bluuebunny/crossref_metadata_2025_split huggingface dataset:
Celastrol attenuates high‐fructose diet‐induced inflammation and insulin resistance via inhibition of 11β‐hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues
Authors: Abu Bakar Mohamad Hafizi , Mohamad Khalid Mohamad Shamil Faris , Nor Shahril Nor Shafiqah , Shariff Khairul Anuar , Karunakaran Thiruventhan 
Published: October 2021

AbstractHigh fructose consumption has been linked to low‐grade inflammation and insulin resistance that results in increased intracellular 11ß‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) activity. Celastrol, a pentacyclic triterpene, has been demonstrated to exhibit multifaceted targets to attenuate various metabolic diseases associated with inflammation. However, the underlying mechanisms by which celastrol exerts its attributive properties on high fructose diet (HFrD)‐induced metabolic syndrome remain elusive. Herein, the present study was aimed to elucidate the mechanistic targets of celastrol co‐administrations upon HFrD in rats and evaluate its potential to modulate 11β‐HSD1 activity. Celastrol remarkably improved glucose tolerance, lipid profiles, and insulin sensitivity along with suppression of hepatic glucose production. In rat adipose tissues, celastrol attenuated nuclear factor‐kappa B (NF‐κB)‐driven inflammation, reduced c‐Jun N‐terminal kinases (JNK) phosphorylation, and mitigated oxidative stress via upregulated genes expression involved in mitochondrial biogenesis. Furthermore, insulin signaling pathways were significantly improved through the restoration of Akt phosphorylation levels at Ser473 and Thr308 residues. Celastrol exhibited a potent, selective and specific inhibitor of intracellular 11β‐HSD1 towards oxidoreductase activity (IC50 value = 4.3 nM) in comparison to other HSD‐related enzymes. Inhibition of 11β‐HSD1 expression in rat adipose microsomes reduced the availability of its cofactor NADPH and substrate H6PDH in couple to upregulated mRNA and protein expressions of glucocorticoid receptor. In conclusion, our results underscore the most likely conceivable mechanisms exhibited by celastrol against HFrD‐induced metabolic dysregulations mainly through attenuating inflammation and insulin resistance, at least via specific inhibitions on 11β‐HSD1 activity in adipose tissues.
Trends in patient‐reported outcome use in early phase dose‐finding oncology trials – an analysis of ClinicalTrials.gov
Authors: Lai‐Kwon Julia , Yin Zhulin , Minchom Anna , Yap Christina 
Published: October 2021

ABSTRACTBackgroundPatient‐reported adverse events (AEs) may be a useful adjunct to clinician‐assessed AEs for assessing tolerability in early phase, dose‐finding oncology trials (DFOTs). We reviewed DFOTs on ClinicalTrials.gov to describe trends in patient‐reported outcome (PRO) use.MethodsDFOTs commencing 01 January 2007 – 20 January 2020 with ‘PROs’ or ‘quality of life’ as an outcome were extracted and inclusion criteria confirmed. Study and PRO characteristics were extracted. Completed trials that reported PRO outcomes and published manuscripts on ClinicalTrials.gov were identified, and PRO reporting details were extracted.Results5.3% (548/10 372) DFOTs included PROs as an outcome. 231 (42.2%) were eligible: adult (224, 97%), solid tumour (175, 75.8%), and seamless phase 1/2 (108, 46.8%). PRO endpoints were identified in more trials (2.3 increase/year, 95% CI: 1.6–2.9) from an increasing variety of countries (0.7/year) (95% CI: 0.4–0.9) over time. PROs were typically secondary endpoints (207, 89.6%). 15/77 (19.5%) completed trials reported results on the ClinicalTrials.gov results database, and of those eight included their PRO results. Eighteen trials had published manuscripts available on ClinicalTrials.gov. Three (16.7%) used PROs to confirm the maximum tolerated dose. No trials identified who completed the PROs or how PROs were collected.ConclusionsPRO use in DFOT has increased but remains limited. Future work should explore the role of PROs in DFOT and determine what guidelines are needed to standardise PRO use.
Protocols for Characterization of Cdk5 Kinase Activity
Authors: Terse Anita , Amin Niranjana , Hall Bradford , Bhaskar Manju , B.K. Binukumar , Utreras Elias , Pareek Tej K. , Pant Harish , Kulkarni Ashok B. 
Published: October 2021

AbstractCyclin‐dependent kinases (Cdks) are generally known to be involved in controlling the cell cycle, but Cdk5 is a unique member of this protein family for being most active in post‐mitotic neurons. Cdk5 is developmentally important in regulating neuronal migration, neurite outgrowth, and axon guidance. Cdk5 is enriched in synaptic membranes and is known to modulate synaptic activity. Postnatally, Cdk5 can also affect neuronal processes such as dopaminergic signaling and pain sensitivity. Dysregulated Cdk5, in contrast, has been linked to neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Despite primarily being implicated in neuronal development and activity, Cdk5 has lately been linked to non‐neuronal functions including cancer cell growth, immune responses, and diabetes. Since Cdk5 activity is tightly regulated, a method for measuring its kinase activity is needed to fully understand the precise role of Cdk5 in developmental and disease processes. This article includes methods for detecting Cdk5 kinase activity in cultured cells or tissues, identifying new substrates, and screening for new kinase inhibitors. Furthermore, since Cdk5 shares homology and substrate specificity with Cdk1 and Cdk2, the Cdk5 kinase assay can be used, with modification, to measure the activity of other Cdks as well. © 2021 Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.Basic Protocol 1: Measuring Cdk5 activity from protein lysatesSupport Protocol 1: Immunoprecipitation of Cdk5 using DynabeadsAlternate Protocol: Non‐radioactive protocols to measure Cdk5 kinase activitySupport Protocol 2: Western blot analysis for the detection of Cdk5, p35, and p39Support Protocol 3: Immunodetection analysis for Cdk5, p35, and p39Support Protocol 4: Genetically engineered mice (+ and – controls)Basic Protocol 2: Identifying new Cdk5 substrates and kinase inhibitors
Continuous Crystallization of Phosphoric Acid Using Suspension Crystallizer: Effect of Operating Conditions on Purity of Crystals
Authors: Tsushima Ippei , Maeda Kouji , Yamamoto Takuji , Arafune Koji , Miki Hideo 
Published: October 2021

AbstractIn this study, batch crystallization via indirect cooling and continuous crystallization via direct and indirect cooling of phosphoric acid hemihydrate (H3PO4.1/2H2O) from the mixed acid solution of phosphoric acid and acetic acid are performed. In batch crystallization, needle‐shaped crystals are obtained, and the impurity concentration of acetic acid in the crystals is 4.2 wt%. Primary nucleation occurred under a high degree of supersaturation, and the metastable zone width for secondary nuclei is narrow. In contrast, in continuous crystallization via indirect cooling, scaly crystals are obtained, and the acetic acid impurity concentration therein is 2.0 wt%. Additionally, continuous crystallization via direct contact cooling is performed, the crystal shape and impurity concentration under direct cooling are similar to those under indirect cooling, suggesting the possibility to downsize the apparatus. Through utilization of the equipment and approach elaborated herein, the correlation between the operating conditions and crystal quality can be assessed.
Electrochemical Detection of Phenol Removal by Using a Biosorbent Originated Factory Solid Waste
Authors: Congur Gulsah , Gül Ülküye Dudu 
Published: October 2021

AbstractBiosorption is a preferable method for phenol (PNL) removal from water sources using a cheap and eco‐friendly biomass. The combination of the biosorption technique with practical, affordable, sensitive, and selective monitoring tools gives a new perspective to environmental monitoring applications. Herein, as the first time, the monitoring of PNL biosorption performed using a factory waste was done by pencil graphite electrodes (PGEs) and cyclic voltammetry (CV) technique. The monitoring of the biosorption process was completed with reproducible and reliable results in just 40s. The biosorption was achieved in different water samples and the presence of different phenolic compounds.
Hepatocellular Carcinoma Risk Assessment for Patients With Advanced Fibrosis After Eradication of Hepatitis C Virus
Authors: Tamaki Nobuharu , Kurosaki Masayuki , Yasui Yutaka , Mori Nami , Tsuji Keiji , Hasebe Chitomi , Joko Kouji , Akahane Takehiro , Furuta Koichiro , Kobashi Haruhiko , Kimura Hiroyuki , Yagisawa Hitoshi , Marusawa Hiroyuki , Kondo Masahiko , Kojima Yuji , Yoshida Hideo , Uchida Yasushi , Tada Toshifumi , Nakamura Shinichiro , Yasuda Satoshi , Toyoda Hidenori , Loomba Rohit , Izumi Namiki 
Published: October 2021

The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum‐based risk model that could identify patients with low‐risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma‐glutamyl transferase < 28 IU/L, alpha‐fetoprotein < 4.0 ng/mL, and Fibrosis‐4 Index < 4.28) were classified as low‐risk and others were classified as high‐risk. When patients were stratified at the SVR24, and 1 year, and 2 years after SVR24, subsequent HCC development was significantly lower in low‐risk patients (0.5‐1.1 per 100 person‐years in the derivation cohort and 0.9‐1.1 per 100 person‐years in the validation cohort) than in high‐risk patients at each point. HCC risk from 1 year after SVR24 decreased in patients whose risk improved from high‐risk to low‐risk (HCC incidence: 0.6 per 100 person‐years [hazard ratio (HR) = 0.163 in the derivation cohort] and 1.3 per 100 person‐years [HR = 0.239 in the validation cohort]) than in those with sustained high risk. Conclusion: The HCC risk model based on simple serum markers at any point after SVR and its change can identify patients with advanced fibrosis who are at low HCC risk, and these patients may be able to reduce HCC surveillance.
Local anaesthesia for dental and oral surgery in cats and dogs
Authors: Oxford Matthew , Gurney Matt 
Published: October 2021

Background: Local and regional anaesthetic techniques are growing in popularity within many areas of veterinary surgery, and rightly so owing to their important modulation of intra‐ and postoperative pain, and with the subsequent improvements in general anaesthesia. Oral local anaesthesia is no exception, with several articles and book chapters devoted to it. However, many of these articles reference a series of historical techniques and injection sites, which on closer evaluation, may not actually achieve what was intended.Aim of the article: The aim of this article is to evaluate the tissues that are traumatised during oral and dental surgery, assess the afferent neural anatomy for these tissues and then discuss injection sites and techniques that are most likely to result in full anaesthesia of these tissues during surgery.
Controlled breeding in dairy cows. Part 1: bovine oestrus cycle and synchronisation
Authors: Lindley George , Willshire Jim , Martin Adam 
Published: October 2021

Background: Timed artificial insemination (TAI) as part of a controlled breeding programme is a reproductive strategy that eliminates the requirement for oestrus detection, guarantees the submission of enrolled cows and attempts to optimise the timing of insemination relative to ovulation. However, the success of TAI requires careful cow selection, diligent herd management and the selection of an appropriate synchronisation protocol.Aim of the article: This article, the first in a two‐part series, outlines the key ovarian follicular wave dynamics in the bovine oestrous cycle and the key goals of any synchronisation protocol. It describes the most commonly used drugs, their actions and how they can be combined into effective synchronisation protocols. The second part of the series, to be published in a subsequent issue of In Practice, discusses how to implement controlled breeding strategies on farms and considers factors aside from the TAI protocol that are essential for the success of any programme.
Inorganic phosphate‐induced cytotoxicity
Authors: Alexander Rachel , Debiec Nicholas , Razzaque Mohammad S. , He Ping 
Published: October 2021

AbstractPhosphate, an essential nutrient, is available in organic and inorganic forms. The balance of phosphate is central for cellular homeostasis through the genomic roles of DNA and RNA synthesis and cell signaling processes. Therefore, an imbalance of this nutrient, manifested, either as a deficiency or excess in phosphate levels, can result in pathology, ranging from cytotoxicity to musculoskeletal defects. Inorganic phosphate (Pi) overdosing can result in a wide spectrum of cytotoxicity processes, as noted in both animal models and human studies. These include rewired cell signaling pathways, impaired bone mineralization, infertility, premature aging, vascular calcification, and renal dysfunction. This article briefly reviews the regulation of phosphate homeostasis and elaborates on cytotoxic effects of excessive Pi, as documented in cell‐based models.
Overview of approval procedures for bioadhesives in the United States of America and Canada
Authors: Dhandapani Vignesh , Saseedharan Prashanth , Groleau Denis , Vermette Patrick 
Published: October 2021

AbstractBioadhesives are useful medical devices to help reduce postoperative complications and as adjuncts to sutures and staples in sealing wounds. Biomedical companies have been promoting research and development into new bioadhesives. As for other medical devices, translating promising candidates to market involves the need to pass through several regulatory steps, wherein their safety and effectiveness are evaluated and the proper reimbursements from payors are assessed. The regulatory procedures involve classification based on the risk factors, support studies, submission of applications to relevant authorities, procurement of certification, and finally commercialization, while keeping a track record of the post‐market data. The importance of real‐world data has been recently realized. The aim of this review is to focus on the translational goals, expectations, and necessities of medical devices focusing on the bioadhesives to be commercialized. It should aid researchers inspired to discover and market new bioadhesives in understanding the need for basic regulatory procedures behind their commercialization for medical usage, most importantly for internal medicine specifically in the United States of America, Canada, and Europe, in part. The key differences in the regulatory aspects among those are highlighted. Regulations keep changing with the introduction of new products and governmental laws. They are updated in this manuscript till March 2021.
circCORO1C promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing the expression of PD‐L1 through NF‐κB pathway
Authors: Wu Fan , Sun Guoqiang , Zheng Wubin , Tang Weiwei , Cheng Ye , Wu LiangLiang , Li Xiao , Tao Jing , Ma Shijie , Cao Hongyong 
Published: October 2021

AbstractBackgroundCircular RNA (circRNA) affects the occurrence and development of human cancers, but the specific mechanism of hepatocellular carcinoma (HCC) has not yet been fully understood.MethodsCircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase chain reaction (qRT‐PCR). Cell viability, migration, invasion, and other indicators were used for cell function analysis. Knockdown and overexpression techniques were used to explore the mechanism of circCORO1C in the occurrence and development of HCC by RNA sequencing, qRT‐PCR, western blot, and other methods.ResultsAmong the thousands of circRNAs, 1238 circRNAs were significantly changed. As for the top 10 upregulated circRNAs, the expression of circRNAs, hsa_circ_0036412, hsa_circ_0036411, hsa_circ_0028071, hsa_circ_0036409, hsa_circ_0000437, hsa_circ_0021427, hsa_circ_0097182, hsa_circ_0028067, hsa_circ_0006852, and hsa_circ_0003620 were significantly increased. In regard to the top 10 downregulated circRNAs, the expression of hsa_circ_0123629, hsa_circ_0096121, hsa_circ_0038932, hsa‐circRNA3310‐44, hsa_circ_0045746, hsa_circ_0016836, hsa‐circRNA10899‐9, hsa_circ_0050116, hsa_circ_0035543, and hsa_circ_0092118 decreased significantly. About these circRNAs, the downregulation of hsa_circ_0006852 (circCORO1C) can inhibit the tumorigenesis of HCC cells in vivo and in vitro, and the overexpression of circCORO1C can enhance the proliferation and metastasis ability of HCC cells. Mechanistically, circCORO1C activated the NF‐κB signaling pathway, increased P65 phosphorylation and upregulation of c‐Myc and COX‐2, leading to increased PD‐L1 expression.ConclusionCircCORO1C upregulates c‐Myc and COX‐2 through NF‐κB signaling pathway, leading to the upregulation of PD‐L1, which jointly promotes the development of HCC, suggesting that circCORO1C is a promising biomarker and therapeutic target for HCC.
Effects of hormonal changes on sarcopenia in chronic kidney disease: where are we now and what can we do?
Authors: Gungor Ozkan , Ulu Sena , Hasbal Nuri Baris , Anker Stefan D. , Kalantar‐Zadeh Kamyar 
Published: October 2021

AbstractSarcopenia or muscle wasting is a progressive and generalized skeletal muscle disorder involving the accelerated loss of muscle mass and function, often associated with muscle weakness (dynapenia) and frailty. Whereas primary sarcopenia is related to ageing, secondary sarcopenia happens independent of age in the context of chronic disease states such as chronic kidney disease (CKD). Sarcopenia has become a major focus of research and public policy debate due to its impact on patient's health‐related quality of life, health‐care expenditure, morbidity, and mortality. The development of sarcopenia in patients with CKD is multifactorial and it may occur independently of weight loss or cachexia including under obese sarcopenia. Hormonal imbalances can facilitate the development of sarcopenia in the general population and is a common finding in CKD. Hormones that may influence the development of sarcopenia are testosterone, growth hormone, insulin, thyroid hormones, and vitamin D. Although the relationship between free testosterone level that is low in uraemic patients and sarcopenia in CKD is not well‐defined, functional improvement may be seen. Unlike testosterone, it is known that vitamin D is associated with muscle strength, muscle size, and physical performance in patients with CKD. Outcomes after vitamin D replacement therapy are still controversial. The half‐life of growth hormone (GH) is prolonged in patients with CKD. Besides, IGF‐1 levels are normal in patients with Stage 4 CKD—a minimal reduction is seen in the end‐stage renal disease. Unresponsiveness or resistance of IGF‐1 and changes in the GH/IGF‐1 axis are the main causes of sarcopenia in CKD. Low serum T3 level is frequent in CKD, but the net effect on sarcopenia is not well‐studied. CKD patients develop insulin resistance (IR) from the earliest period even before GFR decline begins. IR reduces glucose utilization as an energy source by hepatic gluconeogenesis, decreasing muscle glucose uptake, impairing intracellular glucose metabolism. This cascade results in muscle protein breakdown. IR and sarcopenia might also be a new pathway for targeting. Ghrelin, oestrogen, cortisol, and dehydroepiandrosterone may be other players in the setting of sarcopenia. In this review, we mainly examine the effects of hormonal changes on the occurrence of sarcopenia in patients with CKD via the available data.
Should we call it a (middle) class? A socio‐economic exploration of the Vietnamese middle‐income group
Authors: Rougier Eric , Berrou Jean‐Philippe , Clément Matthieu , Combarnous François , Darbon Dominique 
Published: October 2021

AbstractBy combining household survey data on the economic and social characteristics of middle‐income earners and primary survey data on their subjective perceptions, we show that the so‐called Vietnamese ‘middle class’ is strongly heterogeneous in terms of income, occupation and status and includes a large percentage of highly vulnerable households facing high individual risk not covered by social protection. Although marginally driven by public sector employment and formal private sector expansion, it shares common traits that might help consolidate class identification and could lead to more formally organised political influence if the political sphere becomes more open in the future.
Solvent‐Cast 3D Printing of Biodegradable Polymer Scaffolds
Authors: Tolbert John W. , Hammerstone Diana E. , Yuchimiuk Nathaniel , Seppala Jonathan E. , Chow Lesley W. 
Published: October 2021

Abstract3D printing is a popular fabrication technique because of its ability to produce complex architectures. Melt‐based 3D printing is widely used for thermoplastic polymers like poly(caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactic‐co‐glycolic acid) (PLGA) because of their low processing temperatures. However, traditional melt‐based techniques require processing temperatures and pressures high enough to achieve continuous flow, limiting the type of polymer that can be printed. Solvent‐cast printing (SCP) offers an alternative approach to print a wider range of polymers. Polymers are dissolved in a volatile solvent that evaporates during deposition to produce a solid polymer filament. SCP, therefore, requires optimizing polymer concentration in the ink, print pressure, and print speed to achieve desired print fidelity. Here, capillary flow analysis shows how print pressure affects the process‐apparent viscosity of PCL, PLA, and PLGA inks. Ink viscosity is also measured using rheology, which is used to link a specific ink viscosity to a predicted set of print pressure and print speed for all three polymers. These results demonstrate how this approach can be used to accelerate optimization by significantly reducing the number of parameter combinations. This strategy can be applied to other polymers to expand the library of polymers printable with SCP.