bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, adherence and efficacy of PCSK9 inhibitors: a retrospective real-world study
Authors: Chng Bee Ling Kelly , Heng Wei Min Paul , Soon Yu Ming , Hon Jin Shing , Lau Yee How , Tan Ru San , Tan Jack Wei Chieh 
Published: December 2022

Introduction PCSK9 inhibitors demonstrated their effectiveness in reducing low-density lipoprotein cholesterol (LDL-C) and cardiovascular events in landmark trials. It remains unclear whether the results can be translated to Asian populations. This study was designed to assess the real-world safety, adherence and efficacy of PCSK9 inhibitors. Methods A retrospective review for patients newly initiated on PCSK9 inhibitors between 1st June 2017 and 31st July 2021 was conducted in a tertiary cardiology centre. Patients aged ≥ 21 years with a minimum one-month follow-up were included. Adverse drug reactions (ADRs), drug discontinuation, adherence patterns and efficacy between evolocumab and alirocumab groups were compared. Multivariable and propensity score adjusted Cox regression analyses were applied to analyse the outcomes. Results Of 87 patients screened, 80 (51 evolocumab; 29 alirocumab) were included. There were no significant differences between evolocumab and alirocumab groups in ADRs (11.8% vs 3.4%, adjusted HR, 2.97; 95% CI, 0.34 – 25.89 in multivariable analysis; adjusted HR, 3.24; 95% CI, 0.38–27.69 after propensity score adjustment) and discontinuation rates (27.5% vs 34.5%, adjusted HR, 0.89; 95% CI, 0.40–2.02 in multivariable analysis; adjusted HR, 0.88; 95% CI, 0.39–1.99 after propensity score adjustment). High medication cost was the main reason for discontinuation. One-third of patients had inadequate adherence to PCSK9 inhibitors. Both groups showed significant reductions of LDL-C compared to baseline. Conclusions PCSK9 inhibitors are efficacious, safe and well tolerated. Further studies are warranted to examine the cost-effectiveness of PCSK9 inhibitors to rationalise their sustainable use for cardiovascular prevention.
Modeling the Impact of Nonpharmaceutical Interventions on COVID-19 Transmission in K-12 Schools
Authors: Zhang Yiwei , Mayorga Maria E , Ivy Julie , Hassmiller Lich Kristen , Swann Julie L. 
Published: December 2022

Background. The novel coronavirus SARS-CoV-2 spread across the world causing many waves of COVID-19. Children were at high risk of being exposed to the disease because they were not eligible for vaccination during the first 20 mo of the pandemic in the United States. While children 5 y and older are now eligible to receive a COVID-19 vaccine in the United States, vaccination rates remain low despite most schools returning to in-person instruction. Nonpharmaceutical interventions (NPIs) are important for controlling the spread of COVID-19 in K-12 schools. US school districts used varied and layered mitigation strategies during the pandemic. The goal of this article is to analyze the impact of different NPIs on COVID-19 transmission within K-12 schools. Methods. We developed a deterministic stratified SEIR model that captures the role of social contacts between cohorts in disease transmission to estimate COVID-19 incidence under different NPIs including masks, random screening, contact reduction, school closures, and test-to-stay. We designed contact matrices to simulate the contact patterns between students and teachers within schools. We estimated the proportion of susceptible infected associated with each intervention over 1 semester under the Omicron variant. Results. We find that masks and reducing contacts can greatly reduce new infections among students. Weekly screening tests also have a positive impact on disease mitigation. While self-quarantining symptomatic infections and school closures are effective measures for decreasing semester-end infections, they increase absenteeism. Conclusion. The model provides a useful tool for evaluating the impact of a variety of NPIs on disease transmission in K-12 schools. While the model is tested under Omicron variant parameters in US K-12 schools, it can be adapted to study other populations under different disease settings. Highlights A stratified SEIR model was developed that captures the role of social contacts in K-12 schools to estimate COVID-19 transmission under different nonpharmaceutical interventions. While masks, random screening, contact reduction, school closures, and test-to-stay are all beneficial interventions, masks and contact reduction resulted in the greatest reduction in new infections among students from the tested scenarios. Layered interventions provide more benefits than implementing interventions independently.
Retinal Vasculopathy With Cerebral Leukoencephalopathy and Systemic Manifestations: Critical Role of Retina Specialists
Authors: Houghton Odette M. , Carter Jonathan , Dhamija Radhika 
Published: December 2022

Purpose: To describe a case of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) to enhance early recognition of this often-missed diagnosis. Methods: A case report is presented. Results: A 50-year-old woman with a history of Raynaud phenomenon, memory difficulties, and a family history of strokes was referred for evaluation of a bilateral, small-vessel, occlusive disease refractory to immunosuppressive therapy. An extensive workup for treatable causes was unrevealing. Fifteen months after presentation, brain imaging showed white-matter lesions and dystrophic calcification, which led to the discovery of a pathogenic variant in TREX1 and the diagnosis of RVCL-S. Conclusions: Retina specialists play a critical role in the timely diagnosis of RVCL-S. Although the findings in this condition can mimic those in other common retinal vascular disorders, there are key characteristics that increase the suspicion for RVCL-S. Early recognition might decrease unnecessary therapies and procedures.
Neighborhood Modularization-based Artificial Bee Colony Algorithm for Disassembly Planning with Operation Attributes
Authors: Guo Hongfei , Zhang Linsheng , Ren Yaping , Meng Leilei , Zhou Zhongwei , Li Jianqing 
Published: December 2022

AbstractThe recycling and remanufacturing of end-of-life products are significant for environmental protection and resource conservation. Disassembly is an essential process of remanufacturing end-of-life products. Effective disassembly plans help improve disassembly efficiency and reduce disassembly costs. This paper studies a disassembly planning problem with operation attributes, in which an integrated decision of the disassembly sequence, disassembly directions, and disassembly tools are made. Besides, a mathematical model is formulated with the objective of minimizing the penalty cost caused by the changing of operation attributes. Then, a neighborhood modularization-based artificial bee colony algorithm is developed, which contains a modular optimized design. Finally, two case studies with different scales and complexities are used to verify the performance of the proposed approach, and experimental results show that the proposed algorithm outperforms the two existing methods within an acceptable computational time.
MPC-Based Coordinated Control of Gear Shifting Process for a Power-split Hybrid Electric Bus with a Clutchless AMT
Authors: Liu Tong , Zeng Xiaohua , Song Dafeng 
Published: December 2022

AbstractTwo-speed clutchless automated manual transmission (AMT) has been widely implemented in electric vehicles for its simple structure and low cost. In contrast, due to the complex response characteristics of powertrain, utilizing clutchless AMT in a hybrid power system comes with complex coordination control problems. In order to address these issues, a power-split hybrid electric bus with two-speed clutchless AMT is studied in this paper, and a coordinated control method based on model predictive control (MPC) is used in gear shifting control strategy (GSCS) to improve gear shifting quality and reduce system jerk. First, the dynamic model of power sources and other main powertrain components including a single planetary gear set and AMT are established on the basis of data-driven and mechanism modeling methods. Second, the GSCS is put forward using the segmented control idea, and the shifting process is divided into five phases, including (I) unloading of drive motor, (II) shifting to neutral gear, (III) active speed synchronization by drive motor, (IV) engaging to new gear, and (V) resuming the drive motor’s power, among which the phases I and V have evident impact on the system jerk. Then, the MPC-based control method is adopted for these phases, and the fast compensation of driving torque is realized by combining the prediction model and quadratic programming method. The simulation results show that the proposed GSCS can effectively reduce shift jerk and improve driving comfort. This research proposes a coordinated control strategy of two-speed clutchless AMT, which can effectively improve the smoothness of gear shifting and provides a reference for the application of two speed clutchless AMT in power-split hybrid powertrains.
Proteomics profiles of blood glucose-related proteins involved in a Chinese longevity cohort
Authors: Zhang Rong , Liu Fengjuan , Ye Shengliang , Du Xi , Ma Li , Cao Haijun , Wang Zongkui , Li Changqing 
Published: December 2022

Abstract
Background
High blood glucose level is one of the main characteristics of diabetes mellitus. Based on previous studies, it is speculated longevity families may have certain advantages in blood glucose regulation. However, limited information on these items has been reported. The purpose of this study was to profile differences of plasma proteomics between longevity subjects (with normal fructosamine (FUN) level) and non-longevity area participants (with exceeding standard FUN level).

Methods
In this study, a TMT-based proteomics analysis was used to profile differences of plasma proteomics between longevity subjects (with normal FUN level) and non-longevity area participants (with exceeding standard FUN level). Results were validated by Luminex detection.

Results
A total of 155 differentially expressed proteins (DEPs) were identified between these two groups. The DEPs related to blood glucose regulation were mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism and propanoate metabolism, and most of the DEPs were contained in carbohydrate metabolism, PI3K-Akt pathway, glucagon signaling pathway and inflammatory response. Validation by Luminex detection confirmed that CD163 was down-regulated, and SPARC, PARK 7 and IGFBP-1 were up-regulated in longevity participants.

Conclusions
This study not only highlighted carbohydrate metabolism, PI3K-Akt pathway, glucagon signaling pathway and inflammatory response may play important roles in blood glucose regulation, but also indicated that YWHAZ, YWHAB, YWHAG, YWHAE, CALM3, CRP, SAA2, PARK 7, IGFBP1 and VNN1 may serve as potential biomarkers for predicting abnormal blood glucose levels.
Role of serum cathelicidin in diagnosis of patient with prostatitis and prostate carcinoma
Authors: Benlier Necla , Solakhan Mehmet , Sever Özlem Nuray , Yıldırım Zeliha , Orhan Nuri , Çiçek Hülya , Yıldırım Mustafa 
Published: December 2022

Abstract
Background
This study investigated the diagnostic role of 75 levels measured in serum prostatitis and prostate carcinoma and in the differentiation of these two conditions.

Methods
The study was conducted with 75 patients histopathologically diagnosed with prostate carcinoma or prostatitis and followed up at the Departments of Urology and Medical Oncology and 21 healthy male subjects. Serum cathelicidin levels were investigated using the ELISA method. Statistical analyses were performed using the SPSS for Windows 22.0 package software. Compliance of the variables to normal distribution was examined using visual and analytic methods. In the Kolmogorov–Smirnov test, cases with a p value of greater than 0.05 were accepted as normal distribution.

Results
A total of 75 patients including 45 diagnosed with prostate carcinoma and 30 diagnosed with prostatitis, as well as 21 healthy control subjects were included in the study. Prostate-specific antigen (PSA) was detected as 23 (4–1200) ng/mL in the patients with prostate carcinoma and as 9.85 (3.9–405 ng/mL) in the patients with prostatitis. The cathelicidin levels were diagnostically significant when assessed by ROC analysis in the prostate cancer, prostatitis and control groups (p = 0.005). The cutoff values derived from the ROC curve analysis were 3.5151 ng/mL for distinguishing prostate cancer from prostatitis, 2.2620 ng/mL for prostate cancer versus control group and 1.2340 ng/mL for prostatitis versus control group.

Conclusions
In this study we showed that the serum cathelicidin levels were significantly higher in the patients diagnosed with prostate carcinoma. Measurement of serum cathelicidin levels could be used as a diagnostic marker in prostate carcinoma as well as facilitating differential diagnosis to strengthen the diagnostic suspicion before prostate biopsy and distinguish the diagnosis from prostatitis cases.
Genetic Analysis of Platelet-Related Genes in Hepatocellular Carcinoma Reveals a Novel Prognostic Signature and Determines PRKCD as the Potential Molecular Bridge
Authors: Li Xiangyu , Zhao Kai , Lu Yun , Wang Jianming , Yao Wei 
Published: December 2022

Abstract
Background
Hepatocellular carcinoma (HCC) belongs to a representative lethality gastrointestinal malignancy, and comprehensive management of HCC remains intractable at present on account of its invasive biological feature that is easy to relapse and early metastasis. The intimate connection between platelets and tumor progression has been widely reported, and platelet-related indicators are also used in the clinical practice of carcinoma. This work is designed to investigate the significance of platelet-related genes in the prognostic prediction of patients with HCC and their potential role in the cross-talk between HCC cells and platelets in the tumor microenvironment.

Methods
By integrating the RNA-seq data and clinicopathological information of HCC patients, we extracted prognosis-associated platelet-related genes based on the univariate cox analysis and further established a relevant prognostic signature via the lasso cox regression analysis, and two independent HCC cohorts were used as external validation. Multiple bioinformatics methods were utilized to explore the underlying functional discrepancy between different risk groups classified by the risk model. And in vitro proliferation, invasion, and migration assays were conducted to investigate the effect of platelet stimulation on HCC cells’ viability and motility, and flow cytometric analysis was exerted to demonstrate the influence of HCC cells on platelet activation.

Results
A novel platelet-related risk model was developed and patients both in the training and testing cohorts were divided into distinct risk subgroups according to the median risk score. It was observed that the high-risk status was closely associated with poor prognosis and worse clinicopathological parameters. Meanwhile, an obvious discrepancy in the constitution of the immune microenvironment also indicated that distinct immune status might be a potential determinant affecting prognosis as well as immunotherapy reactiveness. Moreover, in vitro experiments demonstrated that PRKCD could act as a molecular bridge between tumor cells and platelets, which could either participate in regulating tumor malignant phenotype or mediating platelet activation.

Conclusions
In brief, this work reveals a novel platelet-related risk signature for prognostic evaluation of HCC patients and confirms that PRKCD is a key messenger in HCC cell-platelet interaction and plays a crucial role in mediating platelet-induced tumor progression.
A robust pipeline for efficient knock-in of point mutations and epitope tags in zebrafish using fluorescent PCR based screening
Authors: Carrington Blake , Ramanagoudr-Bhojappa Ramanagouda , Bresciani Erica , Han Tae-Un , Sood Raman 
Published: December 2022

AbstractBackgroundGenome editing using CRISPR/Cas9 has become a powerful tool in zebrafish to generate targeted gene knockouts models. However, its use for targeted knock-in remains challenging due to inefficient homology directed repair (HDR) pathway in zebrafish, highlighting the need for efficient and cost-effective screening methods. ResultsHere, we present our fluorescent PCR and capillary electrophoresis based screening approach for knock-in using a single-stranded oligodeoxynucleotide donor (ssODN) as a repair template for the targeted insertion of epitope tags, or single nucleotide changes to recapitulate pathogenic human alleles. For the insertion of epitope tags, we took advantage of the expected change in size of the PCR product. For point mutations, we combined fluorescent PCR with restriction fragment length polymorphism (RFLP) analysis to distinguish the fish with the knock-in allele. As a proof-of-principle, we present our data on the generation of fish lines with insertion of a FLAG tag at thetcnbalocus, an HA tag at thegata2blocus, and a point mutation observed in Gaucher disease patients in thegbagene. Despite the low number of germline transmitting founders (1–5%), combining our screening methods with prioritization of founder fish by fin biopsies allowed us to establish stable knock-in lines by screening 12 or less fish per gene.ConclusionsWe have established a robust pipeline for the generation of zebrafish models with precise integration of small DNA sequences and point mutations at the desired sites in the genome. Our screening method is very efficient and easy to implement as it is PCR-based and only requires access to a capillary sequencer.
Comparative analysis of mitochondrial genomes reveals marine adaptation in seagrasses
Authors: Chen Jun , Zang Yu , Liang Shuo , Xue Song , Shang Shuai , Zhu Meiling , Wang Ying , Tang Xuexi 
Published: December 2022

Abstract
Background
Seagrasses are higher marine flowering plants that evolved from terrestrial plants, but returned to the sea during the early evolution of monocotyledons through several separate lineages. Thus, they become a good model for studying the adaptation of plants to the marine environment. Sequencing of the mitochondrial (mt) genome of seagrasses is essential for understanding their evolutionary characteristics.

Results
In this study, we sequenced the mt genome of two endangered seagrasses (Zostera japonica and Phyllospadix iwatensis). These data and data on previously sequenced mt genomes from monocotyledons provide new evolutionary evidence of genome size reduction, gene loss, and adaptive evolution in seagrasses. The mt genomes of Z. japonica and P. iwatensis are circular. The sizes of the three seagrasses (including Zostera marine) that have been sequenced to date are smaller than that of other monocotyledons. Additionally, we found a large number of repeat sequences in seagrasses. The most abundant long repeat sequences were 31–40 bp repeats. Our study also found that seagrass species lost extensive ribosomal protein genes during evolution. The rps7 gene and the rpl16 gene of P. iwatensis are exceptions to this trend. The phylogenetic analysis based on the mt genome strongly supports the previous results. Furthermore, we identified five positive selection genes (atp8, nad3, nad6, ccmFn, and matR) in seagrasses that may be associated with their adaptation to the marine environment.

Conclusions
In this study, we sequenced and annotated the mt genomes of Z. japonica and P. iwatensis and compared them with the genome of other monocotyledons. The results of this study will enhance our understanding of seagrass adaptation to the marine environment and can inform further investigations of the seagrass mt genome.
Genetic analysis of resistance to powdery mildew on 7Mg chromosome of wheat–Aegilops geniculata, development and utilization of specific molecular markers
Authors: Wang Yongfu , Fan Jianzhong , Xiao Yi , Feng Xianbo , Zhang Hong , Chen Chunhuan , Ji Wanquan , Wang Yajuan 
Published: December 2022

Abstract
Background
Powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) is prevalent in the main wheat-producing regions of China, resulting in severe yield losses in recent years. Mining and utilization of resistant genes from wild relatives of wheat is the most environmentally sound measure to control disease. Aegilops geniculata Roth (2n = 2x = 28, UgUgMgMg) is an essential and valuable disease-resistance gene donor for wheat improvement as a close relative species.

Results
In this study, to validate powdery mildew resistance locus on chromosome 7Mg, two genetic populations were constructed and through crossing wheat – Ae. geniculata 7Mg disomic addition line NA0973-5-4-1-2-9-1 and 7Mg (7 A) alien disomic substitution line W16998 with susceptible Yuanfeng175 (YF175, authorized varieties from Shaanxi province in 2005), respectively. Cytological examination, in situ hybridization (ISH), and functional molecular markers analysis revealed that the plants carrying chromosome 7Mg showed high resistance to powdery mildew in both F1 and F2 generation at the seedling stage. Besides, 84 specific markers were developed to identify the plants carrying chromosome 7Mg resistance based on the specific-locus amplified fragment sequencing (SLAF-seq) technique. Among them, four markers were selected randomly to check the reliability in F2 segregating populations derived from YF175/NA0973-5-4-1-2-9-1 and YF175/W16998. In summary, the above analysis confirmed that a dominant high powdery mildew resistance gene was located on chromosome 7Mg of Ae. geniculata.

Conclusion
The results provide a basis for mapping the powdery mildew resistance gene mapping on chromosome 7Mg and specific markers for their utilization in the future.
Perioperative blood pressure and heart rate alterations after carotid body tumor excision: a retrospective study of 108 cases
Authors: Chen Si , Xu Jingjing , Gu Guangchao , Zhang Yuelun , Zhang Jiao , Zheng Yuehong , Huang Yuguang 
Published: December 2022

Abstract
Background
Arising from chemoreceptor cells, carotid body tumors (CBTs) are rare neoplasms associated with hemodynamics. Perioperative changes in blood pressure (BP) and heart rate (HR) are not completely understood.

Methods
This retrospective, observational, controlled study included all CBT patients from 2013 to 2018 in Peking Union Medical College Hospital. Perioperative changes in BP/HR within or between unilateral/bilateral/control groups were investigated. Perioperative details across Shamblin types were also assessed.

Results
This study included 108 patients (116 excised CBTs). The postoperative systolic BP and HR increased in both unilateral (mean difference of systolic BP = 5.9mmHg, 95% CI 3.1 ~ 8.6; mean difference of HR = 3.7 bpm, 95% CI 2.6 ~ 4.9) and bilateral (mean difference of systolic BP = 10.3mmHg, 95% CI 0.6 ~ 19.9; mean difference of HR = 8.4 bpm, 95% CI 0.5 ~ 16.2) CBT patients compared with the preoperative measures. Compared with control group, the postoperative systolic BP increased (difference in the alteration = 6.3mmHg, 95% CI 3.5 ~ 9.0) in unilateral CBT patients; both systolic BP (difference in the alteration = 9.2mmHg, 95% CI 1.1 ~ 17.3) and HR (difference in the alteration = 5.3 bpm, 95% CI 1.0 ~ 9.6) increased in bilateral CBT patients. More CBT patients required extra antihypertensive therapy after surgery than controls (OR = 2.5, 95% CI 1.14 ~ 5.5). Maximum tumor diameter, intraoperative vascular injury, continuous vasoactive agent requirement, total fluid volume, transfusion, estimated blood loss, operation duration, postoperative pathology, overall complications, and intensive care unit/hospital lengths of stay significantly varied among Shamblin types.

Conclusion
CBT excision may be associated with subtle perioperative hemodynamic changes. Perioperative management of CBT patients necessitates careful assessment, full preparation and close postoperative monitoring.