearance. In addition, weight of kidney and histopathological studies were carried out.
Results: Fisetin treatment significantly attenuated reduction in body weight. Also, it significantly decreased the blood glucose level, ameliorate lipid profile and HbA1c (p<0.05) value, but serum insulin level were not much influenced. It also increased albumin in serum, decreased serum urea and creatinine and in urine, it reduced the urine volume, albumin with marked improvement in creatinine excretion and creatinine clearance. Further, the fisetin (10mg/kg) treatment attenuated oxidative stress and cytokines TNF-α (p<0.01), IL-1β (p<0.01), and IL-6 (p<0.05) level in kidney tissue along with amelioration of histopathological alterations compared to diabetic control rats. The standard drug, glimepiride also exhibited similar antidiabetic effect without much influence on oxidative stress, albumin in urine, and cytokine levels.
Conclusions: The results indicated that fisetin ameliorated diabetic nephropathy through its antidiabetic and antioxidant effect which may be attributed to inhibition of downward pathway of glycemia induced oxidative stress, inflammation and necroptosis of renal tissue.
Long-Term Survival of Rectal Cancer With Lung Metastasis–A Case Report of Possible Metronomic Effect of Tegafur-Uracil
Authors: Hsu Tzu-Chi , Chen Ming-Jen 
Published: June 2021

Background
A 76-year-old woman underwent a low anterior resection in May 2000 for a moderately differentiated Dukes' C adenocarcinoma of rectum. She started to take futraful and leucovorin as adjuvant chemotherapy after surgery. A chest X-ray taken 7 months later was reported as having an irregular soft tissue nodule in right middle lung field. A subsequent computerized tomography (CT) scan of chest confirmed the lesion. A thoracotomy was suggested; however, the patient refused surgery. She also refused needle biopsy of the lung lesion for making a definite diagnosis.

Case summary
The patient had been continuously taking futraful and leucovorin as chemotherapeutic agent; in July 2001 she was switched to tegafur-uracil (UFUR) and leucovorin. She was admitted in October 2005 for shortness of breath. After conservative management, her condition improved and she was discharged. The patient still refused any workup for tissue diagnosis and any further aggressive treatment. Since then, she had been continuously taking UFUR and leucovorin then. An abdominal CT scan of in December 2009 was negative for metastasis. Several ultrasound examinations were also reported as having no metastasis in the follow-up period. A chest CT scan did show slow enlargement of the lung metastasis. Her carcinoembryonic antigen level was 3.85 ng/mL prior to surgery, and then fluctuated between 2.42 ng/mL and 6.34 ng/mL. In spite of progressive enlargement of the mass in her lung, the patient is asymptomatic and living well by herself. The only medication she is taking at the moment is UFUR and leucovorin.

Conclusions
This case suggested that long-term survival could be observed in a patient with metastatic disease from rectal cancer without aggressive chemotherapy. The metronomic effect of UFUR and leucovorin might be contributory to the patient's long-term survival. Elevation of CEA level is not necessarily observed with the presence and progress of metastasis of rectal cancer.
What determines violent behavior in men? Predicting physical, psychological, and sexual violent offending based on classification and regression tree analysis
Authors: Leiding Delia , Kaiser Franziska , Steffens Marion , Puiu Andrei A. , Habel Ute 
Published: June 2021

AbstractDespite compelling evidence that victimization and offending co‐occur, it remains unclear what types of victimization are linked to specific forms of perpetration. Here we examined the relationship between physical, psychological, and sexual violence with respect to influencing variables including mental health, risk‐taking behaviors, and coping strategies. Data from 5385 men were collected as part of an epidemiological study on violence experience. A classification and regression tree analysis identified the main predictors of violence perpetration and classified violent offending into high‐ and low‐risk groups. Results indicate that violence is best predicted by previous exposure to violence and polyvictimization. Physical violence is best predicted by prior exposure to physical violence and this is further influenced by the frequency of and the age at which violence was experienced. Drug use was a strong predictor of physical and psychological violence. The latter is best predicted by a history of polyvictimization, the severity and the originator of violence. Sexual violence is strongly predicted by one's sexual violence experience. Other factors such as demographic characteristics are less predictive. Our results may contribute to the development of early prevention and intervention approaches that account for different risk factors. The significance of violence exposure suggest that intervention measures must focus on victims of early and prolonged experience of violence. On the strength of the link between drug use and violence, exposure to violence should be considered in drug prevention and intervention and vice versa.
A novel Schiff base macrocycle based on 1,1′‐binaphthyl for fluorescence recognition
Authors: Tokunaga Hiroki , Kazama Kotoha , Tsuboi Masaki , Miyasaka Makoto 
Published: June 2021

AbstractA novel chiral polyimine macrocycle C‐1 was designed and synthesized by the self‐condensation of the dialdehyde of the chiral dinaphtho[2,1‐d:1′,2′‐f][1,3]dioxepine derivative and o‐phenylenediamine by Schiff base formation, and the corresponding polyamine macrocycle C‐1H was obtained by the reduction of the polyimine macrocycle. The UV–vis and fluorescence spectral studies indicated that both C‐1 and C‐1H form the complex with metal ions in a 1:2 ratio. The fluorescence behaviour of C‐1 upon the addition of Zn2+ or Cd2+ showed a ‘turn‐on’ response accompanied by fluorescence enhancement at 510 nm six times for Cd2+ and 13 times for Zn2+. In contrast, C‐1H revealed a ‘turn‐off’ response upon the addition of Co2+, Ni2+, and Cu2+.
Neuroprotective Activities of Constituents from Phyllosticta capitalensis, an Endophyte Fungus of Loropetalum chinense var. rubrum
Authors: Zhu Xiaoxia , Liu Ying , Hu Yunwei , Lv Xin , Shi Zhaoxia , Yu Yuanyuan , Jiang Xueyang , Feng Feng , Xu Jian 
Published: June 2021

AbstractOne new dioxolanone derivative, guignardianone G (1) and twelve known compounds (2–13) were isolated from the 95 % ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Among these known compounds, isoaltenuene (3), brassicasterol (7), 5,6‐epoxyergosterol (8), citreoanthrasteroid A (9), demethylincisterol A (10), and chaxine C (11) were reported from Phyllosticta sp. for the first time. The structure of 1 was elucidated by 1D‐ and 2D‐NMR experiments and HR‐ESI‐MS data analysis, and its absolute configuration was established through the comprehensive use of the methods of modified Mosher methods, calculations of ECD spectra and optical rotation values. The neuroprotective activity of compounds (1–9, 11–13) were evaluated on PC12 cells damage induced by glutamate, and compounds 9 and 12 showed potential neuroprotective activities with half effective concentration (EC50) of 24.2 and 33.9 μM, respectively.
Re‐Programming and Optimization of aL‐Prolinecis‐4‐Hydroxylase for thecis‐3‐Halogenation of its Native Substrate
Authors: Papadopoulou Athena , Meierhofer Jasmin , Meyer Fabian , Hayashi Takahiro , Schneider Samuel , Sager Emine , Buller Rebecca 
Published: June 2021

AbstractNon‐heme iron/α‐ketoglutarate dependent halogenases acting on freestanding substrates catalyze the regio‐ and stereoselective halogenation of inactivated C(sp3)‐H bonds. Yet, with only a handful of these halogenases characterized, the biosynthetic potential of enzymatic radical halogenation remains limited. Herein, we describe the remodeling ofL‐prolinecis‐4‐hydroxylase fromSinorhizobium melilotiinto a halogenase by introduction of a single point mutation (D108G) into the enzyme's active site. The re‐programmed halogenase displays a striking regio‐divergent reaction chemistry: While halogenation ofL‐proline exclusively occurs at the C3‐position, the retained hydroxylation activity leads to derivatization at the C4‐position, corresponding to the regioselectivity of the wildtype enzyme. By employing several rounds of directed evolution, an optimized halogenase variant with 98‐fold improved apparentkcat/Kmfor chlorination ofL‐proline compared to the parental enzyme SmP4H (D108G) was identified. The development and optimization of this novel halogenation biocatalyst highlights the possibility to rationally harness the chemical versatility of non‐heme Fe/αKG dependent dioxygenases for C−H functionalization.
COVID‐19 outcomes in hospitalized patients with active cancer: Experiences from a major New York City health care system
Authors: Fu Chen , Stoeckle James H. , Masri Lena , Pandey Abhishek , Cao Meng , Littman Dalia , Rybstein Marissa , Saith Sunil E. , Yarta Kinan , Rohatgi Abhinav , Makarov Danil V. , Sherman Scott E. , Morrissey Christy , Jordan Alexander C. , Razzo Beatrice , Theprungsirikul Poy , Tsai Joseph , Becker Daniel J. 
Published: June 2021

BackgroundThe authors sought to study the risk factors associated with severe outcomes in hospitalized coronavirus disease 2019 (COVID‐19) patients with cancer.MethodsThe authors queried the New York University Langone Medical Center's records for hospitalized patients who were polymerase chain reaction–positive for severe acute respiratory syndrome coronavirus 2 (SARS CoV‐2) and performed chart reviews on patients with cancer diagnoses to identify patients with active cancer and patients with a history of cancer. Descriptive statistics were calculated and multivariable logistic regression was used to determine associations between clinical, demographic, and laboratory characteristics with outcomes, including death and admission to the intensive care unit.ResultsA total of 4184 hospitalized SARS CoV‐2+ patients, including 233 with active cancer, were identified. Patients with active cancer were more likely to die than those with a history of cancer and those without any cancer history (34.3% vs 27.6% vs 20%, respectively; P < .01). In multivariable regression among all patients, active cancer (odds ratio [OR], 1.89; CI, 1.34‐2.67; P < .01), older age (OR, 1.06; CI, 1.05‐1.06; P < .01), male sex (OR for female vs male, 0.70; CI, 0.58‐0.84; P < .01), diabetes (OR, 1.26; CI, 1.04‐1.53; P = .02), morbidly obese body mass index (OR, 1.87; CI, 1.24‐2.81; P < .01), and elevated D‐dimer (OR, 6.41 for value >2300; CI, 4.75‐8.66; P < .01) were associated with increased mortality. Recent cancer‐directed medical therapy was not associated with death in multivariable analysis. Among patients with active cancer, those with a hematologic malignancy had the highest mortality rate in comparison with other cancer types (47.83% vs 28.66%; P < .01).ConclusionsThe authors found that patients with an active cancer diagnosis were more likely to die from COVID‐19. Those with hematologic malignancies were at the highest risk of death. Patients receiving cancer‐directed therapy within 3 months before hospitalization had no overall increased risk of death.Lay Summary

Our investigators found that hospitalized patients with active cancer were more likely to die from coronavirus disease 2019 (COVID‐19) than those with a history of cancer and those without any cancer history.

Patients with hematologic cancers were the most likely among patients with cancer to die from COVID‐19.

Patients who received cancer therapy within 3 months before hospitalization did not have an increased risk of death.
Influence of the Number, Nature and Position of Methyl Posttranscriptional Modifications on Nucleobase Stacking in RNA
Authors: Kagra Deepika , Mahmi Amanpreet Singh , Kumar N. V. Suresh , Prabhakar Preethi Seelam , Sharma Purshotam 
Published: June 2021

AbstractDFT calculations are employed to quantify the influence of the presence, number, nature, and position of posttranscriptional methylation on stacking strength of RNA bases. We carry out detailed potential energy scans of the variation in stacking energies with characteristic geometrical parameters in three categories of forty stacked dimers – canonical base homodimers (N||N), methylated base homodimers (mN||mN) and heterodimers of canonical bases and methylated counterparts (N||mN). Our analysis reveals that neutral methylation invariably enhances the stacking of bases. Further, N||mN stacking is stronger than mN||mN stacking and charged N||mN exhibit strongest stacking among all dimers. This indicates that methylations greatly enhance stacking when dispersed in RNA sequences containing identical bases. Comparison of stacks involving singly‐ and doubly‐methylated purines reveal that incremental methylation enhances the stacking in neutral dimers. Although methylation at the carbon position of neutral pyrimidine dimers greatly enhances the stacking, methylation on the 5‐membered ring imparts better stacking compared to methylation on the 6‐membered ring in adenine dimers. However, methylation at the ring nitrogen (N1) provides better stacking than the amino group (N2) in guanine dimers. Our results thus highlight subtle structural effects of methylation on RNA base stacking and will enhance our understanding of the physicochemical principles of RNA structure and dynamics.
Techniques used to assess intussusceptive angiogenesis: A systematic review
Authors: Du Cheyne Charis , Smeets Marloes , De Spiegelaere Ward 
Published: June 2021

AbstractIntussusceptive angiogenesis (IA) is an important physiological form of angiogenesis in which an existing vessel splits in two by the formation of an intraluminal tissue pillar. The presence of these intraluminal pillars form the hallmark of ongoing IA in growing vascular beds. However, their visualization is technically challenging. The goal of this systematic review was to investigate which techniques are being used to identify intraluminal pillars and to formulate important points to keep in mind when studying IA. A systematic literature search resulted in 154 evaluated articles of which the majority (65%) provided sufficient data to unambiguously demonstrate the presence of intraluminal pillars. Scanning electron microscopy imaging of vascular corrosion casts and serial sectioning of ultrathin sections are the most used techniques. New methods such as serial block face scanning electron microscopy and micro computed tomography (μCT) are gaining importance. Moreover, our results indicate that IA was studied in a variety of animals and tissues. IA is a biologically very relevant form of angiogenesis. Techniques to visualize intraluminal pillars need to have a minimal resolution of 1 μm and should provide information on the 3D‐nature of the pillars. Optimally, several techniques are combined to demonstrate ongoing IA.
Effect of sacubitril/valsartan vs. enalapril on changes in heart failure therapies over time: the PARADIGM‐HF trial
Authors: Bhatt Ankeet S. , Vaduganathan Muthiah , Claggett Brian L. , Liu Jiankang , Packer Milton , Desai Akshay S. , Lefkowitz Martin P. , Rouleau Jean L. , Shi Victor C. , Zile Michael R. , Swedberg Karl , Vardeny Orly , McMurray John J.V. , Solomon Scott D. 
Published: June 2021

AbstractAimsSacubitril/valsartan improves morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Whether initiation of sacubitril/valsartan limits the use and dosing of other elements of guideline‐directed medical therapy for HFrEF is unknown. We examined the effects of sacubitril/valsartan, compared with enalapril, on β‐blocker and mineralocorticoid receptor antagonist (MRA) use and dosing in a large randomized clinical trial.Methods and resultsPatients with full data on medication use were included. We examined β‐blocker and MRA use in patients randomized to sacubitril/valsartan vs. enalapril through 12‐month follow‐up. New initiations and discontinuations of β‐blocker and MRA were compared between treatment groups. Overall, 8398 (99.9%) had full medication and dose data at baseline. Baseline use of β‐blocker and MRA at any dose was 87% and 56%, respectively. Mean doses of β‐blocker and MRA were similar between treatment groups at baseline and at 6‐month and 12‐month follow‐up. New initiations through 12‐month follow‐up were infrequent and similar in the sacubitril/valsartan and enalapril groups for β‐blockers [37 (9.0%) vs. 42 (10.2%), P = 0.56] and MRA [127 (7.6%) vs. 143 (9.2%), P = 0.10]. Among patients on MRA therapy at baseline, there were fewer MRA discontinuations in patients on sacubitril/valsartan as compared with enalapril at 12 months [125 (6.2%) vs. 187 (9.0%), P = 0.001]. Discontinuations of β‐blockers were not significantly different between groups in follow‐up (2.2% vs. 2.6%, P = 0.26).ConclusionsInitiation of sacubitril/valsartan, even when titrated to target dose, did not appear to lead to greater discontinuation or dose down‐titration of other key guideline‐directed medical therapies, and was associated with fewer discontinuations of MRA. Use of sacubitril/valsartan (when compared with enalapril) may promote sustained MRA use in follow‐up.
Chemical Synthesis of the Nucleoside Antibiotic Capuramycin
Authors: Xiao Guozhi , He Haiqing 
Published: June 2021

AbstractCapuramycin is an important lead nucleoside antibiotic for the development of new therapeutic agents against the multidrug‐resistant Mycobacterium tuberculosis infections. Due to the poor accessibilities, the heterogeneous issues and difficulties in the modification of capuramycin at the specific positions, in‐depth studies on the structure‐activity relationships (SAR) of capuramycin are hampered. Chemical synthesis is a reliable and effective method to provide capuramycin and its analogues. Thus far, only four different synthetic routes toward capuramycin have been reported. Herein, we provide a comprehensive review on the chemical synthesis of capuramycin.
A Novel Flow‐injection Rhodium Nanoparticles Modified Phosphate Biosensor and its Operation in Artificial Urine
Authors: Kilic Muhammet Samet 
Published: June 2021

AbstractA biosensor for phosphate determination with the flow‐injection system was developed using rhodium nanoparticles modified Poly(pyrrole‐co‐[1‐(2‐aminophenyl) pyrrole])/pyruvate oxidase. The biosensor showed a very wide linearity up to 70 mM phosphate concentration compared to previously reports, response time of 4 s., operational stability with a relative standard deviation of 0.009 % and accuracy of 99.4 %±0.949 at a flow rate of 2.0 Ml min.−1 at exactly −0.68 V. Detection limit were calculated to be 21±0.001 μM by preserving 81.1 % of its initial response at the end of 16th days. Artificial urine was analyzed without dilution to investigate biosensor performance.
Flame‐retardant treatment of Lyocell fibers and effects on various fiber properties
Authors: Peng Kang , Meng Yongwei , Zhang Huihui , Yang Gesheng , Shao Huili 
Published: June 2021

SUMMARYHexamethylolmelamine was used as a cross‐linking agent to graft 3‐(dimethylphosphono)‐N‐methylolpropionamide (MDPA) onto Lyocell fibers in a posttreatment process to reduce flammability. The effects of processing conditions on the mechanical properties and P content of the fibers were examined. The results show that increasing the MDPA concentration, microwave treatment time, baking temperature, and baking time increases the P concentration in the fibers, although the mechanical properties of the fibers are reduced to varying degrees. The optimal processing conditions comprise a 40% MDPA concentration, a 320 W microwave treatment for 3 minutes, and baking at 160°C for 5 minutes. Under these conditions, flame‐retardant Lyocell fibers with a breaking strength of 2.47 cN·dtex−1 and a limiting oxygen index of 34.6% were obtained, which meet the performance requirements for textile fibers. Thermogravimetric data indicate that the residual fiber mass after heating increased from 4.7% before treatment to 21.5% after treatment. There was only a minimal change in the hygroscopicity of the treated Lyocell fibers. In addition, after 30 washes, the limiting oxygen index was decreased to 26.5% while maintaining a good flame‐retardant effect.
Downregulation of circ_0012152 inhibits proliferation and induces apoptosis in acute myeloid leukemia cells through the miR‐625‐5p/SOX12 axis
Authors: Shang Zhen , Ming Xi , Wu Jiaying , Xiao Yi 
Published: June 2021

AbstractAcute myeloid leukemia (AML) is a highly heterogeneous disease featured by a clonal proliferation derived from primitive hematopoietic stem/progenitor cells. Circular RNAs (circRNAs) have been identified as crucial regulators in the progression of various cancers, including AML. However, the molecular mechanism of AML is still not definite. This study aimed to explore the influences of circ_0012152 on cell development in AML cells and the underlying regulatory mechanism. The expression of circ_0012152, microRNA‐625‐5p (miR‐625‐5p) and sex‐determining region Y‐related high mobility group box 12 (SOX12) was detected by quantitative real‐time polymerase chain reaction. The proliferation of AML cells was evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay for cell viability, 5‐ethynyl‐2′‐deoxyuridine incorporation assay for DNA biosynthesis and flow cytometry for cell cycle distribution, respectively. The death of AML cells was detected by flow cytometry. The protein expression was assessed by Western blot assay. Dual‐luciferase reporter and RNA immunoprecipitation assays were carried out to examine the relationships among circ_0012152, miR‐625‐5p and SOX12. The expression of circ_0012152 was increased in AML tissues and cells and circ_0012152 knockdown suppressed proliferation and promoted death in AML cells. Further exploration revealed that circ_0012152 inhibited miR‐625‐5p expression and downregulation of miR‐625‐5p overturned the effects of circ_0012152 knockdown on proliferation and death in AML cells. Moreover, miR‐625‐5p targeted SOX12 and circ_0012152 facilitated the expression of SOX12 by relieving miR‐625‐5p‐mediated inhibitory effect on SOX12 in AML cells. Circ_0012152 knockdown suppressed cell proliferation and promoted death by targeting SOX12 mediated by miR‐625‐5p in AML cells.