bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel small compound TOIDC suppresses lipogenesis via SREBP1-dependent signaling to curb MAFLD
Authors: Shao Yaodi , Yao Zhi , Zhou Junyi , Yu Miao , Chen Suzhen , Yuan Yanmei , Han Liu , Jiang Liqin , Liu Junli 
Published: December 2022

Abstract
Background
Inhibition of hepatic lipogenesis is widely regarded as an effective treatment for metabolic-associated fatty liver disease (MAFLD), although numerous related drugs have failed to reach clinical application. The goal of this study is to identify a novel small compound that can effectively treat MAFLD.

Methods
Primary hepatocytes were first exposed to palmitic acid and oleic acid, then treated with compounds prior to high through screening for cellular lipid content. The efficacy of these compounds was measured by Nile Red staining and triglyceride analysis. The potential cellular toxicity caused by these compounds was evaluated by CCK8 assay. qPCR and Western blot were used to determine expression of RNAs and proteins, respectively. The compound was intraperitoneally injected into diet-induced obese (DIO) mice to examine its efficacy in vivo.

Results
We identified the dimethyl 1-methyl-2-thioxoindoline-3,3-dicarboxylate (TOIDC) as a powerful chemical to reduce cellular lipid with minimal cellular toxicity. When injected intraperitoneally, TOIDC effectively ameliorates MAFLD in DIO mice. Mechanically, TOIDC suppresses de novo lipogenesis through inhibiting sterol regulatory element-binding protein 1 (SREBP1).

Conclusions
Our findings indicate that TOIDC could be a promising lead compound to develop new drugs to treat MAFLD.

Graphical Abstract
Impact of fractionated stereotactic radiotherapy on activity of daily living and performance status in progressive/recurrent glioblastoma: a retrospective study
Authors: Demogeot Nicolas , Salleron J. , Rech F. , Taillandier L. , Royer P. , Vogin G. 
Published: December 2022

AbstractBackgroundThe prognosis of recurrent glioblastoma (GBM) is poor, with limited options of palliative localized or systemic treatments. Survival can be improved by a second localized treatment; however, it is not currently possible to identify which patients would benefit from this approach. This study aims to evaluate which factors lead to a lower Karnofsky performance status (KPS) score after fractionated stereotactic RT (fSRT).MethodsWe retrospectively collected data from patients treated with fSRT for recurrent GBM at the Institut de Cancérologie de Lorraine between October 2010 and November 2017 and analyzed which factors were associated with a lower KPS score.Results59 patients received a dose of 25 Gy in 5 sessions spread over 5–7 days (80% isodose). The median time from the end of primary radiotherapy to the initiation of fSRT was 10.7 months. The median follow-up after fSRT initiation was 8.8 months. The incidence of KPS and ADL impairment in all patients were 51.9% and 37.8% respectively with an adverse impact of PTV size on KPS (HR = 1.57 [95% CI 1.19–2.08],p = 0.028). Only two patients showed early grade 3 toxicity and none showed grade 4 or late toxicity. The median overall survival time, median overall survival time after fSRT, median progression-free survival and institutionalization-free survival times were 25.8, 8.8, 3.9 and 7.7 months, respectively. Initial surgery was associated with better progression-free survival (Hazard ratio (HR) = 0.48 [95% CI 0.27–0.86],p = 0.013).ConclusionsA larger PTV should predicts lower KPS in the treatment of recurrent GBM using fSRT.
Construction and validation of prognostic signature for hepatocellular carcinoma basing on hepatitis B virus related specific genes
Authors: Wang Lei , Qiu Manman , Wu Lili , Li Zexing , Meng Xinyi , He Lu , Yang Bing 
Published: December 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is a frequent primary liver cancer, and it is one of the leading cause of cancer-related deaths. Hepatitis B virus (HBV) infection is a crucial risk factor for HCC. Thus, this study aimed to explore the prognostic role of HBV-positive HCC related specific genes in HCC.

Methods
The HCC related data were downloaded from three databases, including The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO). Univariate Cox regression analysis and LASSO Cox regression analysis were conducted to build the Risk score. Multivariate Cox regression analysis and survival analysis determined the independent prognostic indicators.

Results
After cross analysis of differentially expressed genes (DEGs), we have identified 106 overlapped DEGs, which were probably HBV-positive HCC related specific genes. These 106 DEGs were significantly enriched in 213 GO terms and 8 KEGG pathways. Among that, 11 optimal genes were selected to build a Risk score, and Risk score was an independent prognostic factor for HCC. High risk HCC patients had worse OS. Moreover, five kinds of immune cells were differentially infiltrated between high and low risk HCC patients.

Conclusion
The prognostic signature, based on HMMR, MCM6, TPX2, KIF20A, CCL20, RGS2, NUSAP1, FABP5, FZD6, PBK, and STK39, is conducive to distinguish different prognosis of HCC patients.
A treatment-refractory aggressive MDS-MLD with multiple highly complex chromosome 5 intrachromosomal rearrangements: a case report
Authors: Sasi Ramakrishnan , Senft Jamie , Spruill Michelle , Barua Subit , Dougaparsad Sam , Vos Jeffrey A. , Perrotta Peter L. 
Published: December 2022

Abstract
Background
A patient with a myelodysplastic neoplasm exhibited a karyotype with multiple complex chromosome 5 rearrangements. This patient appeared to have a catastrophic cytogenetic event that manifested as a treatment-refractory aggressive form of disease, which lead to patient demise within one year. Both the clinical presentation and disease course were unusual based on the medical history and morphologic findings. Such cases of myelodysplastic syndrome with multilineage dysplasia (MDS-MLD) with complex abnormalities are not reported in the literature.

Case presentation
The patient was a 62-year-old female who presented with pancytopenia and dyspnea. The morphologic appearance of the peripheral blood smear and bone marrow biopsy, along with flow cytometric findings, favored the diagnosis of MDS-MLD unclassifiable. Myelodysplastic syndrome (MDS) with multilineage dysplasia (MDS-MLD), is an MDS characterized by one or more cytopenias and dysplastic changes in two or more of the myeloid lineages (i.e., erythroid, granulocytic, and megakaryocytic). The bone marrow, in particular, showed prominent dysplasia, including the presence of atypical megakaryocytes with small hypolobated morphology reminiscent of those typically seen in MDS with isolated 5q deletion. Cytogenetic analysis, including interphase and metaphase FISH, karyotype and SNP chromosomal microarray were performed, as well as DNA sequencing studies. Cytogenetic analysis showed a very complex karyotype featuring multiple 5q intrachromosomal rearrangements including a pericentric inversion with multiple interspersed deletions and monosomy 7. FISH studies showed a partial deletion of the PDGFRβ gene, and SNP chromosomal microarray and targeted panel-based sequencing identified biallelic loss of function of the TP53 gene. Based on the pathologic findings, the patient was treated for MDS but did not respond to either lenalidomide or azacitidine.

Conclusion
The genetic changes described, in particular, the complex intrachromosomal rearrangements of chromosome 5, suggest the occurrence of a sudden catastrophic event that led to an aggressive course in the patient’s disease. Conventional karyotyping, metaphase and interphase FISH, SNP chromosomal microarray and NGS helped to identify the complex genetic changes seen in this case. This highlights the importance of utilizing a multimodality approach to fully characterize complex chromosomal events that may significantly impact disease progression, treatment and survival.
In-hospital cardiac arrest: the state of the art
Authors: Penketh James , Nolan Jerry P. 
Published: December 2022

AbstractIn-hospital cardiac arrest (IHCA) is associated with a high risk of death, but mortality rates are decreasing. The latest epidemiological and outcome data from several cardiac arrest registries are helping to shape our understanding of IHCA. The introduction of rapid response teams has been associated with a downward trend in hospital mortality. Technology and access to defibrillators continues to progress. The optimal method of airway management during IHCA remains uncertain, but there is a trend for decreasing use of tracheal intubation and increased use of supraglottic airway devices. The first randomised clinical trial of airway management during IHCA is ongoing in the UK. Retrospective and observational studies have shown that several pre-arrest factors are strongly associated with outcome after IHCA, but the risk of bias in such studies makes prognostication of individual cases potentially unreliable. Shared decision making and advanced care planning will increase application of appropriate DNACPR decisions and decrease rates of resuscitation attempts following IHCA.
Validation of a commercial version of a competitive enzyme linked immunosorbent assay for the detection of antibodies to Besnoitia besnoiti
Authors: Schares Gereon , Bärwald Andrea , Vernet Marie-Astrid , Bernard Frédéric , Blanchard Béatrice , Coppe Philippe 
Published: December 2022

Abstract
Background
Several reports suggest a further spread of besnoitiosis to countries in which Besnoitia besnoiti-infected bovine herds have not been noticed yet. Cattle infected without clinical signs may represent reservoirs. Serological analyses in affected herds or animals from endemic regions are necessary to identify subclinical or inapparent infections and stop transmission to naïve animals or herds. The Monoscreen AbELISA Besnoitia besnoiti (BIO K 466) is based on a previously published in-house competitive ELISA, the Bb-cELISA1, but has a different test architecture. The present study aimed to use sera from a previous evaluation of Bb-cELISA1 to assess whether BIO K466 shows identical results. In addition, further well-characterized positive and negative samples were analysed to estimate diagnostic sensitivity and specificity.

Methods
A first set of sera consisted of a total of 305 bovine sera, collected from German herds infected by B. besnoiti, Neospora caninum or Sarcocystis spp. Sera had been characterized by reference serological tests (i.e. immunoblot, immunofluorescence antibody test and an in-house indirect ELISA). A second set consisted of 200 confirmed B. besnoiti-positive sera from French herds. Negative cattle sera (n = 624) originated from Norway and The Netherlands, countries in which bovine besnoitiosis has not been reported yet.

Results
Using the first set of sera, the BIO K466 showed an estimated diagnostic sensitivity of 97.9% (95% CI: 91.9%–99.6) and a diagnostic specificity of 99.5% (95% CI: 96.9%–100%) relative to reference serological tests. A direct comparison of the results revealed an almost perfect agreement between the results of the in-house Bb-cELISA1 and the commercialized version (kappa 0.98; 95% CI: 0.95–1). The validation using positive bovine sera from France and negative sera from other European countries revealed a diagnostic sensitivity of 97.5% (95% CI: 93.9%–99.1%) and specificity of 99.5% (95% CI: 98.5%–99.9%).

Conclusion
In conclusion, BIO K 466 appears to be a suitable tool to diagnose bovine besnoitiosis, but needs further validation especially in cases of inconclusive, suspected false-positive or -negative results in other serological tests.

Graphic abstract
Real-World Performance of the Afirma Genomic Sequencing Classifier (GSC)—A Meta-analysis
Authors: Nasr Christian E , Andrioli Massimiliano , Endo Mayumi , Harrell R Mack , Livhits Masha J , Osakwe Ibitoro , Polavarapu Preethi , Siperstein Allan , Wei Shuanzeng , Zheng Xingyu , Jiang Ruochen , Hao Yangyang , Huang J I ng , Klopper Joshua P , Kloos Richard T , Kennedy Giulia , Angell Trevor E 
Published: December 2022

Abstract

Context
The Afirma® GSC aids in risk stratifying indeterminate thyroid nodule cytology (ITN). The 2018 GSC validation study (VS) reported a sensitivity (SN) of 91%, specificity (SP) of 68%, positive predictive value (PPV) of 47%, and negative predictive value (NPV) of 96%. Since then, 13 independent real-world (RW) postvalidation studies have been published.

Objective
This study's objective is to compare the RW GSC performance to the VS metrics.

Methods
Rules and assumptions applying to this analysis include: (1) At least 1 patient with molecular benign results must have surgery for that study to be included in SN, SP, and NPV analyses. (2) Molecular benign results without surgical histology are considered true negatives (TN) (as are molecular benign results with benign surgical histology). (3) Unoperated patients with suspicious results are either excluded from analysis (observed PPV [oPPV] and observed SP [oSP]) or assumed histology negatives (false positives; conservative PPV [cPPV] and conservative SP [cSP]) 4. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features is considered malignant.

Results
In RW studies, the GSC demonstrates a SN, oSP, oPPV, and NPV of 97%, 88%, 65%, 99% respectively, and conservative RW performance showed cSP of 80% and cPPV of 49%, all significantly higher than the VS except for SN and cPPV. There was also a higher benign call rate (BCR) of 67% in RW studies compared to 54% in the VS (P &lt; 0.05).

Conclusion
RW data for the Afirma GSC demonstrates significantly better oSP and oPPV performance than the VS, indicating an increased yield of cancers for resected GSC suspicious nodules. The higher BCR likely increases the overall rate of clinical observation in lieu of surgery.
Comment on “Is Leasing Greener Than Selling?” and Remark on the Focal Point Analysis in Durable Goods Models
Authors: Mahmoudzadeh Mahdi 
Published: December 2022

The focal point analysis is a viable approach to analyze models of finitely durable goods in infinite time horizon. Agrawal, Ferguson, Toktay, and Thomas [Agrawal VV, Ferguson M, Toktay LB, Thomas VM (2012) Is leasing greener than selling? Management Sci. 58(3):523–533.] study the focal point of steady-state firm–consumer games for leasing and selling models. We note that the optimal solution for their selling model does not reflect self-replicated leases mirroring the lease offered by the firm and show that the solution is indeed erroneous as it violates the constraint on consumer-type cutoffs. Although this does not affect the structure of their propositions, that is, outlining thresholds for more profitability and greenness of selling compared with leasing, it renders the thresholds incorrect. We first uncover and fix the root cause of the error. We then distinguish the focal point analysis from the rental price approach and note a few remarks for future durable goods models. This paper was accepted by Jayashankar Swaminathan, operations management. Supplemental Material: Data are available at https://doi.org/10.1287/mnsc.2022.4637 .
Assessing future technological impacts of patents based on the classification algorithms in machine learning: The case of electric vehicle domain
Authors: Han Fang , Zhang Shengtai , Yuan Junpeng , Wang Li 
Published: December 2022

IntroductionIdentifying the technologies that will drive technological changes over the coming years is important for the optimal allocation of firms’ R&D resources and the deployment of innovation strategies. The citation frequency of a patent is widely recognized as representative of the patent’s value. Thus, identifying potential highly cited patents is an important goal. A number of studies have attempted to distinguish highly cited patents from others based on statistical models, but a more effective and applicable method needs to be further developed.MethodsThis paper treats the prediction of later patent citations as a classification problem and proposes a novel framework based on machine learning methods. First, a indices system to identify highly cited patents is constructed using multiple factors that are believed to influence citation frequency. Second, various machine learning models are utilized to identify highly cited patents. The optimized model with the best generalization capability is selected to predict the future impacts of newly applied patents, which may be representative of emerging significant technologies. Finally, we select the electric vehicle (EV) domain as a case study to empirically test the validity of this framework.ResultsThe optimized support vector machine (SVM) model performs well in identifying highly cited EV patents. Technological frontiers in the EV domain are identified, which are related to the topics of information systems, batteries, stability control, wireless charging, and vehicle operation.DiscussionThe good performance in prediction accuracy and generalization capability of the method proposed in this paper verifies its effectiveness and feasibility.
Humanidades Digitais e Digitalização Tridimensional (3D)
Authors: Luro Marta , Borges Maria Manuel 
Published: December 2022

As Humanidades Digitais são genericamente consideradas como a aplicação de métodos e tecnologias digitais às áreas mais tradicionais dos estudos em Humanidades. O objetivo principal deste trabalho é investigar se, e de que forma, a digitalização tridimensional (3D) contribui para a afirmação das Humanidades Digitais. Como objetivos específicos procurámos avançar com uma definição de Humanidades Digitais e Digitalização tridimensional (3D) e refletir de que forma é que estes dois conceitos se articulam.
Numa primeira fase refletimos sobre o estado da arte e, para tal, recorremos a bibliografia especializada. Posteriormente foi feita uma análise a sites e locais pertinentes para o assunto visado. O artigo contempla uma reflexão sobre a temática a abordar, sendo para isso utilizado do ponto de vista metodológico, a pesquisa e análise documental.
Os principais resultados e conclusões desta investigação permitem-nos dizer que a digitalização tridimensional (3D) revoluciona a maneira como se faz hoje investigação em Humanidades porque permite ver diferentes perspetivas do que já existiu, possibilitando enormes avanços na pesquisa e investigação. É uma nova forma de abordar o passado, mas projetando-se no futuro. Surgem novos campos e temas de investigação e são criados materiais pedagógicos modernos e atrativos.
HOW BIG ARE THE EMPLOYMENT EFFECTS OF MICROLOANS? EVIDENCE FROM A CASE STUDY IN LATVIA
Authors: BALDI Guido , ŠIPILOVA Viktorija 
Published: December 2022

Microloans to small and medium-sized enterprises have become popular in many countries. However, evidence on the economic and social impact of microfinance is scarce. In an attempt to partly fill this gap, this paper looks at a case study and analyzes the economic impacts of the microloan programme of the Latvian development bank Hipoteku Banka. In our analysis, we focus on the following questions: Did the microloan programme increase employment within the supported firms? And was it able to contribute to the economic development of rural areas and the decrease of economic inequalities across regions? We find that the firms that were granted a loan from Hipoteku Banka on average considerably increased their employment during the loan period, as well as the microloan programme made a successful contribution to the economic development of rural regions in Latvia.
Enhancing International Business Development Between the United States and Africa by Implementing the Vibrant International Trade Alliance Model (VITAL - M)
Authors: Wood Van R. , Muzata Sombo 
Published: December 2022

International Business development requires a complex mix of market opportunities, political stability, confidence in the rule of law, a strong economic base, financial resources, and perhaps most important - an educated, knowledge embracing workforce that translates into global market expertise. Local, regional, national and international business development in Africa has traditionally lacked much of this mix and as it followed a tradition of natural resource exploitation, with little intellectual value added. This, for the most part has resulted in it “underdeveloped” status at worst or “developing” status at best when compared to much of the world. However, important examples exist where Africa in certain sectors is increasingly embracing knowledge resources. One area in particular, entrepreneurship, embedded in small and medium sized enterprises (SMEs) holds much promise for Africa’s development. This is particularly true when innovative entrepreneurs are knowledgeable about global markets, especially those with growing urban consumers and international trade opportunities. Developing such entrepreneurs and connecting them with – 1) government agencies charged with enhancing international trade (AITs), 2) public institutions of higher education (PIHEs) charged with educating the next generation of globally competitive business leaders and 3) domestic small to medium sized enterprises (SMEs) seeking new growth opportunities in the world-wide business markets can result in African business development that is super-charged. This paper explores a proven model for such development, labeled VITAL – Model (Vibrant International Trade Alliances Model). To fully grasp the nature and possibilities of this model for Africa, this paper - 1) over-views the realities of globalization that have created unprecedented opportunities for SMEs around the world, 2) highlights the importance of entrepreneurship in moving SMEs to the next level of wealth creation, 3) presents the VITAL Model developed in a globally engaged U.S. state (Virginia) to foster entrepreneurial expansion into international markets, 4) explains how the model can be applied to African countries and to partnerships between public institutions of higher education (PIHEs) in Africa and their U.S. counterparts, and 5) provides managerial, policy and future research implications related to this boundary spanning way of thinking.
The ‘Critical - Creative’ Divide in Academia: Are They Allies or Strange-Bed-Fellows?
Authors: Kaguhangire-Barifaijo Maria , Karyeija Gerald K. , Komakech Robert Agwot , Kyohairwe Stella B. , Oryema Dan E. 
Published: December 2022

The paper confronts the most controversial debate regarding the “Critical and Creative Thinking” divide, often termed as ‘strange bedfellows’ in academia. The divide is manifested in the way academics often bristle at the suggestion that exists between ‘critical and creative thinking perceptions. We argue that creativity without critical judgment would be fanciful, impractical and ridiculous, with the potential to run other people’s ideas ‘amok’, while critical thinkers would get short shrift if only they were reduced to just critiquing. Hence, it is necessary to have both on the team, those who can create novel ideas and others to critique others’ creations. While we acknowledge the distinction of the concepts, their roles are complementary and necessary to create a balance that must co-exist and shine in the scholarly arena. We conclude that the phrases often used in academia, such as; ‘devil’s advocates’, ‘opponents’ or ‘critical reviewers’ of doctoral candidates or in peer reviews has apparently been taken literally. We recommend that the superficial misconception of ‘greater’ or ‘superior’, is an unnecessary cognitive dissonance that must be resolved to promote co-existence for greater results.