bluuebunny/crossref_metadata_2025_split huggingface dataset:
Business Process Analysis and Modeling Using the Business Process Improvement Framework at the Internal Quality Assurance STMIK STIKOM Indonesia
Authors: Putra Desak Made Dwi Utami , Welda Welda 
Published: January 2022

STMIK STIKOM Indonesia is a college that organizes two study programs namely Informatics Engineering and Computer Systems. STIKI Indonesia has set SPMI in accordance with the PPEPP cycle. To ensure that SPMI can run as stipulated, the monitoring process is carried out with an Internal Quality Audit (AMI) facilitated by the STIKI Indonesia Internal Quality Assurance Institute (LPMI). Repeated business processes cause delays in obtaining the results of AMI's recapitulation, even though the results of the recapitulation are urgently needed as a report in the Senate Meeting to be evaluated as an effort to improve quality management at STMIK STIKOM Indonesia.
Therefore the business process model that runs on the implementation of the Internal Quality Audit of STMIK STIKOM Indonesia will further be identified the existing problems and be analyzed and corrected. Business Process Improvement (BPI) is an approach or method that the writer will use to improve existing business processes at the AMI stage. BPI aims to improve business processes and ensure that issues in an organization's business processes are handled properly. Business process modeling that will be used is Business Process Model and Notation (BPMN) which is a tool to describe or model business process diagrams based on flowchart techniques, arranged to create graphical models of business operations where there are activities and flow controls that define work order
Police, clans and cash in Somalia
Authors: Hills Alice 
Published: January 2022

This article explores the ways in which emergent police forces in conflict-affected Southern societies are shaped by cultural practices operating through social phenomena. It uses the record of the prototypical police forces found in the Somali cities of Kismayo and Baidoa, 2014-2017, to explore the ways in which culture, power relations and local realities — in this case, clan-based calculations, Somali and international politics, and physical insecurity — influence police development. It draws on the cities' experience of a donor-funded 'basic policing' programme to identify the motivating forces shaping police evolution in a society familiar with many aspects of conventional policing operations and vocabulary but positioned at the opposite end of the technical and institutional spectrum to those shaping police studies' canonical literature.
La Telerehabilitación como Estrategia de Atención en Salud
Authors: Nuñez Machuca María Fernanda , Meneses Castaño Cyndi Yacira , Penagos Paola Teresa , Beltrán Arias Andres Felipe 
Published: January 2022

Introducción: la telerehabilitación es considerada como una estrategia de salud innovadora, la cual busca mejorar el acceso a la salud desde un componente de atención integral, favoreciendo la aplicabilidad de diversos componentes y mejorando las condiciones de salud de los pacientes, con el fin de reintegrarlos a sus diversas actividades, este articulo tiene como objetivo presentar la telerehabilitación como una estrategia en salud. Método: se realizó una búsqueda en diversas bases de datos como, Pubmed, Pedro, EBSCO, Scielo encontrando un total de 235 artículos, de los cuales se seleccionaron 29 artículos y 8 guías clínicas de telerehabilitación en fisioterapia. Resultados: Se logro identificar en un gran porcentaje los beneficios de la fisioterapia desde la telerehabilitación en pacientes que cursaban con diversas patologías, sin embargo, algunos estudios no recomiendan esta estrategia ya que manifiestan un bajo grado de evidencia. Conclusión: La telerehabilitación en el ámbito fisioterapéutico es una estrategia fundamental para la atención en salud de pacientes cuya condición de salud lo permite, obteniendo resultados satisfactorios desde la mejora de sus capacidades y la vinculación a diversas actividades.
Palabras Clave: Telerehabilitación, Atención Integral de Salud, Fisioterapia, Estrategias de Salud Digital
Designing and Constructing a Novel Artificial Pathway for Malonic Acid Production Biologically
Authors: Gu Shuying , Zhao Zhen , Yao Yonghong , Li Jingen , Tian Chaoguang 
Published: January 2022

Malonic acid is used as a common component of many products and processes in the pharmaceutical and cosmetic industries. Here, we designed a novel artificial synthetic pathway of malonic acid, in which oxaloacetate, an intermediate of cytoplasmic reductive tricarboxylic acid (rTCA) pathway, is converted to malonic semialdehyde and then to malonic acid, sequentially catalyzed by a-keto decarboxylase and malonic semialdehyde dehydrogenase. After the systematic screening, we discovered the enzyme oxaloacetate decarboxylase Mdc, catalyzing the first step of the artificially designed pathway in vitro. Then, this synthetic pathway was functionally constructed in cellulolytic thermophilic fungus Myceliophthora thermophila. After enhancement of glucose uptake, the titer of malonic acid achieved 42.5 mg/L. This study presents a novel biological pathway for producing malonic acid from renewable resources in the future.
A Broad m6A Modification Landscape in Inflammatory Bowel Disease
Authors: Nie Kai , Yi Jun , Yang Yuanyuan , Deng Minzi , Yang Yan , Wang Tianyu , Chen Xuejie , Zhang Zhaoyu , Wang Xiaoyan 
Published: January 2022

Background and Aims: N6-Methyladenosine (m6A) is the most common post-transcriptional modification on eukaryotic mRNA, affecting the mRNA’s fate. The role of m6A regulation in inflammatory bowel disease is unclear. Here, we investigated the m6A landscape in inflammatory bowel diseases (IBD).Methods: Eleven human IBD microarray datasets were recruited from the Gene Expression Omnibus database and four were selected as discovery cohorts. An RNA-seq dataset from the Inflammatory Bowel Disease Multi’omics Database was used as a validation cohort. m6A regulators were measured in volunteers’ colonic samples. Consensus clustering and immune scoring were used to estimate the characteristics of m6A regulation in IBD. m6A-related characteristics of different sub-phenotypes, sample sources, and biological therapeutic responses were determined using seven independent datasets.Results: m6A modification involves methyltransferases (writers), demethylases (erasers), and methylation-reading proteins (readers). A wide interaction exists between m6A regulators and IBD risk genes. The IBD risk loci can also be modified by m6A modifications in the public m6A sequencing data. Furthermore, m6A regulators displayed extensive differential expression in four independent discovery cohorts that share common differential genes (IGF2BP2, HNRNPA2B1, ZCCHC4, and EIF3I). In the validated cohort and enrolled volunteers’ colonic biopsy samples, the differential m6A regulators were reconfirmed. Two clusters of consensus clustering exhibit different immune phenotypes. m6A-modified positions exist in the core IBD immune cytokines. Another set of IBD datasets revealed m6A-related differences across clinical phenotypes, biological samples, and therapeutic response subgroups in IBD patients.Conclusion: Regulation of m6A methylation is widely involved in IBD occurrence and development. m6A modifications in risk variants, core cytokines, immune cells, and other proteins may deeply influence the pathophysiology and clinical phenotypes. Further studies are needed to determine its role in IBD.
B1 siRNA Increases de novo DNA Methylation of B1 Elements and Promotes Wound Healing in Diabetic Rats
Authors: Yasom Sakawdaurn , Khumsri Wilunplus , Boonsongserm Papatson , Kitkumthorn Nakarin , Ruangvejvorachai Preecha , Sooksamran Apasee , Wanotayan Rujira , Mutirangura Apiwat 
Published: January 2022

Alu (B1 in rodents) hypomethylation, commonly found in diabetes mellitus patients, increases DNA damage and, consequently, delays the healing process. Alu siRNA increases Alu methylation, reduces DNA damage, and promotes cell proliferation.Aim: To explore whether B1 siRNA treatment restores B1 hypomethylation, resulting in a reduction in DNA damage and acceleration of the healing process in diabetic rat wounds.Methods: We generated splinted-excisional wounds in a streptozotocin (STZ)-induced type I diabetic rat model and treated the wounds with B1 siRNA/Ca-P nanoparticles to generate de novo DNA methylation in B1 intersperse elements. After treatment, we investigated B1 methylation levels, wound closure rate, wound histopathological structure, and DNA damage markers in diabetic wounds compared to nondiabetic wounds.Results: We reported that STZ-induced diabetic rat wounds exhibited B1 hypomethylation, wound repair defects, anatomical feature defects, and greater DNA damage compared to normal rats. We also determined that B1 siRNA treatment by Ca-P nanoparticle delivery restored a decrease in B1 methylation levels, remedied delayed wound healing, and improved the histological appearance of the wounds by reducing DNA damage.Conclusion: B1 hypomethylation is inducible in an STZ-induced type I diabetes rat model. Restoration of B1 hypomethylation using B1 siRNA leads to increased genome stability and improved wound repair in diabetes. Thus, B1 siRNA intervention may be a promising strategy for reprogramming DNA methylation to treat or prevent DNA damage-related diseases.
Plasma Lipid Profile and Intestinal Microflora in Pregnancy Women With Hypothyroidism and Their Correlation With Pregnancy Outcomes
Authors: Cai Yanjun , Xu Yajuan , Ban Yanjie , Li Jingjing , Sun Zongzong , Zhang Miao , Wang Biao , Hou Xiaofeng , Hao Yingqi , Ouyang Qian , Wu Bo , Wang Mengqi , Wang Wentao 
Published: January 2022

ObjectiveTo investigate the lipid profiles and intestinal microflora in pregnant patients with hypothyroidism and their correlation with pregnancy outcomes.MethodsIn total, 27 pregnant women with hypothyroidism (study case) and 28 normal pregnant women (control group) were enrolled in this study. The lipid profiles and intestinal microflora in the two groups were compared using untargeted liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA amplicon sequencing, respectively. The association among the differential metabolites, intestinal microflora, serological indicators and pregnancy outcomes was further analyzed.ResultsPatients in study case had higher C-reactive protein (CRP) levels (P = 0.025) and lower birth weight (P=0.005) than the control group. A total of 42 differential lipid metabolites and 7 enrichment KEGG pathways were obtained between the two groups (VIP ≥ 1, P &lt; 0.05). Ten lipid metabolites can be used as characteristic metabolites of study case, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM). The richness and diversity of intestinal microflora in study case were lower than those in the control group (P&gt;0.05). LEfSe analysis revealed that patients in study case had higher abundance of Prevotella and Haemophilus and lower abundance of Blautia than the control group (P &lt; 0.05). Blautia was positively correlated with SM and negatively correlated with PC and PE; the CRP level and Prevotella were positively correlated; the neonatal weight and PC level were negatively correlated (P &lt; 0.05).ConclusionThe lipid profile and intestinal microflora of pregnant women with hypothyroidism significantly differed from those of normal pregnant women and were associated with adverse pregnancy outcomes. The interaction between lipid metabolism and intestinal microflora may be a potential target for further studies investigating the pathogenesis of hypothyroidism during pregnancy.
A Systematic Review on PD-1 Blockade and PD-1 Gene-Editing of CAR-T Cells for Glioma Therapy: From Deciphering to Personalized Medicine
Authors: Abdoli Shadbad Mahdi , Hemmat Nima , Khaze Shahgoli Vahid , Derakhshani Afshin , Baradaran Farzad , Brunetti Oronzo , Fasano Rossella , Bernardini Renato , Silvestris Nicola , Baradaran Behzad 
Published: January 2022

BackgroundProgrammed cell death protein 1 (PD-1) can attenuate chimeric antigen receptor-T (CAR-T) cell-mediated anti-tumoral immune responses. In this regard, co-administration of anti-PD-1 with CAR-T cells and PD-1 gene-editing of CAR-T cells have been suggested to disrupt this inhibitory axis. Herein, we aim to investigate the advantages and disadvantages of these two approaches and propose a novel strategy to ameliorate the prognosis of glioma patients.MethodsScopus, Embase, and Web of Science were systematically searched to obtain relevant peer-reviewed studies published before March 7, 2021. Then, the current study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements. The random-effect model was applied to evaluate the effect size of administrated agents on the survival of animal models bearing gliomas using RevMan version 5.4. The Cochran Q test and I2 were performed to assess the possible between-study heterogeneity. Egger’s and Begg and Mazumdar’s tests were performed to objectively assess potential asymmetry and publication bias using CMA version 2.ResultsAnti-PD-1 can substantially increase the survival of animal models on second-generation CAR-T cells. Also, PD-1 knockdown can remarkably prolong the survival of animal models on third-generation CAR-T cells. Regardless of the CAR-T generations, PD-1 gene-edited CAR-T cells can considerably enhance the survival of animal-bearing gliomas compared to the conventional CAR-T cells.ConclusionsThe single-cell sequencing of tumoral cells and cells residing in the tumor microenvironment can provide valuable insights into the patient-derived neoantigens and the expression profile of inhibitory immune checkpoint molecules in tumor bulk. Thus, single-cell sequencing-guided fourth-generation CAR-T cells can cover patient-derived neoantigens expressed in various subpopulations of tumoral cells and inhibit related inhibitory immune checkpoint molecules. The proposed approach can improve anti-tumoral immune responses, decrease the risk of immune-related adverse events, reduce the risk of glioma relapse, and address the vast inter-and intra-heterogeneity of gliomas.
Oridonin Alleviates LPS-Induced Depression by Inhibiting NLRP3 Inflammasome via Activation of Autophagy
Authors: Li Chunyan , Zhu Yuehua , Wu Yuanyuan , Fu Meiyuan , Wu Yiling , Wu Yuehong , Qiu Yinger , Zhang Hui , Ding Mingxing 
Published: January 2022

Objective: Oridonin (Ori) is a diterpene compound that has multiple biological properties. Here, our study was conducted to observe the therapeutic effect of Ori on depression as well as to uncover the mechanism.Methods: Lipopolysaccharide (LPS)-induced depression models were established both in C57BL/6 mice and primary astrocytes, which were treated with Ori, autophagy agonist Rapamycin (Rap) and autophagy inhibitor 3-Methyladenine (3-MA). The depressive-like behaviors were assessed with behavioral tests. Autophagy was evaluated in the hippocampus and astrocytes by investigating autophagosomes under transmission electron microscope (TEM) and detecting LC3II/I, Beclin1 and P62 through western blotting. Astrocyte marker glial fibrillary acidic protein (GFAP) was investigated by immunofluorescence. NLRP3 inflammasome activation was evaluated by detecting IL-1β, NLRP3, ASC and Caspase-1 expression and reactive oxygen species (ROS) accumulation was quantified via DCFH-DA probe. Autolysosomes, autophagosomes and mitophagy were separately observed through mTag-Wasabi-LC3 plasmid, MitoTracker Deep Red staining, and TEM.Results: Our results showed that Ori administration alleviated LPS-induced depressive-like behaviors and increased GFAP expression in the hippocampus. Furthermore, Ori treatment promoted autophagy activation and cell viability as well as weakened NLRP3 inflammasome activation and ROS accumulation both in LPS-induced mice and astrocytes. Ori promoted the autophagic flux unblocked through enhancing fusion of autophagosomes with lysosomes as well as enhanced mitophagy in LPS-treated astrocytes. The therapeutic effect of Ori was enhanced by Rap and weakened by 3-MA.Conclusion: Collectively, our findings provided a promising antidepressant drug and uncovered that Ori alleviated LPS-induced depression by inhibiting NLRP3 inflammasome through activation of autophagy.
Expression of lncRNAs NEAT1 and lnc-DC in Serum From Patients With Behçet’s Disease Can Be Used as Predictors of Disease
Authors: Mohammed Shereen Rashad , Abdelaleem Omayma O. , Ahmed Fatma A. , Abdelaziz Ahmed Ali , Hussein Hoda Abdelbadie , Eid Hanaa M. , Kamal Marwa , Ezzat Mostafa Ahmed , Ali Marwa A. 
Published: January 2022

Background: Behçet’s disease (BD) is a chronic autoimmune disease. The early diagnosis of BD is very important to avoid serious and/or fatal complications such as eye damage, severe neurological involvement, and large vessel occlusion. New, sensitive biomarkers would aid in rapid diagnosis, the monitoring of disease activity, and the response to treatment.Methods: This study’s aim is to identify two immune system-related BD biomarkers. We measured long non-coding RNAs (lncRNAs) NEAT1 (nuclear-enriched abundant transcript 1), and lnc-DC (lncRNA in dendritic cells) in serum by real-time polymerase chain reaction (RT-PCR) in 52 BD patients and 52 controls. We analyzed the association between NEAT1 and lnc-DC and the clinical parameters of BD. Receiver operating characteristic (ROC) curve analysis was performed to explore the diagnostic performance of the studied genes.Results: Compared to controls, the significant upregulation of NEAT1 {median [interquartile range (IQR)] = 1.68 (0.38–7.7), p &lt; 0.0001} and downregulation of lnc-DC [median (IQR) = 0.2 (0.12–1.39), p = 0.03] were detected in the sera collected from BD patients. Higher serum expression levels of NEAT1 and lnc-DC were significantly associated with the following clinical presentations: cutaneous lesions, vascular manifestations, articular manifestations, neurological manifestations, and higher disease activity score. Also, high NEAT1 levels were significantly associated with a negative pathergy test, while higher lnc-DC was significantly associated with a positive family history. ROC curves showed that NEAT1 and lnc-DC levels in serum could be used as predictors of BD with high specificity and fair sensitivity. NEAT1 had an area under the curve (AUC) of 0.692 (95% CI: 0.591–0.794, p = 0.001), and lnc-DC had an AUC of 0.615 (95% CI: 0.508–0.723, p = 0.043).Conclusion: Serum lncRNAs NEAT1 and lnc-DC are biomarkers for BD.
Potential Metabolite Biomarkers for Early Detection of Stage-I Pancreatic Ductal Adenocarcinoma
Authors: Cao Yingying , Zhao Rui , Guo Kai , Ren Shuai , Zhang Yaping , Lu Zipeng , Tian Lei , Li Tao , Chen Xiao , Wang Zhongqiu 
Published: January 2022

Background &amp; ObjectivesPancreatic ductal adenocarcinoma remains an extremely malignant tumor having a poor prognosis. The 5-year survival rate of PDAC is related to its stage (about 80% for stage I vs 20% for other stages). However, detection of PDAC in an early stage is difficult due to the lack of effective screening methods. In this study, we aimed to construct a novel metabolic model for stage-I PDAC detection, using both serum and tissue samples.MethodsWe employed an untargeted technique, UHPLC-Q-TOF-MS, to identify the potential metabolite, and then used a targeted technique, GC-TOF-MS, to quantitatively validate. Multivariate and univariate statistics were performed to analyze the metabolomic profiles between stage-I PDAC and healthy controls, including 90 serum and 53 tissue samples. 28 patients with stage-I PDAC and 62 healthy controls were included in this study.ResultsA total of 10 potential metabolites presented the same expression levels both in serum and in tissue. Among them, a 2-metabolites-model (isoleucine and adrenic acid) for stage-I PDAC was constructed. The area under the curve (AUC) value was 0.93 in the discovery set and 0.90 in the independent validation set. Especially, the serum metabolite model had a better diagnostic performance than CA19-9 (AUC = 0.79). Pathway analysis revealed 11 altered pathways in both serum and tissue of stage-I PDAC.ConclusionsThis study developed a novel serum metabolites model that could early separate stage-I PDAC from healthy controls.
Insulin Treatment of Hypertriglyceridemia During Pregnancy
Authors: Cheng De-cui , Su Yao , Li Feifei , Xu Xianming 
Published: January 2022

Objective: This study aims to investigate the efficiency of insulin on the reduction of gestational lipid profiles and try to propose a real-world approach to assist clinicians.Methods: A retrospective, single-centered cohort study of 35 cases was conducted from October 2018 to July 2021 in Shanghai General Hospital. SPSS version 25.0 was performed to analyze the whole data. For continuous variables, a paired-sample t test was carried out on each variable to make a comparison between before and after treatment.Results: The average pre-pregnancy TGs and TCs of these patients were about 3.96 ± 1.42 mmol/L and 4.78 ± 1.18 mmol/L, respectively. The maximum of TG before insulin treatment was up to 64.62 and TC 20.43 mmol/L, which decreased to 17.34 and 4.92 mmol/L after intervention of the insulin drip. TG was noticed to fall by 77% and 12.71% of TG, respectively. The difference of TG and TC between pre-treatment and post-treatment were statistically significant (p &lt; 0.01), while this difference has not been found in the other laboratory tests reports. The outcomes of newborns and mothers with management of insulin were proven to be improved.Conclusion: The use of insulin in the management of gestational hypertriglyceridemia is safe and efficient, and insulin may become a mainstream in the near future to mitigate serum TG and TC levels in the pregnancy period besides regulating the blood glucose level.
Immunotherapy and Gene Therapy: New Challenges in the Diagnosis and Management of Drug-Induced Liver Injury
Authors: Delire Bénédicte , De Martin Eleonora , Meunier Lucy , Larrey Dominique , Horsmans Yves 
Published: January 2022

In the last 5 years, the landscape of oncologic treatment has been deeply modified with the development and use of immune checkpoint inhibitors (ICIs) that exert their antitumoral effect by reverting the exhausted phenotype of tumor-infiltrating lymphocytes. This innovative therapeutic strategy has widely changed the prognosis of some advanced neoplastic diseases such as melanoma and lung cancer, providing durable remission for a significant number of patients. Unfortunately, immune-related adverse events (irAEs), especially ICI-induced hepatitis, may be very severe in some cases, impairing the prognosis of the patient. Guidelines available today on the diagnosis and management of ICI-induced hepatitis are mainly based on expert opinions and case series. This lack of large data is explained not only by the low incidence of hepatic adverse events but also by their clinical heterogeneity and variable severity. In this article, we will review the clinical, biological, and histological characteristics of ICI-induced liver injury. We will discuss the current knowledge on their pathological mechanisms and their therapeutic strategy based on immunosuppressive treatment for more severe cases. Regarding severity assessment, we will discuss the gap between the oncologist and the hepatologist’s point of view, highlighting the need for multidisciplinary management. While initially developed for notably less frequent diseases than neoplastic ones, gene therapy is going to be a revolution for the treatment of diseases not responding to pharmacological therapy. Limited but growing data describe liver injury after the administration of such therapy whose exact physiopathology remains unknown. In this article, we will discuss the available data supporting the role of gene therapies in the onset of drug-induced liver injury and related mechanisms. We will describe the clinical context, the biological and histological features, and the management currently proposed.