bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive model for recurrence of renal cell carcinoma by comparing pre‐ and postoperative urinary metabolite concentrations
Authors: Morozumi Kento , Kawasaki Yoshihide , Maekawa Masamitsu , Takasaki Shinya , Sato Tomonori , Shimada Shuichi , Kawamorita Naoki , Yamashita Shinichi , Mitsuzuka Koji , Mano Nariyasu , Ito Akihiro 
Published: October 2021

AbstractTo improve treatment outcomes in real practice, useful biomarkers are desired when predicting postoperative recurrence for renal cell carcinoma (RCC). We collected data from patients who underwent definitive surgery for RCC and for benign urological tumor at our department between November 2016 and December 2019. We evaluated the differences in pre‐ and postoperative urinary metabolites with our precise quantitative method and identified predictive factors for RCC recurrence. Additionally, to clarify the significance of metabolites, we measured the intracellular metabolite concentration of three RCC cell lines. Among the 56 patients with RCC, nine had a recurrence (16.0%). When comparing 27 patients with T1a RCC and 10 with benign tumor, a significant difference was observed between pre‐ and postoperative concentrations among 10 urinary metabolites. In these 10 metabolites, multiple logistic regression analysis identified five metabolites (lactic acid, glycine, 2‐hydroxyglutarate, succinic acid, and kynurenic acid) as factors to build our recurrence prediction model. The values of area under the receiver operating characteristic curve, sensitivity, and specificity in this predictive model were 0.894%, 88.9%, and 88.0%, respectively. When stratified into low and high risk groups of recurrence based on this model, we found a significant drop of recurrence‐free survival rates among the high risk group. In in vitro studies, intracellular metabolite concentrations of metastatic tumor cell lines were much higher than those of primary tumor cell lines. By using our quantitative evaluation of urinary metabolites, we could predict postoperative recurrence with high sensitivity and specificity. Urinary metabolites could be noninvasive biomarkers to improve patient outcome.
Evaluation of the abuse potential of difelikefalin, a selective kappa‐opioid receptor agonist, in recreational polydrug users
Authors: Shram Megan J. , Spencer Robert H. , Qian Jenny , Munera Catherine L. , Lewis Michael E. , Henningfield Jack E. , Webster Lynn , Menzaghi Frédérique 
Published: October 2021

AbstractDifelikefalin, a selective kappa‐opioid receptor agonist with limited central nervous system penetration, is being developed for the treatment of chronic pruritic conditions. This randomized, double‐blind, active‐ and placebo‐controlled, four‐way crossover study was designed to evaluate the abuse potential of difelikefalin in healthy recreational polydrug users. Using a 4 × 4 Williams design, nondependent adult users of opioids and hallucinogens (N = 44) were randomized to receive single intravenous (i.v.) injections of difelikefalin at supratherapeutic doses (5 and 15 mcg/kg); pentazocine (0.5 mg/kg), a schedule IV mu‐opioid partial agonist and kappa‐opioid receptor agonist; and placebo. The abuse potential of difelikefalin was compared with pentazocine and placebo using the maximal score (maximum effect [Emax]) of the Drug Liking visual analog scale (VAS; primary end point), along with multiple secondary end points of subject‐rated measures and pupillometry. Difelikefalin produced significantly lower Drug Liking VAS Emax, and lower peak positive, sedative, and perceptual effects compared with pentazocine. These effects of difelikefalin were small, brief, and not dose‐dependent, although marginally greater than those observed with placebo. Neither dose of difelikefalin elicited significant negative or hallucinogenic effects. On end‐of‐session measures of overall drug liking and willingness to take the drug again, difelikefalin did not differ from placebo, indicating subjects neither liked nor disliked the effects overall and did not feel motivated to take the drug again. Consistent with its lack of mu agonist activity, difelikefalin did not induce miosis compared with pentazocine. All treatments were generally well‐tolerated. This study indicates that difelikefalin presents a low potential for abuse.
Insulin Centennial: Milestones influencing the development of insulin preparations since 1922
Authors: Owens David R. , Monnier Louis , Ceriello Antonio , Bolli Geremia B. 
Published: October 2021

AbstractDuring 1921 to 1922, a team effort by Banting, Macleod, Collip and Best isolated and purified insulin and demonstrated its life‐giving properties, giving rise to the birth of insulin therapy. In the early years (1922‐1950), priorities revolved around the manufacture of insulin to meet demand, improving purity to avoid allergic reactions, establishing insulin standards and increasing its duration of action to avoid multiple daily injections. Shortly after the emergence of insulin, Joslin and Allen advocated the need to achieve and maintain good glycaemic control to realize its full potential. Although this view was opposed by some during a dark period in the history of insulin, it was subsequently endorsed some 60 years later endorsed by the Diabetes Control and Complications Trial and United Kingdom Prospective Diabetes Study. Major scientific advances by the Nobel Laureates Sanger, Hodgkin, Yalow and Gilbert and also by Steiner have revolutionized the understanding of diabetes and facilitated major advances in insulin therapy. The more recent advent of recombinant technology over the last 40 years has provided the potential for unlimited source of insulin, and the ability to generate various insulin ‘analogues’,in an attempt to better replicate normal insulin secretory patterns. The emerging biosimilars now provide the opportunity to improve availability at a lower cost.
Disrupted education trajectories: Exploring the effects of Covid‐19 on adolescent learning and priorities for “building back better” education systems in Ethiopia
Authors: Jones Nicola , Devonald Megan , Dutton Rebecca , Baird Sarah , Yadete Workneh , Gezahegne Kiya 
Published: October 2021

AbstractMotivationThe Covid‐19 pandemic delivered an unprecedented shock to education systems globally, with school closures affecting 1.6 billion children. Education systems in low‐ and middle‐income countries (LMICs) are facing significant budget cuts further constraining capacities to adapt to Covid‐19 impacts. The need for evidence to inform policy dialogues about how best to mitigate impacts and support education systems to “build back better” is pressing.PurposeIn Ethiopia, schools reopened in October 2020 after a seven‐month pandemic‐related closure. Employing an adapted resilience systems analysis framework, this article focuses on the extent to which Ethiopia’s education system—which has in recent decades seen rapid progress in enrolment rates—has adapted to the impacts of the pandemic on adolescents’ education and learning, and has achieved this equitably.Methods and approachThe article draws on mixed‐methods data from Ethiopia collected virtually with a pre‐existing cohort of 3,066 adolescents (1,683 girls and 1,383 boys) during the immediate onset of the pandemic (April–June 2020) and following the reopening of schools (November 2020–February 2021). Adolescent perspectives are complemented by 27 key informant interviews at community and district levels.FindingsRural adolescents, girls, and adolescents with disabilities were less likely to access distance education during school closures due to connectivity challenges and discriminatory norms, and to subsequently re‐enrol. Implementation of adaptive measures, including hygiene guidance, smaller class sizes, and catch‐up classes, has been highly uneven, and outreach to support re‐enrolment of socially marginalized adolescents has been very limited.Policy implicationsFor LMICs like Ethiopia to build back better post‐pandemic and stay on track to achieve Sustainable Development Goal 4’s commitment to inclusive and equitable quality education for all, scaled‐up investments in blended learning approaches, addressing the digital divide, and ensuring targeted outreach and social protection to support re‐enrolment of socially marginalized adolescents are critical.
COVID‐19 induced telogen effluvium
Authors: Aksoy Hasan , Yıldırım Umut Mert , Ergen Pınar , Gürel Mehmet Salih 
Published: October 2021

AbstractCOVID‐19 is a febrile, infectious illness that has previously been associated with telogen effluvium (TE). However, to date, no study has been conducted to determine the incidence of TE in those who have had COVID‐19. To assess the frequency of TE in post‐COVID‐19 patients and the correlation between the development of TE and the severity of COVID‐19, to understand whether emotional stress or medications are responsible for the development of TE. Totally 204 patients with a history of SARS‐CoV‐2 infection in the last 3 months were included in the study. The diagnosis of TE was made by history of excessive hair shedding, hair pull test, diffuse or bitemporal thinning, and absence of anisotrichosis in trichoscopy. Patients who did not have any TE cause other than COVID‐19 and whose hair loss started after COVID‐19 were considered as “COVID‐19 associated TE (CATE).” We found TE in 75 (36.7%) cases and androgenetic alopecia (AGA) in 85 (41.7%) cases. CATE was present in 27.9% of cases and developed on average 53.76 (± 23.772) days after COVID‐19 real‐time reverse transcription polymerase chain reaction (RT‐PCR) positivity. The proportion of patients with CATE was numerically higher in hospitalized patients compared to outpatients (31.7% vs. 24.3%; p = 0.238); and significantly higher in women compared to men (42.3% vs. 6.2%; p < 0.001), in patients with hypertension compared to those without hypertension (40.4% vs. 23.1%; p = 0.014), and in patients who had respiratory symptoms compared to those who had not (31.7% vs. 14.0%; p = 0.021). The patients with and without CATE were similar in terms of stress level and usage of COVID‐19 medications. Patients with AGA had a higher rate of hospitalization (69.4% vs. 35.3%; p < 0.001) and a higher incidence of fever (69.4% vs. 54.6%; p = 0.033) during COVID‐19, compared to those without. TE developed in approximately one‐quarter of people who have had COVID‐19, and our study is the first to detect it. The time to onset of CATE, which was 7–8 weeks after the SARS‐CoV‐2 RT‐PCR positivity, was not much different from post‐infectious TE. Patients with severe COVID‐19 seem to be more prone to develop TE. The presence of AGA is associated with a more severe COVID‐19. During the pandemic, clinicians should consider a previous SARS‐CoV‐2 infection in patients presenting with hair loss.
SME investment and financing under asymmetric information
Authors: Wang Yao , Zhang Hai , Zhao Zhiming 
Published: October 2021

AbstractWe investigate the investment timing and financing decisions of financially constrained small and medium‐sized enterprises (SMEs) in a real‐option setting with asymmetric information. ‘Bad’ firms can sell over‐priced securities by mimicking in a pooling equilibrium. However, ‘good’ firms can separate from bad firms by imposing an adverse selection cost for mimicry only when the benefit of being recognized as the ‘good’ type outweighs the investment distortion costs. Further, asymmetric information induces good firms to accelerate investment, leading to investment distortion and higher guarantee costs. Equity‐for‐guarantee swap not only mitigates SMEs' financing constraints but also reduces the investment and finance distortions.
Computed tomography image and mechanism of spiral neuron T‐type calcification channel of elderly patient with senile sudden deafness under embedded system combined with artificial intelligence algorithm
Authors: Dai Qiong , Ai Wei , Yuan Kun , Jia Min , Sun Jingwu 
Published: October 2021

AbstractTo analyse the computed tomography (CT) images of spiral neuron T‐type calcification channels and the mechanism of action in patients with sudden deafness in the elderly, the artificial intelligence (edge algorithm) algorithm was applied to the embedded system to analyse the CT images of the sudden deafness of the elderly, and then the mechanism of the spiral neuron T‐calcification channel was studied. The results showed that among the 48 patients with labyrinthitis, 26 were acute labyrinthitis, 14 were chronic labyrinthitis, and 8 were sclerosing labyrinthitis. α1G, α1H, and α1I were expressed on the cochlea and spiral neurons in the 66–68‐year‐old population, but the expression levels were significantly different. The expression of the three receptors on spiral neurons was slightly higher than that of the cochlea. α1H was most expressed on spiral neurons compared with the other two calcium channel receptors (p < 0.05). In addition, the minimum intensity projection method, multi‐layer reconstruction method, and surface reconstruction method can fully display the bony labyrinth, cochlea, cochlear duct (2.5 weeks), and shape and edge damage. In summary, the adoption of artificial intelligence algorithms based on embedded systems to analyse CT images can comprehensively and accurately reflect the three‐dimensional structure of the inner surface of the inner ear labyrinth. It can also fully display the scope, shape, density, and edge of the lesion. T‐type calcium channel receptors were expressed on the cochlea and spiral neurons of the C57BL/6J elderly, and decreased with age.
The life evaluation by linear cumulative damage rule for cold dwell fatigue of Ti‐6Al‐4V alloy
Authors: Ota Yutaro , Kubushiro Keiji , Yamazaki Yasuhiro 
Published: October 2021

AbstractLow cycle fatigue (LCF) life at ambient temperature of Ti alloys is well known to decrease with stress dwell. This phenomenon, called cold dwell fatigue (CDF), is influenced by the peak stress, dwell time, and microstructure. For this study, the CDF life was evaluated by the linear cumulative damage rule. The influence of test conditions and microstructure on the linear cumulative damage rule was also verified. By the linear cumulative damage rule, when creep damage is calculated using the time exhaustion rule, theCDF damage was evaluated by the inequality of DTotal = (DF, DC) ≤ (0.01, 10−6). However, the CDF damage can be evaluated in the range of DTotal = 0.6–1.2 when creep damage was calculated using the ductile exhaustion rule. Results indicate that the evaluation was almost independent of the dwell time, peak stress, and microstructure, so it is also a versatile method for evaluating CDF responses.
Indigenous and gendered persons and peoples in business ethics education: Intersections of Indigenous wisdoms and de Beauvoirian existentialism
Authors: Price Shelley T. , Hartt Christopher M. , Mills Albert J. , MacFarlane Nia F. 
Published: October 2021

AbstractThe purpose of this paper is to explore how business ethics textbooks include Indigenous and gendered persons and peoples and whether they acknowledge Indigenous philosophies and theories. We explore 363 cases from eighteen (18) business ethics textbooks. A form and theme based content analysis was employed to help us better understand the inclusion, obfuscation and omission of Indigenous and gendered persons. A purpose of business ethics education is to disrupt injustice and oppressive practices in business. We find that business ethics education can provide more inclusive and respectful cases as it relates to Indigenous and gendered characters. There are cases that marginalize, obfuscate and omit Indigenous peoples, females, and gender diverse persons. This study contributes to diversity scholarship by identifying ways in which Indigenous and gendered persons and peoples can be included in management and business ethics education.
Molecular study of a large cohort of 109 haemophilia patients from Cuba using a gene panel with next generation sequencing‐based technology
Authors: Borràs Nina , Castillo‐González Dunia , Comes Natalia , Martin‐Fernandez Laura , Rivero‐Jiménez René Antonio , Chang‐Monteagudo Arturo , Ruiz‐Moleón Vera , Garrote‐Santana Heidys , Vidal Francisco , Macías‐Abraham Consuelo 
Published: October 2021

AbstractIntroductionIn several countries, molecular diagnosis of haemophilia A (HA) and B (HB) is hampered by a lack of resources for DNA analysis. The advent of next‐generation sequencing (NGS) has enabled gene analysis at a reasonable cost.AimDescribe a collaboration between Cuban and Spanish researchers to identify candidate variants and investigate the molecular epidemiology of 106 Cuban haemophilia patients using NGS.Patients/methodsThe molecular analysis protocol included well‐established LR‐PCR procedures to detect F8 inversions, NGS with a 30‐gene panel to sequence F8 and F9, and multiplex ligation‐dependent probe amplification to identify large structural variants.ResultsOne‐hundred and thirty‐one candidate variants were identified along F8, F9, and VWF; 72 were unique and 28 (39%) had not been previously recorded. Putative variants were identified in 105/106 patients. Molecular characterization enabled confirmation and reclassification of: 90 HA (85%), 15 HB (14%), and one type 2N VWD (1%). Null variants leading to non‐production of FVIII or FIX were common in severe HA (64%), moderate HA (74%), and severe HB (60%), whereas missense variants were frequent in mild HA (57%) and moderate or mild HB (83%). Additional variants in VWF were identified in 16 patients.ConclusionThis is the first description of the molecular epidemiology of HA and HB in Cuba. Variants identified in index cases will be of value for local implementation of familial studies and prenatal diagnosis using the molecular approaches available in Cuba. The results of this protocolled genetic study improved the accuracy of the clinical diagnosis and will facilitate management of these patients.
miR‐378‐3p alleviates contusion spinal cord injury by negatively regulating ATG12
Authors: Zhang Haocong , Yu Hailong , Yang Huifeng , Zhan Yang , Liu Xinwei 
Published: October 2021

AbstractMicroRNAs (miRNAs or miRs) serve essential roles in the pathogenic process of spinal cord injury (SCI). The present study investigated the role of miR‐378‐3p and autophagy‐related 12 (ATG12) in SCI. RT‐qPCR was used to detect the mRNA expression levels of miR‐378‐3p and ATG12. Cell viability and membrane integrity were evaluated using CCK‐8 and LDH assays. For the analysis of the interaction between miR‐378‐3p and ATG12, a dual‐luciferase reporter assay was conducted. The hindlimb function of rats was detected with the Basso, Beattie and Bresnahan score, and the motor deficit index score was used to evaluate nerve function. Using these approaches, it was identified that miR‐378‐3p expression was downregulated, while that of ATG12 was upregulated in SCI tissues and in cells exposed to hypoxia. Hypoxia repressed the expression of miR‐378‐3p via hypoxia‐inducible factor 1‐α. The overexpression of miR‐378‐3p exerted anti‐apoptotic effects on nerve cells by directly repressing ATG12. The infusion of miR‐378‐3p improved hindlimb motor function and the neurological functions of rats with contusion SCI, which contributed to amelioration of functional deficits and the relief of contusion SCI. Therefore, it was concluded that upregulated expression of miR‐378‐3p in PC12 or N2A cells repressed the apoptosis of nerve cells, and the administration of miR‐378‐3p in model rats with contusion SCI improved neurological and motor functions.
EXCESS CAPACITY AND EFFECTIVENESS OF POLICY INTERVENTIONS: EVIDENCE FROM THE CEMENT INDUSTRY
Authors: Okazaki Tetsuji , Onishi Ken , Wakamori Naoki 
Published: October 2021

AbstractStrategic interaction among firms may hinder the reduction of excess capacity in a declining industry. Policy interventions that attempt to reduce excess capacity may increase efficiency by accelerating the capital adjustment but may decrease efficiency by increasing the market power of firms and/or by distorting firms' divestment decisions. We study capacity coordination policies—forcing firms to reduce their capacity simultaneously—applied to the Japanese cement industry. Estimation results suggest that these interventions did not increase market power because reduction in capacity resulted in higher utilization of the remaining plants, and did not distort firms' scrappage decisions.
Circ_0009910 sponges miR‐491‐5p to promote acute myeloid leukemia progression through modulating B4GALT5 expression and PI3K/AKT signaling pathway
Authors: Wu Yingwei , Zhao Bo , Chen Xianghua , Geng Xueli , Zhang Zhihua 
Published: October 2021

AbstractBackgroundAcute myeloid leukemia (AML) is a heterogeneous group of leukemias with an overall poor prognosis. Circular RNAs (circRNAs) have been verified to play important regulatory roles in AML progression. However, the role and molecular mechanism of circ_0009910 in AML development have not be completely clarified.MethodsThe expression levels of circ_0009910, microRNA‐491‐5p (miR‐491‐5p), and β‐1, 4‐galactosyltransferase 5 (B4GALT5) were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR) or Western blot. Cell proliferation and self‐renewal ability were assessed via Cell Counting Kit‐8 (CCK‐8) and sphere formation assay. Cell cycle distribution and cell apoptosis were evaluated by flow cytometry. Caspase‐3 activity was tested by Caspase‐3 Activity Assay Kit. Western blot was used to examine the protein levels of autophagy‐related markers and PI3K/AKT pathway‐related markers. The interaction between miR‐491‐5p and circ_0009910 or B4GALT5 was confirmed by dual‐luciferase reporter assay, RNA immunoprecipitation (RIP) assay, or RNA pull‐down assay.ResultsCirc_0009910 was highly expressed in AML tissues and cells. Silenced circ_0009910 could significantly inhibit the proliferation, sphere formation, and autophagy and promoted the apoptosis of AML cells. Circ_0009910 bound to miR‐491‐5p in AML cells, and circ_0009910 promoted AML progression partly through sponging miR‐491‐5p in vitro. B4GALT5 was a target of miR‐491‐5p, and miR‐491‐5p overexpression‐mediated influences in AML cells were effectually overturned by the addition of B4GALT5 overexpression plasmid. Furthermore, circ_0009910 could regulate the expression of B4GALT5 by downregulating miR‐491‐5p in AML cells. Additionally, circ_0009910 could activate the PI3K/AKT signaling pathway by sponging miR‐491‐5p.ConclusionCirc_0009910 could suppress the proliferation, sphere formation, and autophagy and accelerated apoptosis by modulating B4GALT5 expression and activating the PI3K/AKT signaling pathway via sponging miR‐491‐5p in AML cells, suggesting that circ_0009910 might be a potential biomarker for the treatment of AML.